GHAI Essential Pediatrics 9E
GHAI Essential Pediatrics 9E
GHAI Essential Pediatrics 9E
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Ninth Edition
GHAI
Ninth Edition
Editors
CBS
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Preface to the First Edition
T he health problems of the children in the third world are the most pressing. Physicians in these countries
often have to work under constraints of poor resources and a lack of access to the modern diagnostic
aids. They, therefore, of necessity require a more exhaustive training in clinical skills and a sharper clinical
acumen than their counterparts more fortunately placed. The present textbook is primarily aimed to fulfil
this need.
This book covers a broad spectrum of the subject, laying a special emphasis on the nutritional and
infectious disorders. Rare diseases are referred to only briefly. This has helped to restrict the size of the
book to a manageable level so that the undergraduate medical students may find it handy and useful.
The sections on the applied aspects of anatomy and physiology of the various body systems and
pathophysiology of the disease processes affecting them will appeal to the postgraduate medical students.
These may help them in understanding the biological basis of diagnosis and management. The sections on
the use of drugs, clinical approach to the diagnosis and details of diagnostic and therapeutic procedures
will be useful especially for the general practitioners and clinical residents.
Most references used in the preparation of the manuscript have been cited but if some have been left out
through oversight, I offer my sincere apologies. I thank Prof MMS Ahuja for the permission to include
some excerpts from the chapter on "Nutrition" written by Dr Tara Gopaldas and me from the book Progress
in Clinical Medicine, Series IV, published by Arnold-Heinemann, New Delhi.
I acknowledge my gratitude to all my colleagues in the department who gave me unstinted support and
stood solidly beside me in our joint endeavour for upgrading the status of pediatric services in India. The
erudition and scholarship of Professors KL Wig and V Ramalingaswami have been a great source of
inspiration to me. I am grateful to Professors PN Taneja and Harish Chandra, who encouraged me to write
this book.
I take this opportunity to thank Dr PSN Menon, my erstwhile student, now a dear colleague, who helped
me at every stage of preparation of this edition. The book bears an indelible imprint of his meticulous
efforts. I am grateful to my colleague Dr HS Wasir for his valuable suggestions on the section on
hypertension. Drs RK Menon, Vedanarayanan and Anil Gupta read through several sections and made
helpful suggestions.
Many medical students, especially Mr Gurkirpal Singh, helped at several stages in the preparation of the
book. I am grateful to Messrs Ganguly, Mitra, Ghosh and Awasthi for their help in artwork. Shri Suraj Bhan did
the typing work with great patience. Shri JN Mathur of Mehta Offset Works toiled painstakingly to give the
finishing touches to the book. Shri SN Mehta, our publisher, was very co-operative and took a special pride in
publishing this volume.
1982 OP Ghai
to
Our yarentsfor yravidint] us the oyyortunity to rearn and serve
Our teachers and mentorsfor inparting know(edge and incu(cating va(ues
Our co((eagues for their affection and ins_piration
Our famiUesfor their yatience and unstinted suyyort
-Xditors
Prof. Om Prakash Ghai
P rof. Om Prakash Ghai had a distinguished academic tenure at the All India Institute
of Medical Sciences, New Delhi. He started the Department of Pediatrics in 1959
with six beds for children. Under his leadership, the department evolved into a
multispecialty centre of international repute. After his retirement as Dean of the Institute
and Professor and Head of the Department of Pediatrics, he chaired the Department of
Pediatrics at the University College of Medical Sciences, Delhi, where he served until
1991.
Prof. Ghai was President of the Indian Academy of Pediatrics in 1978 and President
of the International College of Pediatrics from 1987 to 1990. The International Pediatric
Association presented him the prestigious 'Insignia of Merit Medallion' (1977) for his
outstanding contributions to child welfare. The Indian Council of Medical Research 1928-2008
awarded him the Dr Kamla Menon Prize (1983) and Amrut Mody Prize (1985). The
Medical Council of India bestowed on him the Dr BC Roy Memorial Award for 'Eminent Medical Teacher'
(1987). He was awarded honorary fellowships of the American Academy of Pediatrics, the National Academy
of Medical Sciences and the Indian Academy of Pediatrics.
Prof. Ghai served as a short-term consultant to the World Health Organization and Asian Development
Bank. He was a member of the Technical Advisory Group of the Control of Diarrheal Diseases Program of
the World Health Organization (1987-89). He was member of the National Children's Board and several
expert groups of the Government of India, UNICEF and Indian Council of Child Welfare. He was the editor
of Indian Pediatrics and member of the editorial advisory boards of multiple journals.
Prof. Ghai was a teacher par excellence, an inspiring leader and a true visionary. His name shall always
remain etched in the annals of pediatrics of our country.
Preface to the Ninth Edition
As we present the ninth edition of Essential Pediatrics, we are humbled by the role this textbook has played
J-\. in imparting knowledge in child health to generations of doctors. Four decades ago, late Prof. OP Ghai
foresaw the need for a textbook of pediatrics for medical students of the country and South Asia. Thereafter, each
new edition has attempted to present updated knowledge to an expanding group of undergraduate and
postgraduate students.
For India, the next three decades offer a never-before window of opportunity to accelerate its economic growth
and emerge as a nation that would banish poverty forever, and attain heights of prosperity and well-being. We
are transitioning through a demographic phase characterized by an exceptionally high young population
constituting a workforce that is available for economic activity and nation-building. This demographic dividend
can be realized only if children and adolescents are healthy, strong and intelligent. Pediatrics, the science and art
of child healthcare, has thus acquired a new meaning and relevance in the context of new India.
With Ayushman Bharat, the nation has committed itself to a comprehensive primary health system and to
ensure financial protection for the vulnerable families in accessing care for children and adults alike. Preventive
and promotive health and nutrition will gain further ground, and the agenda of health loss due to pneumonia,
diarrhea, other infections, complications of preterm birth and vaccine preventable diseases would receive even
more attention. Adolescent health and development will be increasingly important in the coming years. We are
already witnessing an upsurge in demand for healthcare for chronic systemic diseases, developmental disorders,
disabilities and childhood origins of adult diseases. The realization that children have the right to secondary and
tertiary health care has stimulated the development of pediatric superspecialty programs.
The present edition of Essential Pediatrics continues to respond to these developments. The book maintains its
focus on undergraduate medical students. While we ensure that the 'must know' contents are thoroughly covered,
we provide a glimpse of the 'should know' curriculum. We have ensured that the size of the book enables it to be
readable and handy enough for the classroom and the bedside-as Prof. Ghai always reminded us. Given the
emphasis on updated management of common childhood illnesses, primary care physicians and pediatricians
would find the book useful. As before, there are strong sections on core areas that continue to serve the needs of
postgraduate students.
A number of changes have been incorporated in this edition. We welcome new authors for chapters on disorders
of development, central nervous system, micronutrients, otorhinolaryngology, poisoning and accidents, and
integrated management of childhood illnesses. Most other chapters, especially on growth, nutrition, immunization,
malignancies, genetics, inborn errors of metabolism and infections, have been revised. The CBSiCentral App
featuring illustrations, clinical photographs, tables and algorithms shall serve as a useful educational resource.
The editors are grateful to all the contributing authors for their scholarly inputs and ensuring that the chapters
continue to provide succinct and updated information, meeting the learning needs of students.
We thank our undergraduate and postgraduate students for their suggestions on content. Dr Priyanka
Khandelwal has helped during multiple stages of preparation, ensuring consistent style across chapters. Dr Aditi
Sinha, Dr Biswaroop Chakrabarty and Dr Jitendra Meena read through several sections and made useful
suggestions.
We thank our colleagues at CBSP&D, Mr YN Arjuna and Ms Ritu Chawla, for ensuring the quality of publication
of previous and the present editions. We gratefully acknowledge our colleagues at the AIIMS and other centers
for contributing illustrations and the support of our secretaries, Mr Anil Bhutani and Mr Akhilesh Sharma.
We whole-heartedly thank our readers for the trust, support and suggestions.
Vinod K Paul
Arvind Bagga
List of Contributors
Kamran Afzal Ashok K Deorari Madhullka Kabra
Professor Professor and Head Professor
Department of Pediatrics Department of Pediatrics Department of Pediatrics
Jawaharlal Nehru Medical College All India Institute of Medical Sciences Genetics Unit
Aligarh Muslim University New Delhi All India Institute of Medical Sciences
Aligarh New Delhi
Tushar R Godbole
Anuja Agarwala Consultant Pediatric Endocrinologist Sushil K Kabra
Dietitian Assistant Professor, Dr Vasant Pawar Professor
Department of Pediatrics Medical College, Nashik Department of Pediatrics
All India Institute of Medical Sciences Director, Harmony Health Hub, Nashik Division of Pulmonology and Intensive Care
New Delhi All India Institute of Medical Sciences
Sheffali Gulati New Delhi
Ramesh Agarwal Professor
Professor Department of Pediatrics Neena Khanna
Department of Pediatrics Division of Neurology Professor
Division of Neonatology All India Institute of Medical Sciences Department of Dermatology
All India Institute of Medical Sciences New Deihl All India Institute of Medical Sciences
New Delhi New Delhi
Neerja Gupta
Varun Alwadhi Assistant Professor Ajay Khera
Senior Resident Department of Pediatrics Public Health Specialist and
Kalawati Saran Children's Hospital Genetics Unit Deputy Commissioner
Lady Hardinge Medical College All India Institute of Medical Sciences Ministry of Health and Family Welfare
New Delhi New Delhi Government of India, New Delhi
11. Infections and Infestations 205 15. Disorders of Respiratory System 371
Tanu Singha/, Rakesh Lodha, Sushi/ K Kabra Sushi/ K Kabra
Fever 205 Developmental physiology 371
Common viral infections 209 Common respiratory symptoms 372
HIV infection, acquired immunodeficiency syndrome 224 Investigations for respiratory illnesses 374
Common bacterial infections 234 Upper respiratory tract infections 375
Tuberculosis 243 Lower respiratory tract infections 376
Pneumonia 377
Rickettsial and mycoplasma infections 251
Acute respiratory tract infection control program 380
Fungal Infections 253
Bronchiolitis 380
Protozoa! infections 254
Bronchial asthma 382
Congenital and perinatal infections 264
Foreign body aspiration 390
Helminthic infestations 265
Approach to chronic cough 390
Rational antimicrobial therapy and antimicrobial
Suppurative lung disease 391
resistance 271
Empyema thoracis 391
Health care associated Infections and Infection control 271
Cystic fibrosis 392
Acute respiratory distress syndrome 393
12. Diseases of Gastrointestinal System
and Liver 273 16. Disorders of Cardiovascular
Anshu Srivastava, Barath Jagadisan, System 394
Surender K Yachha
R Krishna Kumar, Manu Raj
Gastrointestinal system 273
Congestive cardiac failure 394
Acute diarrhea 287
Congenital heart disease 398
Persistent diarrhea 293
Acyanotic congenital heart defects 409
Chronic diarrhea 295
Cyanotic heart disease 417
Gastrointestinal bleeding 303
Obstructive lesions 425
Disorders of the hepatobiliary system 306
Rheumatic fever 430
Acute viral hepatitis 310
Rheumatic heart disease 434
Liver failure 311
Infective endocarditis 439
Chronic liver disease 313
Ascites 315 Myocardial diseases 442
Portal hypertension 316 Pericardia! diseases 445
Autoimmune liver disease 319 Systemic hypertension 446
Chronic hepatitis B infection 319 Pulmonary arterial hypertension 450
Hepatitis C infection 320 Rhythm disorders 452
Metabolic liver disease 321 Preventing adult cardiovascular disease 458
Neonatal cholestasis 325
17. Disorders of Kidney and
13. Hematological Disorders 329 Urinary Tract 460
Tulika Seth Arvind Bagga, Aditi Sinha, RN Srivastava
Anemia 329 Renal anatomy and physiology 460
Iron deficiency anemia 333 Diagnostic evaluation 463
Megaloblastic anemia 334 Hematuria 466
Hemolytic anemias 336 Proteinuria 468
Thalassemias 339 Acute glomerulonephritis 469
Sickle cell anemia 342 Nephrotic syndrome 472
Aplastic anemia 343 Chronic glomerulonephritis 478
Hematopoietic stem cell transplantation 345 Interstitial nephritis 478
Disorders of hemostasis and thrombosis 347 Urinary tract infections 478
Thrombotic disorders 354 Vesicoureteric reflux 480
Disorders of white blood cells 355 Acute kidney injury 482
Hemolytic uremic syndrome 487
Chronic kidney disease 488
14. Otorhinolaryngology 357 Renal replacement therapy 492
Prem Sagar, Alok Thakar, Sandeep Samant Disorders of renal tubular transport 492
Diseases of the ear 357 Nephrolithiasis and nephrocalcinosis 497
Diseases of the nose and sinuses 363 Enuresis 499
Diseases of the oral cavity and pharynx 366 Congenital abnormalities of kidney and urinary tract 500
Diseases of the larynx and trachea 368 Antenatal hydronephrosis 501
Diseases of the salivary glands 370 Cystic kidney diseases 502
Contents xv-
18. Endocrine and Metabolic Disorders 504 22. Rheumatological Disorders 620
PSN Menon, Anurag Bajpai Surjit Singh
General principles 504 Arthritis 620
Disorders of pituitary gland 505 Systemic lupus erythematosus 624
Disorders of thyroid gland 510 Juvenile dermatomyositis 625
Disorders of calcium metabolism 516 Scleroderma 626
Disorders of adrenal glands 518 Mixed connective tissue disease 626
Obesity 524 Vasculitides 627
Disorders of the gonadal hormones 529
Disorders of sex development 536
Diabetes mellitus 540
23. Genetic Disorders 631
Neerja Gupta, Madhulika Kabra
Chromosomes and genes 631
19. Diseases of Central Nervous System 552 Chromosomal disorders 632
Rashmi Kumar Down syndrome 635
Neurological diagnosis 552 Turner syndrome 637
Seizures and epilepsy 553 Single gene disorders 639
Congenital malformations 557 Polygenic inheritance 641
Neurocutaneous syndromes 558 Therapy for genetic disorders 641
Infections and acute encephalitis syndrome 559 Prevention of genetic disorders 642
Cerebral palsy 564
Neurological regression 565 24. Inborn Errors of Metabolism 644
Ataxia 567
Neerja Gupta, Madhulika Kabra
Movement disorders 568
Stroke 570 Acute presentation 645
Paraplegia and quadriplegia 573 Chronic and progressive presentation 647
Headache 574
Raised intracranial pressure, space occupying lesions and 25. Ophthalmic Disorders 660
hydrocephalus 575
Radhika Tandon
Coma 578
Pediatric eye screening 660
Congenital and developmental abnormalities 661
20. Neuromuscular Disorders 581 Acquired eye diseases 662
Sheffali Gulati
Approach to evaluation 581 26. Skin Disorders 669
Disorders affecting anterior horn cells 582 Neena Khanna, Neetu Bhari
Peripheral neuropathies 583 Basic principles 669
Acute flaccid paralysis 586 Genodermatoses 672
Neuromuscular junction disorders 587 Nevi 678
Muscle disorders 589 Disorders of skin appendages 683
Dermatitis 681
Bullous disorders 688
21. Childhood Malignancies 593 Disorders of pigmentation 689
Rachna Seth Abnormal vascular responses 690
Leukemias 593 Infections 692
Chronic myeloid leukemia 600 Diseases caused by arthropods 699
Lymphoma 602 Miscellaneous dermatoses 701
Hodgkin lymphoma 602
Non-Hodgkin lymphoma 604 27. Poisonings, Injuries and
Retinoblastoma 607
Wilms tumor 609 Accidents 704
Neuroblastoma 610 Jhuma Sankar
Malignant tumors of the liver 612 Injuries and poisoning 704
Soft tissue sarcoma 612 Road traffic accidents and falls 704
Bone tumors 613 Burns, electrical and inhalational injuries 705
Brain tumors 614 Drowning and near drowning 707
Histiocytoses 615 Choking and suffocation 707
Hemophagocytic lymphohistiocytoses 617 Poisoning 707
Oncologic emergencies 617 Common poisonings 712
Late effects and survivorship 618 Envenomations 716
Bone marrow transplantation 619 Injury control 719
xvi Essential Pediatrics
28. Pediatric Critical Care 721 Bone marrow aspiration and biopsy 743
Liver biopsy 744
Praveen Narsaria, Rakesh Lodha
Assessment of a seriously ill child 721
Pediatric basic and advanced life support 722 30. Rational Drug Therapy 746
Shock 727 Anu Thukral, Kana Ram Jot
Nutrition in the critically ill 731
Sedation, analgesia and paralysis 731
Health care associated infections 732
31. Integrated Management of Neonatal
Blood transfusions 733 and Childhood Illness 766
Ajay Khera, Varun Alwadhi
29. Important Medical Procedures 736 !integrated management of neonatal and childhood illness
strategy 766
Arvind Bagga
Outpatient management of young infants age
Removal of an aspirated foreign body 736 up to 2 months 768
Nasogastric tube insertion 737 Outpatient management of sick child age 2 months up to
Central venous cannulation 737 5 years 770
Capillary blood (heel prick) 738 Assess and classify the sick young infants 775
Umbilical vessel catheterization 738
Arterial catheterization 739
lntraosseous infusion 739 32. Rights of Children 786
Lumbar puncture 740 Rajeev Seth
Thoracocentesis or pleural tap 741 Child abuse and neglect 788
Abdominal paracentesis or ascitic tap 741 Adoption 789
Catheterization of bladder 742
Peritoneal dialysis 742 Index 797
- -
:�
Chapter
1
Introduction to Pediatrics
Vinod K Paul
The branch of medicine that deals with the care of children nephrology, pulmonology, infectious disease, critical care,
and adolescents is pediatrics. This term has roots in the neurology, hemato-oncology, endocrinology and
Greek word pedo pais (a child) and iatros (healer). Pediatrics cardiology). Pediatrics encompasses intensive care of
covers the age group less than 18 years of age. The goal of neonates and children using the most sophisticated
the specialty is to enable a child to survive, remain healthy, technology, on the one hand, and, providing home care
and attain the highest possible potential of growth, to newborns and children, on the other. Child health is
development and intellectual achievement. Child health thus a state-of-the-art clinical science as well as a rich
encompasses approaches, interventions and strategies that public health discipline.
preserve, protect, promote and restore health of children Medical students should possess competencies for the
at individual and population level. A physician who care of healthy and sick children. The agenda of high child
specializes in the healthcare of children and adolescents mortality due to pneumonia, neonatal infections, preterm
is a pediatrician. birth complications, diarrhea, birth asphyxia and vaccine
Children under 15 years of age comprise about 30% of preventable diseases is still unfinished. The benefits of
India's population. Childhood is the state when the human advancing pediatric speciality care must reach all children.
being is growing and developing. It is the age to acquire Besides, an increasing body of knowledge on pediatric
good habits, values and lifestyles that would make origins of non-communicable diseases of the adult is set
children fit, responsible and productive adults and to change the paradigm of child health. Primary
citizens. The family, society and nation are duty-bound prevention and early detection of adult disorders is an
to make children feel secure, cared for, and protected from important goal of pediatrics. Adolescence offers second
exploitation, violence and societal ills. Female children face chance in life to shape good lifestyles and prepare for
gender bias in access to healthcare and nutrition. A adulthood.
civilized society nurtures all its children, girls and boys
alike, with love, generosity and benevolence. HISTORICAL PERSPECTIVE
Child is not a miniature adult. The principles of adult
Medical care of children finds place in the ancient Indian,
medicine cannot be directly adapted to children. Pediatric
Greek and Chinese systems of health. But as a formal
biology is unique and risk factors of disease are distinct.
discipline, pediatrics took root in Europe and the US in
Clinical manifestations of childhood diseases may be
the 19th century when some of the famous children
different from adults. Indeed, many disorders are unique
hospitals were established. BJ Hospital for Children,
to children-these do not occur in adults. Drug dosages
Mumbai was the first child hospital to be established in
in children are specific and not a mathematical derivation
India in 1928. Postgraduate diploma in pediatrics was
of adult dosages. Wholesome nutrition is even more
important for children not only to sustain life, but also to started there in 1944; postgraduate degree programs began
ensure their growth and development. in the fifties. Pediatrics became an independent subject in
MBBS course in mid-nineties. The first DM program in
neonatology started in 1989 at PGIMER, Chandigarh,
PEDIATRICS AS A SPECIALITY followed by one in pediatric neurology at AIIMS in 2004.
Pediatrics is a fascinating speciality. It encompasses care Half a dozen institutions in the country now run DM
of premature neonates on the one hand, and adolescents, programs in various pediatric specialities that include
on the other. The discipline of pediatrics has branched nephrology, pulmonology, critical care, hematology
into well-developed superspecialities (such as neonatology, oncology, oncology, cardiology and endocrinology.
1
2 Essential Pediatrics
CHALLENGE OF HIGH CHILD MORTALITY of life), and the neonatal mortality (NMR) accounts for
70% infant deaths.
India has the highest number of child births as well as
child deaths for any single nation in the world. Each year, There has been a steady decline in child deaths. U5MR
as many as 26 million babies are born in India. This has declined by almost two-thirds between 1990 and 2015
comprises 18% of the global birth cohort. Of the from 126 to 43 per 1000 live births. The country missed
5.95 million under 5 child deaths in the world in 2015 the Millennium Development Goal 4 of achieving U5MR
1.20 million (20%) occurred in our country. Table 1.1 of 42 by 2015 by just one number. Between 2000 and 2016,
provides the most recent figures on the key child mortality IMR declined by 50%, while NMR decreased by 45%
indices. (Fig. 1.1). The early neonatal mortality (deaths under 7
days of life) has been less amenable to change.
At 39 per 1000 live births (2016), under 5 mortality in
the country is unacceptably high given our stature as an In 2016, there were 9.8 lakh under-5 deaths and 5.7 lakh
economic, scientific and strategic power. Under 5 mortality neonatal deaths in the country.
rate (U5MR) in Japan (3), UK (4), USA (7), Sri Lanka (10), National programs focus generally on child deaths
China (11) and Brazil (16) is worth comparing with that under the age of 5 years (under-5 mortality). The U5MR,
of India. Great nations not only have negligible child IMR and NMR targets enshrined in the National Health
mortality, but also ensure good health, nutrition, Policy 2017 are depicted in Table 1.2.
education and opportunities to their children. Almost 60%
Why do Children Die?
of under 5 deaths occur in the neonatal period (<28 days
The eight important causes of under 5 mortality in children
Table 1.1: Child mortality indices in India in 2016 in India (with % contribution) are: (i) complications of
Indices Rate
prematurity (24%), (ii) pneumonia (13%), (iii) neonatal
infections (12%), (iv) diarrhea (11%), (v) birth asphyxia
Under 5 mortality rate (U5MR) 39 per 1000 live births
(11%), (vi) congenital malformations (4%), (vii) measles
Infant mortality rate (IMR) 34 per 1000 live births (3%), and (viii) injuries (3%) (Fig. 1.2). The above causes
Neonatal mortality rate (NMR) 24 per 1000 live births are the proximate conditions that lead to death. Poverty,
Early neonatal mortality rate (ENMR) 18 per 1000 live births illiteracy, low caste, rural habitat, harmful cultural
Late neonatal mortality rate (LNMR) 06 per 1000 live births practices, and poor access to safe water and sanitation are
U5MR: Number of deaths under the age of 5 years per 1000 live births
important determinants of child health. Undemutrition
IMR: Number of deaths under the age of 1 year per 1000 live births is a critical underlying intermediate risk factor of child
NMR: Number of deaths under the age of 28 days per 1000 live births mortality, associated with about 45% of under 5 child
ENMR: Number of deaths under the age of 7 days per 1000 live births deaths. Undernutrition causes stunting and wasting,
LNMR: Number of deaths after completing 7 days of age but before predisposes to infections and is associated with adult
28 days per 1000 live births disorders and low economic productivity.
80
70
60
58 58
60
50
50
44
40
30 - 2",;;;;::::::::--------=:::=====::::::;::;;::;:::::::=----_:::::::::::::::,,,-�::::::�:=---26 25
3 24
28
28 28 29
21 26
20 -----2-5--2!3---=--=----- -------=- ��7=�26�
L=
_,2�=
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23
-------- 20 1 9_�
22
_ _ == __ �
10 -� _ j5 �� = - =- -- _
18
--
12 12 11 11 --;--------: ------------------
--------------
---
7 8 7 7 7 6
0
6 6 6 6
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 201 0 2011 201 2 201 3 201 4 201 5 201 6
Fig. 1.1: Trends in neonatal and infant mortality, sample registration system. IMR infant mortality rate; NMR neonatal mortality rate
Introduction to Pediatrics 3
Pneumonia 13%
�------ Neonatal
pneumonia 2%
Neonatal
infections 12%
Diarrhea 10%
Meningitis 2%
Other
disorders 14%
Other neonatal 5%
Congenital malformations
4%
Fig. 1.2: Causes of under-5 child deaths. The area to the right of the dotted line indicates neonatal conditions
Table 1.2: Child mortality targets in the National Health Policy 2017 The government launched the National Rural Health
Reduce Under Five Mortality Rate (U5MR) to 23 per 1000 live
Mission (NRHM) in 2005. This mission included
births by 2025 investment in public health, improvements in health
systems, focus on communities, decentralisation and
Reduce Infant Mortality Rate (IMR) to 28 per 1000 live births
by 2019.
demand-side interventions to improve effectiveness of the
programs. The RCH program was integrated into the
Reduce Neonatal Mortality Rate (NMR) to 16 per 1000 live
NRHM, with prime focus on child and maternal health.
births by 2025
Strategies include deployment of more than 900 000
ASHAs; an increase in ANMs, nurses and doctors; setting
NATIONAL PROGRAMS ON CHILD HEALTH up of village health and sanitation; strengthened primary
Child health has been at the core of our health policy. The health care infrastructure; strengthened program
Universal Immunization Program launched in 1985 management capacity, establishment of patient-welfare
focused on immunization against six diseases committees at facilities, and creation of emergency
(tuberculosis, poliomyelitis, diphtheria, pertussis, tetanus transport networks.
and measles). The Diarrhoeal Disease Control Programme In 2013, the government reviewed maternal and child
was initiated in 1981 and Acute Respiratory Infections health program under NRHM and launched a Strategic
Control Programme in 1990. In 1992, India launched the Approach to Reproductive, Maternal, Newborn, Child and
Child Survival and Safe Motherhood (CSSM) program by Adolescent Health (RMNCH+A) under the XII Plan. The
combining interventions for child survival (immunization, intervention packages under the RMNCH+A strategy and
control of diarrheal disease, respiratory infections, details are shown in Table 1.3.
vitamin A supplementation, essential newborn care) and With the advent of the National Urban Health Mission,
maternal health (antenatal care, deliveries in institutions, the NRHM is now called as National Health Mission
emergency obstetric care). In 1997, the program for family (NHM). The roles of ASHA, AWW and ANM in maternal,
planning and the CSSM program were merged to create newborn and child health in national programs are shown
the Reproductive and Child Health Programme. In phase in Table 1.4.
2 of the RCH program (2005), adolescent health component In 2014, the country launched India Newborn Action
was added. Plan (INAP) which commits the country to single digit
4 Essential Pediatrics
Table 1.3: Summary of maternal, newborn and child health services under NHM
Pregnancy, childbirth and immediate newborn care Interventions
Skilled obstetric care and essential newborn care Package
including resuscitation Facility deliveries by skilled birth attendants
Neonatal resuscitation (Navjat Shishu Suraksha Karyakram that aims to train
nurses and doctors in neonatal resuscitation)
Emergency Obstetric and Newborn care (EmONC) Essential newborn care (warmth, hygienic care, breastfeeding, extra care of
small babies, sickness detection)
Linkages to Facility-based Newborn Care for sick neonates
Program drivers
Postpartum care for mother and baby Janani Suraksha Yojana (JSY ) that provides cash incentive to the woman
(and to the ASHA) for delivery in the facility
Janani Shishu Suraksha Karyakram (JSSK) that entitles the mother and
infants to free delivery, medicines / blood, diet, pickup and drop in government
facilities
Newborn and child care
Home based newborn care Home visits by ASHAs (six for facility born babies, on days 3, 7, 14, 21, 28
and 42; an extra visit on day 1 for home births)
Interventions for infants
Examination; counsel for warmth; breastfeeding; hygiene; extra care of low
birth weight babies; detection of sickness, referral
Interventions for mother
Postpartum care and counselling for family planning
Program driver
ASHA paid incentive for home care, birth weight record, birth registration
and immunization (BCG, first dose OPV and pentavalent)
Facility based newborn care Special Newborn Care Units (SNCUs)
These specialized newborn units at district hospitals with specialised
equipments including radiant warmers. These units have 12-16 beds with a
staff of 3 physicians, 1O nurses and 4 support staff to provide round the clock
services for newborn requiring special care, such as those with very low
birth weight, neonatal sepsis/pneumonia & common complications.
Newborn Stabilization Units (NBSUs)
These are step down units providing facilities for neonates from the periphery
where babies can be stabilized through effective care. These are set up in
CHCs and provide services, including resuscitation, provision of warmth,
initiation of breastfeeding, prevention of infection and cord care, supportive
care: oxygen, IV fluids, provision for monitoring of vital signs and referral.
Newborn Care Corners (NBCCs)
These are special corners within the labor room at all facilities (PHC, CHC,
DH) where deliveries occur. Services include resuscitation, provision of
warmth, prevention of infections and early initiation of breastfeeding.
Program driver
Janani Shishu Suraksha Karyakram (JSSK) that entitles the mother and
infants to free delivery, medicines/blood, diet, pickup and drop in government
facilities
Integrated management of common Integrated Management of Neonatal and Childhood Illness (IMNCI) by ANMs
childhood illnesses and at first level facility (PHC)
Facility-lMNCI at first referral level (e.g. CHC). Focuses on providing inpatient
management of major causes of childhood mortality such as asphyxia, sepsis,
low birth weight and pneumonia, diarrhea, malaria, meningitis and severe
malnutrition
Program driver
Janani Shishu Suraksha Karyakram (JSSK) that entitles the infants to free
delivery, medicines/blood, diet, pickup and drop in government facilities
Contd...
Introduction to Pediatrics 5
Table 1.3: Summary of maternal, newborn and child health services under NHM (Contd...)
Newborn and child care
Immunization Universal Immunization Programme now includes 7 vaccine preventable diseases
(BCG, polio, diphtheria, pertussis, tetanus, measles and hepatitis B) for all children
given push by Mission lndradhanush to ensure no one is left behind
Pentavalent (DPT, hepatitis B and hemophilus influenza B) vaccine
OPV supplementary doses administered on National Immunization Days
Injectable polio vaccine (IPV)
MR (measles and rubella) vaccine
Rotavirus vaccine in selected states
Pneumococcal vaccine initiated in selected states
Japanese encephalitis B vaccine in endemic districts; combined with routine
immunization
Child health screening and early intervention Launched January 2013; child health screening and early intervention services
services (Rashtriya Bal Swasthya Karyakram; RBSK) through mobile health teams at block level.
Screening of all children (0-6 years' old) enrolled at least twice a year for
30 disorders (4Ds).
Defects (neural tube defect, Down syndrome, cleft lip/palate, club foot,
dysplasia hip, congenital cataract or deafness, congenital heart diseases
and retinopathy of prematurity)
Deficiencies (anemia, vitamin A deficiency, vitamin D deficiency, severe acute
malnutrition and goiter)
Diseases (skin conditions, otitis media, rheumatic heart disease, reactive
airway disease, dental caries and convulsions)
Developmental delays and disabilities (vision or hearing impairment,
neuromotor impairment, motor delay, cognitive delay, language delay,
behaviour disorder, learning disorders, attention deficit hyperactivity disorder)
Optional (congenital hypothyroidism, sickle cell anemia, beta thalassemia)
Free management of these children at district early intervention centres or
identified tertiary level institutions
CHC: Community health centre; PHC: Primary health centre; DH: District hospital; Further reading; State of India's Newborns 2014
NMR and stillbirth rate by 2030 and lays down strategies FUTURE OF CHILD HEALTH
to achieve these targets.
The Nation is addressing child health challenges with
Mission Indradhanush, launched in 2014, is a national greater dynamism than ever before. Investments are being
immunization drive to attain 90% coverage of 7 vaccines made for health programs and health system strengthening.
(BCG, polio, diphtheria, pertussis, tetanus, measles and Likewise, complete conditional cash transfers and
hepatitis B) by 2020. entitlements are enshrined to stimulate demand for
Since 2014, the government also observes the maternal, newborn and child healthcare. The country is
Intensified Diarrhea Control Fortnight (IDCF) in June/ surging ahead with stronger economy and accelerated
July to intensify efforts to reduce child deaths due to development. Child health and survival is at the core of
diarrhoea. Through this initiative, mass awareness about the National Health Policy 2017 as well as country's
prevention and treatment of diarrhea with a combination commitments for the Sustainable Development Goals
of Oral Rehydration Salt (ORS) solution and zinc tablets (SDGs). Ayushman Bharat initiative of the government
is created. announced in 2018 encompasses strengthening of primary
A new program, namely Home-based Care of Young health care by developing 150,000 health and wellness
Child (HBYC), will be introduced in 2018. This encompasses centres, and by providing financial protection for
3 monthly home visits by ASHA workers from 3 months to hospitalizations for 100 million families (500 million
15 months of age. The program aims to ensure introduction persons). The latter will enable families cashless access to
of complementary feed at 6 months of age with adequate in-patient care for pediatric and neonatal illnesses. Swachh
nutritional intake with increasing age, continuing breast Bharat mission will help reduce ill health. India is poised
feeding; counselling for immunization, and early care to attain low child mortality rate, and improve remarkably
seeking in diarrhea and pneumonia; growth monitoring the health and nutrition status of her children in near future.
and care of undernourished child; early childhood
development; and to ensure hygiene and sanitation. Suggested Reading
All these efforts coupled with overall socio-economic • You D, Hug L, Ejdemyr S et al. Global, regional, and national levels
development are paying good dividends. India has and trends in under-5 mortality between 1990 and 2015, with
attained institutional delivery rate of over 80%, a scenario-based projections to 2030: systematic analysis by the UN
remarkable jump from just 39% a decade ago. In 2015-16, inter-agency group for child mortality estimates. The Lancet 2015;
386: 2275-86.
full immunization coverage (BCG, OPV, DPT, measles) • Registrar General of India (2016). Sample Registration System (SRS)
was 62% and use ORS for diarrhea reached 51% (compared statistical report 2016. New Delhi: Registrar General of India.
to 44% and 26% in 2005-06, respectively). • National Family Health Survey 4 (2015-16), National Fact Sheet, 2016.
Chapter
2
Growth
Ramesh Agarwal • Naveen Sankhyan • Vandana Jain
Growth is an essential feature that distinguishes a child placental-fetal unit acts in harmony to provide the needs of
from an adult. The process of growth starts from the time of the fetus.
conception and continues until the child grows into a fully
Genetic potential: Parental traits are usually transmitted to
mature adult. The terms 'growth' and 'development' are
the offspring. Thus, tall parents have tall children; the size
often used together, but are not interchangeable because
of the head is more closely related to that of parents than
they represent two different facets of the dynamics of
are the size and shape of hands and feet. Similarly, the
change, i.e. those of quantity and quality.
structure of the chest and fatty tissue has better genetic
The term growth denotes a net increase in the size or mass association than other somatic characteristics.
of tissues. It is largely attributed to multiplication of cells
and increase in the intracellular substance. Hypertrophy Sex: Boys are generally taller and heavier than girls at the
or expansion of cell size contributes to a lesser extent to the time of birth.
process of growth. Fetal hormones: Human fetus secretes thyroxine from the
Development specifies maturation of functions. It is related 12th week of gestation. Thyroxine and insulin have an
to the maturation and myelination of the nervous system important role in regulating tissue accretion and
and indicates acquisition of a variety of skills for optimal differentiation in the fetus. Both hormones are required for
functioning of the individual. normal growth and development, particularly during late
Growth and development usually proceed concurrently. gestation. Glucocorticoids also play an important role,
While they are discussed separately, both growth and primarily towards the end of gestation and influence the
development are closely related; hence, factors affecting prepartum maturation of organs such as liver, lungs and
one also tend to have an impact on the other. During early gastrointestinal tract. Growth hormone, though present in
embryonic period of life, an exponential increase in the high levels in fetus, is not known to influence fetal growth.
number of cells occurs. At the early embryonic stage, fetal Fetal growth factors: A large number of growth factors
cells divide and differentiate to form tissues and organs. In are synthesized locally in fetal tissues, and act principally
the latter half of pregnancy and early childhood, there is by autocrine and paracrine mechanisms. Their prime effect
also an increase in cell size. This manifests as an increase is on cell division, though they also influence other aspects
in the protein to DNA ratio. The cell size continues to enlarge of tissue growth. These factors can be both growth
until about 10 years of age. The body cells remain in a state promoting or inhibitory. The insulin like growth factor
of dynamic equilibrium; hence aging cells are continuously (IGF)-1 and IGF-11 are among t.he most extensively studied
replaced by new cells. The rate of turnover of cells in fetal growth factors.
different tissues is variable.
Placental factors: As in most species, fetal weight directly
correlates with placental weight at term. Fetal growth is
FACTORS AFFECTING GROWTH highly dependent on the structural and functional integrity
of the placenta. With advancing gestation, the weight of the
Fetal Growth placenta increases to cater to the increased needs of the baby.
Fetal growth is influenced primarily by fetal, placental and There are important functional and structural changes in
maternal factors. In humans, 40% of variation in the birth the placenta that make this adaptation more efficient. The
weight is due to genetic factors while the rest is due to total villous surface area increases, the diffusion distance
environmental factors. The fetus has an inherent growth decreases, the fetal capillaries dilate and the resistance in
potential, and under normal circumstances, grows into a fetoplacental vasculature falls. This positive remodeling
healthy appropriate sized newborn. The maternal- facilitates nutrient transport across the placenta.
7
-8 Essential Pediatrics
Maternal factors: The mother's own fetal and childhood During early infancy, exclusive breastfeeding provides
growth and her nutrient intake and body composition at adequate nutrition, prevents infections and protects the
the time of conception and during pregnancy, play an infants from further undernourishment. However, at 3-5
important role in determining fetal size. Teenage or months, the common practice of supplementing the infants
advanced age, recent pregnancy, high parity and anemia with animal milk increases morbidity due to infections
negatively influence fetal size and health. Maternal intake leading to underweight and stunting. Subsequently, faulty
of tobacco (smoked or chewed) and drug or alcohol abuse complementary feeding practices (starting too late, using
also retard fetal growth. Obstetric complications such as too little and very less calorie dense foods) along with poor
pregnancy-induced hypertension, pre-eclampsia and hygiene lead to a further rise in rates of underweight and
multiple pregnancies produce fetal growth restriction. Pre stunting.
existing chronic systemic disease (chronic renal failure,
Honnonal influence: Normal growth cannot proceed without
congestive heart failure) and acquired infections (rubella,
the right milieu of hormones in the body throughout
syphilis, hepatitis B, HIV, CMV, toxoplasmosis) may childhood and adolescence. Absence of growth hormone or
influence fetal growth.
thyroxine results in dwarfism, underscoring the importance
Postnatal Period of these factors in promoting growth. During adolescence,
androgens and estrogens have an important influence on
The growth of the child during postnatal life is determined the growth spurt and final adult height.
by genetic potential as well as internal and external
influences. Sex: The pubertal growth spurt occurs earlier in girls.
However, their mean height and weight in girls are usually
Genetic factors: Both chromosomal disorders and mutations
less than those in boys of corresponding ages at the time of
in specific genes can affect growth. Chromosomal defects
full maturity.
like Turner syndrome and Down syndrome manifest as
growth retardation. Mutation of single genes may result in Nutrition: Growth of children suffering from protein-energy
inherited retardation of growth, e.g. Prader-Willi syndrome malnutrition, anemia and vitamin deficiency states is
and Noonan syndrome. While most disorders lead to short retarded. Calcium, iron, zinc, iodine and vitamins A and D
stature, some genetic defects can also result in tall stature, are closely related to disorders of growth and development.
e.g. Klinefelter syndrome and Sotos syndrome. On the other hand, overeating and obesity accelerate
Intrauterine growth restriction (IUGR): IUGR resulting in somatic growth.
low birth weight (LBW) constitutes an important risk factor Infections: In low resource settings, one of the commonest
n
for postnatal malutrition and poor growth. LBW increases contributors to poor childhood growth is infections.
the odds of underweight, stunting and wasting in the first Persistent or recurrent diarrhea and respiratory tract
5 years of life by 3 to 5 times. At 6 months of age, infections are common causes of growth impairment.
approximately one-third each of underweight (28%), Systemic infections and parasitic infestations may also retard
stunting (28%) and wasting (22%) are attributable to LBW. the velocity of growth. The risk of stunting at 2 years of age is
At ages between 1 and 5 years, LBW accounts for 16-21% shown to increase with each episode of diarrhea and with
of wasting, 8-16% of stunting and 16-19% of underweight. each day of diarrhea before 2 years of age. It was also shown
Almost one-third and one-fifth of infants have wasting and that the attributable risk for stunting for 5 or more episodes of
stunting, respectively, even at birth (Fig. 2.1). diarrhea before 24 months of age was 25%.
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Chemical agents: Administration of androgenic hormones of early life has permanent effects on structure, physiology
initially accelerates the skeletal growth. However, and metabolism. The "Developmental Origins of Health
androgens cause the epiphyses of bones to close and Diseases; DOHaD; Barker hypothesis" proposes that
prematurely, leading to early cessation of bone growth. alterations in fetal nutrition and endocrine status result
Trauma: A fracture at the end of a bone may damage the in developmental adaptations that permanently change
growing epiphysis, and thus hamper skeletal growth. structure, physiology and metabolism, thereby
predisposing individuals to cardiovascular, metabolic
Social Factors and endocrine disease in adult life. As a result, infants
born with low birth weight have increased risk of diabetes,
Socioeconomic level: Children from families with high
hypertension, coronary artery disease and hyperlipidemia
socioeconomic level usually have better nutritional state.
in adult life.
They suffer from fewer infections because of better nutrition
and hygienic living conditions. Laws of Growth
Poverty: Hunger, undernutrition and infections, often Growth and development of children is a continuous and
associated with poverty, cause poor growth. orderly process: There are specific periods in a child's life
Natural resources: Plentiful natural resources encourage when the rate of growth is steady, accelerates or decelerates
industrial and agricultural enterprise in the country. (Table 2.1). The fetus grows fast in the first half of gestation.
Improved nutrition of children in the community is Thereafter, the rate of growth is slowed down until the
facilitated when there is a climb in gross national product baby is born. In the early postnatal period, the velocity of
and per capita income is high. growth is high, especially in the first a few months.
Climate: The velocity of growth may alter in different Thereafter, there is slower but steady rate of growth during
seasons and is usually higher in spring and low in summer mid-childhood. A second phase of accelerated growth
months. Infections and infestations are common in hot and occurs at puberty. Growth decelerates thereafter for some
humid climate. Weather also has a pivotal effect on time and then ceases altogether. The general body growth
agricultural productivity, ready availability of food and is rapid during the fetal life, first one or two years of postnatal
capacity for strenuous labor by the population. life and also during puberty (Fig. 2.2). In the intervening
years of mid-childhood, the somatic growth velocity is
Emotional factors: Children from broken homes and relatively slowed down.
orphanages do not grow and develop at an optimal rate.
Anxiety, insecurity and lack of emotional support and love Growth pattern of every individual is unique: Order of
from the family prejudice the neurochemical regulation of growth is cephalocaudal and distal to proximal. During
growth hormone release. Parents who had happy fetal life, growth of head occurs before that of neck, and
childhood and carry a cheerful personality are more likely arms grow before legs. Distal parts of the body such as
to have children with similar countenance. hands increase in size before upper arms. In the postnatal
life, growth of head slows down but limbs continue to grow
Cultural factors: Methods of child rearing and infant feeding
rapidly.
in the community are determined by cultural habits and
conventions. There may be religious taboos against
consumption of particular types of food. These affect the Table 2.1: Periods of growth
nutritional state and growth performance of children. Prenatal period
Parental education: Mothers with more education are more Ovum 0 to 2 weeks
likely to adopt appropriate health promoting behaviors, Embryo 3 to 8 weeks
which have direct and indirect influences on growth and Fetus 9 weeks to birth
development. Perinatal period 22 weeks to 7 days after birth
Postnatal period
Consequences of Impaired Growth Newborn First 4 weeks after birth
Infant Birth to <12 months
Maternal and child undernutrition is the underlying cause
(neonate: Birth to 28 days;
of 3-5 million deaths annually and accounts for 35% of the
post-neonate: 29 days to <1 year)
disease burden in children younger than 5 years. It is
Toddler 1 year to 36 months
estimated that India has more than 61 million stunted
Preschool child 37-72 months
children, that amounts to 34% of the global total.
School age child 73 months-12 years
Several major disorders of later life, including coronary
Adolescence
heart disease, hypertension and type 2 diabetes, originate
Early 10-13 years
from impaired intrauterine growth and development.
Middle 14-16 years
These diseases may be consequences of 'programming',
Late 17-20 years
whereby a stimulus or insult at a critical, sensitive period
-10 Essential Pediatrics
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
t t t t r
23 23
22 22
21 21
Gentiles for girls - - - - - - - - - - 97th Gentiles for boys - - - - - - - - - - 97th
20 maturing at _ _ _ _ _ _ 20 maturing at - - - - - -. 90th
eOth average time · · · · · · · · ·
average time -·-·-·-·-·-·-·-·-·- - - - - - - - - - - ?Sth
?Sth 19
19 ------------------------·50th
------------------------· 50th
18 ---- 25th 18 ----25th
------ - 10th -------10th
17 17 - - - - - - - - - - - - - - - - 3rd
- - - - - - - - - - - - - - - - 3rd
16 16
97th and 3rd centiles
t
97th and 3rd centiles I\ /\
i
at peak height
t
at peak height 15
velocity for: V velocity for: V
� 14 Early (+2SD) maturers - - - - - - - - -
Early (+2SD) maturers - - - - - - - - -
Late (-2SO) maturers ___..___. , Late (-2SD) maturers ___ ..___..
·G 13
:E 12
'cii 11
I
10
a
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
2 3 4 5 6 7 8 9 10 11
Age, years
12 13 14 15 16 17 18 19
b Age, years
Fig_ 2_2: Normal height velocl1y (a) girls and (b) boys according to age. Curves for height veloci1y at 50th centile for early and late
maturers are also depicted. The open arrow heads indicate the 3rd and 97th centile for peak height veloci1y for these individuals.
Reprinted from J Pediatr 1985; 107:317-29; with permission from Elsevier
storehouse of energy. It is primarily deposited in the sub proximal toes in both sexes; and (v) distal and middle
cutaneous adipose tissue. Girls have more subcutaneous phalanges in boys and distal and proximal phalanges in
adipose tissue than boys. Moreover, the sites and quantity girls. To determine the skeletal age in infants between 3 and
of adipose tissue differs in girls and boys. Girls tend to add 9 months, a radiograph of shoulder is most helpful. A single
adipose tissue to breasts, buttocks, thighs and back of arms film of hands and wrists is adequate in children between
during adolescence. the ages of 1 and 13 years. For children between 12 and
14 years, radiographs of elbow and hip give helpful clues.
SOMATIC GROWTH
Eruption of Teeth
Skeletal Growth
Primary teeth: The teeth in the upper jaw erupt earlier than
Skeletal growth is a continuous process occurring during those in the lower jaw, except for lower central incisors
the whole of childhood and adolescence. It is steady until and second molar (Table 2.2).
the pubertal growth spurt when it accelerates and
subsequently slows considerably. The skeleton is mature Permanent teeth: The order of eruption is shown in
once the epiphysis or growth plates at the end of long bones Table 2.2. The first molars are the first to erupt.
fuse to the shaft or diaphysis. This occurs by about 18 years
in girls and 20-22 years in boys. The degree of skeletal ASSESSMENT OF PHYSICAL GROWTH
maturation closely correlates with the degree of sexual Weight: The weight of the child in the nude or minimal
maturation. A child who has advanced sexual maturity light clothing is recorded accurately on a lever or electronic
will also have earlier skeletal maturation. type of weighing scale (Fig. 2.4). Spring balances are less
Skeletal maturation is assessed by noting the appearance accurate. It is important that child be placed in the middle
and fusion of epiphysis at the ends of long bones. Apart of weighing pan. The weighing scale should be corrected
from this, bone mineral density can be ascertained by dual
energy X-ray absorptiometry [DXA]. This method allows
assessment of bone mineral content and density at different
ages.
for any zero error before measurement. Serial measurement 3. Position the head such that the child is looking straight up
should be done on the same weighing scale. The weight of (the line joining the external auditory meatus and the lower
a small baby can also be recorded with the mother/ care border of the eyeball is perpendicular to the board
giver using a tared weighing scale (Panel 1). 4. The shoulders and the spine should be in touch with the
board and the knees should be gently straightened.
Panel 1: Steps in weighing a baby using a digital scale with 5. The footboard should be moved to ensure that the feet are
taring facility (Fig. 2.5) firmly against it.
1. Use the tared weighing method to weigh children who 6. Measure the length in this position.
cannot stand on the weighing scale Note: Be very gentle with newborns, their knees may not
2. Place the weighing scale on a flat, hard, and even surface. straighten fully. If it is not possible to position both knees,
3. Babies should be weighed naked or with minimal clothing. then measure with one leg in position.
4. Ask the mother/caregiver to stand in the middle of the scale Reference: World Health Organization. Training Course on Child Growth
(without footwear), feet slightly apart and to remain still. Assessment. Geneva, WHO, 2008.
5. With the mother/caregiver still standing on the scale, press
the tare button.
6. The scale is tarred when the display shows the number
zero (while mother/caregiver is still standing on the scale).
7. Handover the baby to the mother
8. Record the baby's weight that appears on the display.
Note: If the mother is very heavy (e.g. 100 kg), then a lighter
person should hold the baby on the tared scale.
Reference: World Health Organization. Training Course on Child Growth
Assessment. Geneva, WHO, 2008.
Length or height: The infant measures approximately 50 cm Z-score allows comparison of different observations
at birth, 60 cm at 3 months, 65 cm at 6 months 70 cm at between individuals. For example, one can compare the
9 months, 75 cm at 1 year and 90 cm at 2 years. A normal height and weight of two individuals by obtaining the
Indian child is 100 cm tall at the age of 4 years. Thereafter, respective Z-scores.
the child gains about 6 cm in height every year, until the
age of 12 years. After this, increments in height vary Growth Standards
according to the age at the onset of puberty. There is a
Growth standards represent norms of growth and can
marked acceleration of the growth during puberty.
be presented in tabular or graphical manner. These are
Head circumference (HC): Head growth is rapid, especially obtained by either cross-sectional or longitudinal studies
in the first half of infancy. It reflects the brain growth during in large populations. Based on data obtained from US
this period. The head growth slows considerably thereafter. children, the National Center for Health Statistics
Beginning at 34 cm at birth, the head circumference (NCHS) developed growth charts in 1977. In the year
increases approximately 2 cm per month for first 3 months, 2000, revised growth charts provided by CDC offered an
1 cm per month between 3 and 6 months and 0.5 cm per improved tool to assess child health. However, these
month for the rest of the first year of life. The head charts were based on data obtained from US children
circumference is approximately 40 cm at 3 months, 43 cm who were formula fed.
at 6 months, 46-47 cm at 1 year, 48 cm at 2 years. By 12 years, Sensing the need for more internationally applicable
it is 52 cm. growth standards, the WHO conducted the 'Multicentre
Chest circumference: The circumference of chest is about Growth Reference Study' (MGRS) and published new growth
3 cm less than the head circumference at birth. The charts for infants and children up to 5 years of age in 2006.
circumference of head and chest are almost equal by the The MGRS was a community-based, multi-country project
age of 1 year. Thereafter, the chest circumference exceeds conducted in Brazil, Ghana, India, Norway, Oman and the
the head circumference. United States. The children included in the study were raised
in environment that minimized constraints to growth such
Body mass index (BMI): The formula to calculate BMI is as poor nutrition and infection. In addition, their mothers
weight (kg) /height (meter)2. BMI is primarily used to assess
followed healthy practices such as breastfeeding their
obesity.
children and did not smoke during and after pregnancy.
These WHO child growth standards are unique on several
Growth Charts
counts. They provide data on 'how children should grow',
If the growth measurements are recorded in a child over a and go beyond the traditional descriptive references. The
period of time and are plotted on a graph, the deviation in new standards make breastfeeding the biological norm and
the growth profile of the child from the normal pattern of establishes the breastfed infant as the normative growth
growth for that age can be easily interpreted. This is a model. The pooled sample from the six participating countries
satisfactory tool to diagnose deviation of growth from makes it a truly international standard and reiterates the
normal. Allowed normal range of variation in observations fact that child populations grow similarly across the world's
is conventionally taken as values between 3rd and 97th major regions when their needs for health and care are met.
percentile curves. Percentile curves represent frequency These standards also include new growth indicators beyond
distribution curves. For example, 25th percentile for height
height and weight that are particularly useful for monitoring
in a population would mean that height of 75% of
the increasing epidemic of childhood obesity, such as
individuals is above and 24% are below this value. One
skinfold thickness. The study's longitudinal nature further
standard deviation (SD) above the mean coincides with
84th percentile curve. Likewise 16th percentile curve allows the development of growth velocity standards,
represents one SD below the mean. Values between third enabling the early identification of under or over
and 97th percentile curve correspond to mean ±2 SD. nourishment. Figures 2.11 to 2.20 provide percentile curves
for weight, length or height, weight for height and head
Z-scores: In a population with observations in a typical circumference for girls and boys up to 5 years of age based
Gaussian (normal) distribution, any individual value can on WHO MGRS standards. Tables 2.4 to 2.8 summarize the
be expressed as how many SDs it lies above or below the data on length, weight and head circumference for these
mean. This is the Z-score for that observation. Thus, if a children.
child's weight is at 2 SD below the mean, it is equivalent to Growth standards are not available for children older
-2 Z. If the value lies above the mean, Z-score is positive, than 5 years. The Indian Academy of Pediatrics (IAP) has
otherwise it is negative. The formula for calculating the provided updated growth charts for children 5 to 18 years,
Z-score is: based on data from 33148 children (Table 2.9 and 2.10).
Observed value - mean value The charts can also be downloaded from http://iapindia.org/
Z-score= -----------
Standard deviation Revised-IAP-Growth-Charts-2015.php.
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Table 2.6A: Weight-for-length/height (kg) in girls and boys 0-5 years of age
Length Weight (kg) Boys
(cm) -3SD -2SD -1SD Median 1SD 2SD 3SD (cm) -3SD -2SD -1SD Median 1SD 2SD 3SD
45.0 1.9 2.1 2.3 2.5 2.7 3.0 3.3 45.0 1.9 2.0 2.2 2.4 2.7 3.0 3.3
45.5 2.0 2.1 2.3 2.5 2.8 3.1 3.4 45.5 1.9 2.1 2.3 2.5 2.8 3.1 3.4
46.0 2.0 2.2 2.4 2.6 2.9 3.2 3.5 46.0 2.0 2.2 2.4 2.6 2.9 3.1 3.5
46.5 2.1 2.3 2.5 2.7 3.0 3.3 3.6 46.5 2.1 2.3 2.5 2.7 3.0 3.2 3.6
47.0 2.2 2.4 2.6 2.8 3.1 3.4 3.7 47.0 2.1 2.3 2.5 2.8 3.0 3.3 3.7
47.5 2.2 2.4 2.6 2.9 3.2 3.5 3.8 47.5 2.2 2.4 2.6 2.9 3.1 3.4 3.8
48.0 2.3 2.5 2.7 3.0 3.3 3.6 4.0 48.0 2.3 2.5 2.7 2.9 3.2 3.6 3.9
48.5 2.4 2.6 2.8 3.1 3.4 3.7 4.1 48.5 2.3 2.6 2.8 3.0 3.3 3.7 4.0
49.0 2.4 2.6 2.9 3.2 3.5 3.8 4.2 49.0 2.4 2.6 2.9 3.1 3.4 3.8 4.2
49.5 2.5 2.7 3.0 3.3 3.6 3.9 4.3 49.5 2.5 2.7 3.0 3.2 3.5 3.9 4.3
50.0 2.6 2.8 3.1 3.4 3.7 4.0 4.5 50.0 2.6 2.8 3.0 3.3 3.6 4.0 4.4
50.5 2.7 2.9 3.2 3.5 3.8 4.2 4.6 50.5 2.7 2.9 3.1 3.4 3.8 4.1 4.5
51.0 2.8 3.0 3.3 3.6 3.9 4.3 4.8 51.0 2.7 3.0 3.2 3.5 3.9 4.2 4.7
51.5 2.8 3.1 3.4 3.7 4.0 4.4 4.9 51.5 2.8 3.1 3.3 3.6 4.0 4.4 4.8
52.0 2.9 3.2 3.5 3.8 4.2 4.6 5.1 52.0 2.9 3.2 3.5 3.8 4.1 4.5 5.0
52.5 3.0 3.3 3.6 3.9 4.3 4.7 5.2 52.5 3.0 3.3 3.6 3.9 4.2 4.6 5.1
53.0 3.1 3.4 3.7 4.0 4.4 4.9 5.4 53.0 3.1 3.4 3.7 4.0 4.4 4.8 5.3
53.5 3.2 3.5 3.8 4.2 4.6 5.0 5.5 53.5 3.2 3.5 3.8 4.1 4.5 4.9 5.4
54.0 3.3 3.6 3.9 4.3 4.7 5.2 5.7 54.0 3.3 3.6 3.9 4.3 4.7 5.1 5.6
54.5 3.4 3.7 4.0 4.4 4.8 5.3 5.9 54.5 3.4 3.7 4.0 4.4 4.8 5.3 5.8
55.0 3.5 3.8 4.2 4.5 5.0 5.5 6.1 55.0 3.6 3.8 4.2 4.5 5.0 5.4 6.0
55.5 3.6 3.9 4.3 4.7 5.1 5.7 6.3 55.5 3.7 4.0 4.3 4.7 5.1 5.6 6.1
56.0 3.7 4.0 4.4 4.8 5.3 5.8 6.4 56.0 3.8 4.1 4.4 4.8 5.3 5.8 6.3
56.5 3.8 4.1 4.5 5.0 5.4 6.0 6.6 56.5 3.9 4.2 4.6 5.0 5.4 5.9 6.5
57.0 3.9 4.3 4.6 5.1 5.6 6.1 6.8 57.0 4.0 4.3 4.7 5.1 5.6 6.1 6.7
57.5 4.0 4.4 4.8 5.2 5.7 6.3 7.0 57.5 4.1 4.5 4.9 5.3 5.7 6.3 6.9
58.0 4.1 4.5 4.9 5.4 5.9 6.5 7.1 58.0 4.3 4.6 5.0 5.4 5.9 6.4 7.1
58.5 4.2 4.6 5.0 5.5 6.0 6.6 7.3 58.5 4.4 4.7 5.1 5.6 6.1 6.6 7.2
59.0 4.3 4.7 5.1 5.6 6.2 6.8 7.5 59.0 4.5 4.8 5.3 5.7 6.2 6.8 7.4
59.5 4.4 4.8 5.3 5.7 6.3 6.9 7.7 59.5 4.6 5.0 5.4 5.9 6.4 7.0 7.6
60.0 4.5 4.9 5.4 5.9 6.4 7.1 7.8 60.0 4.7 5.1 5.5 6.0 6.5 7.1 7.8
60.5 4.6 5.0 5.5 6.0 6.6 7.3 8.0 60.5 4.8 5.2 5.6 6.1 6.7 7.3 8.0
61.0 4.7 5.1 5.6 6.1 6.7 7.4 8.2 61.0 4.9 5.3 5.8 6.3 6.8 7.4 8.1
61.5 4.8 5.2 5.7 6.3 6.9 7.6 8.4 61.5 5.0 5.4 5.9 6.4 7.0 7.6 8.3
62.0 4.9 5.3 5.8 6.4 7.0 7.7 8.5 62.0 5.1 5.6 6.0 6.5 7.1 7.7 8.5
62.5 5.0 5.4 5.9 6.5 7.1 7.8 8.7 62.5 5.2 5.7 6.1 6.7 7.2 7.9 8.6
63.0 5.1 5.5 6.0 6.6 7.3 8.0 8.8 63.0 5.3 5.8 6.2 6.8 7.4 8.0 8.8
63.5 5.2 5.6 6.2 6.7 7.4 8.1 9.0 63.5 5.4 5.9 6.4 6.9 7.5 8.2 8.9
64.0 5.3 5.7 6.3 6.9 7.5 8.3 9.1 64.0 5.5 6.0 6.5 7.0 7.6 8.3 9.1
64.5 5.4 5.8 6.4 7.0 7.6 8.4 9.3 64.5 5.6 6.1 6.6 7.1 7.8 8.5 9.3
65.0 5.5 5.9 6.5 7.1 7.8 8.6 9.5 65.0 5.7 6.2 6.7 7.3 7.9 8.6 9.4
65.5 5.5 6.0 6.6 7.2 7.9 8.7 9.6 65.5 5.8 6.3 6.8 7.4 8.0 8.7 9.6
66.0 5.6 6.1 6.7 7.3 8.0 8.8 9.8 66.0 5.9 6.4 6.9 7.5 8.2 8.9 9.7
66.5 5.7 6.2 6.8 7.4 8.1 9.0 9.9 66.5 6.0 6.5 7.0 7.6 8.3 9.0 9.9
67.0 5.8 6.3 6.9 7.5 8.3 9.1 10.0 67.0 6.1 6.6 7.1 7.7 8.4 9.2 10.0
67.5 5.9 6.4 7.0 7.6 8.4 9.2 10.2 67.5 6.2 6.7 7.2 7.9 8.5 9.3 10.2
68.0 6.0 6.5 7.1 7.7 8.5 9.4 10.3 68.0 6.3 6.8 7.3 8.0 8.7 9.4 10.3
68.5 6.1 6.6 7.2 7.9 8.6 9.5 10.5 68.5 6.4 6.9 7.5 8.1 8.8 9.6 10.5
69.0 6.1 6.7 7.3 8.0 8.7 9.6 10.6 69.0 6.5 7.0 7.6 8.2 8.9 9.7 10.6
69.5 6.2 6.8 7.4 8.1 8.8 9.7 10.7 69.5 6.6 7.1 7.7 8.3 9.0 9.8 10.8
70.0 6.3 6.9 7.5 8.2 9.0 9.9 10.9 70.0 6.6 7.2 7.8 8.4 9.2 10.0 10.9
70.5 6.4 6.9 7.6 8.3 9.1 10.0 11.0 70.5 6.7 7.3 7.9 8.5 9.3 10.1 11.1
71.0 6.5 7.0 7.7 8.4 9.2 10.1 11.1 71.0 6.8 7.4 8.0 8.6 9.4 10.2 11.2
71.5 6.5 7.1 7.7 8.5 9.3 10.2 11.3 71.5 6.9 7.5 8.1 8.8 9.5 10.4 11.3
72.0 6.6 7.2 7.8 8.6 9.4 10.3 11.4 72.0 7.0 7.6 8.2 8.9 9.6 10.5 11.5
72.5 6.7 7.3 7.9 8.7 9.5 10.5 11.5 72.5 7.1 7.6 8.3 9.0 9.8 10.6 11.6
73.0 6.8 7.4 8.0 8.8 9.6 10.6 11.7 73.0 7.2 7.7 8.4 9.1 9.9 10.8 11.8
73.5 6.9 7.4 8.1 8.9 9.7 10.7 11.8 73.5 7.2 7.8 8.5 9.2 10.0 10.9 11.9
74.0 6.9 7.5 8.2 9.0 9.8 10.8 11.9 74.0 7.3 7.9 8.6 9.3 10.1 11.0 12.1
74.5 7.0 7.6 8.3 9.1 9.9 10.9 12.0 74.5 7.4 8.0 8.7 9.4 10.2 11.2 12.2
75.0 7.1 7.7 8.4 9.1 10.0 11.0 12.2 75.0 7.5 8.1 8.8 9.5 10.3 11.3 12.3
75.5 7.1 7.8 8.5 9.2 10.1 11.1 12.3 75.5 7.6 8.2 8.8 9.6 10.4 11.4 12.5
76.0 7.2 7.8 8.5 9.3 10.2 11.2 12.4 76.0 7.6 8.3 8.9 9.7 10.6 11.5 12.6
76.5 7.3 7.9 8.6 9.4 10.3 11.4 12.5 76.5 7.7 8.3 9.0 9.8 10.7 11.6 12.7
77.0 7.4 8.0 8.7 9.5 10.4 11.5 12.6 77.0 7.8 8.4 9.1 9.9 10.8 11.7 12.8
Contd.
Length
Growth
Table 2.6A: Weight-for-length/height (kg) in girls and boys 0-5 years of age (Contd.)
Weight (kg) Girls Length Weight (kg) Boys
I 23 -
(cm) -3SD -2SD -1SD Median 1SD 2SD 3SD (cm) -3SD -2SD -1SD Median 1SD 2SD 3SD
77.5 7.4 8.1 8.8 9.6 10.5 11.6 12.8 77.5 7.9 8.5 9.2 10.0 10.9 11.9 13.0
78.0 7.5 8.2 8.9 9.7 10.6 11.7 12.9 78.0 7.9 8.6 9.3 10.1 11.0 12.0 13.1
78.5 7.6 8.2 9.0 9.8 10.7 11.8 13.0 78.5 8.0 8.7 9.4 10.2 11.1 12.1 13.2
79.0 7.7 8.3 9.1 9.9 10.8 11.9 13.1 79.0 8.1 8.7 9.5 10.3 11.2 12.2 13.3
79.5 7.7 8.4 9.1 10.0 10.9 12.0 13.3 79.5 8.2 8.8 9.5 10.4 11.3 12.3 13.4
80.0 7.8 8.5 9.2 10.1 11.0 12.1 13.4 80.0 8.2 8.9 9.6 10.4 11.4 12.4 13.6
80.5 7.9 8.6 9.3 10.2 11.2 12.3 13.5 80.5 8.3 9.0 9.7 10.5 11.5 12.5 13.7
81.0 8.0 8.7 9.4 10.3 11.3 12.4 13.7 81.0 8.4 9.1 9.8 10.6 11.6 12.6 13.8
81.5 8.1 8.8 9.5 10.4 11.4 12.5 13.8 81.5 8.5 9.1 9.9 10.7 11.7 12.7 13.9
82.0 8.1 8.8 9.6 10.5 11.5 12.6 13.9 82.0 8.5 9.2 10.0 10.8 11.8 12.8 14.0
82.5 8.2 8.9 9.7 10.6 11.6 12.8 14.1 82.5 8.6 9.3 10.1 10.9 11.9 13.0 14.2
83.0 8.3 9.0 9.8 10.7 11.8 12.9 14.2 83.0 8.7 9.4 10.2 11.0 12.0 13.1 14.3
83.5 8.4 9.1 9.9 10.9 11.9 13.1 14.4 83.5 8.8 9.5 10.3 11.2 12.1 13.2 14.4
84.0 8.5 9.2 10.1 11.0 12.0 13.2 14.5 84.0 8.9 9.6 10.4 11.3 12.2 13.3 14.6
84.5 8.6 9.3 10.2 11.1 12.1 13.3 14.7 84.5 9.0 9.7 10.5 11.4 12.4 13.5 14.7
85.0 8.7 9.4 10.3 11.2 12.3 13.5 14.9 85.0 9.1 9.8 10.6 11.5 12.5 13.6 14.9
85.5 8.8 9.5 10.4 11.3 12.4 13.6 15.0 85.5 9.2 9.9 10.7 11.6 12.6 13.7 15.0
86.0 8.9 9.7 10.5 11.5 12.6 13.8 15.2 86.0 9.3 10.0 10.8 11.7 12.8 13.9 15.2
86.5 9.0 9.8 10.6 11.6 12.7 13.9 15.4 86.5 9.4 10.1 11.0 11.9 12.9 14.0 15.3
87.0 9.1 9.9 10.7 11.7 12.8 14.1 15.5 87.0 9.5 10.2 11.1 12.0 13.0 14.2 15.5
87.5 9.2 10.0 10.9 11.8 13.0 14.2 15.7 87.5 9.6 10.4 11.2 12.1 13.2 14.3 15.6
88.0 9.3 10.1 11.0 12.0 13.1 14.4 15.9 88.0 9.7 10.5 11.3 12.2 13.3 14.5 15.8
88.5 9.4 10.2 11.1 12.1 13.2 14.5 16.0 88.5 9.8 10.6 11.4 12.4 13.4 14.6 15.9
89.0 9.5 10.3 11.2 12.2 13.4 14.7 16.2 89.0 9.9 10.7 11.5 12.5 13.5 14.7 16.1
89.5 9.6 10.4 11.3 12.3 13.5 14.8 16.4 89.5 10.0 10.8 11.6 12.6 13.7 14.9 16.2
90.0 9.7 10.5 11.4 12.5 13.7 15.0 16.5 90.0 10.1 10.9 11.8 12.7 13.8 15 16.4
90.5 9.8 10.6 11.5 12.6 13.8 15.1 16.7 90.5 10.2 11 11.9 12.8 13.9 15.1 16.5
91.0 9.9 10.7 11.7 12.7 13.9 15.3 16.9 91.0 10.3 11.1 12.0 13.0 14.1 15.3 16.7
91.5 10.0 10.8 11.8 12.8 14.1 15.5 17.0 91.5 10.4 11.2 12.1 13.1 14.2 15.4 16.8
92.0 10.1 10.9 11.9 13.0 14.2 15.6 17.2 92.0 10.5 11.3 12.2 13.2 14.3 15.6 17.0
92.5 10.1 11.0 12.0 13.1 14.3 15.8 17.4 92.5 10.6 11.4 12.3 13.3 14.4 15.7 17.1
93.0 10.2 11.1 12.1 13.2 14.5 15.9 17.5 93.0 10.7 11.5 12.4 13.4 14.6 15.8 17.3
93.5 10.3 11.2 12.2 13.3 14.6 16.1 17.7 93.5 10.7 11.6 12.5 13.5 14.7 16.0 17.4
94.0 10.4 11.3 12.3 13.5 14.7 16.2 17.9 94.0 10.8 11.7 12.6 13.7 14.8 16.1 17.6
94.5 10.5 11.4 12.4 13.6 14.9 16.4 18.0 94.5 10.9 11.8 12.7 13.8 14.9 16.3 17.7
95.0 10.6 11.5 12.6 13.7 15.0 16.5 18.2 95.0 11.0 11.9 12.8 13.9 15.1 16.4 17.9
95.5 10.7 11.6 12.7 13.8 15.2 16.7 18.4 95.5 11.1 12 12.9 14.0 15.2 16.5 18.0
96.0 10.8 11.7 12.8 14.0 15.3 16.8 18.6 96.0 11.2 12.1 13.1 14.1 15.3 16.7 18.2
96.5 10.9 11.8 12.9 14.1 15.4 17.0 18.7 96.5 11.3 12.2 13.2 14.3 15.5 16.8 18.4
97.0 11.0 12.0 13.0 14.2 15.6 17.1 18.9 97.0 11.4 12.3 13.3 14.4 15.6 17.0 18.5
97.5 11.1 12.1 13.1 14.4 15.7 17.3 19.1 97.5 11.5 12.4 13.4 14.5 15.7 17.1 18.7
98.0 11.2 12.2 13.3 14.5 15.9 17.5 19.3 98.0 11.6 12.5 13.5 14.6 15.9 17.3 18.9
98.5 11.3 12.3 13.4 14.6 16.0 17.6 19.5 98.5 11.7 12.6 13.6 14.8 16.0 17.5 19.1
99.0 11.4 12.4 13.5 14.8 16.2 17.8 19.6 99.0 11.8 12.7 13.7 14.9 16.2 17.6 19.2
99.5 11.5 12.5 13.6 14.9 16.3 18.0 19.8 99.5 11.9 12.8 13.9 15.0 16.3 17.8 19.4
100.0 11.6 12.6 13.7 15.0 16.5 18.1 20.0 100.0 12.0 12.9 14.0 15.2 16.5 18.0 19.6
100.5 11.7 12.7 13.9 15.2 16.6 18.3 20.2 100.5 12.1 13 14.1 15.3 16.6 18.1 19.8
101.0 11.8 12.8 14.0 15.3 16.8 18.5 20.4 101.0 12.2 13.2 14.2 15.4 16.8 18.3 20.0
101.5 11.9 13.0 14.1 15.5 17.0 18.7 20.6 101.5 12.3 13.3 14.4 15.6 16.9 18.5 20.2
102.0 12.0 13.1 14.3 15.6 17.1 18.9 20.8 102.0 12.4 13.4 14.5 15.7 17.1 18.7 20.4
102.5 12.1 13.2 14.4 15.8 17.3 19.0 21.0 102.5 12.5 13.5 14.6 15.9 17.3 18.8 20.6
103.0 12.3 13.3 14.5 15.9 17.5 19.2 21.3 103.0 12.6 13.6 14.8 16.0 17.4 19.0 20.8
103.5 12.4 13.5 14.7 16.1 17.6 19.4 21.5 103.5 12.7 13.7 14.9 16.2 17.6 19.2 21.0
104.0 12.5 13.6 14.8 16.2 17.8 19.6 21.7 104.0 12.8 13.9 15.0 16.3 17.8 19.4 21.2
104.5 12.6 13.7 15.0 16.4 18.0 19.8 21.9 104.5 12.9 14.0 15.2 16.5 17.9 19.6 21.5
105.0 12.7 13.8 15.1 16.5 18.2 20.0 22.2 105.0 13.0 14.1 15.3 16.6 18.1 19.8 21.7
105.5 12.8 14.0 15.3 16.7 18.4 20.2 22.4 105.5 13.2 14.2 15.4 16.8 18.3 20.0 21.9
106.0 13.0 14.1 15.4 16.9 18.5 20.5 22.6 106.0 13.3 14.4 15.6 16.9 18.5 20.2 22.1
106.5 13.1 14.3 15.6 17.1 18.7 20.7 22.9 106.5 13.4 14.5 15.7 17.1 18.6 20.4 22.4
107.0 13.2 14.4 15.7 17.2 18.9 20.9 23.1 107.0 13.5 14.6 15.9 17.3 18.8 20.6 22.6
107.5 13.3 14.5 15.9 17.4 19.1 21.1 23.4 107.5 13.6 14.7 16.0 17.4 19.0 20.8 22.8
108.0 13.5 14.7 16.0 17.6 19.3 21.3 23.6 108.0 13.7 14.9 16.2 17.6 19.2 21.0 23.1
108.5 13.6 14.8 16.2 17.8 19.5 21.6 23.9 108.5 13.8 15.0 16.3 17.8 19.4 21.2 23.3
109.0 13.7 15.0 16.4 18.0 19.7 21.8 24.2 109.0 14.0 15.1 16.5 17.9 19.6 21.4 23.6
109.5 13.9 15.1 16.5 18.1 20.0 22.0 24.4 109.5 14.1 15.3 16.6 18.1 19.8 21.7 23.8
110.0 14.0 15.3 16.7 18.3 20.2 22.3 24.7 110.0 14.2 15.4 16.8 18.3 20.0 21.9 24.1
WHO: MGRS
-24 Essential Pediatrics
Table 2.68: Weight-for-height/length (kg) in girls and boys 0-5 years of age
Weight (kg) Girls Height Weight (kg) Boys
Height
(cm) -3SD -2 SD -1 SD Median 1 SD 2SD 3SD (cm) -3 SD -2 SD -1 SD Median 1 SD 2SD 3SD
65.0 5.6 6.1 6.6 7.2 7.9 8.7 9.7 65 5.9 6.3 6.9 7.4 8.1 8.8 9.6
65.5 5.7 6.2 6.7 7.4 8.1 8.9 9.8 65.5 6.0 6.4 7.0 7.6 8.2 8.9 9.8
66.0 5.8 6.3 6.8 7.5 8.2 9.0 10.0 66 6.1 6.5 7.1 7.7 8.3 9.1 9.9
66.5 5.8 6.4 6.9 7.6 8.3 9.1 10.1 66.5 6.1 6.6 7.2 7.8 8.5 9.2 10.1
67.0 5.9 6.4 7.0 7.7 8.4 9.3 10.2 67 6.2 6.7 7.3 7.9 8.6 9.4 10.2
67.5 6.0 6.5 7.1 7.8 8.5 9.4 10.4 67.5 6.3 6.8 7.4 8.0 8.7 9.5 10.4
68.0 6.1 6.6 7.2 7.9 8.7 9.5 10.5 68 6.4 6.9 7.5 8.1 8.8 9.6 10.5
68.5 6.2 6.7 7.3 8.0 8.8 9.7 10.7 68.5 6.5 7.0 7.6 8.2 9.0 9.8 10.7
69.0 6.3 6.8 7.4 8.1 8.9 9.8 10.8 69 6.6 7.1 7.7 8.4 9.1 9.9 10.8
69.5 6.3 6.9 7.5 8.2 9.0 9.9 10.9 69.5 6.7 7.2 7.8 8.5 9.2 10.0 11.0
70.0 6.4 7.0 7.6 8.3 9.1 10.0 11.1 70 6.8 7.3 7.9 8.6 9.3 10.2 11.1
70.5 6.5 7.1 7.7 8.4 9.2 10.1 11.2 70.5 6.9 7.4 8.0 8.7 9.5 10.3 11.3
71.0 6.6 7.1 7.8 8.5 9.3 10.3 11.3 71 6.9 7.5 8.1 8.8 9.6 10.4 11.4
71.5 6.7 7.2 7.9 8.6 9.4 10.4 11.5 71.5 7.0 7.6 8.2 8.9 9.7 10.6 11.6
72.0 6.7 7.3 8.0 8.7 9.5 10.5 11.6 72 7.1 7.7 8.3 9.0 9.8 10.7 11.7
72.5 6.8 7.4 8.1 8.8 9.7 10.6 11.7 72.5 7.2 7.8 8.4 9.1 9.9 10.8 11.8
73.0 6.9 7.5 8.1 8.9 9.8 10.7 11.8 73 7.3 7.9 8.5 9.2 10.0 11.0 12.0
73.5 7.0 7.6 8.2 9.0 9.9 10.8 12.0 73.5 7.4 7.9 8.6 9.3 10.2 11.1 12.1
74.0 7.0 7.6 8.3 9.1 10.0 11.0 12.1 74 7.4 8.0 8.7 9.4 10.3 11.2 12.2
74.5 7.1 7.7 8.4 9.2 10.1 11.1 12.2 74.5 7.5 8.1 8.8 9.5 10.4 11.3 12.4
75.0 7.2 7.8 8.5 9.3 10.2 11.2 12.3 75 7.6 8.2 8.9 9.6 10.5 11.4 12.5
75.5 7.2 7.9 8.6 9.4 10.3 11.3 12.5 75.5 7.7 8.3 9.0 9.7 10.6 11.6 12.6
76.0 7.3 8.0 8.7 9.5 10.4 11.4 12.6 76 7.7 8.4 9.1 9.8 10.7 11.7 12.8
76.5 7.4 8.0 8.7 9.6 10.5 11.5 12.7 76.5 7.8 8.5 9.2 9.9 10.8 11.8 12.9
77.0 7.5 8.1 8.8 9.6 10.6 11.6 12.8 77 7.9 8.5 9.2 10.0 10.9 11.9 13.0
77.5 7.5 8.2 8.9 9.7 10.7 11.7 12.9 77.5 8.0 8.6 9.3 10.1 11.0 12.0 13.1
78.0 7.6 8.3 9.0 9.8 10.8 11.8 13.1 78 8.0 8.7 9.4 10.2 11.1 12.1 13.3
78.5 7.7 8.4 9.1 9.9 10.9 12.0 13.2 78.5 8.1 8.8 9.5 10.3 11.2 12.2 13.4
79.0 7.8 8.4 9.2 10.0 11.0 12.1 13.3 79 8.2 8.8 9.6 10.4 11.3 12.3 13.5
79.5 7.8 8.5 9.3 10.1 11.1 12.2 13.4 79.5 8.3 8.9 9.7 10.5 11.4 12.4 13.6
80.0 7.9 8.6 9.4 10.2 11.2 12.3 13.6 80 8.3 9.0 9.7 10.6 11.5 12.6 13.7
80.5 8.0 8.7 9.5 10.3 11.3 12.4 13.7 80.5 8.4 9.1 9.8 10.7 11.6 12.7 13.8
81.0 8.1 8.8 9.6 10.4 11.4 12.6 13.9 81 8.5 9.2 9.9 10.8 11.7 12.8 14.0
81.5 8.2 8.9 9.7 10.6 11.6 12.7 14.0 81.5 8.6 9.3 10.0 10.9 11.8 12.9 14.1
82.0 8.3 9.0 9.8 10.7 11.7 12.8 14.1 82 8.7 9.3 10.1 11.0 11.9 13.0 14.2
82.5 8.4 9.1 9.9 10.8 11.8 13.0 14.3 82.5 8.7 9.4 10.2 11.1 12.1 13.1 14.4
83.0 8.5 9.2 10.0 10.9 11.9 13.1 14.5 83 8.8 9.5 10.3 11.2 12.2 13.3 14.5
83.5 8.5 9.3 10.1 11.0 12.1 13.3 14.6 83.5 8.9 9.6 10.4 11.3 12.3 13.4 14.6
84.0 8.6 9.4 10.2 11.1 12.2 13.4 14.8 84 9.0 9.7 10.5 11.4 12.4 13.5 14.8
84.5 8.7 9.5 10.3 11.3 12.3 13.5 14.9 84.5 9.1 9.9 10.7 11.5 12.5 13.7 14.9
85.0 8.8 9.6 10.4 11.4 12.5 13.7 15.1 85 9.2 10.0 10.8 11.7 12.7 13.8 15.1
85.5 8.9 9.7 10.6 11.5 12.6 13.8 15.3 85.5 9.3 10.1 10.9 11.8 12.8 13.9 15.2
86.0 9.0 9.8 10.7 11.6 12.7 14.0 15.4 86 9.4 10.2 11.0 11.9 12.9 14.1 15.4
86.5 9.1 9.9 10.8 11.8 12.9 14.2 15.6 86.5 9.5 10.3 11.1 12.0 13.1 14.2 15.5
87.0 9.2 10.0 10.9 11.9 13.0 14.3 15.8 87 9.6 10.4 11.2 12.2 13.2 14.4 15.7
87.5 9.3 10.1 11.0 12.0 13.2 14.5 15.9 87.5 9.7 10.5 11.3 12.3 13.3 14.5 15.8
88.0 9.4 10.2 11.1 12.1 13.3 14.6 16.1 88 9.8 10.6 11.5 12.4 13.5 14.7 16.0
88.5 9.5 10.3 11.2 12.3 13.4 14.8 16.3 88.5 9.9 10.7 11.6 12.5 13.6 14.8 16.1
89.0 9.6 10.4 11.4 12.4 13.6 14.9 16.4 89 10.0 10.8 11.7 12.6 13.7 14.9 16.3
89.5 9.7 10.5 11.5 12.5 13.7 15.1 16.6 89.5 10.1 10.9 11.8 12.8 13.9 15.1 16.4
90.0 9.8 10.6 11.6 12.6 13.8 15.2 16.8 90 10.2 11.0 11.9 12.9 14.0 15.2 16.6
90.5 9.9 10.7 11.7 12.8 14.0 15.4 16.9 90.5 10.3 11.1 12.0 13.0 14.1 15.3 16.7
91.0 10.0 10.9 11.8 12.9 14.1 15.5 17.1 91 10.4 11.2 12.1 13.1 14.2 15.5 16.9
91.5 10.1 11.0 11.9 13.0 14.3 15.7 17.3 91.5 10.5 11.3 12.2 13.2 14.4 15.6 17.0
Contd...
Growth 25-
Table 2.68: Weight-for-heighVlength (kg) in girls and boys 0-5 years of age (Contd.)
Height Weight (kg) Girls Height Weight (kg) Boys
(cm) -3SD -2 SD -1 SD Median 1 SD 2SD 3SD (cm) -3 SD -2 SD -1 SD Median 1 SD 2SD 3SD
92.0 10.2 11.1 12.0 13.1 14.4 15.8 17.4 92.0 10.6 11.4 12.3 13.4 14.5 15.8 17.2
92.5 10.3 11.2 12.1 13.3 14.5 16.0 17.6 92.5 10.7 11.5 12.4 13.5 14.6 15.9 17.3
93.0 10.4 11.3 12.3 13.4 14.7 16.1 17.8 93.0 10.8 11.6 12.6 13.6 14.7 16.0 17.5
93.5 10.5 11.4 12.4 13.5 14.8 16.3 17.9 93.5 10.9 11.7 12.7 13.7 14.9 16.2 17.6
94.0 10.6 11.5 12.5 13.6 14.9 16.4 18.1 94.0 11.0 11.8 12.8 13.8 15.0 16.3 17.8
94.5 10.7 11.6 12.6 13.8 15.1 16.6 18.3 94.5 11.1 11.9 12.9 13.9 15.1 16.5 17.9
95.0 10.8 11.7 12.7 13.9 15.2 16.7 18.5 95.0 11.1 12.0 13.0 14.1 15.3 16.6 18.1
95.5 10.8 11.8 12.8 14.0 15.4 16.9 18.6 95.5 11.2 12.1 13.1 14.2 15.4 16.7 18.3
96.0 10.9 11.9 12.9 14.1 15.5 17.0 18.8 96.0 11.3 12.2 13.2 14.3 15.5 16.9 18.4
96.5 11.0 12.0 13.1 14.3 15.6 17.2 19.0 96.5 11.4 12.3 13.3 14.4 15.7 17.0 18.6
97.0 11.1 12.1 13.2 14.4 15.8 17.4 19.2 97.0 11.5 12.4 13.4 14.6 15.8 17.2 18.8
97.5 11.2 12.2 13.3 14.5 15.9 17.5 19.3 97.5 11.6 12.5 13.6 14.7 15.9 17.4 18.9
98.0 11.3 12.3 13.4 14.7 16.1 17.7 19.5 98.0 11.7 12.6 13.7 14.8 16.1 17.5 19.1
98.5 11.4 12.4 13.5 14.8 16.2 17.9 19.7 98.5 11.8 12.8 13.8 14.9 16.2 17.7 19.3
99.0 11.5 12.5 13.7 14.9 16.4 18.0 19.9 99.0 11.9 12.9 13.9 15.1 16.4 17.9 19.5
99.5 11.6 12.7 13.8 15.1 16.5 18.2 20.1 99.5 12.0 13.0 14.0 15.2 16.5 18.0 19.7
100.0 11.7 12.8 13.9 15.2 16.7 18.4 20.3 100.0 12.1 13.1 14.2 15.4 16.7 18.2 19.9
100.5 11.9 12.9 14.1 15.4 16.9 18.6 20.5 100.5 12.2 13.2 14.3 15.5 16.9 18.4 20.1
101.0 12.0 13.0 14.2 15.5 17.0 18.7 20.7 101.0 12.3 13.3 14.4 15.6 17.0 18.5 20.3
101.5 12.1 13.1 14.3 15.7 17.2 18.9 20.9 101.5 12.4 13.4 14.5 15.8 17.2 18.7 20.5
102.0 12.2 13.3 14.5 15.8 17.4 19.1 21.1 102.0 12.5 13.6 14.7 15.9 17.3 18.9 20.7
102.5 12.3 13.4 14.6 16.0 17.5 19.3 21.4 102.5 12.6 13.7 14.8 16.1 17.5 19.1 20.9
103.0 12.4 13.5 14.7 16.1 17.7 19.5 21.6 103.0 12.8 13.8 14.9 16.2 17.7 19.3 21.1
103.5 12.5 13.6 14.9 16.3 17.9 19.7 21.8 103.5 12.9 13.9 15.1 16.4 17.8 19.5 21.3
104.0 12.6 13.8 15.0 16.4 18.1 19.9 22.0 104.0 13.0 14.0 15.2 16.5 18.0 19.7 21.6
104.5 12.8 13.9 15.2 16.6 18.2 20.1 22.3 104.5 13.1 14.2 15.4 16.7 18.2 19.9 21.8
105.0 12.9 14.0 15.3 16.8 18.4 20.3 22.5 105.0 13.2 14.3 15.5 16.8 18.4 20.1 22.0
105.5 13.0 14.2 15.5 16.9 18.6 20.5 22.7 105.5 13.3 14.4 15.6 17.0 18.5 20.3 22.2
106.0 13.1 14.3 15.6 17.1 18.8 20.8 23.0 106.0 13.4 14.5 15.8 17.2 18.7 20.5 22.5
106.5 13.3 14.5 15.8 17.3 19.0 21.0 23.2 106.5 13.5 14.7 15.9 17.3 18.9 20.7 22.7
107.0 13.4 14.6 15.9 17.5 19.2 21.2 23.5 107.0 13.7 14.8 16.1 17.5 19.1 20.9 22.9
107.5 13.5 14.7 16.1 17.7 19.4 21.4 23.7 107.5 13.8 14.9 16.2 17.7 19.3 21.1 23.2
108.0 13.7 14.9 16.3 17.8 19.6 21.7 24.0 108.0 13.9 15.1 16.4 17.8 19.5 21.3 23.4
108.5 13.8 15.0 16.4 18.0 19.8 21.9 24.3 108.5 14.0 15.2 16.5 18.0 19.7 21.5 23.7
109.0 13.9 15.2 16.6 18.2 20.0 22.1 24.5 109.0 14.1 15.3 16.7 18.2 19.8 21.8 23.9
109.5 14.1 15.4 16.8 18.4 20.3 22.4 24.8 109.5 14.3 15.5 16.8 18.3 20.0 22.0 24.2
110.0 14.2 15.5 17.0 18.6 20.5 22.6 25.1 110.0 14.4 15.6 17.0 18.5 20.2 22.2 24.4
110.5 14.4 15.7 17.1 18.8 20.7 22.9 25.4 110.5 14.5 15.8 17.1 18.7 20.4 22.4 24.7
111.0 14.5 15.8 17.3 19.0 20.9 23.1 25.7 111.0 14.6 15.9 17.3 18.9 20.7 22.7 25.0
111.5 14.7 16.0 17.5 19.2 21.2 23.4 26.0 111.5 14.8 16.0 17.5 19.1 20.9 22.9 25.2
112.0 14.8 16.2 17.7 19.4 21.4 23.6 26.2 112.0 14.9 16.2 17.6 19.2 21.1 23.1 25.5
112.5 15.0 16.3 17.9 19.6 21.6 23.9 26.5 112.5 15.0 16.3 17.8 19.4 21.3 23.4 25.8
113.0 15.1 16.5 18.0 19.8 21.8 24.2 26.8 113.0 15.2 16.5 18.0 19.6 21.5 23.6 26.0
113.5 15.3 16.7 18.2 20.0 22.1 24.4 27.1 113.5 15.3 16.6 18.1 19.8 21.7 23.9 26.3
114.0 15.4 16.8 18.4 20.2 22.3 24.7 27.4 114.0 15.4 16.8 18.3 20.0 21.9 24.1 26.6
114.5 15.6 17.0 18.6 20.5 22.6 25.0 27.8 114.5 15.6 16.9 18.5 20.2 22.1 24.4 26.9
115.0 15.7 17.2 18.8 20.7 22.8 25.2 28.1 115.0 15.7 17.1 18.6 20.4 22.4 24.6 27.2
115.5 15.9 17.3 19.0 20.9 23.0 25.5 28.4 115.5 15.8 17.2 18.8 20.6 22.6 24.9 27.5
116.0 16.0 17.5 19.2 21.1 23.3 25.8 28.7 116.0 16.0 17.4 19.0 20.8 22.8 25.1 27.8
116.5 16.2 17.7 19.4 21.3 23.5 26.1 29.0 116.5 16.1 17.5 19.2 21.0 23.0 25.4 28.0
117.0 16.3 17.8 19.6 21.5 23.8 26.3 29.3 117.0 16.2 17.7 19.3 21.2 23.3 25.6 28.3
117.5 16.5 18.0 19.8 21.7 24.0 26.6 29.6 117.5 16.4 17.9 19.5 21.4 23.5 25.9 28.6
118.0 16.6 18.2 19.9 22.0 24.2 26.9 29.9 118.0 16.5 18.0 19.7 21.6 23.7 26.1 28.9
118.5 16.8 18.4 20.1 22.2 24.5 27.2 30.3 118.5 16.7 18.2 19.9 21.8 23.9 26.4 29.2
119.0 16.9 18.5 20.3 22.4 24.7 27.4 30.6 119.0 16.8 18.3 20.0 22.0 24.1 26.6 29.5
119.5 17.1 18.7 20.5 22.6 25.0 27.7 30.9 119.5 16.9 18.5 20.2 22.2 24.4 26.9 29.8
120.0 17.3 18.9 20.7 22.8 25.2 28.0 31.2 120.0 17.1 18.6 20.4 22.4 24.6 27.2 30.1
WHO: MGRS
- 26
Age
Essential Pediatrics
Table 2.7: Body mass index (BMI) for age in girls and boys 0-5 years
BM/ Girls BM/ Boys
(mo) -3SD -2SD -1 SD Median 1SD 2SD 3SD -3SD -2SD -1SD Median 1SD 2SD 3SD
0 10.1 11.1 12.2 13.3 14.6 16.1 17.7 10.2 11.1 12.2 13.4 14.8 16.3 18.1
1 10.8 12.0 13.2 14.6 16.0 17.5 19.1 11.3 12.4 13.6 14.9 16.3 17.8 19.4
2 11.8 13.0 14.3 15.8 17.3 19.0 20.7 12.5 13.7 15.0 16.3 17.8 19.4 21.1
3 12.4 13.6 14.9 16.4 17.9 19.7 21.5 13.1 14.3 15.5 16.9 18.4 20.0 21.8
4 12.7 13.9 15.2 16.7 18.3 20.0 22.0 13.4 14.5 15.8 17.2 18.7 20.3 22.1
5 12.9 14.1 15.4 16.8 18.4 20.2 22.2 13.5 14.7 15.9 17.3 18.8 20.5 22.3
6 13.0 14.1 15.5 16.9 18.5 20.3 22.3 13.6 14.7 16.0 17.3 18.8 20.5 22.3
7 13.0 14.2 15.5 16.9 18.5 20.3 22.3 13.7 14.8 16.0 17.3 18.8 20.5 22.3
8 13.0 14.1 15.4 16.8 18.4 20.2 22.2 13.6 14.7 15.9 17.3 18.7 20.4 22.2
9 12.9 14.1 15.3 16.7 18.3 20.1 22.1 13.6 14.7 15.8 17.2 18.6 20.3 22.1
10 12.9 14.0 15.2 16.6 18.2 19.9 21.9 13.5 14.6 15.7 17.0 18.5 20.1 22.0
11 12.8 13.9 15.1 16.5 18.0 19.8 21.8 13.4 14.5 15.6 16.9 18.4 20.0 21.8
12 12.7 13.8 15.0 16.4 17.9 19.6 21.6 13.4 14.4 15.5 16.8 18.2 19.8 21.6
13 12.6 13.7 14.9 16.2 17.7 19.5 21.4 13.3 14.3 15.4 16.7 18.1 19.7 21.5
14 12.6 13.6 14.8 16.1 17.6 19.3 21.3 13.2 14.2 15.3 16.6 18.0 19.5 21.3
15 12.5 13.5 14.7 16.0 17.5 19.2 21.1 13.1 14.1 15.2 16.4 17.8 19.4 21.2
16 12.4 13.5 14.6 15.9 17.4 19.1 21.0 13.1 14.0 15.1 16.3 17.7 19.3 21.0
17 12.4 13.4 14.5 15.8 17.3 18.9 20.9 13.0 13.9 15.0 16.2 17.6 19.1 20.9
18 12.3 13.3 14.4 15.7 17.2 18.8 20.8 12.9 13.9 14.9 16.1 17.5 19.0 20.8
19 12.3 13.3 14.4 15.7 17.1 18.8 20.7 12.9 13.8 14.9 16.1 17.4 18.9 20.7
20 12.2 13.2 14.3 15.6 17.0 18.7 20.6 12.8 13.7 14.8 16.0 17.3 18.8 20.6
21 12.2 13.2 14.3 15.5 17.0 18.6 20.5 12.8 13.7 14.7 15.9 17.2 18.7 20.5
22 12.2 13.1 14.2 15.5 16.9 18.5 20.4 12.7 13.6 14.7 15.8 17.2 18.7 20.4
23 12.2 13.1 14.2 15.4 16.9 18.5 20.4 12.7 13.6 14.6 15.8 17.1 18.6 20.3
24 12.1 13.1 14.2 15.4 16.8 18.4 20.3 12.7 13.6 14.6 15.7 17.0 18.5 20.3
Age By height By height
(mo) -3SD -2SD -1SD Median 1SD 2SD 3SD -3SD -2SD -1SD Median 1SD 2SD 3SD
24 12.4 13.3 14.4 15.7 17.1 18.7 20.6 12.9 13.8 14.8 16.0 17.3 18.9 20.6
25 12.4 13.3 14.4 15.7 17.1 18.7 20.6 12.8 13.8 14.8 16.0 17.3 18.8 20.5
26 12.3 13.3 14.4 15.6 17.0 18.7 20.6 12.8 13.7 14.8 15.9 17.3 18.8 20.5
27 12.3 13.3 14.4 15.6 17.0 18.6 20.5 12.7 13.7 14.7 15.9 17.2 18.7 20.4
28 12.3 13.3 14.3 15.6 17.0 18.6 20.5 12.7 13.6 14.7 15.9 17.2 18.7 20.4
29 12.3 13.2 14.3 15.6 17.0 18.6 20.4 12.7 13.6 14.7 15.8 17.1 18.6 20.3
30 12.3 13.2 14.3 15.5 16.9 18.5 20.4 12.6 13.6 14.6 15.8 17.1 18.6 20.2
31 12.2 13.2 14.3 15.5 16.9 18.5 20.4 12.6 13.5 14.6 15.8 17.1 18.5 20.2
32 12.2 13.2 14.3 15.5 16.9 18.5 20.4 12.5 13.5 14.6 15.7 17.0 18.5 20.1
33 12.2 13.1 14.2 15.5 16.9 18.5 20.3 12.5 13.5 14.5 15.7 17.0 18.5 20.1
34 12.2 13.1 14.2 15.4 16.8 18.5 20.3 12.5 13.4 14.5 15.7 17.0 18.4 20.0
35 12.1 13.1 14.2 15.4 16.8 18.4 20.3 12.4 13.4 14.5 15.6 16.9 18.4 20.0
36 12.1 13.1 14.2 15.4 16.8 18.4 20.3 12.4 13.4 14.4 15.6 16.9 18.4 20.0
37 12.1 13.1 14.1 15.4 16.8 18.4 20.3 12.4 13.3 14.4 15.6 16.9 18.3 19.9
38 12.1 13.0 14.1 15.4 16.8 18.4 20.3 12.3 13.3 14.4 15.5 16.8 18.3 19.9
39 12.0 13.0 14.1 15.3 16.8 18.4 20.3 12.3 13.3 14.3 15.5 16.8 18.3 19.9
40 12.0 13.0 14.1 15.3 16.8 18.4 20.3 12.3 13.2 14.3 15.5 16.8 18.2 19.9
41 12.0 13.0 14.1 15.3 16.8 18.4 20.4 12.2 13.2 14.3 15.5 16.8 18.2 19.9
42 12.0 12.9 14.0 15.3 16.8 18.4 20.4 12.2 13.2 14.3 15.4 16.8 18.2 19.8
43 11.9 12.9 14.0 15.3 16.8 18.4 20.4 12.2 13.2 14.2 15.4 16.7 18.2 19.8
44 11.9 12.9 14.0 15.3 16.8 18.5 20.4 12.2 13.1 14.2 15.4 16.7 18.2 19.8
45 11.9 12.9 14.0 15.3 16.8 18.5 20.5 12.2 13.1 14.2 15.4 16.7 18.2 19.8
46 11.9 12.9 14.0 15.3 16.8 18.5 20.5 12.1 13.1 14.2 15.4 16.7 18.2 19.8
47 11.8 12.8 14.0 15.3 16.8 18.5 20.5 12.1 13.1 14.2 15.3 16.7 18.2 19.9
48 11.8 12.8 14.0 15.3 16.8 18.5 20.6 12.1 13.1 14.1 15.3 16.7 18.2 19.9
49 11.8 12.8 13.9 15.3 16.8 18.5 20.6 12.1 13.0 14.1 15.3 16.7 18.2 19.9
50 11.8 12.8 13.9 15.3 16.8 18.6 20.7 12.1 13.0 14.1 15.3 16.7 18.2 19.9
51 11.8 12.8 13.9 15.3 16.8 18.6 20.7 12.1 13.0 14.1 15.3 16.6 18.2 19.9
52 11.7 12.8 13.9 15.2 16.8 18.6 20.7 12.0 13.0 14.1 15.3 16.6 18.2 19.9
53 11.7 12.7 13.9 15.3 16.8 18.6 20.8 12.0 13.0 14.1 15.3 16.6 18.2 20.0
54 11.7 12.7 13.9 15.3 16.8 18.7 20.8 12.0 13.0 14.0 15.3 16.6 18.2 20.0
55 11.7 12.7 13.9 15.3 16.8 18.7 20.9 12.0 13.0 14.0 15.2 16.6 18.2 20.0
56 11.7 12.7 13.9 15.3 16.8 18.7 20.9 12.0 12.9 14.0 15.2 16.6 18.2 20.1
57 11.7 12.7 13.9 15.3 16.9 18.7 21.0 12.0 12.9 14.0 15.2 16.6 18.2 20.1
58 11.7 12.7 13.9 15.3 16.9 18.8 21.0 12.0 12.9 14.0 15.2 16.6 18.3 20.2
59 11.6 12.7 13.9 15.3 16.9 18.8 21.0 12.0 12.9 14.0 15.2 16.6 18.3 20.2
WHO: MGRS
Growth 121-
Table 2.8: Head circumference for age (cm) in girls and boys 0-5 years of age
BM/ Girls BM/ Boys
Age
(mo) -3SD -2 SD -1 SD Median 1 SD 2SD 3SD -3SD -2 SD -1 SD Median 1 SD 2SD 3SD
0 30.3 31.5 32.7 33.9 35.1 36.2 37.4 30.7 31.9 33.2 34.5 35.7 37.0 38.3
33.0 34.2 35.4 36.5 37.7 38.9 40.1 33.8 34.9 36.1 37.3 38.4 39.6 40.8
2 34.6 35.8 37.0 38.3 39.5 40.7 41.9 35.6 36.8 38.0 39.1 40.3 41.5 42.6
3 35.8 37.1 38.3 39.5 40.8 42.0 43.3 37.0 38.1 39.3 40.5 41.7 42.9 44.1
4 36.8 38.1 39.3 40.6 41.8 43.1 44.4 38.0 39.2 40.4 41.6 42.8 44.0 45.2
5 37.6 38.9 40.2 41.5 42.7 44.0 45.3 38.9 40.1 41.4 42.6 43.8 45.0 46.2
6 38.3 39.6 40.9 42.2 43.5 44.8 46.1 39.7 40.9 42.1 43.3 44.6 45.8 47.0
7 38.9 40.2 41.5 42.8 44.1 45.5 46.8 40.3 41.5 42.7 44.0 45.2 46.4 47.7
8 39.4 40.7 42.0 43.4 44.7 46.0 47.4 40.8 42.0 43.3 44.5 45.8 47.0 48.3
9 39.8 41.2 42.5 43.8 45.2 46.5 47.8 41.2 42.5 43.7 45.0 46.3 47.5 48.8
10 40.2 41.5 42.9 44.2 45.6 46.9 48.3 41.6 42.9 44.1 45.4 46.7 47.9 49.2
11 40.5 41.9 43.2 44.6 45.9 47.3 48.6 41.9 43.2 44.5 45.8 47.0 48.3 49.6
12 40.8 42.2 43.5 44.9 46.3 47.6 49.0 42.2 43.5 44.8 46.1 47.4 48.6 49.9
13 41.1 42.4 43.8 45.2 46.5 47.9 49.3 42.5 43.8 45.0 46.3 47.6 48.9 50.2
14 41.3 42.7 44.1 45.4 46.8 48.2 49.5 42.7 44.0 45.3 46.6 47.9 49.2 50.5
15 41.5 42.9 44.3 45.7 47.0 48.4 49.8 42.9 44.2 45.5 46.8 48.1 49.4 50.7
16 41.7 43.1 44.5 45.9 47.2 48.6 50.0 43.1 44.4 45.7 47.0 48.3 49.6 51.0
17 41.9 43.3 44.7 46.1 47.4 48.8 50.2 43.2 44.6 45.9 47.2 48.5 49.8 51.2
18 42.1 43.5 44.9 46.2 47.6 49.0 50.4 43.4 44.7 46.0 47.4 48.7 50.0 51.4
19 42.3 43.6 45.0 46.4 47.8 49.2 50.6 43.5 44.9 46.2 47.5 48.9 50.2 51.5
20 42.4 43.8 45.2 46.6 48.0 49.4 50.7 43.7 45.0 46.4 47.7 49.0 50.4 51.7
21 42.6 44.0 45.3 46.7 48.1 49.5 50.9 43.8 45.2 46.5 47.8 49.2 50.5 51.9
22 42.7 44.1 45.5 46.9 48.3 49.7 51.1 43.9 45.3 46.6 48.0 49.3 50.7 52.0
23 42.9 44.3 45.6 47.0 48.4 49.8 51.2 44.1 45.4 46.8 48.1 49.5 50.8 52.2
24 43.0 44.4 45.8 47.2 48.6 50.0 51.4 44.2 45.5 46.9 48.3 49.6 51.0 52.3
25 43.1 44.5 45.9 47.3 48.7 50.1 51.5 44.3 45.6 47.0 48.4 49.7 51.1 52.5
26 43.3 44.7 46.1 47.5 48.9 50.3 51.7 44.4 45.8 47.1 48.5 49.9 51.2 52.6
27 43.4 44.8 46.2 47.6 49.0 50.4 51.8 44.5 45.9 47.2 48.6 50.0 51.4 52.7
28 43.5 44.9 46.3 47.7 49.1 50.5 51.9 44.6 46.0 47.3 48.7 50.1 51.5 52.9
29 43.6 45.0 46.4 47.8 49.2 50.6 52.0 44.7 46.1 47.4 48.8 50.2 51.6 53.0
30 43.7 45.1 46.5 47.9 49.3 50.7 52.2 44.8 46.1 47.5 48.9 50.3 51.7 53.1
31 43.8 45.2 46.6 48.0 49.4 50.9 52.3 44.8 46.2 47.6 49.0 50.4 51.8 53.2
32 43.9 45.3 46.7 48.1 49.6 51.0 52.4 44.9 46.3 47.7 49.1 50.5 51.9 53.3
33 44.0 45.4 46.8 48.2 49.7 51.1 52.5 45.0 46.4 47.8 49.2 50.6 52.0 53.4
34 44.1 45.5 46.9 48.3 49.7 51.2 52.6 45.1 46.5 47.9 49.3 50.7 52.1 53.5
35 44.2 45.6 47.0 48.4 49.8 51.2 52.7 45.1 46.6 48.0 49.4 50.8 52.2 53.6
36 44.3 45.7 47.1 48.5 49.9 51.3 52.7 45.2 46.6 48.0 49.5 50.9 52.3 53.7
37 44.4 45.8 47.2 48.6 50.0 51.4 52.8 45.3 46.7 48.1 49.5 51.0 52.4 53.8
38 44.4 45.8 47.3 48.7 50.1 51.5 52.9 45.3 46.8 48.2 49.6 51.0 52.5 53.9
39 44.5 45.9 47.3 48.7 50.2 51.6 53.0 45.4 46.8 48.2 49.7 51.1 52.5 54.0
40 44.6 46.0 47.4 48.8 50.2 51.7 53.1 45.4 46.9 48.3 49.7 51.2 52.6 54.1
41 44.6 46.1 47.5 48.9 50.3 51.7 53.1 45.5 46.9 48.4 49.8 51.3 52.7 54.1
42 44.7 46.1 47.5 49.0 50.4 51.8 53.2 45.5 47.0 48.4 49.9 51.3 52.8 54.2
43 44.8 46.2 47.6 49.0 50.4 51.9 53.3 45.6 47.0 48.5 49.9 51.4 52.8 54.3
44 44.8 46.3 47.7 49.1 50.5 51.9 53.3 45.6 47.1 48.5 50.0 51.4 52.9 54.3
45 44.9 46.3 47.7 49.2 50.6 52.0 53.4 45.7 47.1 48.6 50.1 51.5 53.0 54.4
46 45.0 46.4 47.8 49.2 50.6 52.1 53.5 45.7 47.2 48.7 50.1 51.6 53.0 54.5
47 45.0 46.4 47.9 49.3 50.7 52.1 53.5 45.8 47.2 48.7 50.2 51.6 53.1 54.5
48 45.1 46.5 47.9 49.3 50.8 52.2 53.6 45.8 47.3 48.7 50.2 51.7 53.1 54.6
49 45.1 46.5 48.0 49.4 50.8 52.2 53.6 45.9 47.3 48.8 50.3 51.7 53.2 54.7
50 45.2 46.6 48.0 49.4 50.9 52.3 53.7 45.9 47.4 48.8 50.3 51.8 53.2 54.7
51 45.2 46.7 48.1 49.5 50.9 52.3 53.8 45.9 47.4 48.9 50.4 51.8 53.3 54.8
52 45.3 46.7 48.1 49.5 51.0 52.4 53.8 46.0 47.5 48.9 50.4 51.9 53.4 54.8
53 45.3 46.8 48.2 49.6 51.0 52.4 53.9 46.0 47.5 49.0 50.4 51.9 53.4 54.9
54 45.4 46.8 48.2 49.6 51.1 52.5 53.9 46.1 47.5 49.0 50.5 52.0 53.5 54.9
55 45.4 46.9 48.3 49.7 51.1 52.5 54.0 46.1 47.6 49.1 50.5 52.0 53.5 55.0
56 45.5 46.9 48.3 49.7 51.2 52.6 54.0 46.1 47.6 49.1 50.6 52.1 53.5 55.0
57 45.5 46.9 48.4 49.8 51.2 52.6 54.1 46.2 47.6 49.1 50.6 52.1 53.6 55.1
58 45.6 47.0 48.4 49.8 51.3 52.7 54.1 46.2 47.7 49.2 50.7 52.1 53.6 55.1
59 45.6 47.0 48.5 49.9 51.3 52.7 54.1 46.2 47.7 49.2 50.7 52.2 53.7 55.2
60 45.7 47.1 48.5 49.9 51.3 52.8 54.2 46.3 47.7 49.2 50.7 52.2 53.7 55.2
WHO: MGRS
Table 2.9: Boys aged 5 to 18 years old: IAP charts for weight, height, body mass index (percentiles) (reproduced with permission from Indian Pediatr, 2015;52:47-55) I\)
11.5 131.5 136.4 145.9 155.1 159.6 7.1 24.8 28.4 37.6 50.6 59.1 9.1 13.2 13.7 14.4 17.6 19.8 23.6 3.3
12.0 134.0 138.9 148.4 157.5 162.0 7.0 26.2 30.0 39.8 53.4 62.1 9.0 13.4 13.9 14.7 18.0 20.2 24.1 3.2
12.5 136.3 141.1 150.5 159.6 164.1 6.7 27.6 31.6 41.8 55.8 64.8 9.7 13.7 14.2 15.0 18.4 20.7 24.7 3.3
13.0 138.2 142.9 152.2 161.3 165.9 6.9 28.9 33.1 43.6 57.9 67.1 9.4 13.9 14.4 15.2 18.8 21.1 25.2 3.2
13.5 139.9 144.5 153.6 162.7 167.2 6.0 30.2 34.4 45.1 59.7 69.0 9.8 14.1 14.6 15.5 19.1 21.5 25.6 3.5
14.0 141.3 145.8 154.7 163.7 168.2 6.6 31.3 35.6 46.4 61.1 70.4 9.6 14.3 14.9 15.7 19.4 21.8 25.9 3.4
14.5 142.4 146.8 155.5 164.5 169.0 5.9 32.3 36.6 47.5 62.2 71.4 9.4 14.5 15.1 16.0 19.7 22.0 26.2 3.3
15.0 143.3 147.5 156.1 165.0 169.5 6.6 33.1 37.5 48.4 62.9 72.1 9.6 14.7 15.2 16.1 19.9 22.3 26.3 3.4
15.5 144.1 148.1 156.6 165.3 169.8 5.9 34.0 38.3 49.1 63.5 72.5 8.7 14.9 15.4 16.3 20.1 22.4 26.4 3.1
16.0 144.7 148.6 156.9 165.6 170.1 6.1 34.7 39.1 49.7 64.0 72.8 8.7 15.0 15.6 16.5 20.3 22.6 26.5 3.1
16.5 145.2 149.1 157.2 165.7 170.2 6.4 35.5 39.8 50.3 64.4 73.1 9.2 15.2 15.8 16.7 20.4 22.8 26.6 3.2
17.0 145.7 149.5 157.4 165.9 170.4 6.5 36.2 40.5 50.9 64.7 73.3 8.8 15.4 16.0 16.9 20.6 22.9 26.7 3.0
17.5 146.2 149.8 157.6 166.0 170.5 6.7 36.9 41.1 51.5 65.0 73.4 9.5 15.5 16.1 17.1 20.8 23.1 26.7 3.1
18.0 146.6 150.2 157.8 166.1 170.6 6.6 37.6 41.8 52.0 65.3 73.5 10.2 15.7 16.3 17.3 21.0 23.2 26.8 3.6
23rd AE: equivalent to BMI of 23 in adults (overweight); 27th AE equivalent to BMI of 27 in adults (obesity) IAP
-
I
-30 Essential Pediatrics
Mobile Applications (Apps) for Analysis of Table 2.14: Causes of short stature
Anthropometric Data Physiological short stature or normal variant
Several mobile applications (apps) are now available for Familial
instant and quick analysis of anthropometric data Constitutional
(Table 2.13). While a few are paid, many of them are free for
download. Some use the CDC charts while others use WHO Pathologlcal
charts for analysis. A few apps allow users to make choice Undernutrition
of charts for calculations and interpretation. Many of these Chronic systemic illness
apps have additional capabilities and calculators. Cerebral palsy
Congenital heart disease, cystic fibrosis, asthma
Suggested Reading Malabsorption, e.g. celiac disease, chronic liver disease
• Agarwal DK, Agarwal KN, et al. Physical and sexual growth Acquired immunodeficiency syndrome, other chronic infections
pattern of affluent Indian children from 5-18 years of age. Indian
Endocrine causes
Pediatrics 1992;29:1203-82
• Agarwal DK, Agarwal KN, et al. Physical growth assessment in
Growth hormone deficiency, insensitivity
adolescence. Indian Pediatrics 2001;38:1217-35 Hypothyroidism
• Graham CB. Assessment of bone maturation-methods and Cushing syndrome
pitfalls. Radiol Clin North Am 1972,10:185-202 Pseudohypoparathyroidism
• World Health Organisation. http://www.who.int/nut-growthdb/ Precocious or delayed puberty
en. Guidelines on growth monitoring from birth to 18 years Psychosocial dwarfism
Children born small for gestational age
DISORDERS OF GROWTH Skeletal dysplasias , e.g. achondroplasia, rickets
Genetic syndromes, e.g. Turner, Down syndrome
Short Stature
Definition and Epidemiology common etiological factors, followed by growth hormone
Short stature is defined as height below third centile or deficiency (GHD) and hypothyroidism.
more than 2 standard deviations (SDs) below the median
height for age and gender ( <-2 SD) according to the Steps in Assessment
population standard. As is evident from the definition, Accurate height measurement: For children below 2 years,
approximately 3% of children in any given populations supine length should be measured using an infantometer
will be short. Children whose stature is more than 3 SD with a rigid headboard on one side and a moveable
below the population mean for age and gender footboard on the other side, while holding the infant
( <-3 SD) are more likely to be suffering from pathological straight on the horizontal board (Fig. 2.6). For older children,
short stature, as compared to those with stature between height should be measured with a stadiometer, as explained
-2 and -3 SD, who are more likely to be affected by in previous section (Fig. 2.7).
physiological, i.e. familial or constitutional short stature.
Assessment of height velocity: Height velocity is the rate of
increase in height over a period of time expressed as
Etiology cm/year. The average height velocity is 25 cm/yr in the
Short stature can be attributed to many causes (Table 2.14}. first year, declines to 4-6 cm/yr in prepubertal children
Undernutrition and chronic systemic illness are the between 4 and 9 years of age and increases during puberty
-32 Essential Pediatrics
to a peak height velocity of 10-12 cm/yr. If height velocity unravel many clues to the etiology of short stature
is lower than expected for age, the child is likely to be (Tables 2.15 and 2.16). The investigative work-up to be done
suffering from a pathological cause of short stature. is guided by clues from history and physical examination.
Comparison with population norms: The height should be Bone age assessment should be done in all children with
plotted on appropriate growth charts and expressed in short stature. The appearance of various epiphyseal centers
centile or as standard deviation score. and fusion of epiphyses with metaphyses tells about the
skeletal maturity of the child. Bone age is conventionally
Comparison with child's own genetic potential: Parents' read from radiograph of the left hand and wrist using either
height significantly affects the child's height. Mid-parental Gruelich-Pyle atlas or Tanner-Whitehouse method. It gives
height (MPH) gives an approximate estimate of the child's an idea as to what proportion of the adult height has been
genetically determined potential. achieved by the child and what is the remaining potential
Mother+ Father height (cm) for height gain. Bone age is delayed compared to
MPH for boys = + 6.5 cm
2 chronological age in almost all causes of short stature.
Mother+ Father height (cm) Exceptions to this are familial short stature, in which bone
MPH for girls= _ 6_5 cm age equals chronological age, and precocious puberty, in
2
This value is then plotted on the growth chart at which bone age exceeds chronological age. In case of
18-20 years (adult equivalent) of age. This gives an estimate constitutional delay, undernutrition and systemic illness,
of the target height for the child and the percentile that bone age is less than chronological age and corresponds to
he/she is likely to follow. height age. In cases of growth hormone deficiency and
Assessment of body proportion: Short stature can be pro Table 2.15: Clues to etiology of short stature from history
portionate or disproportionate. The proportionality is History Etiology
assessed by upper segment (US): lower segment (LS) ratio Low birth weight Small for gestational age
and comparison of arm span with height. US can be
Polyuria Chronic renal failure, renal
measured by taking the sitting height of the child. Child is
tubular acidosis
made to sit on a square stool placed against the vertical rod
of the stadiometer. The headboard is brought down to the Chronic diarrhea, Malabsorption
vertex similarly as for taking height. The height of the stool greasy stools
is subtracted from the reading obtained to get sitting height. Neonatal hypoglycemia, Hypopituitarism
LS can be obtained by subtracting US from height. jaundice, micropenis
Alternatively, LS can be measured by taking the length from Headache, vomiting, Pituitary or hypothalamic space
pubic symphysis to the ground while the child is standing visual problem occupying lesion, e.g.
erect. For measuring arm span, child is asked to stand craniopharyngioma
straight with both arms extended outwards parallel to the Lethargy, constipation, Hypothyroidism
ground. Length between the tips of the middle finger of the weight gain
outstretched hands is the arm span. Inadequate dietary intake Undernutrition
Normally, US : LS ratio is 1.7 at birth, 1.3 at 3 years, 1.1 by Social history Psychosocial dwarfism
6 years, 1 by 10 years and 0.9 in adults. Increase in US : LS Delayed puberty in Constitutional delay of growth
ratio is seen in rickets, achondroplasia and untreated parent(s) and puberty
congenital hypothyroidism. Decrease in US : LS ratio is
seen in spondyloepiphyseal dysplasia and vertebral Table 2.16: Clues to etiology of short stature from examination
anomalies. Arm span is shorter than length by 2.5 cm at
Examination finding Etiology
birth, equals height at 11 years and thereafter is slightly
(usually, <1 cm) greater than height. Disproportion Skeletal dysplasia, rickets,
hypothyroidism
Sexual maturity rating(SMR): SMRstage should be assessed Dysmorphism Congenital syndromes
in older children (see Chapter 5). Height spurt is seen in early Pallor Chronic anemia, chronic kidney
puberty in girls and mid-puberty in boys. Precocious puberty disease
can lead to early height spurt followed by premature
Hypertension Chronic kidney disease
epiphyseal fusion and ultimate short stature. On the other
hand, delayed puberty can also present with short stature in Frontal bossing, Hypopituitarism
depressed nasal
adolescents as the height spurt is also delayed.
bridge, crowded
teeth, small penis
Differential Diagnosis
Goiter, coarse skin Hypothyroidism
Diagnosis is based on a detailed history, examination and
Central obesity, striae Cushing syndrome
laboratory evaluation. Careful history and examination can
Growth 133-
Table 2.17: Investigative work-up for short stature Date Age Status Weight
::i:+�BA
Jl
Level 2 investigations 150
II
Karyotype in girls (to rule out Turner syndrome) 140
45
hypothyroidism, bone age may be lower than height age, if
40
the endocrine condition is diagnosed late.
35
In addition, all children with disproportionate short 30
stature require skeletal survey to rule out skeletal dysplasia 25
and rickets. Essential screening investigations that should 75 20
be done in all children with short stature are listed in 15
Table 2.17. If these investigations are normal and bone age 10 10
is delayed, level 2 investigations should be done. If these � 5
investigations are also normal, then the major diagnostic 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
malabsorption. If the child has borderline short stature, i.e. Fig. 2.21: Growth chart of a girl with familial short stature. The
height between -2 and -3 SD, then it is prudent to wait for child is growing below and parallel to 3rd centile from early
childhood till adulthood, height velocity is normal, bone age
6--12 months and observe for height velocity. On the other
(BA) corresponds to chronological age and target height (range
hand, if the child is significantly short(<-3 SD) or has indicated by vertical bold bar) is low
documented poor height velocity over 6-12 months, one
should proceed to level 3 investigations. continue to grow just below and parallel to the 3rd centile
with a normal height velocity. The onset of puberty and
Specific Etiologies adolescent growth spurt is also delayed in these children
Familial short stature: The child is short as per definition but final height is within normal limits. Bone age is lower
(height <3rd centile) but is normal according to his own than chronological age and corresponds to the height age.
genetic potential determined by the parents' height. These History of delayed puberty and delayed height spurt is
children show catch-down growth between birth and usually present in one or both parents (Fig. 2.22).
2 years of age, so that the height and weight come to lie on Table 2.18 lists features that distinguish between these
their target (mid-parental) centiles by the age of 2 years. two common causes of short stature.
Subsequently, the growth velocity remains normal Undernutrition: Stunted growth caused by chronic
throughout childhood and adolescence. The body undernutrition is one of the commonest cause for short
proportion is appropriate and bone age equals the stature in our country. A detailed dietary history and
chronological age. Puberty is achieved at appropriate age presence of other features of malnutrition such as low mid
and final height is within their target range (Fig. 2.21). upper arm circumference and low weight for height suggest
Constitutional growth delay: These children are born with the diagnosis.
a normal length and weight and grow normally for the first Endocrine causes: These are discussed in detail in Chapter 18.
6--12 months of life. Their growth then shows a deceleration
so that the height and weight fall below the 3rd centile. By Skeletal dysplasias: Inborn errors in the formation of
3 years of age, normal height velocity is resumed and they cartilage and bone, cause chondrodysplasias or skeletal
-34 Essential Pediatrics
5
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Management
Years
The general principles of management for any child who
Fig. 2.22: Growth chart of a boy with constitutional delay of growth presents with short stature include counseling of parents
and puberty. The child falls to a lower centile in early childhood,
and dietary advice. Parents should be counseled to
grows below and parallel to 3rd centile in childhood, with an
apparent downward deviation of growth curve during the normal
highlight the positive aspects in child's personality and
time of pubertal growth, with later acceleration of growth and not put undue emphasis on stature. Intake of a balanced
reaching target height (range indicated by vertical bold bar). diet containing the recommended amounts of macro- and
Bone age (BA) is lower than chronological age by 2-3 years micronutrients is recommended. The specific management
depends on the underlying cause. For physiological causes,
Table 2.18: Distinction between constitutional delay in growth
reassurance and annual monitoring of height and weight
and familial short stature is sufficient. Dietary rehabilitation for undernutrition and
treatment of underlying condition such as renal tubular
Feature Constitutional Familial short
growth delay stature
acidosis or celiac disease are generally associated with
satisfactory catch-up growth. With any form of therapy,
Height Short Short
monitoring with regular and accurate recording of height
Height velocity Normal Normal is mandatory for satisfactory outcome.
Family history Delayed puberty Short stature For skeletal dysplasias, limb lengthening procedures are
Bone age Less than Normal offered at a few orthopedic centers. For hypothyroidism,
chronological age levothyroxine replacement is advised. For growth hormone
Puberty Delayed Normal deficiency, treatment with daily subcutaneous injections of
Final height Normal Low but normal GH is recommended. GH therapy is also approved for several
for target height other conditions though the doses required are generally
higher and improvement in final height smaller and more
dysplasias, that are usually associated with abnormal variable as compared to GH deficiency. Some of these
skeletal proportions and severe short stature (except conditions are Turner syndrome, SGA with inadequate
hypochondroplasia, where growth retardation is mild). catchup growth and chronic renal failure prior to transplant.
Growth 35-
Table 2.21: Causes of macrocephaly previously normal brain causing reduction in the number
of dendritic processes and synaptic connections. Micro
Megalencephaly
encephaly (micrencephaly) is the term used for an
Benign familial abnormally small brain, based on findings on neuro
Neurocutaneous syndromes: Neurofibromatosis, tuberous imaging or neuropathology. Since head growth is driven
sclerosis, Sturge-Weber, Klippel-Trenaunay-Weber, linear by brain growth, microcephaly usually implies micro
sebaceous nevus encephaly (except in craniosynostosis in which skull
Leukodystrophies: Alexander, Canavan diseases; megalen growth is restricted).
cephalic leukoencephalopathy Important causes of rnicrocephaly are listed in Table 2.22.
Lysosomal storage diseases: Tay-Sachs disease, muco Isolated inherited microcephaly, most commonly as an
polysaccharidosis, gangliosidosis
autosomal recessive phenotype, is associated with reduced
Others: Sotos disease, fragile X syndrome
head circumferences since birth, normal cerebral anatomy
Increased cerebrospinal fluid and absence of neurologic signs with or without learning
Hydrocephalus difficulties. Other associations include structural brain
Benign enlargement of subarachnoid space malformations, inherited syndromes, congenital or acquired
Hydranencephaly, choroid plexus papilloma infections, hypoxic ischernic insults and rarely, metabolic
Enlarged vascular compartment disorders.
Arteriovenous malformation Evaluation for microcephaly should be initiated, if a
Subdural, epidural, subarachnoid or intraventricular single head circumference measurement is more than 2-3
hemorrhage SD below the mean or when serial measurements reveal
progressive decrease in head size. Careful history and
Increase in bony compartment
physical examination are necessary, including develop
Bone disease: Achondroplasia, osteogenesis imperfecta, ment assessment and measurement of head size of parents.
osteopetrosis, hyperphosphatasia, cleidocranial dysostosis
Bone marrow expansion: T halassemia major
Miscellaneous causes Table 2.22: Causes of microcephaly
lntracranial mass lesions: Cyst, abscess or tumor Isolated microcephaly
Raised intracranial pressure: Idiopathic pseudotumor cerebri, Autosomal recessive, autosomal dominant or X-linked
lead poisoning, hypervitaminosis A, galactosemia Syndromic
Trisomies 21, 18, 13
when serial measurements reveal progressive enlargement,
Monosomy 1p36 deletion
as suggested by an increase by >2 cm per month during
Syndromes: William, Cri-du-chat, Seckel, Smith-Lemli-Opitz,
first 6 months of life, or the crossing of one or more major Cornelia de Lange, Rubinstein-Taybi, Cockayne, Angelman
percentile lines between routine visits. Measurement of head
size in parents is useful in diagnosing familial cases. Structural diseases
Majority of patients require cranial imaging, ultra Neural tube defects (anencephaly, hydranencephaly,
sonography or computed tomography (CT) scan. encephalocele, holoprosencephaly)
Children with asymptomatic familial megalencephaly Lissencephaly, schizencephaly, polymicrogyria, pachygyria
or benign enlargement of the subarachnoid space do not Metabolic disorders
require treatment. Infants with hydrocephalus may require Phenylketonuria, methylmalonic aciduria, citrullinemia
neurosurgical intervention (e.g. placement of a ventriculo Neuronal ceroid lipofuscinosis
peritoneal shunt). Maternal: Diabetes mellitus, untreated phenylketonuria
Infections
Microcephaly
Congenital: Cytomegalovirus, herpes simplex virus, rubella,
Microcephaly is defined as an occipitofrontal circum varicella, toxoplasmosis, HIV, syphilis, enterovirus
ference more than 3 standard deviations (SD) below the Meningitis
mean for given age, sex and gestation. Defining micro
Teratogens
cephaly as >3 SD below the mean is more likely to be
associated with genetic and non-genetic disorders affecting Alcohol, tobacco, marijuana, cocaine, heroin, toluene
brain than if defined as >2 SD below the mean, since the Antineoplastic agents, antiepileptic agents
latter may include intellectually normal healthy children Radiation
with head circumference at the lower end of the population Perinatal insult
distribution. The term primary microcephaly is used to Hypoxic ischemic encephalopathy, hypoglycemia
describe conditions associated with reduced generation of Endocrine
neurons during neural development and migration.
Hypothyroidism, hypopituitarism, adrenal insufficiency
Secondary microcephaly follows injury or insult to a
Growth 37-
Need for neuroimaging is determined by the age at onset, is associated with hydrocephalus. Patients with tower
severity of microcephaly, head circumference in parents, skull or acrocephaly have combined sagittal, coronal and
history of antenatal insult(s) and associated clinical lambdoid synostosis, often as part of Apert or Crouzon
features. An abnormal head shape and ridges along the syndrome. Oxycephaly or turricephaly refers to a tall
suture lines are suggestive of craniosynostosis. The cranium resulting from delayed repair of brachycephaly,
prognosis depends upon the underlying cause, and is worse and is often syndromic.
for secondary than primary microcephaly. Apert syndrome is an autosomal dominant or sporadic
disorder caused by defects in the fibroblast growth factor
Craniosynostosis (FGF) gene, characterized by bicoronal synostosis and
Craniosynostosis is the premature fusion of one or more maxillary hypoplasia, associated with recessed forehead,
cranial sutures, either major (e.g. metopic, coronal, flat midface, protruding eyes, hypertelorism, antimongoloid
sagittal, and lambdoid) or minor (frontonasal, slant of eyes and low-set ears. Most patients have a high
temporosquamosal, and frontosphenoidal) (Fig. 2.23a). arched palate, malocclusion, cleft palate and complex
Cranial sutures normally fuse during early childhood, syndactyly (mitten hand). Other findings are strabismus,
starting with the metopic suture (beginning at 2 months), conductive hearing loss, airway compromise and severe
followed by sagittal, coronal and lambdoid sutures (22- acne.
26 months), such that the frontonasal and frontozygomatic Crouzon syndrome is an autosomal dominant disorder
sutures close last (68-72 months). Premature fusion caused by mutations in FGFR2 or FGFR3, and characterized
restricts the growth of the skull perpendicular to the by tall, flattened forehead (secondary to bicoronal synostosis),
affected suture. Compensatory skull growth occurs proptosis, beaked nose and midface hypoplasia. Many
parallel to the affected suture in order to accommodate patients have cervical spine abnormalities. The degree of
the growing brain. The resulting skull deformity is termed facial deformity is milder than in Apert syndrome and
as scaphocephaly, plagiocephaly or trigonocephaly based patients do not show cleft palate, syndactyly and mental
on the suture involved (Fig. 2.23b to f). Cloverleaf skull retardation. Other conditions associated with cranio
deformity is caused by the fusion of multiple sutures and synostosis are Carpenter syndrome and Pfeiffer syndrome.
- --- -- - - - -----w
------- -
Metopic suture ----�
��:::s;;:---
--�
I
a I
Occipital bone /
��---��
e
glbJi@
Fig. 2.23: (a) Head of normal neonate showing fontanels and sutures. The common forms of craniosynostosis (secondary to
premature fusion of sutures) include; [bl Trigonocephaly [metopic suture); (c) Brachycephaly (bilateral coronal sutures); (d) Left
anterior plagiocephaly (left coronal suture); (e) Scaphocephaly (sagittal suture); (fl Right posterior plagiocephaly (right lambdoid
suture). Children with deformation plagiocephaly (g) have positional skull flattening without sutural fusion
Chapter
3
Development
Ramesh Agarwal • Naveen Sankhyan
Maternal factors: A host of factors which impair growth Early growth faltering (<24 months) seems to be more
in utero also can potentially affect brain growth, particularly detrimental to childhood development.
if they are severe and/ or sustained:
Iron deficiency: Iron deficiency has been shown to be
i. Maternal nutrition: Maternal malnutrition (of macro
associated with electrophysiological evidence of delayed
nutrient as well as micronutrients) has adverse effect
brain maturation, poorer cognitive, motor and social
on birth weight and child development. Studies from
emotional development in infancy and early childhood.
developing countries suggest that nutrition supple
ments including multiple micronutrient supplements Iodine deficiency: Iodine is a constituent of thyroid
have positive impact on birth weight as well as child hormones, which affect central nervous system
development. development and regulate many physiological processes.
ii. Exposure to drugs and toxins: Various drugs and toxins Iodine deficiency can lead to congenital hypothyroidism
I such as maternal drug or alcohol abuse, antiepileptic
drugs and environmental toxins can have adverse
and irreversible mental retardation, making it the most
common preventable cause of mental retardation.
effect on child development. Children growing in iodine deficient areas have an IQ 12.5
iii. Maternal diseases and infections: Pregnancy-induced points lower than those growing in iodine sufficient areas.
hypertension, hypothyroidism, malnutrition and feta
Infectious diseases: A variety of infectious morbidities
placental insufficiency due to any cause. Acquired
such as diarrhea, malaria, other parasitic infections and
infections (e.g. syphilis, toxoplasmosis, AIDS, rubella,
HIV are associated with poorer neurodevelopment.
CMV, herpes) impact fetal physical and brain growth.
Exposure to free radicals and oxidants in utero (e.g. Environmental toxins: Children exposed to environmental
chorioamnionitis) has been incriminated in the toxins (lead, arsenic, pesticides, mercury and polycyclic
causation of cerebral palsy and developmental aromatic hydrocarbons) prenatally through maternal
impairment. exposure and postnatally through breast milk, food, water,
house dust, or soil can have adverse influence on their
Neonatal Risk Factors neurocognitive development.
Intrauterine growth restriction: Intrauterine growth Acquired insults to brain: Traumatic or infectious insults
restriction (IUGR) indicates constraints in fetal nutrition (meningitis, encephalitis, cerebral malaria) and other
during a crucial period for brain development. In factors (near drowning, trauma), particularly during early
developing countries, IUGR is mainly due to poor years of life, can have a permanent adverse effect on brain
maternal nutrition and infections. IUGR infants are development.
disadvantaged compared to their normal birth weight
counterparts in terms of short-term as well as long-term Associated impairments: Impairments particularly those
neurocognitive development. involving sensory inputs from the eyes or ears can have a
significant impact on attainment of milestones. Early
Prematurity: Babies born before 37 weeks of gestation are detection and management of hearing and visual
more likely to have developmental impairment compared
impairments constitutes an important intervention for
to term counterparts with babies born before 32 weeks
promoting child development.
gestation being at the highest risk.
Perinatal asphyxia: Significant asphyxia occurs in Psychosocial Factors
approximately 2% of total births. Studies have indicated During the critical period of development and learning,
that over 40% of survivors of significant asphyxia suffer several social factors have an important bearing on not
from major neurocognitive disabilities. only cognition but also attitudes, social-emotional
competence and sensorimotor development.
Postneonatal Factors
Parenting: Cognitive stimulation, caregiver's sensitivity
Infant and child nutrition: Severe calorie deficiency, as
and affection (emotional warmth or rejection of child) and
evident by stunting, is associated with apathy, depressed
responsiveness to the child in the setting of other factors
affect, decreased play and activities and insecure
such as poverty, cultural values and practices have an
attachment. Calorie deficiency is often associated with
important bearing on child development. Apart from
deficiency of multiple micronutrients and vitamins that
these, parental attitudes, involvement, education and
contribute to developmental impairment.
desire for the child also have an impact on the develop
Linear growth retardation or stunting occurs in nearly
ment of the child.
one-third of children aged less than 5 years in low-income
and middle-income countries. There is positive association Poverty: This is possibly the most common underlyingfactor
between early height-for-age and cognitive or language for impaired child development worldwide. It acts
ability, rates of school enrolment and grades attained by throughout the lifetime of the individual and also affects
late adolescence and formal employment at age 20-22 years. the next generation.
- 40 Essential Pediatrics
t
Risk factors > protective factors
Fig. 3.6: Ventral suspension; head in line with the trunk at 8--10 weeks
Fig. 3.4: Pull to sit; flexes the head onto chest at 5 months
Fig. 3.5: Ventral suspension; unable to hold neck in the line with Fig. 3.9: The infant lies with flat pelvis and extended hips at
trunk at 4 weeks 6 weeks (Photo courtesy: Dr Vijay K Charchi)
- 42 Essential Pediatrics
support') by the age of 6-7 months (Fig. 3.16). Steady Standing and walking: By 6 months, the child can bear
sitting without any support generally develops at around almost all his weight when made to stand (Fig. 3.19). At
8 months (Fig. 3.17). By 10-11 months, he can pivot in 9 months, the child begins to stand holding onto furniture
sitting position to play around with toys (Fig. 3.18). and pulls himself to standing position. By 10 and
11 months, the child starts cruising around furniture
(Fig. 3.20). At about 12-13 months, the child can stand
independently (Fig. 3.21) and can walk with one hand held
(Fig. 3.22). Between the ages of 13 and 15 months, the child
starts walking independently. He runs by 18 months, and
at this age he can crawl up or down stairs and pulls a doll
or wheeled toy along the floor. By 2 years, the child can
also walk backwards. He climbs upstairs with both feet
on one step at 2 years. By 3 years he can climb upstairs
with one foot per step and by 4 years he can move down
the stairs in the same fashion (Fig. 3.23). He can ride a
tricycle at 3 years. He can hop at 4 years and skip at
5 years (Table 3.1).
Fig. 3.23: The child is able to walk upstairs and downstairs one
foot per step at 4 years Fig. 3.24: Hand regard (between 12 and 20 weeks)
Development 145-
Fig. 3.29: Mature grasp at l year of age, note the use of thumb
and index finger
+ D
/ Personal and Social Development and
0
General Understanding
Much of the cognitive development and understanding
is reflected by the attainment of important milestones in
3 years 4 years 4Y:z years this sphere. Beginning at around 1 month, the child
D
intently watches his mother when she talks to him
0
(Fig. 3.37). He starts smiling back (social smile) when
anyone talks to him or smiles at him by 6-8 weeks of age
(Fig. 3.38). It is important to differentiate social smile from
� spontaneous smile (smile without any social interaction),
5 years 6 years 7 years which is present even in neonates. By 3 months, he enjoys
D
looking around and recognizes his mother. By 6 months,
0
he vocalizes and smiles at his mirror image (Fig. 3.39),
C]
and imitates acts such as cough or tongue protrusion.
The child becomes anxious on meeting strangers
(stranger anxiety) by 6-7 months of age. At this age, he
8 years 9 years 11 years inhibits to "no". At 9 months, he waves ''bye-bye" and
also repeats any performance that evokes an appreciative
Fig. 3.35: Drawing skills at various ages response from the observers. By 1 year, he can understand
15 months 18 months
(tower of 2 blocks) (tower of 3 blocks) 2 years (train)
3 years
5 years (gate) 6 years (steps)
(tower of 9 blocks)
Fig. 3.37: At 1 month, the baby showing intent regard of his 4 years Plays cooperatively in a group; goes to toilet
mother's face as she talks to him alone
5 years Helps in household tasks, dresses and
undresses
Language
Throughout the development of language it is the receptive
ability and understanding, which precedes expressive abilities.
Soon after appearance of social smile at around 6 to 8
Fig. 3.38: Social smile weeks, the child begins to vocalize with vowel sounds
such as 'ah, uh'. At 3-4 months, he squeals with delight
and laughs loud. He begins to say 'ah-goo', 'gaga' by 5
months of age. By 6 months, he uses monosyllables (ba,
da, pa). Later, he joins consonants to form bisyllables
(mama, baba, dada).
Before developing true meaningful speech, at around
9-10 months, the child learns to imitate sounds derived
from his native language. At his first birthday, he can
usually say 1-2 words with meaning. At 18 months, he
has a vocabulary of 8-10 words. Thereafter, the vocabulary
increases rapidly to around 100 words by 2 years, at
which time 2-3 words are joined to form simple sentences.
By 3 years, the toddler continually asks questions and
knows his full name. He can give a coherent account
Fig. 3.39: A child smiles at himself in the mirror at 6 months of of recent experiences and events by the age of 4 years
age (Table 3.4).
Development 149-
Developmental Assessment
Developmental delay is estimated to be present in about
10% of children. It is possible to recognize severe develop
mental disorders early in infancy. Speech impairment,
hyperactivity and emotional disturbances are often not
Fig. 3.40: Infant fixates on her mother as she talks to her at detected until the child is 3--4-year-old. Leaming disabilities
l month are not picked up until the child starts schooling.
-5 0 Essential Pediatrics
H Walking alone
Standing alone
3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Age in months
Fig. 3.43: Windows of achievement of six major motor milestones (WHO; Multlcenter Growth Reference Study Group, 2006)
(10-12 months), may not be able to stand with support Development Screening Tests
(less than 10 months). Such children require evaluation Screening is a brief assessment procedure designed to
for physical disorder affecting a particular domain of identify children who should receive more intensive
development. A child having normal development in all diagnosis or assessment. Screening tools are standardized
domains except language may have hearing deficit. instruments to evaluate development. The administration
Table 3.5 gives the upper limits by which a milestone of these tools should be done after proper training and
must be attained. A child who does not attain the milestone with a sound knowledge of interpretation of the results.
by the recommended limit should be evaluated for cause Some tools are parent reported while others require
of developmental delay. trained personnel. Assessment using screening tools
The predictive value of different domains of develop potentially aids in early identification of children who
ment for subsequent intelligence is not the same. Fine need a more detailed assessment and possibly interven
motor, personal-social and linguistic milestones predict tions. It also provides an opportunity for early identifica
intelligence far better than gross motor skills. In particular, tion of comorbid developmental disabilities.
an advanced language predicts high intelligence in a
child. Developmental Surveillance
Table 3.5: Upper limit of age for attainment of milestone Child development is a dynamic process and difficult to
quantitate by one-time assessment. During surveillance,
Milestone Age
repeated observations on development are made by a
Visual fixation or following 2 months skilled physician over time to see the rate and pattern of
Vocalization 6 months development. Periodic screening helps to detect emerging
Sitting without support 10 months disabilities. The physician should choose a standardized
Standing with assistance 12 months developmental screening tool that is practical and easy to
Hands and knees crawling 14 months use in office setting. Once skilled with the tool, it can be
used as screening method to identify at risk children.
Standing alone 17 months
Screening tests popular in the west include Parents'
Walking alone 18 months Evaluations of Development Status (PEDS) and Ages and
Single words 18 months Stages Questionnaires (ASQ). Screening tools used in India
Imaginative play 3 years are described below.
Loss of comprehension, single words or phrases at any age
Phatak's Baroda screening test: This is India's best known
Adapted from WHO; MGRS group, WHO motor development study. Acta development testing system that was developed by Dr.
Pediatr 2006;450:86-95 Promila Phatak. It is meant to be used by child
-5 2 Essential Pediatrics
8
early childhood development is likely to be more effective
and less costly than addressing problems at a later age.
•
Autism spectrum disorder
Diagnostic Approach
Seizures
Feeding problem The Diagnostic and Statistical Manual of Mental Disorders
Behavioral problems: Aggression, impulsivity, hyperactivity, (DSM) IV required fulfillment of a minimum number of
inattention, sleep related problems symptoms listed in the three domains (social interaction,
Cognitive impairment communication and behavior) to label a child as having
an ASD. Guidelines, according to DSM 5, have combined
Attention deficit hyperactivity disorder
social interaction and communication domains into one.
Sleep problems Thus to be labeled as having an ASD, a child has to fulfill
Enuresis, encopresis; obesity a minimum number of symptoms in two domains (social
Learning disability interaction and communication, and behavior). Common
Behavioral comorbidities: Autism spectrum disorder, tics, comorbidities are shown in Table 4.2.
conduct disorder, delinquency
Anxiety, bipolar illness Management
Specific learning disability The chief therapy is behavioral intervention; the role of
Epilepsy pharmacotherapy is limited (Table 4.5).
Attention deficit hyperactivity disorder, tics
Obsessive compulsive disorder Attention Deficit Hyperactivity Disorder
Tic disorder Attention deficit hyperactivity disorder (ADHD) is the most
Obsessive compulsive disorder; anxiety, depression common neurobehavioral disorder of childhood. Its
Attention deficit hyperactivity disorder prevalence in India was estimated at 1.3 per 1000. The
Learning disability American Academy of Pediatrics recommends evaluating
Autism spectrum disorder any child between 4 and 18 years of age for ADHD, if he or
she presents with academic or behavioral problems with
symptoms of inattention, hyp eractivity and impulsivity
Autism Spectrum Disorder (Table 4.4).
Autism spectrum disorder (ASD) is characterized by the
triad of qualitative impairment of social behavior, Diagnosis
communication (verbal and non-verbal) skills and ADHD is diagnosed clinically. The DSM 5 criteria require
associated stereotypic and restrictive behavioral patterns, fulfillment of predefined number of criteria in inattention,
with onset before 3 years of age (Table 4.4). The estimated hyperactivity and impulsivity domains. The onset of
global prevalence is 1 to 2%. symptoms can be up to 12 years of age and they should
(Table 4.6). The age of onset is 4-6 years with peak at 10-12 delay, psychosocial stress (maternal deprivation, parental
years and significant attenuation by 18-20 years. The neglect and abuse) and other behavioral disorders can
prevalence is around 10-15% with higher rate in boys. predispose to pica. Children with pica are at increased
Tourette syndrome is characterized by onset before risk for lead poisoning and parasitic infestations.
18 years of age, presence of both motor and vocal tics and Management comprises behavior modification, alleviating
persistence beyond 1 year, including the waning phase. Tics the psychosocial stress, screening for lead poisoning,
can be associated with neurological ailments like Huntington deworming and iron supplementation.
and Wilson disease, or with parainfectious illnesses, e.g.
pediatric autoimmune neuropsychiatric disorders associated Temper Tantrums
with streptococcal infection (PANDAS). Temper tantrums are a child's response to physical or
It is important to differentiate stereotypies from tics. emotional challenges by attention seeking tactics like
Although stereotypies may have similar vocal and motor yelling, biting, crying, kicking, pushing, throwing objects,
manifestations, classically they are rhythmic and hitting and head banging. Tantrums typically begin at
distractable, and usually remain stable over a time period, 18-36 months of age and gradually subside by the age of
unlike tics which may evolve temporally. Stereotypies 3-6 years. Parents are counseled to handle this behavioral
usually have an early onset (before 3 years of age) and, problem strategically, by staying calm, firm and consistent
along with neurodevelopmental disorders, may affect so that the child is unable to take advantage from such
normal children, as well. behavior. The child should be protected from injuring
himself or others. Distraction and 'time out' techniques are
Management useful.
The essential component is behavioral therapy.
Medications like haloperidol and clonidine are considered Breath-Holding Spells
in situations where the tics are socially and functionally Breath-holding spells are reflex events typically initiated
disabling despite adequate behavioral therapy. by a provocation that causes anger, frustration or pain
making the child cry. The crying stops at full expiration,
Eating Disorders and the child becomes apneic and cyanotic or pale. In
This group consists of primarily two disorders, anorexia some cases, the child may become unconscious and
nervosa and bulimia that chiefly affect girls and have in hypotonic. In prolonged events, brief tonic-clonic
common a disturbed body image perception. Anorexia movements may happen. Breath-holding spells are rare
nervosa usually affects 15-19 years old girls. Characteristic before 6 months of age, peak at 2 years and abate by
features are an intense fear of becoming fat even though 5 years of age. The differential diagnoses include seizures
the child is underweight, with body weight <85% of and cardiac arrhythmias. The history of a provoking
expected. Two subtypes are recognised, with either event and stereotyped pattern of events help in
restricted eating or increased physical activity. Induced distinguishing breath-holding spells from seizures. In
vomiting or use of laxatives and diuretics may be present. relevant clinical scenarios, seizures and cardiac
Complications include secondary amenorrhea and arrhythmias including long QT syndrome should be
metabolic complications related to malnutrition. ruled out.
Bulimia affects 10-19 years old children, chiefly girls. The essential component of management is parental
There are recurrent episodes of binge eating alternating reassurance. The family should be advised to be consistent
with inappropriate compensatory behavior such as self in handling the child, to remain calm during the event,
induced vomiting, misuse of laxatives, diuretics or tum him sideways so that secretions can drain and avoid
enemas, each occurring at least twice a week for 3 months. picking the child up (since this decreases blood flow to
Depression, anxiety, suicidal ideation and/ or obsessive the brain). The family should avoid exhibiting undue
compulsive disorder are often present. Management of concern nor give into the child's demands, if the spell was
both conditions focuses on psychotherapy, along with provoked by anger or frustration.
nutritional rehabilitation and treating comorbidities and
complications. Thumb Sucking
This entity is normal in infants and toddlers. It peaks by
Pica 18-21 months of age and usually disappears by the age of
Pica is the persistent ingestion of non-nutritive substances 4 years. Its persistence in older children is socially
such as plaster, charcoal, paint and soil for at least 1 month, unacceptable and can lead to dental malalignment. In
inappropriate to the child's development level and cultural children below 4 years, parents should be reassured.
practice. It is common in children less than 5 years of age. Beyond 4 years of age, the child should be motivated
Poor socioeconomic status, malnutrition and iron to refrain from this habit. Both positive and negative
deficiency are commonly associated. Developmental reinforcements can be used.
-58 Essential Pediatrics
is targeted at reassurance and management of stress if any; • American Psychiatric Association: Diagnostic and Statistical
benzodiazepines may occasionally be used. Manual of Mental Disorders, 5th edn. Arlington, VA, American
Psychiatric Association, 2013.
Suggested Reading • Flore LA, Milunsky JM. Updates in the genetic evaluation of the
child with global developmental delay or intellectual disability.
• Almanac BB, Nutt DJ, Adamou M, et al. Evidence-based guidelines Semin Pediatr Neurol 2012;19:173-180.
for pharmacological management of attention deficit hyperactivity • Kotagal S. Parasomnias in childhood. Sleep Med Rev 2009; 13: 157-68.
disorder: Update on recommendations from the British Association • Lagae L. Learning disabilities: definitions, epidemiology, diagnosis
for Psychopharmacology. J Psychopharmacol 2014;28:1-25. and intervention strategies. Pediatr Clin North Am 2008;55:1259-68.
• American Academy of Pediatrics. Autism toolkit, physician fact • Tchaconas A, Adesman A. Autism spectrum disorders: a pediatric
sheet. 2012; available at www.autismsciencefoundation.org overview and update. Curr Opin Pediatr 2013;25:130-143.
Chapter
5
Adolescent Health and
Development
Tushar R Godbole • Vijayalakshmi Bhatia
•
Appearance of breast bud
V
Sparse straight hair along the labia
1
Generalized breast enlargement (extending beyond the
areola)
Pigmented pubic hair, coarse, begin to curl
\
Nipple and areola form a second mound over the breast
Hair increase in amount, spread over entire mons
Fig. 5.1: Sexual maturity rating [l-5) in girls (Courtesy: Anil Kumar, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow)
60
Adolescent Health and Development ls1-
years (range 10-16 years); experts now believe the age of increase in trunk size. There is an exuberant increase in
menarche is advancing to -9 years in many populations. muscle mass and bone diameter, particularly in boys and
The breast buds may be tender and there may be total bone mass in both the sexes. Lean body mass
asymmetry in the breast size during early phases of increases during the early stages in both the sexes, fat mass
puberty. Menarche usually occurs after 2-21h years of increases in girls at later stages of puberty. Under the
thelarche. influence of sex steroids, rapid calcium accretion occurs
In boys, the earliest change is increase in testicular size during puberty, achieving almost 50% of adult bone mass.
(volume reaching 4 mL or length 2.5 cm) that occurs The recommended dietary allowance (RDA) for calcium
between 9 and 14 years (Fig. 5.2). This is followed by is 800 mg/ day and an intake of 500 mL milk is
appearance of pubic hair and lengthening of the penis. recommended in order to achieve this with a cereal-based
Spermarche or production of sperms starts during mid Indian diet. With minimal sun exposure, the RDA for
adolescence. Laryngeal growth under androgenic vitamin Dis 600 IU/day.Since dietary vitamin Dis mainly
stimulus, manifesting as cracking of voice, begins in available from fatty fish, intake as a pharmacological
midpuberty in males and deepening of voice is complete supplement may be necessary. Increase in body structure
by the end of puberty. Mild degree of breast enlargement is paralleled by increase in blood volume and muscle mass;
is seen in more than half of boys in early puberty which both of these tissues have high iron content. With
subsides spontaneously over several months. The onset commencement of menstruation, nutritional requirements
of puberty is variable; thus in an age cohort (e.g. students of iron are further increased. With predominantly cereal
of 7th class), many will have advanced puberty while based diet and poor bioavailability, an adolescent needs
others will be awaiting its onset. to have a daily intake of 25-30 mg iron in order to meet
the daily requirements of 1.3 mg.
Physical Growth and Nutritional Requirements
During puberty, boys gain about 20-30 cm and girls about Cognitive and Social Development
16-28 cm. Peak growth velocity in girls occurs before Volumetric and functional imaging techniques show that
attainment of menarche (stage 3), while boys show peak the adolescent brain undergoes subtle structural changes
growth velocity during later stages of puberty (stages 4-5). and differential growth. Though the exact implications of
The growth spurt affects the distal skeleton first, hence these changes are largely unknown, these indicate re
enlargement of limbs and extremities is followed by organizational or accommodating effort of brain
0
<3 ml
Prepubertal
0 !�
Reddening of scrotum, testicular volume reaching 4 ml or length 2.5 cm
Scanty hair at penile base
2 4 ml 3
01�
I
Increase in length of penile shaft
Further increase in testicular volume
Hair begin to curl and darken
3 � 10 ml
3
or�
4
16 ml
5
25 ml
Fig. 5.2: Sexual maturity rating (1-5) in boys (Courtesy: Anil Kumar, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow)
62 Essential Pediatrics
paralleling the multi-fold increase in its functional 53% Indian adolescent girls are anemic; the prevalence of
capabilities. anemia has remained unchanged over the last two
decades. There is lack of sun exposure due to clothing
Early phase: The 'concrete thinking model' of childhood coupled with dark skin pigment. Insufficient intake of
persists into early adolescence, where the concepts are dairy products results in poor intake of calcium and
perceived more 'literally'. Teens are impulsive and have vitamin B12• The resulting low bone mineral density is
limited ability to perceive future implications of their more pronounced in underprivileged girls as t�ey �ave
current behavior. They prefer same sex peers. Many are low protein intake in addition to calcium and vitamin D
excessively conscious of other people's concerns about deficiency. Vitamin A deficiency is also an important issue
their appearance and actions. Curiosity about sexual in economically deprived adolescents. Undernutrition
anatomy and comparison with peers is common. often delays the onset of puberty and sexual maturation,
Mid-phase: This phase is marked by emotional autonomy; results in stunting, poor bone mass accrual and reduced
they might seem detached from their fa�ily. �he _youth work capacity. Girls from poor families are likely to suffer
starts to think beyond self and there 1s begmnmg of from malnutrition due to gender discrimination in food
abstract reasoning. Acceptance by the peer group becomes distribution, whereas girls from urban upper socio
important. Sexual experimentation, such as masturbation, economic group show malnutrition due to eating
starts at this age. disorders. Anorexia nervosa and bulimia are increasingly
reported.
Late phase: By this time, most of the pubertal changes are
Mental h ealth problems: Adjustment and anxiety
already achieved. Moral values and strong self identity
disorders, depression, suicide, delinquent behavior, poor
are now established. They are now able to suppress
body image and low self-esteem are major concerns.
impulsivity and are less affected by peer pressure.
Suicide rates are increasing, with higher number of
Personal relations become more important than the peer
completed suicide in boys and attempted suicides in girls.
group. The youth becomes career-oriented and starts
Adolescents are at high risk of committing suicide because
short- and long-term planning for his or her goals in life.
of cognitive immaturity and impulsivity. Psychological
Many start engaging in sexual activity.
disorders like depression or mood disorders, substance
abuse, parent-child conflict, physical or sexual abuse and
Attitude Towards Health family history of suicide make them prone for such
Adolescents are considered to be at the peak of their health; attempts.
yet, adolescence coincides with the onset o! n:i-any h�alth
Sleep disturbances: During the period of rapid growth,
disorders. Girls are often unprepared for their first periods.
adolescents have increased sleep requirements. Under the
High-risk behavior is common in mid-adolescent age
effect of physiologic delay in melatonin secreti?n,
group. The National Family Health Survey 4 (NFHS4)
adolescents have a delay in sleep onset and awakerung
reported the median age of sexual debut in boys and girls
by almost an hour. In urban adolescents, this may be
to be 24 years and 19 years, respectively, but a significant
compounded by increasing academic activity or watching
proportion are sexually active much before. Knowledge
television late into the night. Poor sleep habits are likely
about contraception is improving among adolescents.
to reflect in school performance and cause daytime
Though awareness about HIV is increasing among Indian
drowsiness, aggressive behavior, conduct disorders,
youth, most of them lack comprehensive knowledge of
anxiety, restless leg syndrome and depression.
the disease.
Infections: With increased outdoor activity, teens are
PROBLEMS FACED BY ADOLESCENTS exposed to TB, HIV, skin and parasitic infections and
sexually transmitted diseases. Early sexual activity is not
Adolescents are under immense pressure because of the uncommon. Various biological (immature, incompletely
rapid changes in their hormonal milieu, changing ideas estrogenized mucosa) and psychosocial factors (lack of
and concepts about the world, having to cope up with the preparedness, knowledge regarding barrier contraceptives)
expectations from the society and the need to establish make adolescents susceptible to these infections.
their own identity. The problems faced by an adolescent
in India are diverse and are often not addressed by the Problems Specific to Females
health care system. It is common to have anovulatory and irregular menstrual
cycles during first two years after menarche. The
Health Problems polycystic ovary syndrome, a combination of menstrual
Nutrition and eating disorders: There is increase in irregularities and ovarian cysts with androgen excess like
nutritional requirements during this period of rapid acne or hirsutism, occurs in -9% adolescent girls. The
growth, micronutrients being as important as energy and condition is associated with other metabolic derangements
protein (see Chapter 8). Data from the NFHS4 shows that like obesity, insulin resistance and type 2 diabetes.
Adolescent Health and Development 63-
Menstrual hygiene: There are many social taboos about overweight have been reported and similar figures are
menstruation in Indian families. Many adolescent girls are available from other parts of urban India as well. The
found to miss school during their menstruation because prevalence of obesity and overweight is higher in boys
of lack of access to safe sanitary products or lack of privacy. than girls. Obesity has strong association with asthma,
Poor menstrual hygiene may contribute to reproductive sleep disorders, reflux disease, Blount disease, slipped
infections. With the introduction of government and femoral epiphysis, gallstones, fatty liver and metabolic
private run 'Menstrual Hygiene Schemes', 57% young derangements like type 2 diabetes, dyslipidemia,
women now use hygienic methods during menses. hypertension and polycystic ovary disease. Essential
[NHFS4] hypertension is rising, with prevalence of 6% in urban and
3.4% in rural youth in some studies from India.
Genital infections and sexually transmitted infections:
Vaginal discharge is common in adolescent girls and may Substance abuse: Most tobacco and alcohol use starts
indicate physiological leukorrhea of puberty, and during adolescence, in urban as well as rural India. The
endogenous or sexually transmitted infections. Gonorrhea Global Youth Tobacco Survey 2009 showed that 14% of
can cause vulvovaginitis, urethritis or proctitis; Chlamydia school youth reported using tobacco currently. Apart from
may cause intermenstrual or post-coital bleeds. Both may tobacco, alcohol (21%), cannabis (3%) and opium (0.4%)
be asymptomatic in majority and can cause vaginal are most abused substances. Addicts are prone to
discharge. Candida! infections become common with accidents, injuries, violence, trading sex-for-drugs, HIV,
starting of menstruation and often have a cyclic nature. hepatitis C, sexually transmitted diseases and tuberculosis.
Pelvic inflammatory disease (PID) is a spectrum of
inflammatory disorder of female genital tract, which Vulnerability
occurs in sexually active females and can present with
abdominal pain with vaginal discharge. Lower abdominal, Abuse and violence (physical and sexual): Physical and
cervical or adnexal tenderness is suggestive of the sexual violence is common in India, with 20-30% young
diagnosis (Table 5.1). females suffering from domestic violence and 5-9% young
females reporting sexual violence (NFHS4). Accidents are
Lifestyle diseases: Obesity is the other end of the spectrum the major cause of mortality in this age group. Road traffic
of malnutrition and is epidemic in the urban settings. accidents, burns and poisoning are leading causes of
Among Delhi school children, 5% obesity and 17-19% traumatic mortality and disability in Indian youth. Motor
vehicle and industrial accidents are common in boys Illiteracy: Though the situation is improving over the
whereas burns are more common in girls. years, still 33% of Indian youth are not able to complete
their primary education. Female gender and families from
Migration: Many adolescents migrate from rural to urban rural and poor background are the risk factors for
settings, for labor or educational opportunities. Trafficking illiteracy.
of youth is a serious problem in India and happens for
industrial or domestic labor, forced marriages and Academic and emotional stress: Examinations cause
prostitution. In states like Bihar, 70% of new HIV infections significant physiological and psychological stress. Apart
are related to outward male migration. from change in body structure, various other factors like
peer acceptance, discrimination, academic burden,
Adolescent pregnancy: Unmarried adolescents are likely parental expectations and changing social environments
to resort to unsafe methods of abortions, which increase cause stress among youth. Switching from vernacular to
risk of septicemia and mortality. As compared to adult English medium schools, long hours of school and tuitions
pregnancy, they are also at a higher risk for pre-eclampsia, are additional stress factors that are un-addressed. While
preterm labor and postpartum hemorrhage. Prolonged most adolescents have adequate coping skills, some have
and obstructed labor are common in adolescent serious adjustment problems resulting in psychological
pregnancies and they are 2-4 times more likely to die and somatic effects.
during childbirth as compared to adult females. Neonatal,
infant and child mortality rates are higher in children Early marriage: Though the legal age for marriage in
delivered to adolescent mothers. Fortunately, the India is 18 years for girls (Table 5.2), many states still
prevalence of adolescent pregnancy [8%] is lower in the have the practice of childhood and early marriage.
results of NFHS 4, due to schooling and knowledge about Almost 30% of Indian girls between the ages of 15 and
contraception. 19 years are married; the proportions are higher in rural
areas.
Lack of sex education: The majority of Indian youth do
not get formal sex education in an effective way. Peers, Discrimination: Young people are often treated as second
books and magazines are their main sources of information class citizens, under the control of adults and often not
about sex. Parents and teachers often fail to discuss issues involved in any decision making. Adolescent girls are
like masturbation, safe sex, dating, abortion, HIV and often asked to limit their outdoor/ extracurricular
sexually transmitted diseases. activities, confined to their houses and expected to do the
household work. Gender-based discrimination is seen in
Environmental and Social Challenges education and even food distribution.
Pollution: The incidence of asthma is increasing. There Role of Health Care Provider
is ongoing research into the role of electromagnetic
exposure from communication devices in disorders like A checklist for the adolescent clinic visit is provided in
childhood leukemia, brain tumors and immune Table 5.3. During each visit, the following are important:
dysregulation. Identifying risks: The physician needs to detect risk factors
like obesity, hypertension, possible substance/drug abuse,
Media: With easy availability of electronic media,
behavioral and social problems and risky behavior. Subtle
adolescents are exposed to unsupervised information from
cues like sad or depressed mood, avoidance of eye contact,
all across the world. Adolescents often succumb to
bruises or undue resistance to examination are the likely
glamorous portrayal of tobacco or alcohol consumption,
pointers towards physical or sexual abuse.
unrealistic expectations, physical aggression, destructive
behavior and unprotected sex. Spending much of spare
time indoors on social networking sites, teenagers are Table 5.2: Legal age definitions relevant to adolescence
deprived of sunlight and physical activity and socially Definition of child Below 18 years
isolated. Minimum age for marriage Boys 21 years; girls 18 years
Peer pressure: Peer formation is a part of adolescent social Responsibility for crime 12 years
development. Pressure for conforming to norms drives Juvenile criminal 12-18 years
many of their actions and decisions, including risk taking Compulsory free education 6-14 years
behavior and initiation of substance abuse. Consumption of alcohol Beyond 18-25 years in
Poverty: Adolescents belonging to poorer families are different states (illegal in
likely to have inadequate diets. Studies have shown that some states and union
territories)
children belonging to poorer families had higher chances
of having depression, anti-social behavior and engaging Employment in hazardous 14 years
in drugs or sexual activity at earlier ages. occupation or hotels
Adolescent Health and Development lss-
Table 5.3: Checklist for adolescent health visit
History from parents and adolescent History of presenting problems
Parental concerns on growth, development
Academic success; school absenteeism
Diet history including calcium, protein and iron intake; junk food
Menstrual history; sleep problems
History on separate questioning of adolescent Emotional problems; relationship with family and peers
Outlook towards physical and sexual changes
Involvement in relationship or sexual activity
Awareness about safe sex and contraception
Specific problems related to sex organs
Tobacco or other substance use
Counsel and clear doubts on sensitive topics
History on separate questioning of parents Relationship with family
Level of communication on sensitive matters
Physical examination Anthropometry
Blood pressure, markers of obesity, acanthosis
Sexual maturity rating
Signs of malnutrition, anemia and vitamin deficiencies
Signs of skin and genital infections
Level of general hygiene
Signs of trauma; abuse
Signs of drug abuse or tobacco use
Counseling Nutritional intervention
Hygienic practices
Building rapport between parents and adolescent
Providing information and sources on sex education
Investigations Hemoglobin level
Blood sugar, lipid profile
Genital swabs
Ultrasound of ovaries
Referrals Counselor
Dietitian
Psychiatrist
Gynecologist
Voluntary and confidential HIV testing
Social services, child protection agencies, support groups
Establishing rapport: Being empathetic and non Consent: For a child who is less than 12 years, consent for
judgmental is the key to effective communication. Direct examination or medical/ surgical procedure is obtained
questioning of the adolescent is as important as questioning from the parent or guardian. While an adolescent aged
the parents. Beginning the interview with icebreakers, use 12-18 years can give consent for examination, consent for
of open-ended non-sensitive questions and then moving medical/ surgical procedure can be given only after
to sensitive/targeted questions is helpful. 18 years. This also includes consent for medical termination
of pregnancy, blood and organ donation.
Confidentiality: One may need to interview a young
patient separately, as he/she may not want to discuss Nutritional intervention: Improving the nutritional status
sensitive topics in the presence of parents. While of adolescent girls helps in two ways. It breaks the cycle
examining the genitalia, the doctor can ask patient's of malnutrition and low birth weight babies, and prevents
preference for presence of their parent inside the long-term complications of the latter in future generations.
examination room. A boy may prefer his parents standing
outside the exam room, whereas a girl may find it Providing health information: The adolescent health visit
comforting, if her mother accompanies her during the is an excellent opportunity to talk to the parents and their
examination. adolescent about the pubertal changes. It is likely that they
66 Essential Pediatrics
have not received any formal sex education in school and Box 5.1: Healthy adolescence: Package of interventions
need to be provided correct educational resources for the Healthy lifestyle
same. • Healthy food
Referral to social services, psychological evaluation and • Exercise and Yoga
support: National Commission for Protection of Child • No to tobacco, alcohol, drugs
Rights Act 2005 considers a person below 18 years as a • Safe conduct on road
'child'. It is mandatory for a health care provider to report Vaccines
all cases of child abuse (even suspected) to the Chairperson • Papilloma virus, rubella
of the Commission; the complaint can be lodged online Anemia
or in writing. Doctors are protected in case of erroneous • Prevention, detection and management of anemia, especially
reporting but punishable, if they fail to report. Adolescents for adolescent girls
with special needs or victims of any kind of abuse need
Sexual health
social and psychological support. • Sexuality education
Adolescent-friendly health services: Adolescents have • Menstrual hygiene
diverse problems and special needs. The services include • Marriage after 18 years, childbirth after 20 years
provision of reproductive health services, nutritional • Counseling and services for comprehensive sexual and
counseling, sex education and life skill education. reproductive health, including contraception
Confidentiality, easy accessibility, friendly attitude and Mental health
quick comprehensive health care delivery have made a • Supportive family; counseling and peer/ family support in
positive impact on adolescent clients. 'Adolescent anxiety, depression
reproductive and sexual health' has been identified as a • Prevention and management of hazardous and harmful
key strategy under RCH II programme. Adolescent substance use
friendly clinics are functional at many centers in the • Prevention of suicide and management of self-harm/ suicide
country. Box 5.1 lists the key services and interventions risk
that should be provided for comprehensive care for Violence prevention
adolescents. • Prevention and management of unintentional injury
• Prevention of and response to sexual and other forms of
Management of sexual violence: This includes the gender-based violence
following measures:
1. Forensic examination and collection of blood or body Communicable and non-communicable diseases
fluid samples by trained staff. • Prevention, detection and treatment of communicable and
ii. Care of the injuries. non-communicable diseases
iii. Prophylaxis against pregnancy: Two doses of Preparing for adulthood
levonorgestrel 12 hours apart, first dose being given • Parenting skills, responsible husband, wife and father
within 72 hours of intercourse.
iv. Prophylaxis against sexually transmitted infections event of abuse must be informed to legal authorities;
includes a single oral dose of azithromycin 1 g along failing which, the knowing person [including the health
with cefixime 400 mg and metronidazole or tinidazole care provider] is liable to legal actions including
2 g, protects against syphilis, gonorrhea, Chlamydia and imprisonment.
Trichomonas. Hepatitis B vaccination is recommended,
if the person is not previously immunized. Contraception: A pediatrician should advocate for
v. Prophylaxis against HIV requires referral to the abstinence and delayed initiation of sex to adolescent
nearest integrated counseling and testing center. patients. In case the adolescent is already sexually active,
vi. Psychological support includes counseling and condom seems a better choice compared to other methods.
referral to a psychiatrist. Informing concerned Adolescents with disabilities or mental retardation are
authorities or social services is important as patient wrongly assumed to be at low risk for STis and pregnancy.
may need shelter and legal help. A teen may not be Parents of such children need to be counseled regarding
willing to disclose this assault to his parents. these issues.
Childline (1098) is a support service provided by
Adolescent immunization: India has low coverage for
Government of India focussed on child care and
booster doses of TT at 10 and 16 years. Papilloma virus
protection.
vaccine is recommended for peripubertal girls (before
Protection of Childrenfrom Sexual Offenses [POCSOJ Act initiation of sexual activity) for prevention of infection
2012: The POCSO Act protects individuals below 18 years with human papillomavirus and cervical cancer. Parents
from sexual offense or harassment of any form, be it need to be counseled thoroughly as the principle behind
physical or pornographic. It also explicitly states that an giving the vaccine might alarm them (Table 5.4).
Adolescent Health and Development 67-
Transition to adult care: With better medical care, a large health, National Health Mission now follows
number of chronically ill or disabled children are surviving Reproductive, Maternal, Neonatal, Child and Adolescent
into adulthood. As the problems of these children are Health (RMNC+A) approach. Under this program, weekly
diverse, they need multidisciplinary care even in their iron and folic acid supplementation (WIFS) program
adulthood. Transition to adult care is not mere transfer of provides 100 mg of iron and 500 µg folic acid with biennial
the case to a different physician. It is a gradual and planned deworming to all adolescents attending government
process; keeping in mind the abilities of the child to schools.
participate in self-care, taking responsibilities and decision
making. The age at transfer is not fixed; a window of age Suggested Reading
14-18 years is used in some countries for a gradual 1. National Family Health Survey [NFHS3, 2005-6) and [NFHS4, 2015-
transfer. 16). International Institute for Family Survey, Mumbai.
2. WHO Media Centre Fact Sheet 2014. Adolescents: health risks and
solutions.
GOVERNMENT INTERVENTIONS IN
3. Contraception and Adolescents: Committee on Adolescents,
ADOLESCENT HEALTHCARE Pediatrics 2007;120:1135.
Kishori Shakti Yojana and SABLA Yojana aim to provide 4. National Guidelines on Prevention, Management and Control of RTis/
STis. Ministry of Health and Family Welfare, Govt of India, 2007.
health, nutrition, education and vocational skills to 5. Dietary Guidelines for Indians [Second Edition]. National Institute
adolescent girls. National Youth Policy believes in youth of Nutrition, 2011.
empowerment through education. Recognizing the 6. Juvenile Justice Act 2015. The Gazette of India, Ministry of Law
contribution of adolescent care to maternal and child and Justice.
Chapter
6 Fluid and
Electrolyte Disturbances
Kamran Afzal
COMPOSITION OF BODY FLUIDS cellular volume depletion. The interstitial space, especially
in skin and connective tissue, is an important reservoir of
The major component of body mass is water. The contri
extracellular fluid.
bution of total body water to body weight varies with age,
lean body weight and adiposity. Total body water (TBW) Water Balance
as a percentage of body weight declines from as high as
90% in early fetal life to nearly 75-80% at the time of birth. In the steady state, water balance represents the difference
Thereafter, it declines progressively to 60% by the end of between water intake (including that generated from
the first year and remains so till puberty. Since adipose endogenous metabolism) and water losses (Fig. 6.2). Much
tissue has lower water content, therefore, adolescent of the water output involves obligatory losses in the urine,
females and overweight children have lower TBW as a stool and, by evaporation from the moist surfaces of the
percentage of body weight. skin and respiratory tract (insensible losses). The kidneys
Total body water is distributed in two major compart are the major regulators of water output with nearly two
ments, two-thirds is intracellular fluid (ICF) and one-third thirds of daily water losses being urine. The obligatory
is extracellular fluid (ECF). Nearly one-fourth of ECF is renal water loss is directly related to solute excretion. The
distributed in the intravascular space (plasma water) and evaporative losses play an important role in thermo
the remaining in the extravascular (interstitial) space regulation. In contrast to these insensible losses, sweat
(Fig. 6.1). The relative size of the two main compartments which is hypotonic (Na+ concentration 35 to 65 mEq/L) is
varies with age. Increase in extracellular fluid volume actually 'sensible loss'. It also contributes to thermo
contributes to the increased TBW in neonates, especially regulation and may reflect the majority of total daily loss
preterm babies. of water in presence of high ambient temperatures or
when endogenous heat production is enhanced, as with
The interstitial fluid component of extracellular fluid is exercise or fever.
actually a matrix, a collagen/gel substance that allows the Changes in sodium concentration in the extracellular
interstitium to provide structural rigidity during extra- fluid are linked to extracellular fluid volume and are
Interstitial fluid associated with dysregulated water balance. The effectors
for volume regulation are primarily renin-angiotensin
aldosterone system and atrial natriuretic peptide, both of
which affect Na+ excretion. Besides this regulation of body,
water is made possible by interplay of multiple other
factors, including vasopressin, prostaglandins, dopa
minergic receptors, a.-adrenergic receptors, thirst
mechanism and intrinsic renal properties.
Input I Output I
Water intake is regulated Water intake: Urine (60%) Water loss is regulated by
by osmoreceptors in fluid (60%), Stool (8%) antidiuretic hormone from
hypothalamus food (30%) Sweat (4%) posterior pituitary
Insensible loss
Water of
(28%)
oxidation (10%)
skin, lungs
Fig. 6.2: Balance of water intake and losses maintains normal plasma osmolali1y. Only water intake and urinary losses can be
regulated
... - - - - - - - - - - - - - - - - - - - - - - - - - - ...
I
140
140 Plasma Intracellular
120
104
100
:::::! 80
E 60
E
-·�-- - -
40
20 14
0
�-..w.------ Cl) C
�
Q)
3
i&a'
ro 2
I Q) Q)
Cl) ro I :::J :::J :::J C'C Q) (U � I
.c .8 a_e o 5l-
C ..C ..C
\ ._ - ·m- - ::0- - _·u5_ - - - - � - - � - -§ - - Q.-
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the brain having the least and the liver the most per and the secretion of antidiuretic hormone (ADH) (Fig. 6.4).
meability. However, water readily crosses cell membranes Plasma osmolality can be measured directly using
to achieve an osmotic equilibrium between the two osmometers, as well as estimated indirectly as follows:
compartments. The balance and appropriate distribution glucose blood urea nitrogen
of fluid within these spaces is maintained by the colloid . = 2[Na•1 + --- + -----�-
Plasma osmolahty
18 2.8
oncotic pressure, membrane permeability and hydrostatic
pressure. Plasma and interstitial fluid are rich in proteins, Measured values are generally higher than calculated
which determine plasma colloid oncotic pressure. values by up to 10 mOsm/kg and this difference is called
osmolal gap. Increase in osmolal gap may occur due to
Osmolality increase in unmeasured osmoles.
Osmolality (expressed as milliosmoles per kilogram of Normal Maintenance Fluid and
water, mOsm/kg) is the solute concentration of a fluid. Electrolyte Requirements
Changes in osmolality can produce grave neurologic
consequences and even death, primarily due to water The normal maintenance water requirement is equal to the
movement into and out of the brain. To prevent this, the insensible and urinary water losses. Holliday and Segar
plasma osmolality, which is primarily determined by the guidelines (1957) calculate maintenance fluid volumes to
plasma Na+ concentration, is normally maintained closely match electrolyte-free water requirements from estimates
between 1 and 2% of the normal (285 to 295 mOsm/kg) by of water of evaporation (heat dissipation) and caloric
appropriate variations in water intake and water excretion. expenditure (heat production). They estimated a daily
This regulatory system is governed by different osmo sodium requirement of 3 mEq/kg, potassium and chloride
receptors in the hypothalamus that influence both thirst 2 mEq/kg each and daily glucose requirement as 5 g/kg
-7 0 Essential Pediatrics
Fluid loss
{
High osmolarity stimulates Decrease in blood
+
osmoreceptors volume
Decrease in renal
Thirst / blood flow
1
Decrease in GFR Renin
i
ADH secretion
i +
Angiotensin I +--Angiotensinogen
Angiotensin-converting enzyme
+
Free water reabsorption Angiotensin II
in distal tubules and Adrenal
collecting ducts Aldosterone release
based on the electrolyte composition of human and cow 5% dextrose in water or 0.2% or 0.45% saline (without
milk and recommended 30 mEq/L sodium chloride (saline) dextrose) should be avoided. There is considerable
for maintenance fluid in children. Maintenance IV fluids in evidence that use of hyp otonic fluids in sick hospitalized
an unwell child may be initiated with 0.45% normal saline patients increases the risk of hyponatremia several fold.
along with 5% dextrose and 20 mEq/L of potassium Normal saline (0.9%) can be safely administered in
chloride (provided urine output is adequate). This standard maintenance volume without risks of
composition may be modified according to the clinical state. hypematremia or fluid overload, except in patients who
The guidelines for maintenance volume (Table 6.1) assume are fluid restricted (e.g. congestive heart failure, liver and
average calorie expenditure in a healthy child. Fluid renal failure) and those with renal concentrating defect
requirements change considerably in different clinical (e.g. diabetes insipidus). Hyp otonic fluid should only be
conditions (Table 6.2). used to achieve a positive free-water balance as in
IV fluid with osmolality lower than plasma osmolality replacing renal or non-renal loss of electrolyte-free water.
can cause movement of free water from plasma to red The ideal volume for maintenance fluid is debated.
blood cells leading to hemolysis. Therefore, infusing plain Conventional calculation using weight-based formulae
often lead to overestimation of electrolyte-free water, and
Table 6.2: Conditions that alter maintenance fluid needs excess free water retention that predispose to
Increased fluid requirement Decreased fluid requirement hyponatremia. Therefore, it may be prudent to restrict
Fever (10-15% per C °
Oliguria or anuria maintenance fluids to 40-60%, especially in critically sick
above 38 ° C) Humidified ventilator or children. Fluids should be limited around 400 mL/m2 in
Radiant warmer, incubator renal failure with oliguria. There is no single maintenance
phototherapy Hypothyroidism intravenous fluid which is suitable for all clinical scenarios
Burns, sweating and maintenance fluid prescriptions should be
Physical activity; individualized. All children receiving IV maintenance
hyperventilation fluid should be monitored with daily weight, fluid
Diarrhea, vomiting
balance, clinical and biochemical parameters in order to
Polyuria, renal
maintain homeostasis. Additionally, maintenance IV
concentrating defects
fluids do not replace daily nutrient requirements and
Very low birth weight babies
(large surface area)
provide only 20% of daily calories (enough to avoid
starvation ketoacidosis and diminish protein degradation).
Fluid and Electrolyte Disturbances 111-
DEFICIT THERAPY lactate, that mimic plasma composition better than normal
saline may be considered, especially in the setting of
The degree of volume depletion is assessed by physical
acidosis.
examination (Table 6.3). The process of hyp ematremia or
hyp ertonicity decreases the severity of physical signs of
SODIUM
volume depletion. All fluid lost should be replaced daily
to maintain euvolemic state. Steps for providing fluids Physiology
and electrolytes to volume depleted patients are: Sodium is the most abundant ion of the extracellular fluid
• If the patient shows signs of shock, compensated shock compartment and is critical in determining extracellular
or features of severe dehydration (Table 6.3), rapidly and intracellular osmolality. Normal serum sodium
infuse isotonic fluids to restore intravascular volume. concentration varies between 135 and 145 mEq/L.
This is done by infusing 1 to 3 fluid boluses of isotonic Extracellular sodium balance is determined by sodium
saline or Ringer's lactate, 20 mL/kg body weight. intake relative to sodium excretion. Daily sodium
• Provide fluids to replace calculated/observed volume requirement is 2 to 3 mEq/kg body weight although
deficit. This is calculated as volume at the rate of 10 mL intakes are generally well in excess. The requirement
for each percentage weight loss. For example, in varies with age. It is nearly two- to threefolds higher in
patients with moderate (some) dehydration, which is term and very low birth weight preterm babies, a reflection
on an average 7.5% weight loss, the replacement of immaturity of renal tubular function and higher
volume is 75 mL/kg body weight. If the pre-dehy requirements for growth. Adult requirements decrease to
dration weight is known, the volume of fluid needed 1.5 mEq/kg/d. Urinary sodium excretion represents the
is 1 liter for every kg of weight loss. majority of sodium losses and approximately equals the
• Provide fluid and electrolytes to replace the amounts daily intake of sodium. Fractional excretion of sodium is
lost in normal daily metabolism (maintenance fluids). generally less than 1% of filtered load. Extrarenal sodium
• Provide enough fluid to replace ongoing losses of losses can be significant via profuse sweating, burns,
various body fluids (Table 6.4). severe vomiting or diarrhea.
While current literature does not advocate use of one A fall in blood pressure, decrease in sodium delivery
type of fluid over another, there is a growing concern of to the macula densa, or sympathetic stimulation may
hyperchloremic metabolic acidosis with fluid resuscitation activate the renin-angiotensin axis, generating angiotensin
with normal saline. Balanced fluids, such as Ringer's IL This results in increase in blood pressure and sodium
retention caused by enhanced aldosterone secretion. The
effective circulating volume refers to that part of the
Table 6.4: Electrolyte composition of body fluids
extracellular fluid that is in the arterial system and is
Losses Na + K+ c, HC03- effectively perfusing the tissues. The effective circulating
(mEq/L) (mEq/L) (mEq/L) (mEq/L) volume usually varies directly with the extracellular fluid
Gastric 60-100 5-20 90-130 0 volume, and both are proportional to total body Na +
Small intestine 80-140 5-15 90-140 40 stores. As a result, the regulation of Na + balance (by
Colon 60 30 40 15 alteration in its urinary excretion) and maintenance of
Pancreas 135-145 5-10 70-90 95-120 effective circulating volume are closely related. Sodium
loading tends to produce volume expansion, whereas loss
Diarrhea 10-90 10-80 90-130 40
leads to volume depletion.
-72 Essential Pediatrics
i ... ...
I U [Na·1 >20 I I U [Na·1 >20 I I U [Na·1 <20 I
+ + +
Renal losses Extrarenal SIAD Acute, chronic Nephrotic syndrome
Diuretics losses Glucocorticoid deficiency renal failure Cirrhosis
Mineralocorticoid deficiency Vomiting Hypothyroidism Congestive heart failure
Salt losing nephropathy Diarrhea Stress
Cerebral salt wasting Third spacing Drugs
Renal tubular acidosis
Fig. 6.5: Diagnostic approach to hyponatremia. U(Na + ) urinary sodium, mEq/L; i increased; .!. decreased
Box 6.1: Treatment of hyponatremia of ADH to its V2 receptor, are yet not recommended for
treatment of hyponatremic encephalopathy. These agents
• Treat hypotension first with 20 mL/kg of normal saline or may have a role in treating euvolemic hyponatremia from
Ringer's lactate SIAD and hypervolemic hyponatremia in congestive
• Symptomatic hyponatremia heart failure.
- 3-5 mL/kg 3% sodium chloride infused over 1 hour,
monitor sodium hourly. Hypernatremia
- Aim for first hour of mangement is to increase serum
sodium by 5-6 mEq/L with resolution of symptoms, Hyp ernatremia is defined as increase in serum sodium
indicating that patient is awake, alert, responding to concentration to levels more than 150 mEq/L. It may be
commands with no headache and nausea accompanied by the presence of low, normal or high total
- Continue 3% saline infusion till patient is asymptomatic body sodium content. The major cause of hyp ernatremia
and serum sodium approaches 130 mEq/L or rises 10 is loss of body water, inadequate intake of water, a lack of
mEq/L in 4--6 hours; monitor serum sodim 2-4 hourly antidiuretic hormone (ADH), or excessive intake of
• Asymptomatic and chronic hyponatremia sodium (e.g. solutions with high sodium such as sodium
- Treat underlying etiology bicarbonate) (Table 6.6). Diabetes insipidus may result from
- Calculate Na+ deficit (mEq/kg) = (130 - serum Na+) x a deficiency of ADH or its end organ unresponsiveness.
0.6 x body weight (kg) In the presence of an intact thirst mechanism, a slight
- Rise of serum sodium should not exceed 0.5 mEq/hour increase in serum sodium concentration (3 to 4 mEq/L)
or 10 mEq/L in the first 24 hours and an additional 8 above normal elicits intense thirst. The lack of thirst in
mEq/L during every next 24 hours thereafter until the the presence of hypernatremia in a mentally alert child
serum sodium reaches 130 mEq/L. indicates a defect in either the osmoreceptors or the cortical
- Hypovolemia: Sodium deficit estimated is given as normal thirst center. The most objective sign of hyp ernatremia is
saline; WHO ORS rehydration solution is preferable for
patients able to accept orally
lethargy or mental status changes, which proceeds to coma
- SIAD: Fluid restriction; furosemide and oral salt
and convulsions. With acute and severe hyp ematremia,
supplementation, if required the osmotic shift of water from neurons leads to shrinkage
- Hypervolemia: Sodium and fluid restriction, diuretics of the brain and tearing of the meningeal vessels and
- Cerebral salt wasting: Fludrocortisone intracranial hemorrhage; slowly developing hypematremia
is generally well tolerated. The latter adaptation occurs
is often unclear at initial evaluation. Therefore, initially by movement of electrolytes into cells and later
hyponatremia should be assumed as chronic and corrected by intracellular generation of organic osmolytes, which
gradually (:<,;10-12 mEq/L/day). counter plasma hyp erosmolarity.
In a volume expanded state, fluid restriction alone or
in combination with diuretics is useful. Fluid restriction Treatment
alone has no role in the management of symptomatic Treatment involves restoring normal osmolality and
hyponatremia. Normal saline is also inappropriate for volume. The speed of correction depends on the rate of
treating hyponatremic encephalopathy due to non development of hyp ematremia and associated symptoms
hemodynamic states of vasopressin excess, such as SIAD (Box 6.2). Because chronic hypernatremia is well tolerated,
and postoperative hyponatremia, as it is not sufficiently rapid correction offers no advantage and may be harmful
hypertonic to induce reduction in cerebral edema. V2 since it may result in brain edema. Usually, a maximum
receptor antagonists or vaptans that block the binding of 10% of the serum sodium concentration or about
-74 Essential Pediatrics
Table 6.6: Causes of hypernatremia stasis until the glomerular filtration rate drops to less than
15-20 mL/min. Excretion is increased by aldosterone, high
Net water loss
sodium delivery to the collecting duct (e.g. diuretics), urine
Pure water loss
flow (e.g. osmotic diuresis), blood potassium level,
Insensible losses
Diabetes insipidus glucocorticoids, ADH and delivery of negatively charged
Inadequate breastfeeding ions to the collecting duct (e.g. bicarbonate). In renal failure,
Hypotonic fluid loss the proportion of potassium excreted through the gut
Renal: Loop, osmotic diuretics, postobstructive, polyuric phase increases, chiefly by the colon in exchange for luminal
of acute tubular necrosis sodium.
Gastrointestinal: Vomiting, nasogastric drainage, diarrhea; Aldosterone and insulin play important roles in
lactulose potassium homeostasis. Insulin stimulated by potassium
Hypertonic sodium gain ingestion increases uptake of potassium in muscle cells,
Excess sodium intake through increased activity of the sodium pump. High
Sodium bicarbonate, saline infusion potassium levels stimulate its renal secretion via aldos
Hypertonic feeds, boiled skimmed milk terone-mediated enhancement of distal expression of
Ingestion of sodium chloride secretory potassium channels (ROMK). Insulin, beta
Endocrine: Primary hyperaldosteronism, Cushing syndrome adrenergic stimuli and alkalosis enhance potassium entry
into cells. The reverse happens with glucagon, a.-adrener
Box 6.2: Treatment of hypernatremia gic stimuli and acidosis.
• Restore intravascular volume with 20 mL/kg normal saline Hypokalemia
over 20 min (repeat until intravascular volume restored) Hypokalemia is defined as a serum potassium level below
• Determine time for correction on basis of initial sodium 3.5 mEq/L. The primary pathogenetic mechanisms result
concentration: ing in hypokalemia include increased losses, decreased
Serum sodium level Time intake or transcellular shift (Table 6.7). Vomiting, a
145-157 mEq/L 24 hours common cause of hypokalemia, produces volume deple
158-170 mEq/L 48 hours tion and metabolic alkalosis. Volume depletion leads to
171-183 mEq/L 72 hours secondary hyperaldosteronism, which enhances sodium
184-196 mEq/L 84 hours resorption and potassium secretion in the cortical
• Fluid for correction D5 N/3 to N/4 normal saline (with collecting tubules. Metabolic alkalosis also increases
20 mEq/L KCl unless contraindicated)
potassium secretion due to the decreased availability of
• Fluid rate: 1.25-1.5 times maintenance
hydrogen ions for secretion in response to sodium
• Monitor serum sodium q 4 hourly; should not fall by >0.5
reabsorption.
mEq/L/hour
Regardless of the cause, hypokalernia produces similar
• Adjust fluid on basis of clinical status and serum sodium
concentration; if child develops seizures (due to rapid signs and symptoms. Symptoms are nonspecific and
correction) 3% NaCl (4-6 mL/kg over 30 min) is indicated. predominantly are related to muscular or cardiac function.
• Replace ongoing losses as they occur Severe hypokalemia (<2.5 mEq/L) may cause muscle
• Identify and treat the underlying cause weakness (neck flop, abdominal distension, ileus) and
produce cardiac arrhythmias. Chronic hypokalemia is
0.5 mEq/L/hr should be the goal rate of correction. Renal associated with interstitial renal disease of uncertain
replacement therapy is indicated for concurrent renal pathogenesis. Hyp okalernia increases the risk of digoxin
failure and volume overload. toxicity by promoting its binding to myocytes, potentiating
its action and decreasing clearance.
POTASSIUM Treatment
Physiology Patients should be evaluated to determine the underlying
Potassium being a predominantly intracellular cation, its causes and determine whether it is associated with
blood level is unsatisfactory indicator of total body stores. hypertension and acidosis or alkalosis (Fig. 6.6). Hypertension
Normal serum concentration of potassium ranges between may be a clue to primary hyperaldosteronism, renal artery
3.5 and 5 mEq/L. Common potassium-rich foods include stenosis, or the rarer forms of genetically inherited hyper
meats, beans, fruits and potatoes. Gastrointestinal tension such as congenital adrenal hyperplasia, gluco
absorption is complete and potassium homeostasis is corticoid remediable hypertension or Liddle syndrome.
maintained predominantly through the regulation of renal Relative hypotension and alkalosis suggests diuretic use, or
excretion. The fractional excretion of potassium is about a tubular disorder such as Bartter or Gitelman syndrome.
10%, chiefly regulated by aldosterone at the collecting duct. Therapy involves decreasing ongoing losses (e.g.
Renal adaptive mechanisms maintain potassium homeo- discontinuation of diuretics, a.i-agonists), replenishing
Fluid and Electrolyte Disturbances 75-
Hypokalemia
+
(serum K <3.5 mEq/L)
+
Urine K <20 mEq/L, TTKG <4 Spot urine potassium, serum and +
._____, Urine K >20 mEq/L, TTKG >4
(nonrenal cause) urine osmolality, TTKG +
(renal K losses)
Fig. 6.6: Diagnostic approach to hypokalemia. K + potassium; RTA renal tubular acidosis; TTKG transtubular potassium gradient
volume depletion. Volume expansion, increased sodium bones. Decrease in extracellular calcium concentration,
intake and diuretics such as mannitol and frusemide stimulates the CaSR in parathyroid glands, resulting in
promote calcium excretion. an increase in PTH secretion (Fig. 6.7). PTH increases
The intestine serves as a long-term homeostatic mecha distal renal tubular reabsorption of calcium within
nism for calcium. Although the major source of calcium minutes and stimulates osteoclast activity, with release
is dietary, less than 15% of dietary calcium is absorbed, of calcium from the skeleton within 1-2 hours. More
primarily in the ileum and jejunum by means of active prolonged PTH elevation stimulates la-hydroxylase
transport and facilitated diffusion. Calcium is controlled activity in the proximal tubular cells, which leads to 1,
primarily by major regulatory hormones, PTH, calcitonin 25-dihydroxyvitamin D production. In the kidney,
and vitamin D. Additionally thyroid hormones, growth vitamin D and PTH stimulate the activity of the epithelial
hormone, adrenal and gonadal steroids also have minor calcium channel and the calcium-binding protein (i.e.
influences on calcium metabolism. calbindin) to increase active transcellular calcium
Role of the calcium-sensing receptor. The calcium-sensing absorption in the distal convoluted tubule. These
receptor (CaSR) is a G protein-coupled receptor, which mechanisms help to maintain normal levels of serum
allows the parathyroid chief cells, the thyroidal C cells calcium.
and the ascending limb of the loop of Henle (renal tubular Plasma calcium exists in three different forms: 50% as
epithelial cells) to respond to changes in the extracellular biologically active ionized form, 45% bound to plasma
calcium concentration. The ability of the CaSR to sense proteins (mainly albumin) and 5% complexed to phosphate
the serum calcium is essential for the appropriate and citrate. In the absence of alkalosis or acidosis, the
regulation of PTH secretion by the parathyroid glands proportion of albumin-bound calcium remains relatively
and for the regulation of passive paracellular calcium constant. Metabolic acidosis leads to increased ionized
absorption in the loop of Henle. Calcitonin secretion and calcium from reduced protein binding and alkalosis has
renal tubular calcium reabsorption are directly regulated the opposite effect. Plasma calcium is tightly regulated
by the action of calcium ion on its receptor. Ionized despite its large movements across the gut, bone, kidney
calcium acts through calcitonin, to inhibit its release from and cells in the normal range of 9-11 mg/ dL.
I�-�i------�
skin Vil 0 (ergocalciferol)
2
Vil 0 3 (cho ralciferol)
{
�frrfrfr
1 '
1 =">•=�·
Cholecalciferol (vitamin D)
--
--------+iPTH release
... ......
...
\
...I
I 25-(0H)D3
., " 1 1 a-hydroxylase
/ +
/ 2
i Ca and Pi resorption
•
I
1 25 (OH) 0 I
·=-ll from booes I
( I Renal
I 24a-hydroxylase
\ I
I
�
'' i Ca
I
•
2
• reabsorption I
'' by kidneys I
I
'' /
''
/
,, .,, 24,25-(0H)2 0 3
..- "' (inactive)
Fig. 6.7: Regulation of plasma calcium. Reduction in ionized calcium results in parathormone secretion, which through direct and
indirect actions on the bones, intestine and the kidneys results in positive calcium balance. Calcitonin results in accretion of bone
mass. Discontinuous lines indicate inhibitory control
-7 8 Essential Pediatrics
Because calcium binds to albumin and only the unbound Table 6.9: Causes of hypocalcemia
(free or ionized) calcium is biologically active, the serum level
Neonatal: Early (within 48-72 hours after birth) or late (3-7
must be adjusted for abnormal albumin levels. For every days after birth) neonatal hypocalcemia; prematurity; infant of
1 g/dL drop in serum albumin below 4 g/dL, measured diabetic mother; neonates fed high phosphate milk
serum calcium decreases by 0.8 mg/dL. Corrected calcium
can be calculated using the following formula: Parathyroid: Aplasia or hypoplasia of parathyroid glands,
DiGeorge syndrome, idiopathic; pseudohypoparathyroidism;
Corrected Ca = autoimmune parathyroiditis; activating mutations of calcium
[4 - plasma albumin in g/ dL] x 0.8 + measured serum calcium sensing receptors
Alternatively, serum free (ionized) calcium levels can
Vitamin D: Deficiency; resistance to vitamin D action; acquired
be directly measured, negating the need for correction for or inherited disorders of vitamin D metabolism
albumin.
Others: Hypomagnesemia; hyperphosphatemia (excess intake,
Hypocalcemia renal failure); malabsorption syndromes; metabolic alkalosis;
hypoproteinemia; acute pancreatitis
Hypocalcemia is defined as serum calcium less than
8 mg/dL or ionized calcium below 4 mg/dL. The causes Drugs: Prolonged therapy with frusemide, corticosteroid or
and algorithm for investigating the etiology are shown in phenytoin
Table 6.9 and Fig. 6.8. Hypocalcemia manifests as central
nervous system irritability and poor muscular contractility. Box. 6.5: Clinical features of hypocalcemia
Newborns present with nonspecific symptoms such as
• Carpopedal and muscle spasms
lethargy, poor feeding, jitteriness, vomiting, abdominal
• Tetany
distension and seizures. Children may develop seizures,
twitching, cramps and rarely laryngospasm (Box 6.5). • Laryngospasm
Tetany and signs of nerve irritability may manifest as • Paresthesias
muscular twitching, carpopedal spasm and stridor. Latent • Seizures
tetany can be diagnosed clinically by clinical maneuvers • Irritability, depression, psychosis
such as Chvostek sign (twitching of the orbicularis oculi • Intracranial hypertension
and mouth elicited by tapping the facial nerve anterior to • Prolonged QTc interval
the external auditory meatus) and the Trousseau sign
Normal Low
Parathormone 25
•
Low
High
i
Low 25
i
(0H) D3 low 25 (0H) D3 normal
1, 25 (0H 2 D3 low
l
1, 25 (0H' 2D3
high
Renal failure
Pseudohypoparathyroidism
I Hypoparathyroidism ! Vit?�in D
def1c1ency
VDDR type I
Renal failure
j VDDR type 111
Tumor lysis
Fig. 6.8: Algorithm for evaluation of hypocalcemia. VDDR vitamin D dependent rickets
Fluid and Electrolyte Disturbances 179-
(carpopedal spasm elicited by inflating a blood pressure Table 6.10: Causes of hypercalcemia
cuff on the arm to a pressure above the systolic pressure
Neonates
for 3 min). ECG shows prolonged corrected QT interval
Neonatal primary hyperparathyroidism, secondary hyper
(QTc) to more than 0.45 seconds. Cardiac function may be
parathyroidism
impaired because of poor muscle contractility. Prolonged
Familial hypocalciuric hypercalcemia
hypocalcemia can present with features of rickets. Excessive supplementation of calcium
William syndrome, hypophosphatasia, idiopathic infantile
Management hypercalcemia
Tetany, laryngospasm and seizures must be treated
immediately with 2 mL/kg of 10% calcium gluconate, Older children
administered IV slowly under cardiac monitoring. Calcium Hyperparathyroidism (parathyroid adenoma, autosomal
gluconate 10% (100 mg/mL) IV solution contains dominant hereditary hyperparathyroidism, multiple endocrine
9.8 mg/mL (0.45 mEq/mL) elemental calcium; calcium neoplasia type 1 )
chloride 10% (100 mg/mL) contains 27 mg/mL (1.4 mEq/ Malignancies: Non-Hodgkin or Hodgkin lymphoma, Ewing
mL). Initially, IV calcium boluses are given every 6 hr. sarcoma, neuroblastoma, Langerhans cell histiocytosis,
Thereafter, oral calcium supplementation is provided at rhabdomyosarcoma
40-80 mg/kg/ day. Oral calcium therapy is used in Granulomatous disease: Sarcoidosis, tuberculosis, Wegener
asymptomatic patients and as follow-up to intravenous disease, berylliosis
(IV) calcium therapy. Intravenous infusion with calcium Others: Vitamin D or A intoxication; thiazide diuretics; milk
containing solutions can cause severe tissue necrosis; alkali syndrome; dietary phosphate deficiency; subcutaneous
fat necrosis; thyrotoxicosis; prolonged immobilization
therefore, integrity of the IV site should be ascertained
before administering calcium through a peripheral vein.
with epigastric pain and vomiting. Ectopic calcification can
Rapid infusion of calcium-containing solutions through manifest as conjunctivitis or band keratopathy. Renal
arterial lines can cause arterial spasm and if administered manifestations due to renal stones and nephrocalcinosis can
via an umbilical artery catheter, intestinal necrosis. progress to renal failure, and polyuria and polydipsia occur
Magnesium administration is necessary to correct any due to nephrogenic diabetes insipidus.
hypomagnesemia because hypocalcemia does not respond
until the low magnesium level is corrected. In patients Treatment
with concurrent acidemia, hypocalcemia should be
The initial treatment of hypercalcemia involves hydration
corrected first. Acidemia increases the ionized calcium
to improve urinary calcium excretion. Rapid lowering of
levels by displacing calcium from albumin. If acidemia is
serum calcium can be expected with isotonic sodium
corrected first, ionized calcium levels decrease.
chloride solution, because increasing sodium excretion
Calcium carbonate is an oral supplement providing 40% increases calcium excretion. Addition of a loop diuretic
elemental calcium. Therapy with cholecalciferol is used inhibits tubular reabsorption of calcium but attention
in patients with vitamin D deficiency. Calcitriol, an active should be paid to other electrolytes (e.g. magnesium,
metabolic form of vitamin D (i.e. 1,25-dihydroxychole potassium) during saline diuresis. Bisphosphonates serve
calciferol), is administered in liver or renal disease. to block bone resorption and decrease serum calcium within
a couple of days but have not been used extensively in
Hypercalcemia
children. Pamidronate and etidronate have been used in
Hypercalcemia is defined as a serum calcium level greater the treatment of hypercalcemia due to malignancy,
than 11 mg/dL. Because calcium metabolism normally is immobilization and hyperparathyroidism but may cause
tightly controlled by the body, even mild persistent mineralization defects. IV calcitonin may also be used with
elevations should be investigated. Etiologies of hyper bisphosphonates.
calcemia vary by age and other factors (Table 6.10). Peritoneal dialysis or hemodialysis can be used in
Hypercalcemia is often asymptomatic, although it can cause extreme situations, particularly in patients with renal
symptoms at levels as low as 12 mg/dL and consistently at failure. Calcimimetics (cinacalcet hydrochloride) change the
values above 15 mg/dL. Such high values are, however,
rarely encountered and present as stupor and coma.
Box 6.6: Clinical features of hypercalcemia
Neonates may be asymptomatic or may have vomiting,
hypotonia, hypertension or seizures. Clinical features in older Lethargy, confusion, Bradycardia, systemic
children are summarized in Box 6.6 and include irritability, depression, coma hypertension, headache
Hyporeflexia Nephrocalcinosis,
malaise, headache, confusion, unsteady gait and proximal Muscle weakness nephrolithiasis
muscle weakness. Abdominal pain with paralytic ileus, Constipation Reduced QTc interval
nausea, vomiting and constipation are often observed. Polyuria
Ectopic calcification can lead to symptoms of pancreatitis,
-80 Essential Pediatrics
configuration of the CaSR in a manner that makes it more nonspecific T wave changes, U waves and prolonged QT
sensitive to serum calcium. Surgical intervention may be interval and arrhythmias.
needed in patients with hyper-parathyroidism, particularly
with recurrent renal stones or serum calcium levels higher Treatment
than 12.5 mg/ dL. Subtotal parathyroidectomy can be Therapy can be oral for patients with mild symptoms or
performed, or complete parathyroidectomy can be chosen intravenous for patients with severe symptoms or those
with reimplantation of a small amount of tissue in the unable to tolerate oral administration. Severe hypoma
forearm. gnesemia is treated with slow intravenous infusion of
magnesium sulfate (50% solution) at a dose of 25-50 mg/kg
MAGNESIUM (2.5-5.0 mg/kg of elemental magnesium). The dose is
repeated every 6 hr, for a total of 2-3 doses. Doses need to be
Physiology reduced in children with renal insufficiency. Oral replace
Magnesium is the third-most abundant intracellular cation ment should be given in the asymptomatic patient, or those
predominantly located in muscle and liver cells. Most requiring long-term replacement, preferably with a
intracellular magnesium is bound to proteins; only sustained-release preparation to avoid diarrhea. Oral
approximately 25% is exchangeable. magnesium preparation provides 5-7 mEq of magnesium
Magnesium plays a fundamental role in many functions per tablet. Two to four tablets may be sufficient for mild,
of the cell, including energy transfer and storage and nerve asymptomatic disease while severe cases require up to six
conduction. Magnesium also plays important role in to eight tablets, to be taken daily in divided doses. Patients
protein, carbohydrate, and fat metabolism, maintenance with renal magnesium wasting may benefit from diuretics
of normal cell membrane function and regulation of PTH with magnesium-sparing properties, such as spironolactone
secretion. and amiloride.
Dietary sources include green leafy vegetables, cereals,
nuts and meats. Absorption of magnesium takes place Hypermagnesemia
primarily in the small intestine and is inversely related to Serum magnesium >2.5 mg/ dL is uncommon in children
the amount of magnesium, calcium, phosphate and fat. and may be seen in the setting of renal insufficiency,
PTH and glucocorticoids increase magnesium absorption. prolonged use of magnesium containing antacids or in
Absorption is diminished in presence of substances that neonates born to mothers given magnesium sulfate as a
complex with magnesium (free fatty acids, fiber, phytate, treatment for eclampsia. Symptoms of hyp ermagnesemia
phosphate, oxalate); increased intestinal motility and are nonspecific at lower levels: nausea, vomiting,
calcium also decrease magnesium absorption. Vitamin D flushing, lethargy, weakness and dizziness. At higher
and PTH enhance absorption. Renal excretion is the levels, deep tendon reflexes are depressed which may
principal regulator of magnesium balance. Reabsorption progress to coma and respiratory depression. Effects on
occurs chiefly in the thick ascending loop of Henle (70%) the heart may result in prolongation of intervals on ECG
and to a smaller extent in the proximal (15%) and distal or manifest as arrhythmias, complete heart block and
(5-10%) tubules. Fractional excretion of magnesium asystole.
exceeding 4% indicates renal magnesium wasting.
Treatment
Hypomagnesemia In patients with mildly increased levels, the source of
Hypomagnesemia develops from decreased intake or magnesium may simply be removed. Intravenous calcium
more commonly increased losses which could be directly antagonizes the cardiac and neuromuscular effects
gastrointestinal (diarrhea, vomiting, nasogastric suction) of excess extracellular magnesium. Dialysis may be used
or renal (chronic use of thiazide diuretics, recovery phase for patients with severe hypermagnesemia and renal
of acute tubular necrosis, Gitelman syndrome, familial impairment, or those with serious cardiovascular or
h ypomagnesemia-h ypercalci uria -nephrocalcinosis). neuromuscular symptoms.
Symptomatic magnesium depletion (occurs at levels below
1.2 mg/ dL) is often associated with multiple biochemical ACID-BASE DISORDERS
abnormalities, including hypokalemia, hypocalcemia and
metabolic acidosis. As a result, hypomagnesemia is Regulation of Acid-Base Equilibrium
sometimes difficult to attribute solely to specific clinical The body is sensitive to changes in blood pH level, as
manifestations. Hypomagnesemia often leads to hypo disturbances in acid-base homeostasis can result in
calcemia, possibly by inhibition of PTH activity. denaturation of proteins and inactivation of enzymes that
Neuromuscular manifestations of hypomagnesemia may be potentially fatal. Strong mechanisms exist to
include muscle weakness, tremors, seizures, paresthesias, regulate acid-base balance and maintain arterial pH (7.35
tetany, positive Chvostek sign, Trousseau signs and to 7.45), pC02 (35 to 45 mm Hg) and HC03- (20 to 28 mEq/L)
nystagmus. Cardiovascular manifestations include within a narrow range.
Fluid and Electrolyte Disturbances la1-
pH of body fluids is calculated using the Henderson of disturbances occurs, the disorder is classified as a mixed
Hasselbach equation: acid-base disorder. The latter are suspected when the
compensation in a given patient differs from the predicted
pH= pK + log (HC03 /pC02]
values in Table 6.11.
where pK is the dissociation constant of the acid. In order to maintain body homeostasis, changes in pH
Alteration in either serum bicarbonate concentration or are resisted by a complex system of intracellular and extra
the partial pressure of carbon dioxide causes acidosis (pH cellular buffers that reversibly bind hydrogen ions and
<7.35) or alkalosis (pH >7.45). Metabolic activity results in resist change in pH. In metabolic disorders, the
production of two types of acids, carbonic acid (a volatile extracellular buffers rapidly titrate the addition of strong
acid, derived from carbon dioxide) and nonvolatile acids acids or bases. Intracellular buffers chiefly accomplish the
(including sulfuric acid, organic acids, uric acid and buffering of respiratory disorders. Secondary respiratory
inorganic phosphates). Accumulation of H + ions of compensations to metabolic acid-base disorders occur
nonvolatile acids due to excess production or inadequate within minutes and is completed by 12 to 24 hours. In
buffering, failure to excrete H+ or loss of bicarbonate results contrast, secondary metabolic compensation of respiratory
in metabolic acidosis. If the reverse occurs, it results in disorders begins more slowly and takes 2 to 5 days for
metabolic alkalosis. The principle mechanism for carbon completion. The compensatory mechanisms do not return
dioxide handling is by the lungs. Hyperventilation results the pH to normal until the underlying disease process has
in CO2 washout and drop in arterial pC02 (respiratory been appropriately treated. Extracellular buffers include
alkalosis), hypoventilation has the opposite effect bicarbonate and ammonia, whereas proteins and
(respiratory acidosis). When only one primary acid-base phosphate act as intracellular buffers. Hemoglobin is a
abnormality occurs and its compensatory mechanisms are powerful intracellular buffer because its negatively
activated, the disorder is classified as simple acid-base charged histidine moieties accept H+, normalizing the pH.
disorder. A simple algorithm for defining simple acid Other proteins also have negative charges that can accept
base disorders is shown in Fig. 6.9. When a combination H+.
•
Blood pH
I
Acidemia Alkalemia
(..J, pH) (i pH)
Bicarbonate-carbonic acid buffer in the extracellular fluid, anhydrase, to regenerate HC03-that is reabsorbed into the
is the key buffer as carbon dioxide (CO2) can be shifted bloodstream, thus conserving the filtered HC03 .
through carbonic acid (H2 C03) to hydrogen ions and Monohydrogen phosphate-dihydrogen phosphate buffer: This
bicarbonate (HC03-): luminal buffer system buffers H+ ions secreted from the
H20 + CO2 H H2C03 H H+ + HCQ3- tubular cells, as follows:
Acid-base imbalances that overcome the buffer system H+ + Na2HP04 � NaH2P04 + Na+. The weakly acidic
can be compensated in the short-term by altering the rate sodium dihydrogen phosphate is excreted in the urine.
of ventilation, which alters the pC02• While this is a rela Ammonia-ammonium buffer: In tubular cells, glutamine
tively weak buffer, it accounts for 55% of the buffering capa is converted to glutamic acid and ammonia, the reaction
city because of its sheer abundance. When H+ concentration catalyzed by glutaminase. Ammonia is secreted in the
increases the above reaction shifts to the left, more CO2 is lumen and combines with H+ to form ammonium ions,
generated and exhaled from the lungs, moderating the which are excreted in urine.
change in pH.
Sodium-hydrogen exchange in the distal tubule: The distal
Renal Regulation of Acid-Base Balance tubular cells actively reabsorb Na+; to maintain electro
neutrality, H+ ions are exchanged. The latter combine with
The kidneys are slower to compensate, but renal either monohydrogen phosphate or ammonia and are
physiology has several powerful mechanisms to control
excreted.
pH by the excretion of excess acid or base. Kidneys are
the principal regulators of bicarbonate mainly by two Anion Gap
methods: (i) resorption of HC0 3- mostly in proximal
To achieve electrochemical balance, the number of
convoluted tubules and (ii) excretion of H+ and, therefore,
negatively charged ions (anions) should equal the
generation of HC03, primarily by the distal tubules and positively charged ions (cations). Measured plasma anions
collecting ducts. In response to acidosis, tubular cells are chloride and bicarbonate, and the unmeasured anions
reabsorb more bicarbonate from the tubular fluid, include phosphates, sulfates and proteins (e.g. albumin).
collecting duct cells secrete more hydrogen and generate Under typical conditions, unmeasured anions exceed
more bicarbonate, and ammoniagenesis leads to increased unmeasured cations; this is referred to as the anion gap
formation of renal ammonia (Fig. 6.10). In responses to and can be represented by the following formula:
alkalosis, the kidneys excrete more bicarbonate by
decreasing hydrogen ion secretion from the tubular Anion gap = (Na+) - (Cl- + HC03)
epithelial cells, and lowering rates of glutamine meta The anion gap is normally 8 to 12 mEq/L. When a strong
bolism and ammonia excretion. acid is added to or produced in the body, hydrogen ions are
Bicarbonate-carbonic acid in the kidney tubules: H+ ions neutralized by bicarbonate, resulting in a fall in bicarbo
secreted from the tubular cells combines with luminal nate. These acids include inorganic (e.g. phosphate or
HC03- to form water and CO2• The CO2 enters the tubular sulfate), organic (e.g. ketoacids or lactate) or exogenous
cell and combines with water, in presence of carbonic (e.g. salicylate) acids incompletely neutralized by bicar-
+ �H·+Hco;�
H
+
Na2HP0 4
11 (�)
I rt:-
H 20+C0 2
i
NaH P0 + Na
2 4
L,,-• +
l .-',,
Glutamine
,� 3;,
L,,-4
NH 3 + Glutamate
Fig. 6.1 O: Renal regulation of acid-base disorders. l = bicarbonate-carbonic acid buffer; 2 = monohydrogen phosphate
dihydrogen phosphate buffer; 3 = ammonia-ammonium buffer
Fluid and Electrolyte Disturbances Isa-
bonate. The accompanying unmeasured anion results in as in gastrointestinal or renal loss of bicarbonate or when
increased anion gap proportional to the fall in bicarbonate. hydrogen ions cannot be secreted because of renal failure)
In contrast, when the bicarbonate is lost from the body, no (Table 6.12).
new anion is generated; therefore, there is a reciprocal Another useful tool in the evaluation of metabolic
increase in chloride ions (proportional to the fall in bicarbo acidosis with normal anion gap is urinary anion gap.
nate) resulting in normal anion gap. Hypoalbuminemia is Urinary anion gap = urinary [Na+ ] + [K+ ] - [CI-J
the most common cause of a low anion gap. Albumin
Urinary anion gap is negative in patients with diarrhea
represents about half of the total unmeasured anion pool; regardless of urinary pH, and urinary anion gap is positive
for every decrease of 1 g/dL of plasma albumin, the plasma in renal tubular acidosis. An elevated osmolal gap (>20
anion gap decreases by 2.5 mEq/L. mOsm/kg) with metabolic acidosis suggests the presence
of osmotically active agents such as methanol, ethylene
Metabolic Acidosis
glycol or ethanol.
Metabolic acidosis is an acid-base disorder characterized
by a decrease in serum pH that results from either a loss Clinical Features
in plasma bicarbonate concentration or an increase in Initially, patients with a metabolic acidosis develop a
hydrogen ion concentration (Table 6.12). Primary meta compensatory tachypnea and hyperpnea, which may
bolic acidosis is characterized by an arterial pH of less progress if the acidemia is severe, and the child can present
than 7.35 due to a decrease in plasma bicarbonate in the with significant work of breathing and distress (Kussmaul
absence of an elevated PaC02 • If the measured PaC02 is breathing). An increase in H+ concentration results in
higher than the expected PaCO2, a concomitant respiratory pulmonary vasoconstriction, which raises pulmonary
acidosis is also present (caused by a depressed mental artery pressure and pulmonary vascular resistance.
state, airway obstruction or fatigue). Acutely, medullary Tachycardia is the most common cardiovascular effect
chemoreceptors compensate for metabolic acidosis seen with mild metabolic acidosis. Cerebral vasodilation
through increase in alveolar ventilation, which results in occurs as a result of metabolic acidosis and may contribute
tachypnea and hyperpnea that washes off CO 2 and to an increase in intracranial pressure. Acidosis shifts the
corrects pH. oxygen-hemoglobin dissociation curve to the right,
Calculation of plasma anion gap helps to classify decreasing hemoglobin's affinity for oxygen. During
metabolic acidosis into those with elevated anion gap (i.e. metabolic acidosis, excess hydrogen ions move toward the
>12 mEq/L as in increased acid production or decreased intracellular compartment and potassium moves out of the
losses) and those with normal anion gap (i.e. 8-12 mEq/L cell into the extracellular space. Untreated severe
metabolic acidosis may be associated with life-threatening
Table 6.12: Causes of metabolic acidosis arrhythmias, myocardial depression, respiratory muscle
fatigue, seizures, shock and multiorgan failure.
Normal anion gap (hyperchloremic acidosis)
Renal loss of bicarbonate Treatment
Proximal (type 2) renal tubular acidosis, carbonic anhydrase
inhibitors (e.g. acetazolamide), tubular damage due to drugs
It is important to identify the cause of metabolic acidosis
or toxins as most cases resolve with correction of the underlying
Gastrointestinal bicarbonate loss disorder. The role of alkali therapy in acute metabolic
Diarrhea, ureteral sigmoidostomy, rectourethral fistula, fistula acidosis is limited. It is definitely indicated in some
or drainage of small bowel or pancreas situations, e.g. salicylate poisoning, inborn errors of
Decreased renal hydrogen ion excretion metabolism, or in those with pH below or equal to 7.0 or
Renal tubular acidosis type 1 and type 4 (aldosterone [HC03-] less than 5 mEq/L, as severe acidosis can produce
deficiency) myocardial dysfunction. The amount of bicarbonate
Potassium sparing diuretics required is
Increased hydrogen chloride production Body weight (kg) x base deficit x 0.3.
Parenteral alimentation, increased catabolism of lysine and
arginine One mL of 7.5% sodium bicarbonate provides 0.9 mEq
Ammonium chloride ingestion bicarbonate. The recommendation is to replace only half
of the total bicarbonate deficit during the first few hours
Elevated anion gap
of therapy. This amount is given as continuous infusion
Increased acid production/accumulation: Sepsis, shock, over two hours. Rapid correction of acidosis with sodium
poisonings (ethanol, methanol, ethylene glycol); inborn errors bicarbonate can lead to extracellular volume expansion,
of metabolism exacerbating pulmonary edema in patients with cardiac
Ketoacidosis: Diabetic ketoacidosis, starvation failure. In the latter, the rate of infusion should be slower.
Exogenous acids: Salicylates, iron, isoniazid, paraldehyde
If hypematremia is a concern, sodium bicarbonate may
Failure of acid excretion: Acute or chronic kidney disease
be used as part of the maintenance intravenous solution.
-84 Essential Pediatrics
During correction of acute metabolic acidosis, the effect Table 6.13: Causes of metabolic alkalosis
of sodium bicarbonate in lowering serum potassium and Chloride responsive
ionized calcium concentrations must also be considered
Gastric fluid loss (e.g. vomiting, nasogastric drainage)
and monitored. Since bicarbonate therapy generates large
Volume contraction (e.g. loop or thiazide diuretics, metolazone)
amount of CO2, ventilation should increase proportion
Congenital chloride diarrhea, villous adenoma
ately otherwise this might worsen intracellular acidosis.
Cystic fibrosis
The inability to compensate may be especially important
Post-hypercapnia syndrome (mechanically ventilated patients
in patients with diabetic ketoacidosis who are at risk for with chronic lung disease)
cerebral edema. In diabetic ketoacidosis, insulin therapy
generally corrects the acidosis. Chloride resistant
In newborns, frequent administration of hypertonic Primary aldosteronism (adenoma, hyperplasia)
solutions such as sodium bicarbonate have led to intracranial Renovascular hypertension, renin secreting tumor
hemorrhage resulting from hyperosmolality and resultant Bartter and Gitelman syndromes
Apparent mineralocorticoid excess
fluid shifts from the intracellular space. Children with Glucocorticoid remediable aldosteronism
inherited metabolic abnormalities, poisoning, or renal failure Congenital adrenal hyperplasia (11 �- and 17a-hydroxylase
may require hemodialysis. deficiency)
Mild to moderate acidosis in renal failure or renal tubular Liddle syndrome
acidosis improves on oral alkali therapy, the dose being 0.5 Excess bicarbonate ingestion
to 2 mEq/kg/day of bicarbonate in 3-4 divided doses. In
cases of acidosis due to volume depletion, the volume deficit seizures. Generalized weakness may be noted, if the patient
should be corrected. also has hypokalemia. Patients who develop metabolic
alkalosis from vomiting can have symptoms related to
Metabolic Alkalosis severe volume contraction, with signs of dehydration.
Metabolic alkalosis (pH >7.45) is an acid-base disturbance Although diarrhea typically produces a hyperchloremic
caused by elevation in the plasma bicarbonate (HC03-) metabolic acidosis, diarrheal stools may rarely contain
concentration in the extracellular fluid that results from a significant amounts of chloride, as in the case of congenital
net loss of acid, net gain of base or loss of fluid with more chloride diarrhea. Children with this condition present at
chloride than bicarbonate. There are two types of birth with watery diarrhea, metabolic alkalosis, and hyp o
metabolic alkalosis classified based on the amount of volemia. Weight gain and hypertension may accompany
chloride in the urine, i.e. chloride-responsive or chloride metabolic alkalosis that results from a hypermineralo
resistant (Table 6.13). Chloride-responsive metabolic corticoid state.
alkalosis shows urine chloride levels of less than 10 mEq/L
and is characterized by decreased ECF volume and low Treatment
serum chloride levels, such as occurs with vomiting or The overall prognosis in patients with metabolic alkalosis
use of diuretics. This type responds to administration of depends on the underlying etiology. Prognosis is good
chloride salt (usually as normal saline). Chloride-resistant with prompt treatment and avoidance of hypoxemia. Mild
metabolic alkalosis is characterized by urine chloride or moderate metabolic alkalosis or alkalemia rarely
levels of more than 20 mEq/L. Primary aldosteronism is requires correction. For severe metabolic alkalosis, therapy
an example of chloride-resistant metabolic alkalosis and should address the underlying disease state, in addition
this type resists administration of therapy with chloride. to moderating the alkalemia. The initial target pH and
The body compensates for metabolic alkalosis through bicarbonate level in correcting severe alkalemia are
buffering of excess bicarbonate and hypoventilation. Intra approximately 7.55 and 40 mEq/L, respectively.
cellular buffering occurs through sodium-hydrogen and Therapy with diuretics (e.g. furosemide, thiazides)
potassium-hydrogen ion exchange, with eventual should be discontinued. Chloride-responsive metabolic
formation of CO2 and water from HC03. Within several alkalosis responds to volume resuscitation and chloride
hours, elevated levels of HC03 and metabolic alkalosis repletion. Chloride-resistant metabolic alkalosis may be
inhibit the respiratory center, resulting in hypoventilation more difficult to control. As with correction of any electrolyte
and increased pC02 levels. This mechanism produces or acid-base imbalance, the goal is to prevent life-threatening
a rise in pC02 of as much as 0.7 to 1 mm Hg for each complications with the least amount of correction.
1 mEq/L increase in HC03. For persistent severe metabolic alkalosis in the setting
of fluid overload, wherein saline cannot be given, cautious
Clinical Features use of HCl or ammonium chloride may be considered.
Signs and symptoms observed with metabolic alkalosis Acetazolamide may help patients with chloride-resistant
usually relate to the specific disease process that caused the metabolic alkalosis provided GFR is adequate. Correction
acid-base disorder. Increased neuromuscular excitability of metabolic alkalosis in patients with renal failure may
(e.g. from hypocalcemia), sometimes causes tetany or require hemodialysis or continuous renal replacement
Fluid and Electrolyte Disturbances 85-
therapy with a dialysate that contains high levels of (Table 6.15). In a child, this may result from high fever,
chloride and low HC03. sepsis, mild bronchial asthma, central nervous system
disorders or overventilation of an intubated child in
Respiratory Acidosis intensive care setting. In acute respiratory alkalosis,
Respiratory acidosis occurs when the alveolar ventilation titration is done by intracellular buffers. Renal compen
falls or when carbon dioxide production is increased, so sation begins within several hours and takes several days
that the arterial partial pressure of carbon dioxide (PaCO2) for the maximal response.
is elevated above the normal range (>45 mm Hg) leading
to a blood pH lower than 7.35 (Table 6.14). pC02 is directly Clinical Features
proportional to carbon dioxide production and inversely Patients primarily have clinical manifestations of the
proportional to alveolar ventilation. The kidneys compen underlying disorder. Alkalosis, by promoting the binding
sate for respiratory acidosis by increasing HC03- reabsor of calcium to albumin, can reduce the fraction of ionized
ption, a process that begins in 6-12 hours but takes calcium in blood which may manifest as feeling of tingling,
3-5 days for maximal compensation. paresthesias, dizziness, palpitations, tetany and seizures.
The kidneys increase excretion of hydrogen ions (pre Therapy is directed towards the causal process.
dominantly in the form of ammonium) that increases the
plasma bicarbonate concentration by approximately Table 6.15: Causes of respiratory alkalosis
3.5-4 mEq/L for every 10 mm Hg increase in CO2 • Hypoxia and hypoxemia
Clinical Features High altitude or low fraction of inspired oxygen, anemia,
hypotension or lung disease
Patients with acute respiratory acidosis frequently demon
strate air-hunger with retractions and use of accessory Pulmonary disorders
muscles. Neurologic findings include anxiety, disorien Pulmonary edema, embolism, airway obstruction, pneumonia,
tation, confusion and lethargy followed by tremors, som interstitial lung disease
nolence or coma at higher pC02 • Hypercapnic neurologic Mechanical ventilation (ventilatory rate or tidal volume too high)
changes are reversible with no residual effect. Cardio Extrapulmonary disorders (severe respiratory alkalosis)
vascular findings include tachycardia, bounding arterial Stress, neurologic disease (stroke, infection, trauma, tumor)
pulses and in severe cases hypotension. Medications: Catecholamines, progesterone, methylxanthines,
salicylates, doxapram, nicotine
Treatment Hyperthermia, hepatic encephalopathy, sepsis, recovery from
The goal of therapy is to correct or compensate for the metabolic acidosis
underlying pathologic process. Failure to consider a mixed
acidosis can lead to missed therapies and diagnosis. Suggested Reading
Assisted ventilation is required in many cases.
• Achinger SG, Ayus JC. Treatment of hyponatremic encephalopathy
Respiratory Alkalosis in the critically ill. Crit. Care Med 2017;45:1762-1771.
• Carmody JB, Norwood VF. A clinical approach to pediatric acid
Respiratory alkalosis occurs in the setting of a primary base disorders. Postgrad Med J 2012;88:143-51.
decrease in pC02 as a consequence of hyperventilation • Holliday MA, Ray PE, Friedman AL. Fluid therapy for children:
facts, fashions and questions. Arch Dis Child 2007;92:546-50.
• Hoom EJ. Intravenous fluids: balancing solutions. J Nephrol. 2017;
Table 6.14: Causes of respiratory acidosis 30: 485-492.
Decrease in alveolar ventilation • Lietman SA, Germain-Lee EL, Levine MA. Hypercalcemia in
Depressed central respiratory drive children and adolescents. Curr Opin Pediatr 2010;22:508-15.
Acute paralysis of the respiratory muscles • Masilamani K, van der Voort J. The management of acute
Acute or chronic parenchymal lung and airway diseases hyperkalemia in neonates and children. Arch Dis Child
2012;97:376-80.
Progressive neuromuscular disease
• Stems RH. Disorders of plasma sodium causes, consequences and
Worsening scoliosis (restrictive lung disease) correction. N Engl J Med 2015; 372(1): 55-65.
High carbon dioxide production and inability to increase • Spasovski G, Vanholder R, Adolio B. Clinical practice guidelines
minute ventilation on diagnosis and treatment of hyponatremia. Eur J Endocrinol
2014;170:41-47.
Extensive burn injury
• Zieg J, Consorcikova L, Landaw D. Current views on diagnosis
Malignant hyperthermia and management of hypokalemia in children. Acta Paediatr
Fever 2016;105:762-72.
Chapter
7
Nutrition
Vinod K Paul • Anuja Agarwala • Rakesh Lodha
+
sunflower oil
the total calories or 1.0-1.5 g/ day.
Cholesterol is the component of cell membrane, helps
Essential fatty acids the body produce steroid hormones and bile acids.
Linoleic acid
Linolenic acid
Requirements: Fats are major source of energy in diet. In
Fig. 7 .1: Classification of fats normally growing children, about 25-30% of energy intake
-88 Essential Pediatrics
should be derived from fat which includes 10-15% body weights, the energy requirements are calculated
invisible fat. However, in malnourished children, up to roughly as shown in Table 7.2.
45% of calories can be safely provided from fat.
DIETARY STANDARDS
Invisible fat: Fat present naturally in our food but cannot
be seen and separated from food such as milk and milk Infants and children have higher requirements of nutrients
products, egg and meat, nuts contain good amount, while than adults. While adults need nutrients for maintaining
cereals, pulses, vegetables and fruits contain negligible constant body weight and functions, infants and children
amount. require nutrients not only for maintenance but also for
promoting and supporting their rapid rate of growth and
Visible fat: Fat which is used for cooking or added while development.
cooking such as edible vegetable oils and ghee.
A range of acceptable or safe intake levels have been
To provide a healthy balance of visible fat, daily diet established for almost all the important nutrients at
should provide <7% saturated fat, 10% polyunsaturated different ages, which are recognized as recommended
fat and rest 13% should be derived from monounsaturated dietary allowances (RDA).
fats. A minimum of 3% energy should be derived from
linoleic acid and 0.3% from linolenic acid. Recommended Dietary Allowances (RDAs)
There is no single oil/ fat with the ideal composition; it
RDAs are nutrient specific and technical in nature. These
is recommended to use blend of two or more vegetable
are formulated based on the current knowledge of
oils.
nutritional requirements of different age and sex groups
Energy depending on anthropometry (weight, height), body
composition, climate and environment, physical activity,
Energy needs of children are computed keeping in mind physiological status and body demands. All these factors
the increase in body size, high metabolic rate that regulates lead to differences in food intake and nutrient requirements.
body temperature and maintains high level of activities, Summary of Recommended Dietary Allowances (RDA)
and marked developmental changes in organ function and for energy and protein revised in 2010 is shown in
composition. Table 7.3.
Energy requirements vary through childhood because
of variations in growth rate and physical activity. Nutritive Value of Some Common Foods
Although growth rate slows in toddlers, their activity
Table 7.4 portrays energy, protein, carbohydrates and fat
levels are high, and appetite and food intake tends to be
composition of common Indian food items and portions.
erratic. In older children, growth is more constant but
energy needs vary within and between individuals.
During adolescence, energy needs increase due to rapid
growth and development. Table 7.3: Daily energy and protein requirements at different
There are three critical periods in early life of a young ages
child with regards to energy requirements: Around Group Age Energy Protein
6 months when complementary feeding is initiated,
(kcalld) (g/d)
between 1 and 2 years when physical activity is increased
and between 10 and 12 years for girls and 15--18 years for Infants 0-6 months 90 kcal/kg/d 1.2 g/kg/d
boys when puberty is attained. 6-12 months 80 kcal/kg/d 1.7 g/kg/d
Calculation of energy requirement should account for Children 1-3 years 1050 17
the level of physical activity and the energy required 4 -6 years 1350 20
allowing for optimal growth. For children with normal 7 -9 years 1700 30
Boys 10-12 years 2200 40
Table 7.2: Simple calculation of daily energy requirements for Girls 10-12 years 2000 40
children Boys 13-15 years 2750 54
At 10 kg body weight 1000 kcal Girls 13-15 years 2300 52
Weight >10 kg-20 kg 1000 kcal + 50 kcal for each kg Boys 16-17 years 3000 62
above 1 O kg, e.g. for a 15 kg child, Girls 16-17 years 2450 56
requirement will be 1250 kcal Adult male Sedentary 2300 60
Weight >20 kg 1500 kcal + 20 kcal for each kg Adult female Sedentary 1900 55
above 1 O kg, e.g. for a 30 kg child,
requirement will be approximately Adapted from Nutrient Requirements and Recommended Dietary
1700 kcal Allowances for Indians, ICMR 2010 [Values have been rounded off at
places]
Nutrition
]
Dhooli dais (moong/arhar, etc.) 25 g raw 1 katori 80 6.0 14.0 0.3
Sabut dais (Rajma/Chana, etc.) 25 g raw cooked 70 5.0 10.0 1.0
Soyabean (white) 25 g raw (100-125 g) 95 10.0 2.5 5.0
Vegetables
Green leafy and seasonal 100 to 125 g Y2 katori cooked 25 2.0 2.5 0.6
vegetables (spinach, bathua,
bhindi, cauliflower, beans, etc.)
Root vegetables (includes arbi, 100 g 1 small size 60 1.5 13.0 0.2
potato, zimikand, etc.)
Peas fresh 100 g 1 katori 80 7.0 13.0 0.1
Low carb vegetables (Lauki/ 100 g Y2 katori 10 0.53 1.7 0.13
tori/ tinda/kaddu/cucumber)
Dried nuts
Groundnuts 25 g Handful 130 6.0 4.0 10.0
Almond/walnuts/ 25 g -do- 150 4.5 1.0 14.5
Cashew nuts 25 g -do- 140 4.5 6.5 10.0
Fruits
Banana 100 g 1 small 110 1.5 25.0 0.5
Mango/chikoo/apple 100 g 1 medium 70 0.6 13.0 1.7
Guava/pear/orange 100 g 1 medium 35 1.0 7.0 0.2
Kharbooja/papaya 100 g 2 pieces 25 0.5 5.0 0.2
Tomato/water melon 100 g A few pieces 20 0.8 3.0 0.3
(Contd...)
- 90 Essential Pediatrics
Drinks
Sugarcane juice 100 ml Y2 glass 60 15.0
Coconut water 100 ml Y2 glass 14 0.2 3.0 0.1
Soft drinks 100 ml Y2 glass 37 9.2
Processed dairy products
Full cream milk 100 ml Y2 glass 90 3.5 5.0 6.2
Toned milk 100 ml Y2 glass 58 3.2 4.5 3.0
Double toned milk 100 ml Y2 glass 48 3.0 5.0 2.0
Skimmed milk 100 ml Y2 glass 33 3.0 5.0
Dahi (plain)/Curd 100 ml 1cup 75 3.7 5.0 4.5
Buttermilk (lassi-plain) 100 ml Y2 glass 32 2.0 2.0 2.0
Sweet lassi 100 ml Y2 glass 95 2.5 15.5 2.5
Salted lassi 100 ml Y2 glass 32 1.8 2.0 1.8
Cottage cheese 30g 1small pc 93 5.5 0.7 7.5
Ice cream 100 ml 1 small cup 180 4.0 23.0 8.0
Ice cream (sugar free) 100 ml 1 small cup 113 5.0 12.0 5.0
kcal: Kilocalories; tsp: Tea spoon
NB: Some approximations made in values of nutrient contents
Adapted from:
1. Indian Food Composition tables, NIN, ICMR, 2017
2. Compilation of Food Exchange list (Technical series 6), Lady Irwin College, Delhi University, 2017
3. For processed foods, nutritional facts are taken from the packets
BALANCED DIET or more food items from each of these groups is essential
to label a diet as 'balanced'.
Balanced diet is defined as nutritionally adequate and
The nutrient characteristics of common foods are
appropriate intake of food items that provide all the
depicted in Table 7.5.
nutrients in required amounts and proper proportions, to
Cereals, millets and pulses are the major source of most
ensure normal growth, development and disease free
nutrients in Indian diet. Milk provides good quality
optimum health amongst children and adolescents. Wide
protein and calcium and hence is an essential item of our
variety and combination of foods are used to formulate
diet. Eggs, flesh foods and fish enhance the quality of diet
balanced diet for various categories of people to meet their
but Indians are predominantly vegetarian society and
needs as per nutritional standards (RDA).
most of our nutrients are derived from cereal/ pulse and
In order to plan nutritionally adequate balanced diet
milk based diets. Oils and nuts are calorie rich foods and
as per RDA, "food group system" is used that converts
are useful in increasing the calorie density. Vegetables and
quantitative nutrient data into food-based information.
fruits provide protective substances such as vitamins,
Based on major content of nutrients, foods are minerals, fiber and antioxidants.
conventionally placed into 5 groups: (i) Cereals, millets
and cereal grains; (ii) Pulses, legumes and nuts; (iii) Milk, In a normal balanced Indian diet, recommended macro
egg and flesh foods; (iv) Vegetables and fruits; (v) Fats nutrients as a proportion of total energy intake should be:
and sugar. Food groups differ in their nutrient quality and carbohydrates (55-60%), fats (25-30%) and proteins
quantity and hence while planning a diet, inclusion of one (10-12%).
Nutrition 191-
NORMAL BALANCED DIET FOR VARIOUS AGE GROUPS for breastfeeding and complementary feeding are given
in Table 7.6.
Exclusive Breastfeeding (0-6 months of age)
Between 6 and 12 months, child goes through a major
An infant should be exclusively breastfed till six months food transition that depends on several cardinal factors,
of age. During this phase, additional food or fluids are essential to be considered in feeding the child.
not required as breast milk is nutritionally complete for
the child's growth and development; it protects from
infections and strengthens immune system. Breastfeeding Factors to be Considered while
issues are discussed in Chapter 8. Planning Food for Young Child
Energy density: Most of our traditional foods are bulky
Complementary Feeding (6 months onwards) and a child cannot eat large quantities at a time. Children
After six months of age, breast milk alone is not enough have low stomach capacity. Hence, it is important to give
to make an infant grow well. Complementary feeding small energy-dense feeds at frequent intervals to ensure
refers to food which complements breast milk and ensures adequate energy intakes by the child.
that the child continues to have enough energy, protein Energy density of foods given to infants and young
and other nutrients to grow normally. children can be increased without increasing the bulk by
Complementary feeding is started six months of a ge adding:
(180 days), while continuing breastfeeding. • Oil or ghee: Fat is a concentrated source of energy and
Breastfeeding is encouraged up to two years of age or increases energy content of food without increasing the
more in addition with normal food. Key recommendations bulk. The false belief that a young child cannot digest
-92 Essential Pediatrics
12 months to 2 years Breastfeed as often as the child wants; offer food from the family pot
Give at least 1111 katori serving at a time of mashed roti/rice bread mixed in thick dal or khichri with added
ghee or oil
Add cooked vegetables in the servings, or mashed roti/rice/bread/biscuit mixed in sweetened undiluted
milk, or sevian, dalia, halwa or kheer prepared in milk or any cereal porridge cooked in milk, or mashed
boiled/fried potatoes
Frequency: 3-5 times a day
Offer banana, biscuit, cheeku, mango or papaya as snacks in between the servings
Remember: Sit by the side of child and help him to finish the serving; wash your child's hands with soap
and water every time before feeding
2 years and older Give family food as 3-4 meals each day
Twice daily, also give nutritious snacks between meals, e.g. banana, biscuit, cheeku, mango, or papaya
Remember: Ensure that the child finishes the serving; teach your child to wash his hands with soap and
water every time before feeding
fat is not true. A young infant can digest fat present in to ensure intakes of all macronutrients and micro
breast milk as well as all other foods like cereals and nutrients.
pulses. Sugar and jaggery are also rich in energy though
not as high in calories as fat but can easily be added in
Amount of feed: At 6 months of age, feed should be started
with small amount as much as 1-2 teaspoons and the
infant foods.
quantity is increased gradually as the child gets older and
• Thickening the gruel: Thin gruels do not provide enough
starts to accept food better. Child should be given time to
energy. A young infant particularly during 6--9 months
adapt gradually to larger quantities from teaspoon to table
requires thick but smooth mixtures. For instance,
spoon and then to a katori.
advising dal ka paani as a complementary food recipe is
absurd. Infant should be given medium thickness gruel Consistency of feed: Infants can eat pureed, mashed and
of 'dal' with added oil instead. semi-solid foods beginning at six months. By 8 months,
• Amylase rich foods (ARF) such as malted foods reduce most infants can also eat "finger foods" (snacks that can
the viscosity of the foods and therefore the child can be eaten by children alone). By 12 months, most children
eat more quantities at a time. (Malting is germinating can eat the same types of foods as consumed by the rest
whole grain cereal or pulse, drying and then grinding). of the family. As the child grows older, he should be
shifted to more appropriate foods suitable for his age. Help
Often the energy needs of the child are no t well
children to accept the usual family food gradually which
appreciated by caregivers. A child between the age of
is safely prepared and fed.
1 or two years of age needs as musch as 50% the nutrition
required by an adult. Frequency offeeding: An average healthy breastfed infant
needs complementary foods 3-4 times per day at 6-8
Nutrient density of the feed can be ensured by including months of age and 3-4 times per day at 9-11 months and
a variety of foods in order to meet all the nutrients. Even 4-5 times at 12-24 months of age, with additional
as early as 9 months, infants need small portions of food nutritious snacks such as a piece of fruit, offered 1-2 times
items from all food groups to be included in their diet per day or as desired. Snacks are defined as foods eaten
Nutrition 193-
between meals, usually convenient and easy to prepare. In this chapter, we will focus on undernutrition among
If energy density or amount of food per meal is low, or children less than 5 years of age.
the child is no longer breastfed, more frequent meals may
be required. Consequences of Undernutrition
Undernourished children have higher risk of infections and
Hygiene: Good hygiene and proper food handling should mortality. Undernutrition is associated with 35% of under-5 child
be practiced to prevent children from infections and deaths. Undernutrition is strongly associated with shorter adult
malnutrition. Simple hygiene practices include: (a) Washing height, poor lean weight, less schooling, low cognition, reduced
hands before food preparation and eating, (b) Serving economic productivity and, for women, lower offspring
freshly cooked foods (cooked should not be kept for 2- birthweight. Low birthweight and undernutrition in childhood
3 hours), (c) Using clean utensils and covered properly, are important risk factors for diabetes mellitus, hypertension
(d) Using clean cups and bowls when feeding children, and dyslipidemias in adulthood.
and (e) Avoiding use of feeding bottles.
Underweight, Stunting and Wasting
Planning Diet for Individual Child Undernutrition has three subgroups: Underweight, wasting
In clinical practice, it is imperative to plan diets for and stunting (Table 7.8 and Fig. 7.2)
different conditions among children with various ages, An underweight child has low-weight-for-age. It means
both healthy and sick. In this exercise, it is important to that the weight of this child is less than minus 2 standard
ensure the right balance of macronutrients and food deviations (-2SD) on the WHO Growth Standard for her/
groups. A sample diet plan for 1000 kcal is shown in his age. An underweight child could be wasted or stunted,
Table 7.7. This can serve as a template to plan diets of or both.
lower or higher energy content by varying amounts of
ingredients.
Stunting denotes low-height-for-age. The height (or length)
of a stunted child is below minus 2 standard deviations
UNDERNUTRITION (<-2SD) at her/his age on the WHO Growth Standard. A
stunted child is short for her/his age. Stunting indicates
Undernutrition is a set of conditions that result from chronic undernutrition.
inadequate consumption, poor accretion or excessive loss
of nutrients. Overnutrition includes overweight and Wasting implies low-weight-for-height. A child whose
obesity, and is caused by overindulgence or excessive weight for her /his actual height is less than minus 2
intake of nutrients, or pathological conditions. standard deviations (<-2SD) at her/his age on the WHO
Malnutrition refers to deficiencies, excesses or Growth Standard has wasting. A wasted child has a thin
imbalances in a person's intake of energy and/or nutrients appearance. Wasting indicates acute undemutrition as
(WHO). Thus, malnutrition connotes both undernutrition result of recent food deficit or an acute illness such as
as well as ovemutrition. In practice, however, often the diarrhea.
terms malnutrition and protein energy malnutrition (PEM) Growth charts based on WHO Growth Reference
are used interchangeably with undemutrition. Standards are given in Chapter 2.
Table 7.7: A 1000 kcal sample, balanced diet plan based on the food measures. The food portions are to be spread over 24 hours
in multiple meals and snacks
Food Amount/ready to eat portion Energy (kcal) Protein (g)
Cow's milk/curd 1 glass milk (200 ml) plus % katori curd (50 ml milk) 180 8.0
Pulses 25 g raw dal (1 katori cooked ) 80 6.0
Cereals wheat/rice 100 g
4 chapatis (100 g wheat flour) OR
2 chapatis (50 g wheat flour) plus 2 katoris rice cooked (50 g grain) OR
2 chapatis (50 g wheat flour) plus 1 katori cooked suji (25 g wheat flour)
plus 1 katori rice cooked (25 gm raw grain) 340 9-10 g
Vegetables 150 g
Green/seasonal 100 g (1 katori cooked) 25 2.0
Potato 50 g (1/2 katori cooked)) 30 1.0
Fruit (banana) 100 g 110 1.5
Oil/ ghee (4 tsp) 20 ml (in cooking plus added) 180
Sugar (3 tsp) 15 g (in cooking plus added) 60
Total -1000 kcal -28 g
• Note-Energy from protein 11-12% in this sample diet
• tsp: Tea spoon
-94 Essential Pediatrics
Normal height - - - - - - - - - - - - - - - - - - - - - - - -
60%
50%
40%
30%
20%
10%
0%
Underweight Stunting Wasting
Normal Wasted Stunted •2005-05 •2015-16
(thin) (short)
Fig. 7.3: Trends in undernutrition in India: proportion of under-5
Fig. 7.2: Appearance of undernourished children children with underweight. stunting and wasting. Source:
National Family Health Surveys 3 (2005-06) and 4 (2015-16))
The term 'edematous malnutrition' is used if edema is During the first six months of life, 20-30% of children
also present in an underweight child. Clinical classification are already undernourished, often because they were born
of undernutrition as marasmus, kwashiorkor and low birthweight. The proportion of undernutrition and
marasmic kwashiorkor is also helpful (discussed below). stunting starts rising after 4-6 months of age (Fig. 7.4).
After 6 months of age, breast milk alone is not enough to
Epidemiology meet the energy requirement of the child, and therefore solid
Childhood undernutrition is an underlying cause in an food (complementary feeding) must be introduced, in addition
estimated 45% of all deaths among under-5 children. to continuing breastfeeding. This often does not happen.
According to the National Family Health Survey (NFHS) It is estimated that only 10% of children between the
4, carried out in 2015-16, 36% of India's children under age of 6-24 months have adequate nutritional intake
the age of five are underweight, 38% are stunted and 21% (NFHS 4). Most children in the country are thus 'nutrition
are wasted (Fig. 7.3). Comparable figures for 2005-06 were hungry' in this critical phase of life. In addition, the child
43%, 48% and 20%, respectively. There has been a slow becomes more prone of infections, particularly diarrhea,
reduction in undernutrition in the country over the years, due as she becomes mobile and puts unhygienic objects
especially stunting. Yet we continue to have the highest into mouth and ingests unhygienic food products.
burden of childhood undernutrition in the world. Late introduction of complementary feeding and
Undernutrition rates are highest among the scheduled inadequate food intake leads to increasing predisposition
tribes and scheduled caste families. Proportion of to undernutrition. The proportion of children who are
underweight children in rural areas (38%) is higher than stunted or underweight increases rapidly with the child's
urban areas (29%). age until about 18-24 months of age (Fig. 7.4).
Nutrition 195-
Importance of fetal life and the first two years of life (the first Three cardinal determinants of undernutrition
1000 days 'window') for linear and brain growth. 1. low bi rth weight: Infants born small often remain
Length at 2 years is the predictor of adult height and undernourished. About 20% childhood undernutrition is
productivity. Brain achieves a near adult size by two years attributable to fetal growth restriction.
of age. It is practically impossible to reverse the height 2. Infections: Diarrhea, pneumonia and other infections consume
and brain growth deficit after 2 years of age with nutrition energy and hamper growth. Diarrhea causes nutrient loss in
and other interventions; it is simply too late. stools. About 25% childhood undernutrition is attributable to
diarrhea, pneumonia and other infections.
Thus, nutrition during the first 1000 days since
3. Low food intake: Inadequate breastfeeding, delayed
conception, encompassing pregnancy and the first 2 two complementary feeding and insufficient food intake means
years of life, is of profound importance for realizing the less energy and protein available for growth. This underlies
physical and intellectual potential. Nutritional corrections about 55% of childhood undernutrition.
after two years will not change these outcomes.
Hence, ensuring optimum nutrition of the mother Clinical Syndromes of Undernutrition
before and during pregnancy, and optimum feeding of Moderate and severe malnutrition is associated with one
children in the first 2 years of life (including breastfeeding of classical syndromes, namely, marasmus, kwashiorkor,
for first 2 years, and adequate solid feeding after 6 months or with manifestations of both. Another classification, the
of age) is absolutely crucial in human life. severe acute malnutrition (SAM) is used in the program
setting.
Determinants
The causes of malnutrition could be viewed as immediate, Marasmus
underlying and basic as depicted in Fig. 7.5. Marasmus is characterized by severe form of wasting.
The immediate determinants of a child's nutritional There is marked wasting of fat and muscle as these tissues
status work at the individual level. These include low are consumed to make energy. Acute starvation or acute
birthweight, illnesses (particularly infections such as illness over a borderline nutritional status precipitates this
diarrhea and pneumonia) and inadequate dietary intake. form of undemutrition. Sever marasmus is a typical form
Finally, the underlying determinants are influenced by of severe acute malnutrition (SAM).
the basic determinants. These include the socioeconomic • The main sign is severe wasting. The child appears very
status and education level of the families, women's thin (skin and bones) and has no fat. There is severe
empowerment, cultural taboos regarding food and health, wasting of the shoulders, arms, buttocks and thighs
access to water and sanitation, etc. Access to safe water (Fig. 7.6).
and sanitation, will reduce a significant proportion of • The loss of buccal pad of fat creates the aged or wrinkled
undemutrition. appearance that has been referred to as monkey fades
-96 Essential Pediatrics
Nutritional status
Immediate
Low birth weight determinants
POVERTY
Kwashiorkor
Uncommon in India now, it usually affects children aged
1--4 years. The main sign is pitting edema, usually starting
in the legs and feet and spreading, in more advanced cases,
to the hands and face. Because of edema, children with
kwashiorkor may look healthy so that their parents view
them as well fed.
• General appearance: Child may have a fat sugar baby
appearance.
• Edema: It ranges from mild to gross and may represent
up to 5-20% of the body weight.
• Muscle wasting: It is always present. The child is often
weak, hypotonic and unable to stand or walk.
• Skin changes: The skin lesions consist of increased
pigmentation, desquamation and dyspigmentation.
Pigmentation may be confluent resembling flaky paint
or in individual enamel spots. The distribution is
typically on buttocks, perineum and upper thigh.
Petechiae may be seen over abdomen. Outer layers of
skin may peel off and ulceration may occur. The lesions
may sometimes resemble burns. Fig. 7 .6: A child with severe acute malnutrition. Note the
• Mucous membrane lesions: Smooth tongue, cheilosis and (a) dull, lustreless, sparse hair; temporal hollowing; loss of buccal
angular stomatitis are common. Herpes simplex pad of fat; anxious look; (bl Loose folds of skin in the gluteal
stomatitis may also be seen. region giving a 'baggy pant' appearance
Nutrition 197-
• Hair: Changes include dyspigmentation, loss of managed in hospital. The management of low birth weight
characteristic curls and sparseness over temple and infants is discussed in Chapter 8.
occipital regions. Hair lose their lustre and are easily
pluckable. A flag sign which is the alternate bands of Mild and Moderate Malnutrition
hypopigmented and normally pigmented hair pattern Mild and moderate malnutrition make up the greatest
is seen when the growth of child occurs in spurts. portion of malnourished children and account for >80%
• Mental changes: Includes unhappiness, apathy or of malnutrition associated deaths. It is, therefore, vital to
irritability with sad, intermittent cry. They show no intervene in children with mild and moderate malnutrition
signs of hunger and it is difficult to feed them. at the community level before they develop complications.
• Neurological changes: Changes such as tremors are seen The mainstay of treatment is provision of adequate amounts
during recovery. ofprotein and energy; at least 150 kcal/kg/day should be given.
• Gastrointestinal system: Anorexia, sometimes with Nutritious home food is recommended. The ICDS
vomiting, is the rule. Abdominal distension is programme provides extra ration for such children.
characteristic. Stools may be watery or semisolid, bulky In order to achieve these high energy intakes, frequent
with a low pH and may contain unabsorbed sugars. feeding (up to seven times a day) is often necessary.
• Anemia: Nutritional anemia is almost always associated. Because energy is so important and because carbohydrate
• Cardiovascular system: The findings include cold, pale energy sources are bulky, oil is usually used to increase
extremities due to circulatory insufficiency and are the energy in therapeutic diets. Nutrient-dense foods
associated with prolonged circulation time, bradycardia, enable children to consume and maximize the absorption
diminished cardiac output and hypotension. of nutrients in order to fulfil their requirements of energy
• Renal function: Glomerular filtration and renal plasma and all essential nutrients.
flow are diminished. There is aminoaciduria and According to WHO, animal-source foods are more
inefficient excretion of acid load. likely to meet the amino acid and other nutrient needs of
recovering children. Milk and eggs are excellent animal
Marasmic Kwashiorkor origin foods for children. Plant-source foods, in particular
legumes or a combination of cereals and legumes, also
It is a mixed form of undernutrition and manifests as
have high-quality proteins, although they may also
edema occurring in children who may or may not have
contain some anti-nutrients such as phytates, tannins or
other signs of kwashiorkor and have varied manifestations
inhibitors of digestive enzymes, which may limit the
of marasmus.
absorption of some micronutrients, particularly minerals.
Severe Acute Malnutrition [SAM] It is recognized increasingly that a relatively small
increase over normal protein requirements is sufficient
This special classification is recommended by WHO for for rapid catchup growth, provided energy intake is high.
identifying and managing children with life threatening A protein intake of 3 g!kg/day is sufficient. Milk is the most
undernutrition in public health programme settings. frequent source of the protein used in therapeutic diets,
Children with SAM have a mix of features of marasmus though other sources, including vegetable protein
and kwashiorkor. mixtures, have been used successfully. Adequate minerals
Severe acute malnutrition (SAM) among children and vitamins should be provided for the appropriate
6-59 months of age is defined by WHO and UNICEF as duration. The best measure of the efficacy of treatment of mild
any of the following three criteria: and moderate malnutrition is weight gain.
i. Weight-for-height below -3 standard deviation
(<-3SD) on the WHO Growth Standard; or Severe Acute Malnutrition (SAM):
ii. Presence of bipedal edema; or Children 6 to 59 Months
iii. Mid upper arm circumference (MUAC) below 11.5 cm. The World Health Organization has developed guidelines
In a child below 6 months of age, the MUAC is not used for the management of severe acute malnutrition (SAM)
as a criterion. and these have been updated in 2013. Guidelines are
Children with SAM have a high risk of death. In mainly for children of more than 6 months of age.
addition to debilitating undernutrition, they often have Once a child, 6 months or older, is diagnosed as SAM,
serious infections such as diarrhea, pneumonia, sepsis, she/he should be thoroughly assessed by a physician for
malaria and skin infections. They require urgent attention. complications by looking for severe edema (+++), lack of
appetite, medical complications on clinical examination
(e.g. severe anemia, pneumonia, diarrhea, dehydration,
MANAGEMENT OF MALNUTRITION
cerebral palsy, tuberculosis, HIV, heart disease etc.) and
The management of malnutrition depends on its severity. danger signs according to IMNCI algorithm (Fig. 7.7). If
While mild to moderate malnutrition can be managed on any of these are present, it is classified as complicated
ambulatory basis, severe malnutrition is preferably SAM, and the child is referred for inpatient management.
-9 8 Essential Pediatrics
• •
oil with added minerals and vitamins. RUTF has a pasty,
I smooth consistency, and good taste. It is easy for the child
to eat and digest. RUTF can be locally produced or be
No Yes
i i
commercially available.
Caregiver should wash hands and utensils used for
Uncomplicated SAM Complicated SAM feeding. Breastfeeding should be continued, if the child is
breastfed. The caregiver lovingly engages the child, talks
Supervised home Inpatient management to her, plays with her and makes feeding exercise an
management in a facility
interactive affair. In addition, the child should be provided
Fig. 7.7: Approach to child with severe acute malnutrition sensory stimulation (play, physical activity, laughter,
exposure to colors and shapes, storytelling, massage, etc.).
If the above mentioned signs are absent, the child has Optimum home management of a child with SAM is
uncomplicated SAM and can be managed in the outpatient not possible without effective support by the health
setting with care at home (Fig. 7.7). Good appetite is worker. Families will invariably need close facilitation and
critically important in home care of the child with SAM guidance by the health worker (ASHA ANM or AWW).
because oral intake of adequate energy dense food is the A home contact every day initially, and then twice a week
fundamental requirement for recovery. is essential (Panel 1).
Supervised Home Management of Uncomplicated SAM The child should be monitored by health workers for
signs of undernutrition (weight, height, MUAC, edema,
Children with uncomplicated SAM can be managed at anemia, etc.) every week.
home provided: In addition to nutrition, every child on SAM treatment
• Family is counseled and fully engaged. should receive the following interventions: an antibiotic
• Community health worker(s) and peer counselors are course (amoxicillin for 5 days), mega dose of vitamin
involved to support the family. (100 000 units) in the presence of clinical deficiency
• Supply of adequate home food and ready to use (xerophthalmia, Bitot's spots or keratomalacia), and
therapeutic food (RUTF), if possible. albendazole single dose (for children over 2 years of age).
• Periodic monitoring for growth and medical condition (It may be noted that RUTF contains appropriate
can be ensured. supplements of minerals and vitamins). The child should
Table 7.9: Composition and nutrition value of the standard ready to use therapeutic food (RUTF)
Composition Food value per 100 g
Peanut paste 30% Energy 543 kcal
Sugar 29% Nutrients
Milk solids 20% Protein 15 g
Vegetable oil 18% Lipids 35 g
With added mineral mix 1 , vitamin mix2 , emulsifier and antioxidant Carbohydrates 43 g
1
Minerals per 100 g: Calcium 400 mg, phosphorus 400 mg, potassium 1100 mg, magnesium 110 mg, sodium <290 mg, iron 10 mg, zinc 12 mg,
copper 1.5 m, iodine 100 µg, selenium 30 µg.
2
Vitamins per 100 g: vitamin A 0.9 mg, vitamin 0 3 18 µg, vitamin K 21 µg, vitamin E 27 µg, vitamin C 54 mg, vitamin 8 1 0.5 mg, vitamin 82 1.8 mg,
vitamin 8 6 0.7 mg, vitamin 8 12 1.6 µg, niacin 5.8 mg, Ca-D pantothenate 3 mg, folic acid 225 µg, biotin 70 µg.
Nutrition 99-
1. Hypoglycemia
2. Hypothermia
3. Dehydration
4. Electrolytes
5. Infection
No iron With iron
6. Micronutrients
7. Initiate feeding
8. Catch-up growth
9. Sensory stimulation
Fig. 7 .8: The time frame for initiating and achieving l O steps
-1001 Essential Pediatrics
which can be dangerous and may lead to heart failure. started at 0.3-0.5 mEq/kg/hr infusion of potassium
In case of signs of overhydration, ORS should be stopped chloride in intravenous fluids, preferably with continuous
immediately and child reassessed after one hour. On the monitoring of the ECG.
other hand a decrease in the heart rate and respiratory Once severe hypokalemia is corrected, all severely
rate (if increased initially) and increase in the urine malnourished children need supplemental potassium at
output indicate that rehydration is proceeding. The 3-4 mEq/kg/day for at least 2 weeks. Potassium can be
return of tears, a moist oral mucosa, less sunken eyes given as syrup potassium chloride; the common
and fontanelle and improved skin turgor are also preparation available has 20 mEq of potassium/15 mL.
indicators of rehydration. Once any four signs of On day 1, 50% magnesium sulfate (equivalent to
hydration (child less thirsty, passing urine, tears, moist 4 mEq/mL) should be given at 0.3 mL/kg to a maximum
oral mucosa, eyes less sunken, faster skin pinch) are of 2 mL intramuscularly. Thereafter, 0.8-1.2 mEq/kg
present, ORS for rehydration must be stopped and magnesium should be given orally as a supplement mixed
continued to replace the ongoing losses. with feeds.
Severe dehydration with shock: It is important to recognize
severe dehydration in malnourished children. Severe Step 5: Treat/Prevent Infection
dehydration with shock is treated with intravenous fluids. Infection may not produce the classical signs of fever and
Ideally, Ringer lactate with 5% dextrose should be used tachycardia in severely malnourished children. Instead,
as rehydrating fluid. If not available, half normal saline severe infection may be associated with hypothermia.
(N/2) with 5% dextrose or Ringer lactate alone can be Localizing signs of infection are often absent. The most
used. After providing supplemental oxygen, the common sites for infection are the skin, the alimentary
rehydrating fluid should be given at a slow infusion rate tract, the respiratory tract (including the ears, nose and
of 15 mL/kg over the first hour with continuous throat) and the urinary tract. Majority of the infections
monitoring of pulse rate, volume, respiratory rate, and septicemia are caused by gram-negative organisms.
capillary refill time and urine output. Therefore, all severely malnourished children should be
If there is improvement (pulse slows, faster capillary assumed to have a serious infection on their arrival in
refill) at the end of the first hour of IV fluid infusion, a hospital. In addition, hypoglycemia and hypothermia are
diagnosis of severe dehydration with shock should be considered markers of severe infection in children.
considered and the rehydrating fluid repeated at the same The following investigations are done for identifying
rate of 15 mL/kg over the next hour. This should be infections: (i) Hb, TLC, DLC, peripheral smear, (ii)
followed by reduced osmolarity ORS at 5-10 mL/kg/hr, urinalysis and culture, (iii) blood culture, (iv) chest X-ray,
either orally or by nasogastric tube. Patients should be (v) Mantoux test, (vi) gastric aspirate for AFB, (vii)
monitored for features of overhydration and cardiac peripheral smear for malaria (in endemic areas), and (viii)
decompensation. CSF examination (if meningitis is suspected).
All children with suspected infection should be treated
Septic shock: If at the end of the first hour of IV with broad spectrum parenteral antibiotics; ampicillin and
rehydration, there is no improvement or worsening, septic gentamicin or amikacin (Table 7.11). Antimalarial and
shock must be considered and appropriate treatment anti tuberculous treatment should only be given when the
started. particular conditions are diagnosed.
Response to treatment will be indicated by resolution
Step 4: Correct Electrolyte Imbalance
of initial symptoms and signs of infection, if any.
In severely malnourished children excess body sodium The child's activity, interaction with parents and appetite
exists even though the plasma sodium may be low. should improve. If there is no improvement or
Sodium intake should be restricted to prevent sodium deterioration of the symptoms/signs of infection, the
overload and water retention during the initial phase of child should be screened for infection with resistant
treatment. Excess sodium in the diet may precipitate bacterial pathogens, tuberculosis, HIV and unusual
congestive cardiac failure. pathogens.
All severely malnourished children have deficiencies
of potassium and magnesium, which may take two weeks Prevention of hospital acquired infection: The health care
or more to correct. Severely malnourished children may personnel should follow standard precautions. The
develop severe hypokalemia and clinically manifest with effectiveness of hand hygiene should be emphasized to
weakness of abdominal, skeletal and even respiratory all health care providers, attendants and patients. It is
muscles. This may mimic flaccid paralysis. Electro essential that adequate safety measures are taken to
cardiography may show ST depression, T waves inversion prevent the spread of hospital acquired infections, since
and presence of U waves. If serum potassium is <2 mEq/L these children are at higher risk of acquiring infections
or <3.5 mEq/L with ECG changes, correction should be due to their compromised immune status.
-1041 Essential Pediatrics
Step 6: Correct Micronutrient Deficiencies less than 4 g/ dL or between 4 and 6 g/ dL but with
All severely malnourished children have vitamin and respiratory distress, a blood transfusion should be given
mineral deficiencies. Micronutrients should be used as an with whole blood 10 mL/kg bodyweight slowly over
adjunct to treatment in safe and effective doses. Up to 3 hours. Furosemide should be given at the start of the
twice the recommended daily allowance of various transfusion. If the severely anemic child has signs of
vitamins and minerals should be used. Although anemia cardiac failure, packed cells rather than whole blood
is common, iron should not be given initially due to danger should be transfused.
of promoting free radical generation and bacterial The hemoglobin concentration may fall during the first
proliferation. It should be added only after a week of week of treatment. This is normal and no transfusion
therapy when the child has a good appetite and starts should be given. In mild to moderate anemia, iron should
gaining weight. be given for two months to replete iron stores but this
Vitamin A deficiency is not an infrequent association should not be started until after the initial stabilization
and is an important cause of blindness caused by phase has been completed.
keratomalacia. Vitamin A should therefore be given to all
severely malnourished children on day 1 at 50,000 IU, Step 7: Initiate Reteeding
100,000 IU and 200,000 IU for infants 0-5 month, 6-12 Feeding should be started as soon as possible with a diet
months and children>1 year of age unless there is definite which has osmolarity less than 350 mOsm/L; lactose not
evidence that a dose has been given in the last month. In more than 2-3 g/kg/day; appropriate renal solute load
presence of xerophthalmia, the same dose should be (urinary osmolarity <600 mOsm/L); initial percentage of
repeated on the next day and 2 weeks later. Children calories from protein of 5%; adequate bioavailability of
>1 year but weighing <8 kg should receive half the age micronutrients and low viscosity. The preparation should
related dose. In presence of clinical evidence of be easy to prepare and socially acceptable and there
xerophthalmia the administration of vitamin A should be should be facilities for adequate storage, cooking and
considered an emergency as the changes may progress to refrigeration.
keratomalacia within hours.
Children with SAM receiving F-75, F-100 or RUTF Start cautious feeding: The suggested starter formulae
complying with WHO specifications do not need vitamin are usually milk based, such as starter F-75 diet
A supplementation because these preparations already (containing with 75 kcal/100 mL). The protein content is
contain sufficient vitamin A. 0.9 g of protein/100 mL. Feeding should be started with
Vitamin K should be administered in a single dose of F-75 as soon as possible as frequent small feeds. If child
2.5 mg intramuscularly at the time of admission. Daily is unable to take orally with a cup and spoon or takes
multivitamin supplements containing thiamine 0.5 mg/ <80% of the target intake, nasogastric feeds should be
1000 kcal, riboflavin 0.6 mg/1000 kcal and nicotinic acid initiated. Breastfeeding should be continued ad libitum.
(niacin equivalents) 6.6 mg/1000 kcal should be given. It Older children could be started on cereal based diets
is better to give a formulation that is truly multivitamin (Table 7.12).
(e.g. one that has vitamin A, C, D, E and B12). Folic acid One should begin with 80 kcal/kg/day and gradually
1 mg/day (5 mg on day 1), zinc 2 mg/kg/day and copper increase to 100 kcal/kg/day. To fulfill this, one should
0.2-0.3 mg/kg/day should be given daily. Iron 3 mg/kg/ start with 2 hourly feeds of 11 mL/kg/feed. Night feeds
day should be added once child starts gaining weight, after are essential. The volume of feeds are increased gradually
the stabilization phase. while decreasing the frequency of administration. The
Emergency treatment of severe anemia: If a severely calories are increased only after the child can accept the
malnourished child has severe anemia with a hemoglobin increased volume of feeds.
Nutrition 1105-
Step 8: Achieve Catch-up Growth with F-100 Diet and RUTF offered 200 mL/kg/ day of F-100 diet. Breastfeeding
For catch-up growth, energy and protein intake has to be should be continued Ad libitum.
enhanced further; F-75 diet (F-75 kcal/100 mL) would not Once the child achieves rapid weight gain, F-100 should
be enough. Starter F-75 feeds should be gradually replaced be changed to RUTF and gradually to home food.
with feeds which have a higher calorie density (100 kcal/ The daily amount of RUTF to be consumed varies
100 mL) and have at least 2.5-3.0 g protein/100 mL. These according to body weight as follows: 3-4.9 kg: 105-130 g;
feeds are called F-100 diets or Catch-up diets (Table 7.13). 5-6.9 kg: 200-260 g; 7-9.9 kg: 260-400 g and 10-14.9 kg:
Once appetite returns, increasing intakes of F-100 400-460 g. This amount is to be given along with plenty
should be encouraged. It is recommended that each of water in 2-3 hourly feeds. The child should continue to
successive feed is increased by 10 mL until some is left receive other foods and breastfeeding during medical
uneaten. The frequency of feeds gradually decreased to nutrition therapy with RUTF.
6 feeds I day and the volume increased till the child is being Home foods should be added as soon as possible to
prepare the child for home foods at discharge. They should
Table 7.13: Catchup diets have comparable energy and protein concentrations once
the catchup diets are well tolerated. Khichri, dalia, banana,
Diet contents F-100 F-100
(per 100 ml) Catch-up Catch-up
curd-rice and other culturally acceptable and locally
(cereal based) available diets can also be offered liberally.
Cow milk/toned dairy milk (ml) 95 75 Special diets for diarrhea: For children with persistent
(approximate measure of one katori) (3/4) (1/2) diarrhea, who do not tolerate low lactose diets, lactose
Sugar (g) 5 2.5 free diet can be started. In these diets, carbohydrates (rice,
(approximate measure of one (1) (1/2) sugar and glucose) can be given in varying proportions
level teaspoon) according to the patients' individual tolerance to achieve
Cereal: Puffed rice (g) 7 optimal balance between osmolarity and digestibility.
(approximate measure of one (2) Monitoring progress during treatment: If there is a good
level teaspoon)
weight gain of> 10 g/kg/day, the same treatment should
Vegetable oil (g) 2 2
be continued till recovery. If there is a moderate weight
(approximate measure of one (1/2) (1/2)
gain of 5-10 g/kg/day; food intake should be checked
level teaspoon)
and the children should be screened for systemic infection.
Water to make (ml) 100 100
In case of poor weight gain of <5 g/kg/day possible causes
Energy (kcal) 101 100
like inadequate feeding, untreated infection, psychological
Protein (g) 2.9 2.9
problems and coexisting infections like tuberculosis and
Lactose (g) 3.8 3
HIV should be looked for and managed appropriately.
-1061 Essential Pediatrics
Step 9: Provide Sensory Stimulation and a. Any serious clinical condition or medical complication
Emotional Support as outlined for infants who are 6 months of age or older
Delayed mental and behavioral development often occurs with severe acute malnutrition;
in severe malnutrition. In addition to the above b. Recent weight loss or failure to gain weight;
management, one should encourage a cheerful, c. Ineffective feeding (attachment, positioning and
stimulating environment; structured play therapy for at suckling) directly observed for 15-20 min, ideally in a
least 15-30 min/day; physical activity as soon as the child supervised separated area;
is well enough and tender loving care. d. Any pitting edema;
e. Any medical or social issue needing more detailed
Step 10: Prepare for Follow-up assessment or intensive support (e.g. disability,
Ideally, 6-8 weeks of hospitalization is required for depression of the caregiver, or other adverse social
optimum recovery. SAM children admitted to hospital can circumstances);
be transferred to outpatient care when their medical Infants less than 6 months of age with SAM should
complications have settled, edema, is resolving and they receive the same general medical care as infants with
have a good appetite, they are consuming adequate RUTF, severe acute malnutrition who are 6 months of age or
and are clinically well and alert. older:
The decision to transfer children from inpatient to a. Infants with severe acute malnutrition who are
outpatient care should be determined by their clinical admitted for inpatient care should be given parenteral
condition and not on the basis of specific anthropometric antibiotics to treat possible sepsis and appropriate
outcomes such as a specific mid-upper arm circumference treatment for other medical complications such as
or weight-for-height/length. tuberculosis, HIV, surgical conditions or disability;
National guidelines recommend treatment for b. Infants with severe acute malnutrition who are not
helminthic infections should be given to all children with admitted should receive a course of broad-spectrum
SAM before discharge. Give a single oral dose of oral antibiotic, such as amoxicillin, in an appropriately
Albendazole 200 mg of for children aged 12-23 months, weight adjusted dose.
400 mg for children aged 24 months or older. Feeding approaches for infants who are less than
6 months of age with severe acute malnutrition should
Post-Discharge Care at Home prioritize establishing, or re-establishing, effective
A child with SAM may be considered to have completed exclusive breastfeeding by the mother.
treatment when: Infants who are admitted:
• There is no edema for at least 2 weeks, plus a. Should be breastfed where possible and the mothers
• Weight-for-height (or length) reaches -2 SD or higher should be supported to breastfeed the infants. If an
on WHO Growth Standard or mid-upper-arm infant is not breastfed, support should be given to the
circumference is more than 12.5 cm mother to re-lactate
After discharge, the principles of care are the same for b. Should also be provided a supplementary feed:
supervised home care of uncomplicated SAM (as above). supplementary suckling approaches should, where
This is a very important phase and full support needs to feasible, be prioritized; for infants with severe acute
be extended to the family by involving the frontline malnutrition but no edema, expressed breast milk
workers and community. The treatment of the child is not should be given, and, where this is not possible,
complete till the weight-for-height and MUAC reaches commercial (generic) infant formula or F-75 or diluted
normal range (see below). F-100 may be given (prepared F-100 should be further
The caregiver should be advised to bring child back diluted by adding 30% water), either alone or as the
for regular follow-up checks, ensure booster immuni supplementary feed together with breast milk; and for
zations, make sure that vitamin A is given every 6 months, infants with severe acute malnutrition and edema,
feed frequently with energy and nutrient dense foods and infant formula or F-75 should be given as a supplement
give structured play therapy. to breast milk;
Until the above is reached, the child must be under c. Should not be given undiluted F-100 at any time (owing
constant care at hospital and/or home by a frontline health to the high renal solute load and risk of hypematremic
team. Support to the family must be continued during this dehydration); prepared F-100 should be further diluted
phase and after discharge from treatment. by adding 30% water.
d. If there is no realistic prospect of being breastfed, should
Severe Acute Malnutrition: Under 6 Months of Age be given appropriate and adequate replacement feeds
Infants less than 6 months of age with SAM and any of such as commercial (generic) infant formula, with
the following complicating factors should be admitted for relevant support to enable safe preparation and use,
inpatient care: including at home when discharged.
Nutrition 107-
e. Assessment of the physical and mental health status of Panel 2: Preventing undernutrition in children
mothers or caregivers should be promoted and relevant
treatment or support provided Individual Level Action
Mother
Infants less than 6 months of age with SAM and have
been admitted to inpatient care can be transferred to • Care of the adolescent girl
outpatient care when: • Childbirth after 20 years
• Spacing between pregnancies
a. All clinical conditions or medical complications,
• No more than 2 children
including edema, are resolved, and
• Iron and folic acid to ensure good hemoglobin
b. The infant has good appetite, is clinically well and alert, • Antenatal checks as per national program
and • Additional food and micronutrients (especially iron and folic
c. Weight gain on either exclusive breastfeeding or acid) in pregnancy
replacement feeding is satisfactory, e.g. above the
Child
median of the WHO growth velocity standards or more
• Initiation of breastfeeding within one hour
than 5 g/kg/day for at least 3 successive days, and
• Exclusive breastfeeding for first 6 months, continuing till
d. The infant has been checked for immunizations and 2 years or more
other routine interventions, and • Special support to low birth weight babies for breastfeeding
e. The mother or caregiver is linked with needed and kangaroo mother care
community-based follow-up and support • Complementary feeding introduction at 6 months
For infants who are less than 6 months of age with • Optimum intake of food that is balanced, energy-dense and
severe acute malnutrition and who do not require of good quality
inpatient care, or whose caregivers decline admission for • Hygiene, handwashing
assessment and treatment: • Full immunization especially, measles, BCG, rotavirus,
a. Counseling and support for optimal infant and young H. influenzae and pneumococcal
child feeding should be provided, based on general • Prompt treatment of diarrhea with ORS and zinc
recommendations for feeding infants and young • Prompt treatment of pneumonia and other illnesses
children, including for low-birth-weight infants; • Growth monitoring and periodic checks
b. Weight gain of the infant should be monitored weekly Adolescent girls: Future mothers
to observe changes; • Optimum nutrition
c. If the infant does not gain weight, or loses weight while • Education in parenting and mothercraft
the mother or caregiver is receiving support for • Marriage after 18 years of age
breastfeeding, then he or she should be referred to Society Level Action
inpatient care; • Safe water and sanitation
d. Assessment of the physical and mental health status of • A culture of good nutrition
mothers or caregivers should be promoted and relevant • Maternity and child care leave to enable women to breastfeed
treatment or support provided. and to take care of infants and children
• Creches for children of working women
Preventing Undernutrition • Promoting breastfeeding at workplace
Since childhood undernutrition is multifactorial, it can • Cash support to pregnant and lactating women (as being
only be prevented through interventions across sectors. provided by the government)
Action is required at the individual and societal level • Socio-economic development, high income, equity
(Panel 2). Health and wellbeing of girls, women and • Education of women and men
children must be ensured. Underlying social determinants • Women's empowerment
such poverty, illiteracy, discrimination and social • Food security at the household level
insecurity must be addressed. Convergence of health • Nutrition promoting agriculture
programs (antenatal care, facility birth, home based
newborn care, immunization, IMNCI, etc.) with ICDS provided at a center called the 'Anganwadi'. A package
initiatives (feeding counseling, supplementary nutrition of six services is provided under the ICDS Scheme:
and preschool education) must converge. a. Supplementary nutrition for mother and the child. The
norms are given in Table 7.14.
Integrated Child Development Services {/CDS) b. Immunization of pregnant women and infants as per
The ICDS program seeks to directly reach out to children, the national program.
below six years, especially from vulnerable groups and c. Nonformal preschool education. Stimulating learning.
remote areas. The Scheme provides an integrated d. Health check-up. This includes health care of children
approach for converging basic services through less than six years of age, antenatal care of expectant
community-based workers and helpers. The services are mothers and postnatal care of nursing mothers. These
-1oal Essential Pediatrics
Table 7.14: Norms for supplementary nutrition in ICDS • Reduce prevalence of anemia amongst women and
adolescent girls (15-49 years)@3% per annum
Beneficiaries Energy Protein
Under the POSHAN (PM's Overarching Scheme for
kcal (g) Holistic Nutrition) Abhiyaan the focus is on health and
Children (6 to 72 months) 500 12-15 nutrition in first 1000 days of life, convergence across
Severely malnourished children (SAM) 800 20-25 sectors (including Swachh Bharat and Health), IT driven
(6 to 72 months) tracking of beneficiaries apart from growth monitoring.
Pregnant women and lactating mothers 600 18-20 A major thrust of the mission will be to create an
Source: http://icds-wcd.nic.in/icds/icds.aspx unprecedented Jan Andolan for nutrition and health.
services are provided by the ANM and medical officers Suggested Reading
under the RCH programme. The various health services • Bhandari N, Mohan SB, Bose A, et al. Efficacy of three feeding
include regular health check-ups, immunization, regimens for home-based management of children with
management of malnutrition, treatment of diarrhea, uncomplicated severe acute malnutrition: a randomized trial in
India. BMJ Global Health 2016;1:e000144. doi:10.1136/bmjgh-2016-
deworming and distribution of simple medicines. 000144.
e. Referral services. During health check-ups and growth • Dalwai S, Choudhury P, Bavdekar SB, Dalal R, et al. Indian
monitoring, sick or malnourished children are referred Academy of Pediatrics. Consensus statement of the Indian
to the primary health center or its subcenter. Academy of Pediatrics on integrated management of severe acute
f. Nutrition and health education. Healthy behaviors and malnutrition. Indian Pediatr 2013;50:399--404.
detection and treatment of sickness. • National Family Health Survey 4. http://rchiips.org/NFHS/pdf/
NFHS4/lndia.pdf
Under the POSHAN Abhiyaan, a flagship mission of
• WHO Child Growth Standards and the identification of severe
the Prime Minister launched in February 2018, a new acute malnutrition in infants and children. A joint statement by
impetus has been given to nutrition program. The goals WHO and UNICEF. 2009. Accessed from http//who.int/nutrition/
for this three-year mission are to: publications/severemalnutrition/9789241598163-eng.pdf
• Reduce stunting in children (0-6 years)@2% per annum • WHO. Guideline updates on the management of severe acute
malnutrition in infants and children, 2013.
• Reduce under-nutrition (underweight prevalence) in
• World Health Organization. Technical note Supplementary foods
children (0-6 years)@ 2% per annum
for the management of moderate acute malnutrition in infants and
• Reduce low birth weight (LBW)@ 2% per annum children 6-59 months of age. 2012
• Reduce prevalence of anemia amongst young children • World Health Organization. The management of nutrition in major
(6-59 months)@ 3% per annum emergencies. Geneva: World Health Organization; 2000
Chapter
8
Micronutrients in
Health and Disease
Rajni Sharma • Arvind Bagga
Vitamins are organic compounds, required in small Intakes of micronutrients recommended by the National
amounts, for maintenance of health and normal growth that Academy of Science 2006 are available at www.nap.edu.
are not synthesized in the body and must be obtained from Intakes proposed by the Indian Council of Medical
the diet. They can be categorized into fat-soluble (A, D, E, Research in 2010 are listed in Table 6.1 and are also
K) and water-soluble forms (B complex vitamins, C and available at icmr.nic.in/final RDA-2010.pdf
folate). The former control protein synthesis at either
transcriptional or post-transcriptional level and perform FAT-SOLUBLE VITAMINS
diverse biochemical functions, as hormones (e.g. vitamin
D), antioxidants (e.g. vitamin E) and regulators of tissue Vitamin A
growth and differentiation (e.g. vitamin A). Several Vitamin A (retinol) is derived from natural plant pigments
vitamins (e.g. B complex vitamins) function as precursors called carotenoids (provitamin A) that are converted to
for enzyme cofactor biomolecules (coenzymes) that act as retinol in the body and stored as retinol palmitate in the
catalysts and substrates in metabolism. Breast milk is liver. Retinol is further converted to the active forms of
deficient in vitamins D and K and exclusively breastfed vitamin A: Retinal and retinoic acid.
infants must be supplemented with these vitamins (Box 8.1). Being a fat-soluble vitamin, vitamin A is absorbed as a
Certain minerals are essential to support biochemical part of chylomicrons.
processes involved in cell structure and function.
Important minerals include calcium, chloride, cobalt, Physiological Functions
copper, iodine, iron, magnesium, manganese, molybdenum, Retinol is converted to retinal which plays an important
nickel, phosphorus, potassium, selenium, sodium, sulfur role in vision especially night vision. Within the eye, 11-
and zinc. The amount required varies from > 100 mg/day cis-retinal, an isomer of retinal, is bound to rhodopsin (rod
(major minerals including sodium, potassium, chloride, cells) and iodopsin (cones). As light enters the eye, 11-cis
calcium, magnesium and phosphorus) to <100 mg/day retinal is isomerized to the all-trans form. The all-trans
(trace minerals including iron, copper, zinc). Ultra-trace retinal dissociates from the opsin in a series of steps called
minerals are required in miniscule amounts ( <1 mg/day). bleaching. This isomerization induces a nervous signal
Marginal or severe imbalances in trace elements are risk along the optic nerve to the visual center of the brain.
factors for several diseases. In addition to deficiencies of Subsequently, the all-trans-retinal is recycled and
iron and iodine, features of deficiency of copper, zinc and converted to 11-cis-retinal form via a series of enzymatic
selenium are recognized. reactions. Deficiency in vitamin A inhibits the reformation
of rhodopsin and leads to night blindness. Retinal and its
Box 8.1: Breast milk and vitamins derivative retinoic acid bind to intracellular receptor,
Breast milk is the complete food for infants. However, breast regulate gene expression and induce the synthesis of
milk is deficient in vitamins D and K. proteins involved in growth and cell differentiation.
Breast milk contains only 30--40 IU /L of vitamin D, whereas Retinol is also required for production of glycoproteins
the RDA is higher. Exclusively breastfed babies require vitamin and mucus and helps to maintain the integrity of epithelial
D supplementation in the dose of 400 IU / day to prevent tissues. Vitamin A deficiency leads to drying of epithelial
rickets. surfaces and excessive keratin formation of the surface.
Vitamin K is produced by the gut microflora. It may take
sometime for a newborn gut to be colonized by bacteria and Sources
start producing the vitamin. All babies should receive vitamin
Carotenoids (provitamin A) are found in green and yellow
K at birth to prevent hemorrhagic disease of the newborn.
plants including carrots, dark-green leafy vegetables,
109
110 Essential Pediatrics
the coverage. Hence, a dose of 100,000 IU is given with chylomicrons and transported to the liver. Being a fat
measles vaccine at 9 months and 200,000 IU with the DPT soluble vitamin, vitamin D absorption is decreased in
booster at 15-18 months. In endemic areas, 3 more doses conditions of fat malabsorption such as chronic
are administered at 24, 30 and 36 months. Dietary pancreatitis, cystic fibrosis, etc.
improvement is necessary to prevent vitamin A deficiency. In the liver, the enzyme 25a-hydroxylase hydroxylates
Children with measles and severe malnutrition should vitamin D2 and D3 to form 25-hydroxyvitamin D2 [250HD2
receive vitamin A at 100,000 IU, if <1-year-old and 200,000 or ergocalcidiol] and 25-hydroxyvitamin D3 [250HD3 or
IU, if older. cholecalcidiol], respectively. This biochemical step is
substrate dependent and occurs without any negative
Carotenemia feedback control. 250HD (predominantly in the form of
Beta-carotene is an important precursor of vitamin A in cholecalcidiol) is then released into the bloodstream and
vegetable-based diets; 10 µg �-carotene has the biological has a biological half-life of approximately 3 weeks. Due
potency of 1 µg retinol. Excessive dietary intake of carotene to its long half-life, serum cholecalcidiol level is considered
containing foods, most commonly carrots and carrot the biochemical marker for vitamin D status in the body.
containing products, can lead to deposition of carotenoids Cholecalcidiol (250HD3) undergoes further hydroxyla
in keratin and subcutaneous fat. At high plasma levels, tion in the kidneys by the enzyme la-hydroxylase to form
yellow pigmentation (carotenemia) shows in superficial 1,25-dihydroxyvitamin D3 [l,25(0H)iD3] or cholecalcitriol.
skin (face, palms and soles), but not in sclerae. The color Cholecalcitriol is the active form of vitamin D and affects
returns to normal within 2-6 weeks of discontinuing calcium homeostasis through its action on the intestine,
intake of carrots. kidney and bones. In the intestine, it increases absorption
of calcium by inducing the formation of calcium transport
Hypervitaminosis A and Teratogenicity proteins and intracellular calcium-binding protein
Vitamin A toxicity occurs ingesting more than 50,000 IU / (calbindin) in the enterocytes. In the kidney, cholecalcitriol
day of vitamin A for several months in the form of fish enhances calcium resorption in the renal tubules by a similar
liver oil, therapeutic vitamin preparations or, in mechanism. It decreases the activity of renal 1-a
adolescents, as retinol or retinoic acid for acne. Acute hydroxylase enzyme via feedback inhibition, and stimulates
manifestations include pseudotumor cerebri (vomiting, renal 24-hydroxylase enzyme activity (that inactivates both
irritability, bulging fontanel, diplopia, headache). Patients calcidiol and calcitriol). In the bone, calcitriol helps in
with chronic hypervitaminosis may have anorexia, dry stimulating osteoclast activity and proper mineralization
skin, alopecia, painful joints and hepatosplenomegaly. of bone. Thus, the overall effect of cholecalcitriol in the body
Vitamin A is teratogenic, if taken in high doses in early is to increase serum levels of calcium.
gestation. The WHO recommends that vitamin A in The activity of renal la-hydroxylase enzyme is affected
take during pregnancy should not exceed 3000 µg daily by other factors as well: Both parathyroid hormone and
or 7500 µg every week. low serum phosphate levels increase the activity of 1-a
hydroxylase, whereas the hormone fibroblast growth
Vitamin D factor-23 (FGF-23), produced by bone, decreases its activity
(Fig. 8.3).
Vitamin D, the 'sunshine vitamin', is produced in the
upper layers of the skin on exposure to solar ultraviolet B Sources
(UVB) radiation. Under normal conditions, endogenous The dietary sources of vitamin D include fish and fish oils,
synthesis of vitamin D is sufficient to meet the body's egg yolk and some plants. However, natural diet contains
needs. However, when endogenous production is low, very little vitamin D and adequate endogenous production
due to a variety of factors, diet becomes an important or dietary supplementation is essential to prevent
source of the vitamin. deficiency.
Adequate vitamin D synthesis in the skin depends on
Metabolism and Mechanism of Action various factors including time spent outdoors and the
There are two forms of vitamin D: Vitamin D 2 amount of clothing. The dermal pigment melanin
(ergocalciferol, made in plants) and D3 (cholecalciferol, decreases the amount of UVB rays that reach the epidermal
made in animals). Vitamin D3 is synthesized from layers containing the substrate, 7-dehydrocholesterol.
7-dehydrocholesterol in the dermis after exposure to UVB Hence, individuals with dark skin require more duration
solar irradiation of wavelength 290-315 nm. It is then of sun exposure to make the same amount of vitamin D.
bound to vitamin D-binding protein and transported to Moreover, the amount of UVB radiation reaching the skin
the liver. Vitamin D can also be derived from the diet from depends on the time of the day, latitude, season, cloud
either plant (vitamin D2) or animal (vitamin D3) sources. cover and presence of air pollutants. Excessive exposure
Dietary vitamin D is readily absorbed from the duodenum to sunlight does not increase vitamin D production as
by an active transport system and incorporated into previtamin D3 is degraded into inert products such as
112 Essential Pediatrics
�
l /
Vitamin D
Liver
25-hydroxylase
24,25-dihydroxyvitamin D 24-hydroxylase
25-hydroxyvitamin D
(inactive)
+ Kidney
_I
i1
1a-hydroxylase
Parathormone
1 + Low phosphorus
+ -::. - - - - - - - Fibroblast growth factor
Fig. 8.3: Vitamin D metabolism. Serum levels of fibroblast growth factor-23 are elevated in response to increased serum phosphate
and also inhibit the production of parathormone
lumisterol-3 and tachysterol-3, and vitamin 03 photo Pathophysiology: Vitamin D deficiency leads to
isomerizes to suprasterol and inert products. hypocalcemia which stimulates the parathyroid gland to
secrete parathormone (PTH). Increased PTH levels
Vitamin D Requirements stimulate osteoclastic activity of bone and help restore the
The daily requirement of vitamin Dis 10 µg (400 IU) per blood calcium levels to normal. However, PTH leads a
day in infants and 15 µg (600 IU) per day in children concomitant loss of phosphate from the kidney leading to
> 1 year age. When endogenous production is inadequate, low serum phosphate levels.
vitamin Dneeds to be supplied through dietary supplemen Under normal conditions of growth, the cartilaginous
tation. growth plate undergoes mineralization by enchondral
The risk factors that predispose to vitamin Ddeficiency calcification. In this process, the chondrocytes
include limited exposure to sunlight, full body clothing, hypertrophy and then undergo apoptosis followed by
dark skin, debilitation, living at high latitudes, disability mineralization. Adequate amount of phosphate is essential
and predominant indoor living. for the apoptosis of the chondrocytes. In the absence of
Breast milk is a poor source of vitamin D containing adequate phosphate, the chondrocytes continue to
only 30--40 IU per liter and exclusively breastfed infants hypertrophy and this leads to the characteristic swellings
are at high risk of developing vitamin D deficiency and at the growth plates. Mineralization of the bone is also
rickets unless supplemented. Therefore, exclusively decreased leading to osteomalacia and bending of weight
breastfed babies should receive 400 IU of supplemental bearing bones.
vitamin Dper day. Formula milk has 400 IU of vitamin D Osteomalacia is a term used for decreased mineraliza
per litre and children getting less than 1 litre formula per tion of the bony matrix and is seen both in children and
day also require supplementation. Pregnant and lactating adults, whereas rickets is a disease of growing bones.
mothers should receive 600 IU of vitamin D per day in Osteomalacia is different from osteoporosis; the latter
order to meet their daily requirements. refers to a proportionate loss of bone volume, both organic
matrix (osteoid) and mineral, which occurs most
Rickets commonly due to prolonged intake of corticosteroids.
Rickets is a disease of growing bone. It is derived from
the word 'wrickets' meaning 'twisted' referring to the Nutritional Rickets
characteristic bony deformities or 'bow legs' of rickets. The Vitamin Ddeficiency is the leading cause of rickets, both
most common cause of rickets is a nutritional deficiency in developing and developed countries. Though
of vitamin Dand less commonly, a dietary deficiency of nutritional rickets had once been virtually eradicated in
calcium or phosphorus. developed nations by fortification of milk or direct
Micronutrients in Health and Disease 1113-
administration of vitamin D, recent reports suggest that is an increased risk of fracture even with minimal trauma.
it is becoming increasingly common in exclusively Pelvic deformities can develop including outlet narrowing
breastfed infants particularly those who not get vitamin which can be troublesome for females at a later age by
supplements. Apart from poor dietary intake and increasing the risk of obstructed labor.
insufficient exposure to sunlight, vitamin D deficiency Evaluation: The initial evaluation of rickets includes
may result from various malabsorption syndromes, serum biochemistry and radiographs of the wrists and/
chronic liver disease and use of anticonvulsant drugs. or knee joints. Serum levels of calcium may be normal or
Anticonvulsant drugs and antitubercular drugs (isoniazid, low, serum phosphate will be low and alkaline phosphatase
rifampicin) induce hepatic cytochrome P450 oxidase that high. Radiologic changes are characteristically seen at the
leads to conversion of 250HD3 into its inactive metabolites. metaphysis. The first change is loss of normal zone of
As mentioned, nutritional rickets may also occur provisional calcification adjacent to the metaphysis seen
secondary to severe dietary deficiency of calcium that can as a blurring or a frayed appearance of the metaphyseal
occur with or without concomitant vitamin D deficiency. margin (fraying). Cartilage hypertrophy leads to widening
Dietary deficiency of phosphate is rare due to the of the growth plate giving the appearance of cupping and
widespread availability of phosphate in the diet but may widening of metaphyseal ends (splaying) (Fig. 8.5).
occur in preterm babies who have high phosphate Weight-bearing and stress on uncalcified bone gives rise
requirements for growth. to bowing of limbs. Eventually, a generalized reduction
Clinical features: The classical features of rickets include in bone density is seen (osteopenia).
swellings of the wrist and ankles and leg deformities in The diagnosis of vitamin D deficiency is based on low
the form of bow-legs (genu varum) or knock-knees (genu circulating levels of 250HD3• Values above 20 ng/mL are
valgum) (Fig. 8.4). From head to toe, the following signs considered normal, between 10 and 20 ng/mL are
may be seen: Frontal bossing, delayed closure of anterior insufficient and below 10 ng/mL are indicative of
fontanelle, craniotabes (soft skull bones), delayed dentition deficiency (Table 8.2).
and beaded appearance of the anterior costochondral Management: Treatment of nutritional rickets requires
junctions (rachitic rosary). A depression (termed Harrison administration of high doses of vitamin D. Previously, oral
sulcus) may be evident along the lower border of the chest bolus doses of vitamin D (also called Stoss therapy) were
at the site of insertion of the diaphragm which appears preferred which consisted of 60,000 IU of vitamin D daily
due to the pull of the diaphragm on the weakened chest or on alternate days to reach a maximum total dose of
wall. Apart from this, other features of rickets include 6,00,000 IU. There is now consensus to use lower daily
hypocalcemic seizures, muscle weakness, hypotonia, doses of 2000 IU, 3000-6000 IU, and 6000 IU for infants
failure to thrive and irritability (due to bony pains). There below 12 months, 1-12 years and more than 12 years,
VDDR type I: This condition is characterized by a enzyme is responsible for the breakdown of FGF-23 and
deficiency of the enzyme, 25-hydroxyvitamin D la enzyme deficiency leads to high FGF-23 levels and
hydroxylase. Reduced blood levels of calcium, normal to excessive renal loss of phosphate. FGF-23 also decreases
low phosphate and elevated alkaline phosphatase are the activity of renal la-hydroxylase. Therefore, the blood
characteristics. Blood levels of 25(0H)D3 are normal but levels of l,25(0H)iD3 are low despite hypophosphatemia
those of l,25(0H)iD3 are markedly decreased despite (which normally activates la-hydroxylase activity).
hypocalcemia.
Clinical features: Lower limb deformities, such as coxa
The clinical features are similar to vitamin D deficiency vara, genu valgum, genu varum and short stature, are
rickets and include hypotonia, growth failure, motor common in hypophosphatemic rickets. Abnormalities of
retardation (poor head control, delayed standing and maxillofacial region and premature fusion of cranial
walking), convulsions due to hypocalcemia, anemia and sutures may lead to deformities of skull. Dental
occasionally respiratory difficulty. Physical examination abnormalities are commonly seen including pulp
shows thickening of wrists and ankles, frontal bossing, deformities with intraglobular dentin, and frequent dental
widely open anterior fontanelle, rickety rosary, bony abscesses. Symptoms of hypocalcemia including tetany
deformities and positive Trousseau and Chvostek signs. and muscle weakness, which are generally seen in
Dentition is delayed and development of tooth enamel disorders of vitamin D metabolism, are absent in
impaired. hypophosphatemic forms. The mother of affected
The treatment of VDDR type I consists of physiological patient(s) may have bowing of legs and short stature or
doses of alpha-calcidiol or calcitriol (0.25 µg daily). Most fasting hypophosphatemia.
subjects require concomitant treatment with calcium with
or without phosphate supplements. With appropriate Evaluation: The level of serum calcium is normal or
therapy, the serum calcium levels rise and radiological slightly low (9-9.5 mg/dL), that of phosphate decreased
healing occurs within 6 to 8 weeks. (1.5-3 mg/dL). Serum alkaline phosphatase level is raised.
PTH levels are normal. Blood levels of l,25(0H)iD3 are
VDDR type II: The features are similar to VDDR type I. inappropriately low for the level of serum phosphate.
There is end organ resistance to l,25(0H)iD3• This leads Urinary phosphate excretion is increased with decreased
to virtual abolition of actions of l,25(0H)iD3, despite its tubular reabsorption of phosphate.
markedly raised levels in circulation (secondary to
Management: Oral phosphate and vitamin D supplements
hypocalcemia and low 24-hydroxylase activity).
are the mainstay of therapy. Phosphates are provided at a
Early onset of rickets, a high prevalence of alopecia and dosage of 30-50 mg/kg (total 1-3 g elemental phosphorus)
ectodermal defects (oligodontia, milia and epidermal divided into 5 to 6 equal parts and can be given in the
cysts) are characteristic. Hypocalcemia, secondary form of Joulie solution or as neutral phosphate effervescent
hyperparathyroidism, elevated circulating levels of 1, tablets. Joulie's solution contains 30.4 mg of phosphate/
25(0H)iD3 and an absence or decreased response to mL. Diarrhea is a frequent problem with higher doses.
vitamin D analogs are seen. The response to treatment in
Vitamin D supplementation is necessary for the healing
patients with VDDR type II is not satisfactory. An
of rickets. Treatment is started with alpha-calcidiol at a
occasional patient may get clinical and biochemical
dose of 25-50 ng/kg/day (maximum 2 µg/day) until there
improvement and radiological healing following long
is biochemical and radiological evidence of healing of
term administration of large amounts of intravenous or
rickets. Periodic monitoring of serum and urine levels of
oral calcium.
calcium and phosphate is essential. A level of serum
phosphate greater than 3.0 to 3.2 mg/dL is desirable.
Familial Hypophosphatemic Rickets
Normal level of serum phosphate is essential for Other Causes of Rickets
mineralization of the growth cartilage. Some inherited Chronic kidney disease: Patients with chronic kidney
clinical disorders lead to excessive loss of phosphate in disease have low l,25(0H) i D 3 levels due to poor
the urine with very low serum phosphate levels and can la-hydroxylase activity in the kidney. Rickets may
present as refractory rickets. The most common inheritance occasionally be the presenting manifestation of patients
pattern of these familial hypophosphatemic disorders is with tubulointerstitial disease. Serum levels of calcium
an X-linked dominant form with variable penetrance. are low and those of urea, creatinine, and PTH are
Rarely, an autosomal recessive inheritance or sporadic increased. In contrast to other causes of vitamin D
forms can also occur. deficiency, serum phosphate levels are high. Therapy
consists of restricting phosphate intake and providing
Pathogenesis: The gene for X-linked hyp ophosphatemic supplements of calcium and active vitamin D analogs.
rickets is termed the PHEX gene (phosphate regulating
gene with homology to an endopeptidases on the X Renal tubular acidosis: Proximal or distal renal tubular
chromosome) which produces an endopeptidase. This acidosis (RTA) are important causes of refractory rickets
116 Essential Pediatrics
Table 8.4: Essential B vitamins: Function, sources, deficiencies and at-risk groups
Vitamin Function Sources Daily requirement Deficiency At-risk groups
B 1 (Thiamine) Oxidative Human milk, <6 mo: 0.2 mg Beriberi: peripheral Groups with diets
decarboxylation cow milk, 6-12 mo: 0.3 mg neuritis, irritability, based on polished
of pyruvate unpolished grains, 1-3 yr: 0.5 mg paralysis, congestive rice, alcoholics
eggs, organ meats 4-8 yr: 0.6 mg heart failure
(liver, kidney), 9-13 yr: 0.9 mg Wernicke
legumes >14 yr: 1.2 mg encephalopathy
B2 (Riboflavin) Part of Meat, milk, eggs, <1 yr: 0.3 mg Photophobia, glossitis, Malabsorption states,
flavoproteins cereals and 1-3 yr: 0.5 mg cheilosis, angular deficient diets
FMN, FAD vegetables 4-8 yr: 0.6 mg stomatitis, seborrheic
9-13 yr: 0.9 mg dermatitis, corneal
>14 yr: 1.2 mg vascularization
B3 (Niacin) Forms cofactors Milk, eggs, cereals <1 yr: 2-4 mg Pellagra Groups on predomi-
NAD,NADP and leafy vegetables 1-3 yr: 6 mg nant maize-based
4-8 yr: 8 mg diet
9-13 yr: 12 mg
>13 yr: 16 mg
B6 (Pyridoxine) Synthesis of Yeast, sunflower <6 mo: 0.1 mg Peripheral Malabsorption states,
amino acids, seeds, wheat germ, 6-12 mo: 0.3 mg neuropathy, isoniazid use
myelin, unpolished rice/ 1-3 yr: 0.5 mg refractory seizures,
neurotransmitters, cereals, soya beans, 4-8 yr: 0.6 mg dermatitis,
hemoglobin walnuts 9-13 yr: 1 mg microcytic anemia
>13 yr: 1.3 mg
B 12 (Cobalamin) Regeneration of Dairy products, eggs <6 mo: 0.4 µg Subacute combined Intrinsic factor
folate, metabolism and meat 6-12 mo: 0.5 µg degeneration of cord, deficiency, ileal
of amino acids 1-3 yr: 0.9 µg peripheral neuropathy, resection, vegan diets
and myelin 4-8 yr: 1.2 µg megaloblastic anemia exclusively breastfed
9-13 yr: 1.8 µg infants of vegan
>13 yr: 2.4 µg mothers
Folate DNA synthesis, Leafy vegetables, <6 mo: 65 µg Megaloblastic anemia Preterm babies,
cell growth fruits, fortified cereal 6-12 mo: 80 µg pregnancy,
products, sunflower 1-3 yr: 150 µg malabsorption states,
seeds 4-8 yr: 200 µg hemolytic anemia,
9-13 yr: 300 µg anticonvulsant
>13 yr: 100 µg therapy
FAD: Flavin adenine dinucleotide, FMN: Flavin mononucleotide, mo: Months, NAD: Nicotinamide adenine dinucleotide, NADP: NAD phosphate
Treatment: Children are treated with 3-10 mg of oral Pyridoxine deficiency may cause peripheral neuro
riboflavin daily for several weeks; infants respond to pathy, refractory seizures, dermatitis and microcytic
1 mg daily. Therapeutic doses of vitamin help in anemia. Pyridoxine is given 10-50 mg/day to patients on
improving corneal lesions rapidly. INH (isoniazid) to prevent peripheral neuropathy and
other neurologic effects. For refractory seizure, 100 mg of
Niacin (Vitamin B3 ) pyridoxine is injected intramuscularly.
Nicotinic acid and nicotinamide, biologically equivalent
Biotin
vitamins, are both referred to as niacin. This vitamin can
be synthesized in the body from tryptophan, however, Biotin deficiency has been observed in individuals who
the conversion ratio is 60:1, requiring large amounts of consume a large number of raw eggs (rich in avidin) for
tryptophan to meet niacin needs. several months. The avidin is not hydrolyzed by gastro
intestinal enzymes; it binds biotin and prevents its
Sources: Milk, eggs, cereals and leafy vegetables are good absorption. Cooking of eggs destroys avidin.
sources of typtophan. Deficiency occurs in areas where Clinical features of biotin deficiency include anorexia,
maize is the staple food as the niacin in maize is present vomiting, dry scaly dermatitis, glossitis and hyper
in bound form and not easily absorbed. The vitamin is cholesterolemia. Long-term parenteral alimentation
resistant to heating. Human milk contains 30 mg/100 cal without biotin can also lead to deficiency in pediatric and
of niacin compared with 0.12 mg/100 cal in cow milk. adult patients. Multiple carboxylase deficiency is a genetic
Niacin requirements: Requirements are expressed in terms disorder affecting the activity of carboxylase synthetase.
of niacin equivalents (NE). One NE equals 1 mg of niacin This condition responds to large doses of biotin. Another
or 60 mg of tryptophan. RDA for niacin is related to dietary genetic defect affects the activity of biotinidase, an enzyme
energy intake; the recommended intake is 6.4 to 8 NE/ involved in the recycling of biotin.
1000 cal, human milk provides about 8 NE/1000 cal. Dietary sources of biotin include liver, egg yolk, milk,
yeast extracts and meat. Recommendations are 0.15 mg
Niacin deficiency: Niacin deficiency leads to pellagra biotin in the multivitamin supplements for infants and
which is characterized by three Ds: dermatitis, diarrhea children. For treatment of biotin deficiency, oral
and dementia. The cutaneous lesions consist of a administration of 2-5 mg daily for 2 to 3 weeks is
symmetrical pigmented rash in body parts exposed to recommended for mild cases. A parenteral biotin dose of
sunlight especially the neck (Casal necklace). More acute 200 µg daily for 2 to 5 days is used in severe cases.
cases may progress to vesiculation, ulceration and
secondary infection. Neurologic symptoms include Pantothenic Acid
apathy, headache and loss of memory. In most chronic Pantothenic acid (vitamin B5) is present in virtually all
forms, posterolateral cord degeneration and peripheral naturally occurring foods and is also synthesized by micro
nerve lesions are seen. organisms. Pantothenate is absorbed in the proximal small
Diagnosis of niacin deficiency: The diagnosis is suspected intestine; in the liver, it becomes a part of coenzyme A,
on history of inadequate diet, isoniazid treatment or which is essential for metabolism of fatty acid, proteins
chronic alcohol ingestion when typical manifestations are and carbohydrates. Isolated pantothenate deficiency is
present. Determination of urinary excretion of N 1- rare and includes burning feet, insomnia and
methylnicotinamide is most helpful; normal 24 hours gastrointestinal symptoms. The suggested daily intake is
excretion is between 4 and 6 mg, values below 3 mg 2-3 mg for infants and 3-5 mg for children.
indicate deficiency. In pellagra, these values are usually Cobalamin (Vitamin B 12)
between 0.5 and 0.8 mg/day.
Cobalamin or vitamin B12 consists of three compounds:
Treatment of pellagra: The daily dose for treatment is methykobalamin, 5'-deoxyadenosyl cobalamin and
about 10 times the recommended dietary intake (50-300 cyanocobalamin. The first two are active forms of vitamin
mg/ day). Parenteral therapy is considered when B12 in the body while cyanocobalamin is most common
gastrointestinal absorption is deficient. Prevention of commercially available preparation.
pellagra is achieved by an adequate protein diet containing
tryptophan and niacin-rich foods. Sources: Vitamin B 12 is produced by intestinal micro
organisms in animals. Humans do not produce vitamin
Pyridoxine (Vitamin B6 ) B12 and have to depend on animal sources including dairy
products, eggs and meat. Organs such as liver, kidney,
Rich sources of vitamin B6 include yeast, sunflower seeds,
heart and muscle meat, clams and oysters are rich sources
wheat germ, unpolished rice/ cereals, soya beans and
of vitamin B 12•
walnuts. Primary dietary deficiency is rare but secondary
deficiency can occur in malabsorption states and with Absorption and metabolism: Vitamin B12 binds to intrinsic
drugs like isoniazid. factor, a glycoprotein produced by the gastric parietal cells,
120 Essential Pediatrics
and the complex is absorbed by specific receptor-mediated maintenance of cells, since it acts as a coenzyme for normal
process in the ileum. Absence of intrinsic factor results in DNA and RNA synthesis. Leafy vegetables such as
an inability to absorb ingested vitamin B 12 known as spinach, turnip greens, lettuces, dried beans and peas,
pernicious anemia. Passive diffusion accounts for a fortified cereal products, sunflower seeds and certain
fraction of total absorption, but may be useful in the fruits and vegetables are rich sources.
management of pernicious anemia with megadoses of the
vitamin. Cobalamin undergoes enterohepatic recirculation; Requirements: The recommended daily allowance of folic
this process accounts for a long half-life of the vitamin. acid varies from 25 µg in infancy to 200 µg by adolescence.
Vitamin B 12 is transported in plasma bound to Deficiency: Folate is absorbed in the small intestine.
transcobalamin II. The average total body pool in an adult Deficiency can occur in malabsorption states such as
is enough to sustain daily vitamin B12 needs for several chronic gastrointestinal infections, short bowel syndrome
years. and celiac disease. Preterm babies are at risk of folate
deficiency due to increased tissue demands and lack of
Requirements: The recommended intake of vitamin B 12
adequate stores as maternal transfer occurs in the last
for infants is 0.3 µg/day. Older children should receive
trimester of pregnancy. Children with hemolytic anemia
0.5-1.5 µg/day and adolescents 2.0 µg/day.
have high folate requirements due to increased
Deficiency: Vitamin B12 deficiency can occur in patients erythropoiesis predisposing them to deficiency.
with impaired intestinal absorption due to defects in Anticonvulsant drugs increase the catabolism of folate
intrinsic factor, or distal ileal disease. True dietary vitamin leading to secondary deficiency.
B12 deficiency occurs in persons who follow vegan diets Deficiency of folate impairs DNA synthesis, limits cell
containing no animal or fish products. Content of vitamin division and affects normal growth and repair of tissues.
B12 in breast milk is determined by maternal intake. Hence, The tissues that have the fastest rate of cell replacement
exclusively breastfed infants of strict vegan mothers can are affected first. Erythropoiesis is hindered, resulting in
become vitamin B 12 deficient over a period of time megaloblastic anemia.
especially if weaning is not initiated at an appropriate age. Maternal deficiency of folate, during pregnancy, is
Vitamin B12 status is assessed by measurement of serum implicated in neural tube defects. Periconceptional folate
cobalamin levels, with values below 150 pg/mL indicative supplements, begun 1 month before conception and
of negative vitamin B 12 balance. Plasma levels of continued for 3 months after, is recommended to reduce
methylmalonic acid and homocysteine are increased the risk.
because of block in vitamin B 12 -dependent steps of In patients with megaloblastic anemia, it is imperative
metabolism. to exclude and treat vitamin B 12 deficiency before treating
Characteristic features of vitamin B12 deficiency include with folate. Otherwise the neurological signs of vitamin
progressive demyelination, which begins in peripheral B 12 deficiency may develop and progress irreversibly.
nerves and progresses to involve the posterior and lateral Deficiency is corrected using folic acid at a dose of 0.5-1
columns of the spinal cord and central nervous system mg/day orally for 3-4 weeks.
(subacute combined degeneration). These lesions are
possibly due to a generalized methyl group deficiency in Vitamin C
the nervous system and faulty myelin production. Vitamin C (L-ascorbic acid or ascorbate) plays many
Secondary folate deficiency results in megaloblastic important roles in the body; it is needed for formation of
anemia, neutrophil hypersegmentation and thrombo protocollagen and maintenance of normal connective
cytopenia. tissue, wound healing and bone (osteoid) formation.
Vitamin C is a reducing agent required for oxidation
Diagnosis of deficiency: The anemia is macrocytic and reduction reactions including the hydroxylation of lysine
nucleated RBC showing megaloblastic morphology may and proline. Additionally, it reduces ferric to ferrous state
be seen in blood. Levels of red cell folate are low; serum and helps in iron absorption in the gut. Due to its
LDH levels are elevated. antioxidant properties, it stabilizes a number of other
Treatment: Deficiency is treated with parenteral adminis compounds, including vitamin E and folic acid. Humans,
trations of vitamin B 12 (1 mg). Reticulocytosis is seen unlike other animals, lack the enzyme (gulonolactone
within 2-4 days. Patients with neurologic involvement oxidase) required for conversion of glucose to ascorbic
require daily therapy for 2 weeks. acid hence vitamin C is must be obtained from the diet.
Sources: Rich sources of vitamin C include fresh citrus
Folic Acid (Pferoylmonoglutamic Acid) fruits (oranges, grapefruit, lime and gooseberry) and
Folic acid is the parent compound of a group of naturally vegetables (cabbage, cauliflower, spinach, cucumber).
occurring, structurally related compounds known as the Much of the vitamin is lost in cooking and storage, but is
folates. Folic acid is essential for normal growth and stable in canned and frozen foods. Human milk is rich
Micronutrients in Health and Disease 1121-
transmission contributing to the action of more than Deficiency: Infants, children, adolescents, pregnant and
300 enzymes. Over 80% of the total body magnesium is in lactating women have increased demand of zinc due to
bone and skeletal muscle. Rich sources of magnesium active growth and tissue synthesis. Deficiency is also seen
include legumes, nuts, bananas and whole grains. as a part of malnutrition and malabsorption syndromes,
Magnesium is efficiently absorbed in the intestine and caused by low dietary intake or poor absorption due to
regulation of its balance depends on renal tubular intestinal disease. Excessive loss of zinc in stools can occur
reabsorption. Primary deficiency is common in children with recurrent or chronic diarrhea. Severe zinc deficiency
with protein energy malnutrition. Deficiency may also syndromes can occur in patients on prolonged intravenous
develop secondary to intestinal malabsorption, excessive feeding.
gastrointestinal losses (fistulae or continuous suction) or Poor physical growth is an important feature of zinc
renal losses (tubular disease or diuretics). Clinical depletion in preschool and school-age children. Delayed
manifestations of magnesium deficiency include sexual maturation and hypogonadism is a prominent
irritability, tetany and hypo- or hyper-reflexia and cardiac feature of zinc deficiency in adolescents. Other features
arrhythmias in severe cases. Magnesium requirements in include anemia, anorexia, diarrhea, alopecia, dermatitis,
the first 6 months range between 40 and 50 mg/day; impaired immune function, poor wound healing and
60 mg/day for 6-12 months and approximately 200 mg/ skeletal abnormalities.
day for older children. Acrodermatitis enteropathica is an autosomal recessive
disorder of severe zinc deficiency, caused by impaired
TRACE ELEMENTS intestinal absorption due to defect in intestinal zinc
transporter protein. It presents in early infancy, with
Eleven 'major' elements constitute 99% of human body vesicobullous, dry, scaly or eczematous skin lesions chiefly
weight: Hydrogen, carbon, nitrogen, oxygen, sodium, in the periorificial (around the mouth and perineum) and
potassium, chlorine, calcium, phosphorus, sulfur and acral areas. Alopecia and eye changes, such as
magnesium. In addition, the body is composed of conjunctivitis, blepharitis and photophobia, may be
numerous "trace" elements. The term trace elements present. Chronic diarrhea, growth retardation, stomatitis,
comprise an increasing number of compounds with loss of taste sense, irritability and delayed wound healing
proven or putative essentiality for human nutrition. Each are seen. Catchup growth and resolution of symptoms is
of these contributes less than 0.01% of total body weight. noted following oral zinc therapy.
Their major functions are related to enzyme systems where The diagnosis of zinc deficiency is based on the
they act either as cofactor for metal-ion-activated enzymes combination of dietary history of chronic low zinc intake
or as specific constituents of metallo-enzymes. or excessive intestinal losses, presence of clinical features
compatible with deficiency and low levels of zinc in
Zinc plasma or hair.
Functions: Zinc is the second most common trace element
in the body after iron. It is an essential micronutrient with Requ irement and trea tment of defi ciency: Normal
diverse but critical physiological role being part of more requirements for children range between 3.5 and 5.0 mg/
than 200 enzymatic reactions. As a component of zinc day. Acquired zinc deficiency states can be treated with
finger proteins, zinc regulates gene transcription and 0.5 to 1.0 mg elemental zinc/kg/day for several weeks or
participates in nucleic acid metabolism, protein synthesis months. Malnourished children have much higher
and thereby, cellular growth. Zinc is a major antioxidant requirements of 2-4 mg/kg/day due to zinc depletion and
being part of the enzyme superoxide dismutase. intestinal disease. One mg of elemental zinc is available
from 4.5 mg zinc sulfate or 3 mg zinc acetate.
Dietary sources: Zinc is derived mainly from animal
protein. Liver, oyster, meat, fish, nuts and eggs are a rich Copper
source. Diets based on cereals/starch, plants and legumes Copper is a component of several metallo-enzymes
are associated with zinc deficiency, due to the presence of required for oxidative metabolism.
dietary phytic acid that decreases the bioavailability of zinc.
Absorption and metabolism: Most of the ingested copper
Absorption and metabolism: Zinc is absorbed throughout is absorbed in stomach and small intestine, from where it
the small intestine by a process of facilitated diffusion. In is transported to the liver and released into the systemic
the systemic circulation, the major fraction of plasma zinc circulation bound to ceruloplasmin, the main transport
is loosely bound to albumin. Almost 90% of total body protein for copper. Copper is mainly stored in the liver
zinc is localized in bone and skeletal muscle. Zinc status and muscle. It is excreted through biliary secretions in the
is regulated both at the absorptive step and by intestinal feces; urinary excretion is minimal.
re-excretion. The major excretory route for endogenous
zinc is via the intestinal tract; fecal losses are increased in Sources : The richest sources are meats, liver, seafood, nuts
children with intestinal diseases or diarrhea. and seeds. Additional copper may enter the food chain
Micronutrients in Health and Disease 1123-
through pesticides and contamination of water by pipes in soil especially in mountainous regions due to leaching
and cooking utensils. and erosion. The Himalayan belt and Ganges valley are
areas of severe iodine deficiency in India.
Deficiency: Primary dietary deficiency is infrequent.
Secondary deficiency may develop in malabsorption Recommended daily intake: The recommended iodine
syndromes, liver disease, peritoneal dialysis and other intake is around 90 µg/day from birth to 5 years of age
conditions causing excessive copper losses. Copper increasing to 120 µg/ day at ages 6-12 years, and
deficiency decreases the life span of the erythrocyte and 150 µg/day in adolescents and adults. Pregnant and
impairs mobilization of stored iron from liver and bone lactating women require higher amounts (200 µg/day).
marrow. Features of deficiency are microcytic, hypochromic Iodine is excreted in urine and 24-hour urinary iodine
anemia unresponsive to iron therapy, depigmentation of excretion is a useful measurement of iodine sufficiency in
hair, neutropenia, neurological problems and osteoporosis. a community. Urinary iodine <100 µg/L indicates iodine
Copper transport is disrupted in two human diseases: insufficiency with values <20 µg/L pointing to severe
Wilson disease and Menke disease. Both have defects in deficiency.
copper transporting membrane proteins. Menke disease
is a rare X-linked fatal disorder of impaired copper Iodine deficiency disorders: Nearly 1.5 billion people in
absorption presenting in early infancy with kinky hair, 130 countries around the world live in areas of iodine
skin hypopigmentation, neurological regression and deficiency and are at risk of developing iodine deficiency
seizures. Laboratory findings include hypocupremia, low disorders (100). 100 are the commonest cause of mental
plasma ceruloplasmin, neutropenia and anemia. retardation in these populations and are responsible for
an average lowering of IQ scores by 13.5 points compared
Selenium to populations living in iodine-sufficient areas. Goitre is
the earliest manifestation of iodine deficiency and is an
Selenium is a constituent of glutathione peroxidase, an
adaptive response to increase thyroid hormone production
antioxidant in red blood cells and other tissues. Selenium
under the influence of increased TSH levels, but eventually
also helps maintain normal immune function and is a part
leads to decompensation in the form of hypothyroidism.
of the enzyme type 1-deiodinase which converts thyroxine
Goitre rates can be as high as 10-30% in endemic
to triiodothyronine. Dietary sources include whole grain,
populations suffering from iodine deficiency (Table 8.5).
meat, egg, seafood, garlic and mushrooms. Endemic
selenium deficiency results in Keshan disease, a form of Iodine deficiency in the fetus: Maternal hypothyroidism
cardiomyopathy in young children seen in some regions due to iodine deficiency leads to an increased risk of
of China. In combination with iodine deficiency, lack of abortions and stillbirths. The fetal thyroid gland begins
selenium can result in myxedematous endemic cretinism, to function from the second half of gestation. Inadequate
seen in certain parts of Africa. Selenium deficiency may availability of T4 due to maternal iodine deficiency
be seen in patients on total parenteral nutrition and adversely affects early brain development in the fetus
manifests with macrocytosis, brown hair and whitening leading to permanent manifestations of endemic cretinism,
of nails. including mental retardation, hearing impairment ( deaf
mutism), spastic diplegia and squint.
Chromium
Glucose intolerance, which complicates malnutrition in Iodine deficiency in the neonate: Iodine deficiency affects
young children, has been attributed in part to chromium functioning of the thyroid gland leading to neonatal goitre
deficiency. Chromium acts in glucose homeostasis by and hyp othyroidism The brain of the human infant at birth
potentiating insulin action, possibly by facilitating binding has only reached about one-third of its full size and
to its receptor. Symptoms of chromium deficiency are continues to grow rapidly until the end of the second year.
usually in the setting of total parenteral alimentation and The thyroid hormone, dependent on an adequate supply
include glucose intolerance, peripheral neuropathy and of iodine, is essential for normal brain development at this
evidence of disturbed nitrogen and lipid metabolism. critical time. Neonatal hypothyroidism persists into
infancy and childhood, if the deficiency is not corrected
Iodine and results in retardation of physical and mental
development.
Iodine, a micronutrient present in small quantities in the
thyroid gland, is essential for the formation of thyroid Iodine deficiency in children: Moderate iodine deficiency
hormones thyroxine (T 4 ) and triiodothyronine (T 3 ). is associated with abnormalities in psychoneuromotor and
Thyroid hormones play a key role in body growth and intellectual development of children who are clinically
brain development, especially in the fetus and first three euthyroid, but who do not exhibit other features of
years of postnatal life. endemic cretinism (Table 8.5). Some patients may show
Iodine is most commonly found in sea water and sea goiter (Fig. 8.9) (see Chapter 18). Studies in moderately
food/plants are rich sources. Iodine is relatively deficient iodine-deficient areas indicate that fine motor skills and
124 Essential Pediatrics
Table 8.5: Spectrum of iodine deficiency disorders (IDD) visual problem solving improved in school children after
iodine repletion.
Fetus Abortions, stillbirths
Congenital anomalies Therapy: Universal iodization of salt is a successful public
Endemic cretinism health intervention to prevent 100 in populations at risk
Increased perinatal mortality of deficiency throughout the world. In India, the National
Neonate Neonatal goiter Iodine Deficiency Disorders Control Programme (formerly
Endemic mental retardation known as National Goitre Control Programme) has
Neonatal hypothyroidism established salt iodination plants to ensure an adequate
Child, adolescent Goiter supply of iodized salt in the country. The target iodine
Impaired mental function content of salt as per the program is 30 and 15 parts per
Subclinical hypothyroidism million (ppm) at the manufacturing and distribution
Retarded physical development levels, respectively.
Iron
Iron deficiency remains a major nutritional problem
among infants and young children. The National Family
Health Survey (NFHS) IV (2015-16), showed that 56%
urban and 59% rural children between 6 and 59 months
are anemic. Iron deficiency anemia is associated with
impaired performance in mental and physical functions,
including physical coordination and capacity, cognitive
abilities, and social and emotional development. Health
consequences of iron deficiency in young children are
serious and often irreversible (Chapter 13).
Suggested Reading
• Elder CJ, Bishop NJ. Rickets. Lancet. 2014 May 10;383(9929):1665-76.
• Global Consensus Recommendations on P revention and
Management of Nutritional Rickets. J Clin Endocrinol Metab. 2016
Feb;101(2):394-415.
• ICMR 2010. Nutrient requirements and recommended dietary
allowance for Indians. Report of the Expert Group of ICMR, New Delhi.
• ICMR Dietary guidelines for Indians. ninindia.org/Dietary
GuidelinesforNINwebsite.pdf
• Suskind DL. Nutritional deficiencies duringnormal growth. Pediatr
Clin North Am. 2009 Oct;56(5):1035-53.
Fig. 8. 9: A 14-year-old girl with goiter • Sethuraman U. Vitamins. Pediatrics in Review. 2006;27:44-55.
Chapter
9
Newborn Infants
Ramesh Agarwal • Vinod K Paul • Ashok K Deorari
Newborn infants are unique in their physiology and the 40% occur within first 24 hours, half within 72 hours and
health problems that they experience. Neonatal period is three-fourths within one week of birth. Health of the
characterized by transition to extrauterine life and rapid mother and care during pregnancy and at childbirth has
growth and development. Newborn period, just first profound influence on neonatal outcome. As noted in
28 days of life, carries the greatest risk of mortality. Despite Chapter 1, decline in neonatal mortality is critical to
being less than 2% of total period of under-5 childhood, achieve national health goals. The stagnant early neonatal
the newborn period accounts for over half of under-5 child mortality is a cause for concern.
mortality. Good care, therefore, not only improves
survival of children but lays foundation of optimal long Definitions
term physical and neurocognitive development. Neonatal period: From birth to under four weeks (0 to 27
Newborn health is the key to child health and survival. days or 1 to 28 days, depending on whether the first day
In india (SRS 2012), neonatal deaths account for 56% of has been taken as day O or day 1 of life) of age. An infant
under-5 (Fig. 9.1) and 69% of infant deaths. First week is called a neonate during this phase. First week of life (<7
deaths (<7 days; early neonatal deaths) alone account for days or <168 hours) is known as early neonatal period.
45% of total under-5 deaths. Preterm birth complications Late neonatal period extends from 7th to <28th days.
account for 35% of all neonatal deaths and constitute the
most important cause of neonatal mortality. Bacterial Postneonatal period: Period of infancy from 28 to
infections (sepsis, pneumonia and diarrhea) contribute to <365 days (<1 year) of life.
21% of neonatal deaths. Other causes of neonatal mortality Weeks ofgestation refer to completed weeks of gestation,
are birth asphyxia and congenital malformations. Almost e.g. 36 weeks gestation, refer to range of gestation from
three-fourths of all neonatal deaths occur among the low 36 weeks O day to 36 weeks and 6 days.
birth weight newborns. Of all the neonatal deaths, about
Perinatal period: Perinatal period extends from 22ndweek
�--- Neonatal of gestation (>154 days or fetal weighing 500 g or more)
pneumonia 2% to less than 7 days of life.
Neonatal sepsis and
meningitis 10% Live birth: A product of conception, irrespective of weight
or gestational age, that, after separation from the mother,
Preterm birth shows any evidence of life such as breathing, heart-beat,
complication
24% pulsation of umbilical cord or definite movement of
Meningitis voluntary muscles.
2%
Malaria Fetal death: A fetal death is a product of conception that,
1%
after separation from the mother, does not show any
Other evidence of life.
14%
Stillbirth: Fetal death at a gestational age of 22 weeks or
more or weighing 500 g or more at birth.
Term neonate: A neonate born between 37 and 42 weeks
Other Congenital (259-293 days) of gestation.
neonatal 5% malformations
4% Preterm neonate: A neonate born before 37 weeks (<259
Fig. 9.1: Causes of under-5 deaths at global level (2013) days) of gestation irrespective of the birth weight.
125
126 Essential Pediatrics
pulmonary blood flow by quickly restoring ventilation. Table 9.1: Neonatal resuscitation supplies and equipment
However, pulmonary perfusion in severely asphyxiated
Suction equipment
infants may not improve with ventilation alone. The
combination of oxygenation and correction of metabolic Mechanical suction
acidosis would be necessary to open the pulmonary Suction catheters 10, 12 or 14 F
arterioles to improve pulmonary blood flow. Meconium aspirator
Bag and mask equipment
Cardiac Function and Systemic Circulation Neonatal resuscitation bags (self-inflating)
Asphyxia causes redistribution of blood flow to preserve Face-masks (for both term and preterm babies)
blood supply to vital organs. There is vasoconstriction in Oxygen with flow meter and tubing
the bowel, kidney, muscles and skin while the blood flow Intubation equipment
to the heart and brain is relatively preserved (diving-in
Laryngoscope with straight blades no. 0 (preterm) and no. 1
reflex).
(term)
As asphyxia is prolonged, myocardial function and Extra bulbs and batteries (for laryngoscope)
cardiac output too deteriorate and blood flow to all the Endotracheal tubes (internal diameter of 2.5, 3.0, 3.5 and
organs is further reduced. This sets in the stage for 4.0 mm)
progressive organ damage.
Medications
Preparing for Resuscitation Epinephrine
Normal saline or Ringer lactate
With careful consideration of antepartum and intrapartum
Naloxone hydrochloride
risk factors, asphyxia can be anticipated in up to only half
of the newborns who will eventually require some form Miscellaneous
of resuscitation. In others, the need for resuscitation can Linen, shoulder roll, gauze
come as a surprise. Therefore, each delivery should be Radiant warmer
viewed as an emergency and basic readiness must be Stethoscope
ensured to manage asphyxia. Syringes 1, 2, 5, 10, 20, 50 ml
Preparation for delivery should include: Feeding tube 6 F
i. Assessing perinatal risk factors, ensuring availability Umbilical catheters 3.5, 5 F
of at least one person who is capable of undertaking Three way stopcocks
full resuscitation and whose sole responsibility is that
Gloves
of newborn only. In an anticipated need for resuscita
tion, there may be need of more than one person.
sequential time points following birth can reflect how well
ii. All resuscitation equipment immediately available and
the baby is responding to resuscitative efforts. Extended
in working order (Table 9.1)
Apgar scores should be obtained every 5 minutes for up
iii. Ensuring a good teamwork and proper communication to 20 minutes, if the 5-minute Apgar score is less than 7.
between teammates.
TABC of Resuscitation
Role of Apgar Scores in Resuscitation
The components of the neonatal resuscitation can be
The Apgar score is an objective method of evaluating the summarized as TABC:
newborn's condition (Table 9.2). It is generally performed
at 1 minute and again at 5 minutes after birth. However, T-Temperature: Provide warmth, dry the baby and remove
resuscitation must be initiated before the 1-minute score the wet linen.
is assigned. Therefore, the Apgar score is not used to guide the A-Airway: Position the infant, clear the airway, if required
resuscitation. (by wiping or suction of baby's mouth and nose).lf
While the Apgar score is not useful for decision making necessary, insert an endotracheal (ET) tube to ensure an
at the beginning of resuscitation, the change of score at open airway.
Antenatal counselling
Team briefing and equipment check
Yes
Yes
Position and clear airway
PPV
Sp02 monitor
Sp0 2 monitor
Supplementary 0 2 as needed
..
Consider ECG monitor
Consider CPAP
No
HR below 100/min? Postresuscitation care
Team debriefing
Yes
No 1 min 60-65%
HR below 60/min? 2 min 65-70%
3 min 70-75%
Yes
4 min 75-80%
Intubate, if not already done 5 min 80-85%
Chest compressions
10 min 85-95%
Coordinate with PPV
100% 0 2
ECG monitor
Consider emergency UVC
+
HR below 60/min?
Yes
IV epinephrine
If HR persistently below 60/min
Consider hypovolemia
Consider pneumothorax
Fig. 9.2: The algorithm of neonatal resuscitation. CPAP continuous positive airway pressure; PPV positive pressure ventilation; Sp02
saturation of oxygen [Adapted with permission from American Academy of Pediatrics 2015).
Newborn Infants 1129-
iii. Good muscle tone? (flexed posture and active The secretion can be removed from the airway by
movement of baby denotes good tone) wiping the nose and mouth with a clean cloth or by
If answers to all the three questions are 'Yes', the infant suctioning with a bulb syringe or suction catheter. The
stays with mother and receives just "Routine care". Routine mouth is suctioned before nose ('M' before 'N') to ensure
care consists of four steps: the infant does not aspirate, if she should gasp when the
i. Warmth: Provided by putting the baby directly on the nose is suctioned. If the infant has copious secretion from
mother's chest in skin-to-skin contact. the mouth, the head should be turned to the side. This
will allow secretions to collect in the side of mouth, where
ii. Clearing of airway, if required: Position the baby and
they can be easily removed.
wipe the baby's mouth and nose using a clean cloth.
No need to suction routinely. For suctioning, the size of suction catheter should be
12 or 14 Fr. The suction pressure should be kept around
iii. Dry the baby
80 mm Hg (100 cm H20) and should not exceed 100 mm
iv. Ongoing evaluation for vital parameters. Helping Hg (130 cm H20). One should not insert the catheter too
mother in breastfeeding will facilitate easy transition deep in mouth or nose for suction as it may stimulate
to extrauterine environment. posterior pharynx producing vagal response resulting in
If answer to any of the three questions is "No", the baby bradycardia or apnea.
requires at least some resuscitation. After cutting the cord,
the baby should be subjected to a set of interventions Dry and Stimulate
known as initial steps.
After suctioning, the baby should be dried adequately
Initial Steps using prewarmed linen to prevent heat loss. The wet linen
should be removed away from the baby. The act of
Warmth suctioning and drying itself provides enough stimulation
The baby should be placed under the heat source, to initiate breathing. If the newborn continues to have poor
preferably a radiant warmer. The baby should not be respiratory efforts, additional tactile stimulation by gently
covered with blankets or towels to ensure full visualization rubbing trunk, back and extremities for several seconds
and to permit the radiant heat to reach the baby. may be provided to stimulate the breathing. However,
one should not waste too much of time in providing tactile
Positioning stimulation.
The baby should be placed on her back or side with the
neck slightly extended. This helps in keeping the airway Management of Infant Born through
open and facilitates breathing. Care should be taken to Meconium-Stained Liquor (MSL)
prevent hyperextension or flexion of the neck, since either A baby born through meconium-stained liqor (MSL) may
may interfere with respiration. aspirate the meconium into the trachea and lungs. The
To help maintain the correct position, one may place a procedures like intrapartum suctioning of the mouth and nose
rolled blanket or towel under the shoulders of the infant before delivery of the shoulders and postnatal tracheal suctioning
elevating her by% or 1 inch off the mattress. This 'shoulder of non-vigorous babies are no more recommended.
roll' is particularly helpful, if the infant has a large occiput If a term baby born through MSL is vigorous (breathing
resulting from molding, edema or prematurity (Fig. 9.3). well and good tone), the baby is provided initial steps.
The gentle suction of mouth and nose may be required to
Clear Airway, if Necessary clear airways and the baby is kept with mother with
The appropriate method for clearing the airway will continued observation for development of any respiratory
depend on the presence or absence of meconium. difficulty. If non-vigorous (feeble breathing or low tone),
the baby is provided initial steps under radiant warmer
and PPV is provided, if required.
Evaluation
After providing initial steps, the baby should be evaluated
by assessing respiration, HR and color (or oxygen
saturation by pulse oximetry).
Respiration is evaluated by observing the infant's chest
movements. HR can be assessed by auscultating the heart
or by palpating the umbilical cord pulsation for 6 seconds.
The number of beats or pulsation is multiplied by 10 to
obtain the HR per minute (e.g. a count of 12 in 6 seconds
Fig. 9.3: Rolled towel under the shoulders is an HR of 120 per minute). Color is evaluated by looking
130 Essential Pediatrics
at tongue, mucous membranes and trunk. A blue hue to It is, therefore, recommended that term babies should
the lips, tongue and central trunk indicates central be initiated on room air resuscitation. Ideally, oxygen
cyanosis. Presence of cyanosis in extremities (acrocyanosis) saturation should be monitored by pulse oximetry and
does not have any significance. oxygen delivery should be titrated to maintain the oxygen
• If the baby has good breathing, HR 100/min or more saturation in the targeted range (Fig 9.2). In absence of
and no cyanosis, then she does not require any pulse oximetry, room air should be substituted by 100%
additional intervention and the baby should be
oxygen, if the baby fails to improve (improvement in HR
monitored frequently.
and breathing) by 90 seconds.
• If the baby has labored breathing or persistent central
cyanosis, administration of CPAP in preterm babies and PPV in preterm babies ( <35 weeks) is recommended
supplemental oxygen in term babies is recommended. using intermediate concentration of oxygen (21 to 30%).
Baby should have its oxygen saturation monitored and The oxygen concentration should be titrated by
supplemental oxygen is titrated to achieve the targeted continuously monitoring of oxygen saturation by pulse
saturations (Fig. 9.2). oximetry. BMV is indicated, if:
• If the baby is apneic, has gasping breathing or heart i. The infant is apneic or gasping
rate below 100 min, positive pressure ventilation (PPV) ii. HR is less than 100 beats per minute
is needed. In suspected or confirmed diaphragmatic hernia, bag and
Supplemental Oxygen mask ventilation is contraindicated.
Central cyanosis requires supplemental oxygen, which can Procedure
be provided by an oxygen mask or oxygen tube held in
cupped hand over baby's face or by flow inflating bag and The infant's neck should be slightly extended to ensure
mask. The flow of oxygen should be at least 5 L/minute. an open airway. The care provider should be positioned
at head end or at the side of baby so as to have an
Positive Pressure Ventilation (PPV) unobstructed view of infant's chest and abdomen. Select
PPV is usually given by using a self-inflating bag and face an appropriate sized face mask that covers the mouth and
mask (bag and mask ventilation or BMV). The self nose, but not eyes of the infant (Fig. 9.5). The face mask
inflating bag is easy to use as it reinflates completely should be held firmly on face to obtain a good seal. The
without any external compressed source of gas. bag should be compressed using fingers and not by hands.
The resuscitation bag (Fig. 9.4) should have a capacity PPV is the single most effective step in babies who fail to
of 240 to 750 mL. The bag is attached to sources of oxygen breath at birth. Ensuring adequacy of ventilation is the most
and air and a blender which provides a desired important priority in such babies.
concentration of supplemental oxygen.
Oxygen should be treated as a drug. Both too little and
too much of oxygen are bad for the baby. Even a brief
exposure to high concentration of oxygen can have
detrimental effect on the baby. Studies have shown that
term babies resuscitated with room air compared to 100%
oxygen have better survival and long-term outcomes. The
evidence in favor or against the use of oxygen in preterm
babies is yet lacking.
Oxygen Pressure gauge
Pressure release
(pop-off) valve
Valve assembly
Oxygen reservoir
/
Oxygen inlet
Patient outlet
Fig. 9.4: Self-inflating bag (Adapted with permission from MP Fig. 9.5: Properly fitting mask (Adapted with permission from AAP
2005) 2005)
Newborn Infants 131-
Fig. 9.6: Correct rhythm of providing positive pressure ventilation (Adapted with permission from American Academy of Pediatrics
2005)
If the baby is not responding to PPV by prompt increase Table 9.3: Ventilation corrective steps (MR SOPA)
in HR, ventilation corrective steps are taken: Observe for Action Condition
an appropriate rise of the chest and auscultate for breath Inadequate seal Re-apply mask
sounds. If chest does not rise and there are no audible
Blocked airway Reposition the infant's head
breath sounds, the steps outlines in Table 9.3 should be
undertaken. Blocked airway Clear secretions by suction
When normal rise of the chest is observed, one should Blocked airway Ventilate with mouth slightly open
begin ventilating. Ventilation should be carried out at a Inadequate pressure Increase pressure slightly
rate of 40 to 60 breaths per minute, following a 'squeeze, Consider alternate Blocked airway(endotracheal tube)
two, three' sequence (Fig. 9.6). airway
Usual pressure required for the first breath is 30--40 cm
H20. For subsequent breaths, pressure of 15-20 cm H20 is Chest compressions are indicated, if HR is below 60/min even
adequate. After the infant has received 30 seconds of PPV, after 30 seconds of PPV. Once the HR is 60/min or more, chest
evaluate the HR and take a follow-up action as in Fig. 9.2. compressions should be discontinued.
Improvement in the infant's condition is judged by
Procedure
increasing HR, spontaneous respiration and improving
color. If the infant fails to improve, check adequacy of The CC are delivered by the thumb technique (Fig. 9.7).
ventilation in form of visible chest rise. If chest rise is With the thumb technique, the two thumbs are used to
inadequate, one should take necessary action as described depress the sternum, with the hands encircling the torso
earlier. and the fingers supporting the back. The earlier used two
PPV may cause abdominal distension as the gas escapes finger technique for CC is no more recommended.
into the stomach via esophagus. Distended stomach When CC is performed on a neonate, pressure is
presses on the diaphragm and compromises the applied to the lower third of sternum. Care must be taken
ventilation. Therefore, if ventilation is continued for more to avoid applying pressure to xiphoid. To locate the area,
than two minutes, an orogastric tube (feeding tube size one should slide the fingers on the lower edge of thoracic
6-8 Fr) should be inserted and left open to decompress cage and locate xiphisternum. The lower third of the
the abdomen. sternum is just above it.
Procedure
The infant's head should be in midline and the neck kept
Fig. 9.7: Chest compression with thumb technique (Adapted slightly extended. The laryngoscope is held in the left hand
with permission from MP 2005) between the thumb and the first three fingers, with the
blade pointing away from oneself. Standing at the head
To determine efficiency of chest compressions, the end of the infant, the blade is introduced in the mouth
carotid or femoral pulsation should be checked and advanced to just beyond the base of the tongue so
periodically. that its tip rests in the vallecula. The blade is lifted as
Possible complications of chest compressions include shown in Fig. 9.8 and landmarks looked for; the epiglottis
broken ribs, laceration of liver and pneumothorax. and glottis should come into view. The glottic opening is
surrounded by vocal cords on the sides. Once the glottis
Evaluation and vocal cords are visualized, the ET is introduced from
After a period of 30 seconds of chest compressions, the the right side of the mouth and its tip inserted into the
heart rate is checked.
Table 9.4: Appropriate endotracheal tube size
HR below 60. Chest compressions should continue along
with bag and mask ventilation. In addition, medications Inner diameter Weight Gestational age
of tube (mm) (g) (weeks)
(epinephrine) have to be administered.
2.5 <1000 <28
HR 60 or above. Chest compressions should be dis 3.0 1000-2000 28-34
continued. BMV should be continued until the heart rate
is above 100 beats per minute and the infant is breathing
3.5 2000-3000 34-38
spontaneously. 4.0 >3000 >38
Endotracheal Intubation
Endotracheal (ET) intubation is required only in a small
proportion of asphyxiated neonates. Intubation is a
relatively difficult skill to learn and it requires frequent
practice to maintain the skill.
Indications
The indications of ET intubation are: (i) when tracheal
suction is required (in non-vigorous babies born through
MSL), (ii) when prolonged BMV is required, (iii) when
BMV is ineffective, and (iv) when diaphragmatic hernia
is suspected. The other conditions where ET intubation Correct Incorrect
may be considered are: before starting chest compressions Fig. 9.8: Direction of pull on the laryngoscope (Adapted with
and for administering epinephrine. permission from MP 2005)
Newborn Infants 1133-
glottis until the vocal cord guide is at the level of the glottis, LEVEL OF NEWBORN CARE
thus positioning it half way between the vocal cords and
Level-1 units: Provide care to normal term newborns and
carina.
stable newborns of 35 to 36 weeks gestation. These units
Medications stabilize small and sick infants and transfer them to higher
level facilities.
The majority of infants requiring resuscitation will have a
response to prompt and effective ventilation with 100% Level-2 units (special care nursery): Look after babies born
oxygen. Only a few require medications. at or after 32 weeks of gestation or weighing 1500 gm or
more at birth or those with moderate sickness. These units
Medications used in resuscitation include epinephrine
can provide CPAP and ventilation for brief periods. They
and volume expanders (Table 9.5). Sodium bicarbonate
can serve as step-down units for level-3 and level-4 care.
and naloxone are indicated only for special circumstances.
There is no role of atropine, dexamethasone, calcium, Level-3 units (intensive care units): Provide care to babies
mannitol and dextrose for newborn resuscitation in the less than 32 weeks and 1500 gm and ones with critical
delivery room. illnesses. These units can offer full range of respiratory
support.
Route of administration: Since veins in scalp or
extremities are difficult to access during resuscitation, Level-4 care includes full range of advanced subspecialities
umbilical vein is the preferred route. No intracardiac including options of cardiac surgery.
injection is recommended. The Indian health system defines level of care in
following manners:
For umbilical vein catheterization, 3.5 Fr or 5 Fr
umbilical catheter is inserted into the umbilical vein such Newborn care corner (NBCC): All birthing facilities must
that its tip is just inside the skin surface and there is free have NBCC to provide resuscitation (care at birth) and
flow of blood. Direct injection into the umbilical cord is care to well babies. These units identify and refer at risk
undesirable. and sick neonates to higher facilities.
Epinephrine may be injected directly into the tracheo Newborn stabilization units (NBSU): In addition to NBCC
bronchial tree through ET. Since absorption is erratic, this services, these units provide sick newborn care to babies
method is to be used, only if venous access cannot be above 1800 gm.
obtained. The drug is injected by a syringe or a feeding Special newborn care units (SNCU): In addition to services
tube (5 Fr) into the endotracheal tube, flushed with 0.5 mL provided by NBCC and NBSU, these units provide care
of normal saline and dispersed into the lungs by PPV. to babies <1800 gm and limited ventilation facilities.
Indications CARE OF NORMAL NEWBORN BABIES
Use of adrenaline is indicated, if HR remains below 60
Care at Birth
despite adequate ventilation and chest compressions for
30 seconds. Standard precautions and asepsis at birth: The personnel
attending the delivery must exercise all the universal/
Suggested Reading standard precautions in all cases. All fluid from the baby/
• Textbook of Neonatal Resuscitation.; 7th ed. American Academy mother should be treated as potentially infectious. Gloves,
of Pediatrics and American Heart Association, 2015 masks and gowns should be worn when resuscitating the
134 Essential Pediatrics
be administered. Vitamin K3 can cause hemolysis in G6PD • The newborn is not having significant jaundice or any
deficient babies. other illness requiring closer observation by a health
Communication with the family: Before leaving the birth provider.
place, the health professional should communicate with • The mother has been counseled regarding routine
the mother and the family members. The following facts newborn care and her queries are answered.
should be clearly told to the family: (i) gender of the baby, • Follow-up advice should be communicated to the
(ii) birth weight, (iii) well-being of the baby, (iv) need for mother. Babies, particularly born to primigravida
initiation of breastfeeding within one hour and need for mothers should be called for follow-up visit at 48 hours
continued observation for any problem. of discharge, if discharged before 72 hours.
• Parents have been explained the following 'danger
Rooming in: Normal newborn should not be separated signs' when they need to bring the baby to the hospital:
from the mother. In the initial a few hours of life, the baby i. Difficulty in feeding or poor feeding
is very active and co-bedding of the baby with mother
ii. Convulsion
facilitates early breastfeeding and bonding. Studies have
shown that any separation during initial hours may have iii. Lethargy (movement only when stimulated)
a deterimental effect on successful breastfeeding. iv. Fast breathing (RR >60/min)
v. Severe chest indrawing
Care of Baby beyond a Few Hours after Birth vi. Temperature of more than 37.5° C or below 35.5 °C
• A date for follow-up has been assigned. A normal
Care of the cord: The umbilical stump should be kept dry
newborn with adequacy of breastfeeding and no
and devoid of any application. The nappy of the baby
significant jaundice by 72 hours of age can be seen at
should be folded well below the stump to avoid any
6 weeks of age. In presence of any high-risk factor (e.g.
contamination.
low birth weight, prematurity significant jaundice, or
Exclusive breastfeeding: A proactive and a systematic feeding not established), the baby should be seen within
approach should be followed to initiate, support and 2-3 days of discharge.
maintain breastfeeding. The various advantages of the
breastfeeding should be discussed with the mother to Common Parental Concerns
motivate her. Availability of dedicated lactation nurse or • Weight loss in first week: Normally, babies lose 8-10% of
counsel or significantly improves the chances of successful birth weight in the first week of life which is regained
breastfeeding. by 7-10 days age. Subsequently, there should be a gain
Position of sleep: Evidence has linked prone position to of 20 to 40 g per day.
the occurrence of sudden infant death syndrome (SIDS). • Crying during micturition: The sensation of a full bladder
All healthy term newborns should be put to sleep on their is uncomfortable to many babies who cry before passing
back (supine position). urine and they quieten as soon as the act of micturition
starts. Crying during passage of urine as opposed to
Traditional practices that should be discouraged: The before the act of micturition should alert clinician to
application of kajal or surma in the eyes, putting oil in the the possibility of urinary tract infection.
ear or applying cow-dung on cord must be strongly • Bathing: During the first week, till cord falls off, only
discouraged. sponging is recommended which can be given after the
Timing of discharge in a normal newborn. A normal first 24 hours of life. Later, bathing every 2-3 days is
baby should stay in the health facility for at least 24 hours quite sufficient. A draught-free warm room, warm
and preferably for 48 hours. Smaller babies or those with water and quick completion of bath ensure that the baby
feeding problems or sickness should remain in hospital does not get cold during bathing. The head constitutes
as required. a large surface area of the baby; therefore, it should be
The following criteria should be met in all the babies washed last and dried first. Bathing time can be used
prior to discharge: to inspect baby's cord, eyes and skin for any discharge,
• The routine formal examination of the newborn has rash or redness.
been performed and documented. • Cosmetics: Babies have a sensitive skin and use of
• The newborn is breastfeeding properly. The adequacy cosmetics should be minimized. A low alkalinity, mild,
of feeds can be determined by: non-perfumed/non-medicated soap should be used.
- Passage of urine 6 to 8 times every 24 hours Any oil except mustard oil can be used. Sprinkling
- Baby sleeping well for 2-3 hours after feeds. talcum powder on babies can result in its inhalation
• The newborn has received the immunization as per and should be avoided. Avoid products containing
schedule. boric acid (present in most prickly heat preparations).
• The mother is confident and trained to take care of the • Regurgitation (posseting): Babies commonly regurgitate
neonate. small amount of curdled milk soon after feeding. This
136 Essential Pediatrics
Table 9.6: Newborn history and examination: Format for case presentation
History
General Mother's name and age, parity, last menstrual period, expected date of delivery
Past obstetric history Past pregnancies: When, gestation, fetal or neonatal problems, current status of children
Antenatal Number of antenatal visits, tests (hemoglobin; urine albumin, sugar; ultrasound; blood group, VDRL,
HIV), tetanus toxoid immunization, supplements (iron, folic acid, calcium, iodine)
Obstetric or medical Obstetric complications (toxemia, urinary tract infections, twins/triplets, placenta previa, accidental
complications hemorrhage); fetal problems (IUGR, hydrops, Rh isoimmunization); medical problems (diabetes,
hypertension); investigations, medications, course
Labor Presentation, onset of labor (spontaneous/induced), rupture of membranes (spontaneous/artificial),
liquor (clear/meconium stained); duration of first and second stage of labor; fetal heart rate (tachycardia,
bradycardia, irregular)
Delivery Place of delivery, vaginal (spontaneous/forceps/vacuum), cesarean (indication, elective/emergency);
local/general anesthesia; duration of third stage; postpartum hemorrhage
Immediate care at birth Resuscitation; time of first breath and cry; Apgar score; cord care; passage of urine/stool
Feeding history Breastfeeding (when initiated, frequency, adequacy); other feeds
Postnatal problems Feeding problems, jaundice, eye discharge, fever; current problems
Family history History of perinatal illness in other siblings
Past medical problems History of past medical problems, if any
Personal/social history Socioeconomic status, family support
General examination
Immediately after birth Weight, gestation, congenital anomalies, sex assigning, Apgar scores, examination of umbilical vessel,
and placenta
Appearance Overall appearance: Well or sick looking; alert/unconscious
Vital signs Temperature, cold stress; respiratory rate, retractions, grunt/stridor; heart rate, palpable femoral
arteries; blood pressure, capillary refill time; cry; apneic spells
Anthropometry Weight, length, head circumference, chest circumference
Gestation Assessment by physical criteria; more detailed assessment by expanded New Ballard examination
Classification by Appropriate/small/large for gestational age; symmetric or asymmetric small for gestational
intrauterine growth age; signs of IUGR
Congenital anomalies Head to toe examination for malformations
Birth trauma Signs of trauma; cephalohematoma
Common signs Cyanosis, jaundice, pallor, bleed, pustules, edema, depressed fontanel
Special signs Caput; eye discharge; umbilical stump; discharge or redness; jitteriness; eye discharge; oral thrush;
development peculiarities (toxic erythema, Epstein pearls, breast engorgement, vaginal bleeding,
capillary hemangioma, mongolian spot)
Feeding Observe feeding on breast (check positioning and attachment)
Reflexes Moro, grasp, rooting
Systemic examination
Chest Shape; respiratory rate; retractions; air entry; adventitious sounds
Cardiovascular system Apical impulse, heart sounds, murmur
Abdomen Distension, wall edema, tenderness, palpable liver/spleen/kidneys, any other lump, ascites, hernial
sites, gonads, genitalia
Musculoskeletal system Deformities; tests for developmental dysplasia of hip; club foot
Central nervous system State of consciousness; vision, pupils, eye movements; facial sensation; hearing; sucking and
swallowing; muscle tone and posture; power; tendon reflexes
IUGR: Intrauterine growth retardation
and plethora should be made. One should also look at the the apex of the baby's axilla by holding the thermometer.
spontaneous movements shown by the baby. The finding of hypothermia (temperature of less than
36.5 ° C) in neonate has very important connotations.
Vital Signs Neonates have a normal respiratory rate of 40--60 breaths/
In a sick baby, assessment of vital parameters takes priority minute. The HR is faster in preterm babies compared to
over all other examination. Temperature is measured in term babies. The normal HR range is 110-160 beats per
138 Essential Pediatrics
---
thickness, transparency and edema, rashes and lesions like
-
4000
Fig. 9 .12: Salient difference in physical characteristics of preterm and term neonates: (a) Well-curved pinna, cartilage reaching
up to periphery; (b) Flat and soft pinna, cartilage not reaching up to periphery; (c) Well-pigmented and pendulous scrotal sacs,
with fully descended testes: (d) Light pigmentation and not yet descended testes: (e) Deep transverse creases on the soles: (f) Faint
marks on the sole, no deep creases; (g) Well-formed breast bud (>5 mm); (h) Poorly developed breast bud; (i) Silky hair, where
individual strands can be made out; (j) Fuzzy hair; (kl Labia majora covering clitoris and labia minora; and (I) Prominent labia
minora and clitoris
tightly shut while crying (Fig. 9.13). Nose is looked for its Subconjunctival hemorrhages are common after vaginal
size, shape, secretions, patency and flaring. The flaring of delivery and resolve spontaneously. The cornea should
the nostrils indicates an increase in respiratory efforts be clear. Pupils should be equal in size, reactive to light
regardless of the cause. and symmetrical.
Gross hearing is often assessed by looking for blink on
The alveolar ridge may have natal teeth or retention response to noise. More formal hearing screening for all
cysts (also called Epstein pearls) that disappear in a newborns is now recommended. Accessory auricles and
few weeks. It is very important to examine the palate for preauricular tags are common finding that may be
cleft. associated with renal anomalies.
140 Essential Pediatrics
Fig. 9.15: Sinus in lower back may signify underlying neural tube
defect
Neurological Examination
This consists of the assessment of the level of alertness
and examination of cranial nerves, motor and sensory
system and neonatal reflexes.
Cranial nerves: Neonates respond to cotton soaked in
peppermint by 32 weeks of gestation. By 26 weeks, the
infant consistently blinks in response to light and by term
a gestation, fixation and following (tested using fluffy red
yarn ball) is well established.
By 28 weeks, the infant startles or blinks to loud
noise. Sucking and swallowing are important aspects
that should be examined as they give insight into the
proper functioning of the V, VII, IX, X and XII cranial
nerves.
The act of sucking requires the coordinated action of
breathing, sucking and swallowing. Suck-swallow
coordination so as to accept paladai feeding is present by
32 weeks. Suck-swallow and breathing coordination
occurs by 34 weeks when baby can breastfeed. However,
perfect coordination of suck-swallow and breathing
develops only by 38 weeks of gestation.
Fig. 9.16: (a) Congenital talipes equinovarus deformity; (b) A Motor examination: By 28 weeks, there is minimal
newborn delivered by extended breech. Note lower limbs with resistance to passive manipulation of all the limbs and a
extended knees and flexed hips
distinct flexor tone is appreciated in lower extremities by
32 weeks. By 36 weeks, flexor tone is palpable in both the
Cardiovascular System lower and upper extremities.
An infant with heart disease manifests with tachypnea, Primary neonatal reflexes: Moro reflex is best elicited by
cyanosis or both. The position of apical impulse may give the sudden dropping of the baby's head in relation to trunk;
idea regarding presence of conditions like congenital the response consists of opening of the hands and extension
diaphragmatic hernia (CDH) and pneumothorax. Presence and abduction of the upper extremities, followed by anterior
of a cardiac murmur requires complete evaluation of a flexion (embracing) of upper extremities with an audible
neonate. Bilateral femoral artery pulsation may be absent cry (Fig. 9.17). The hand-opening is present by 28 weeks,
in the coarctation of aorta. extension and abduction by 32 weeks and anterior flexion
by 37 weeks. Moro reflex disappears by 3-6 months in
Abdomen normal infants. The most common cause of depressed or
absent Moro reflex is a generalized disturbance of the
Inspection of abdomen may reveal unusual flatness or
central nervous system. An asymmetrical Moro reflex is
scaphoid shape of abdomen that may be associated with
indicative of root plexus injury.
CDH. Visible gastric or bowel patterns may indicate ileus
or other obstruction. Normally, 1-2 cm of liver, tip of The palmar grasp is clearly present at 28 weeks of
gestation and is strong by 32 weeks. This allows the lifting
the spleen and the lower pole of the left kidney may be
of the baby at 37 weeks of gestation. This becomes less
palpated.
consistent on development of voluntary grasping by
4 months. The tonic neck response is another important
Musculoskeletal System
response elicited by rotation of the head, that causes
The common alterations are deformations caused by extension of the upper extremity on the side to which the
adverse mechanical factors in utero. Most positional face is rotated and flexion of the upper extremity on the
deformities are mild and resolve in time. The hips are to side of the occiput. This disappears by 4 months.
142 Essential Pediatrics
Fig. 9.17: Moro reflex: (a) Abduction and extension of arms is followed by; (b) Adduction and flexion component;
(c) Asymetric Moro reflex in brachial plexus injury (Erb's palsy on the right side-the upper limb does not move)
Hypothermia
Displace bilirubin
bound to albumin Anaerobic metabolism, glycolysis
Hyperbilirubinemia Hypoxemia
Metabolic acidosis
Management
Methods for temperature maintenance include skin-to
skin contact, warm room, radiant warmers, incubators and
increasing ambient temperature by use of hot air blowers,
or a 200 watt bulb.
Severe Hypothermia
Fig. 9.20: (a) An incubator; and (bl Radiant warmer. Note that • Remove all wet clothing and place baby in an incubator
incubator is covered with cloth to prevent excessive light or (air temperature 35-36 °C), preheated radiant warmer
noise for adequate comfort of the baby or thermostatically controlled heated mattress set at
37-38 °C. Alternately, one may use a room heater.
temperature inside incubator by altering heater output • Once baby's temperature reaches 34 °C, the rewarming
based on baby's temperature and thereby maintains the process should be slowed down.
temperature of baby in the normal range. • Temperature is measured every hour for 3 hours. If rise
A radiant warmer is an open system (as compared to of temperature has been by 0.5 °C per hour, then heating
incubator which is a closed cabinet) and the neonate lies is considered adequate and temperature measurement
on a crib. There is overhead radiant warmer that is continued 2 hourly until normal body temperature
modulates its heater output based on baby's temperature is attained and thereafter 3 hourly for 12 hours. If rise
sensed by a skin probe. of temperature is not adequate, one should check the
Radiant warmers and incubators should be used in the heating technique.
servo-control mode with the abdominal skin temperature • Provide oxygen, empirical antibiotics, saline bolus if
maintained at 36.5 °C to 37 °C. shock, IV dextrose and vitamin K. Monitor vitals.
Signs and Symptoms
Suggested Reading
Peripheral vasoconstriction results in acrocyanosis, cool
• Guidelines for perinatal care. Second Edition, American Acade my
extremities and delayed peripheral capillary refill time of Pe di a trics and American College of Obste trici ans and
(CRT). The baby becomes restless and then lethargic. Gynecologists, 1998
Chronic or recurrent episodes of hypothermia result in • Thermal protection of the newborn: A practical guide. WHO/
poor weight gain. Cardiovascular manifestations may FHW/MSM/97.2
Newborn Infants 1145-
• •
diarrhea.
• Giving supplements such as sugar water, gripe water,
honey, breast milk substitutes or formula, either as Thinks lovingly of baby
prelacteal(before initiation of breastfeeding) or Sound and sight of baby
supplemental (concurrent to breastfeeding) feeds. instils confidence
Studies have reported that even 1 or 2 supplemental
feeds reduce the chances of successful breastfeeding. These help reflex
• Painful breast conditions like sore or cracked nipples
and engorged breast.
• Lack of night feeding, as the prolactin reflex is not
adequately stimulated.
C
• Inadequate emptying of breast such as when baby is
sick or small and the mother does not manually express Fig. 9.22: (a) Prolactin; (bl Oxytocin reflex; and (c) Factors which
breast milk or when baby is fed less frequently. help and hinder oxytocin reflex
Newborn Infants 1147-
Reflexes in the Baby iv. Preterm milk is the milk of a mother who delivers before
A baby is born with certain reflexes which help the baby 37 weeks. It contains more proteins, sodium, iron,
to feed. These include rooting, suckling and swallowing immunoglobulins and calories as per the requirement
reflexes. of preterm baby.
v. Foremilk is the milk secreted at the start of a feed. It is
The rooting reflex: When cheek or the side of the mouth is watery and is rich in proteins, sugar, vitamins, minerals
touched, the baby opens her mouth and searches for the
and water that quenches the baby's thirst.
nipple. This is called rooting reflex. This reflex helps the baby
vi. Hindmilk comes later towards the end of feed and is
to find the nipple and in proper attachment to the breast.
richer in fat that provides more energy and gives a
The suckling reflex: When baby's palate is touched with sense of satiety. Thus, the composition of milk also
nipple, the baby starts sucking movements. This reflex is varies during the phase of feeding. For optimum
very strong immediately after birth. The suckling reflex growth, the baby needs both fore- as well as hind-milk.
consists of: Therefore, the baby should be allowed to empty out
• Drawing in the nipple and areola to form an elongated one breast completely before switching over to the
teat inside the mouth. other.
• Pressing the stretched nipple and areola with the jaw
and tongue against the palate. Technique of Breastfeeding
• Drawing milk from the lactiferous sinuses by wave Mothers require substantial assistance to learn the technique
like peristaltic movement of the tongue underneath the of breastfeeding. With correct technique, breastfeeding is
areola and the nipple and compressing them against natural and a pleasurable experience for the mother.
the palate above. However, a variety of breastfeeding problems do occur
To suckle effectively, the baby has to attach (latch) well. in large proportion of mothers that require counseling and
Obtaining good attachment at breast is a skill, which both support from the health providers for their prevention and
the mother and the baby have to learn. appropriate treatment.
The method of suckling at the breast and bottle is
Positioning
entirely different. Suckling on a bottle filled with milk is a
passive process and the baby has to control the flow of milk Position of the mother: The mother can assume any
into the mouth with her tongue. While breastfeeding requires position that is comfortable to her and the baby. She can
active efforts by the baby. A bottlefed baby develops sit or lie down. Her back should be well supported and
nipple confusion and refuses to feed on the breast. Single she should not be leaning on her baby (Fig. 9.23).
session of bottle-feeding lessens the chances of successful Position of baby: Make sure that baby is wrapped
breastfeeding. Bottle-feeding of babies is fraught with risk properly in a cloth
of serious infections and consequent ill-health. i. Baby's whole body is supported not just neck or
The swallowing reflex: When the mouth is filled with milk, shoulders.
the baby reflexly swallows the milk. It requires a couple ii. Baby's head and body are in one line without any twist
of suckles before baby can get enough milk to trigger in the neck.
swallowing reflex. It requires coordination with breathing. iii. Baby's body turned towards the mother (abdomens
The suckle-swallow-breathe cycle lasts for about one of the baby and the mother touching each other).
second. iv. Baby's nose is at the level of the nipple.
�
Step two ..----
11 �
� '--fl
r-lJ
Insert piston
� ..--- from cut end
Resuscitation
Problems
• Compromised intrauterine environment with higher
chances of perinatal asphyxia.
• Preterm babies have immature lungs that may be more
difficult to ventilate.
• Immature blood vessels in the brain are prone to
hemorrhage.
• Thin skin and a large surface area, which contribute to
rapid heat loss.
Fig. 9.28: Baby with intrauterine growth retardation showing • Increased risk of hyp ovolemic shock caused by small
many loose folds of skin blood volume.
Management
Table 9.8: Major problems in preterm babies and those with • Adequate preparation for higher need for resuscitation
intrauterine growth retardation (IUGR) • Gentle resuscitation using small bags for positive
pressure ventilation, use of CPAP
Preterm babies
• Take extra care to avoid hypothermia
Hypothermia
Perinatal asphyxia Temperature Control
Respiratory (hyaline membrane disease, pulmonary hemorr Problems
hage, pneumothorax, bronchopulmonary dysplasia, pneumonia)
• Higher surface area to body weight ratio
Bacterial sepsis
• Low glycogen stores
Apnea of prematurity
• Low subcutaneous fat
Metabolic (hypoglycemia, hypocalcemia)
Hematologic (anemia, hyperbilirubinemia) Management
Feeding problems and poor weight gain • Frequent monitoring and educating parents
• Special attention to maintenance of the warm chain
Babies with IUGR • Kangaroo mother care
Perinatal asphyxia
Meconium aspiration Fluids and Feeding
Hypothermia These have been discussed under the section on feeding.
Hypoglycemia
Feed intolerance Infection
Polycythemia Problems
Poor weight gain • Immature defenses
• Greater probability of invasive interventions like
mechanical ventilation, umbilical vessel catheterization.
• Asymmetric IUGR: The insult on the fetal growth occurs
Management
during late gestation producing a brain sparing effect.
• Strict adherence to asepsis, hand hygiene
Head circumference is relatively preserved compared
• Minimal handling of babies
to length and weight. Causes include placental
insufficiency, pregnancy-induced hypertension or • High index of suspicion of sepsis, rationale use of
antibiotics
maternal medical diseases.
• Decreasing exposure to adults/other children with
Small for gestational age (SGA): It is a statistical definition communicable diseases particularly respiratory.
and denotes weight of infant being less than 2 standard
deviation or less than the 10th percentile of the population Metabollc Derangements
norms (plotted on intrauterine growth chart). For the Problems
practical purpose, SGA and IUGR are considered • Low hepatic glycogen stores with rapid depletion in stress
synonymous. places these infants at increased risk of hypoglycemia.
Newborn Infants l1s1-
Birth weight
1200 to 1800 g
May take days to May take a few days before KMC can be initiated
weeks before KMC can KMC can be initiated immediately after birth
be initiated
Fig. 9.30: (a) Mother and (b) Father practicing KMC in front open gown and shawl; (c) AIIMS KMC jacket; (d) Mother performing
KMC using AIIMS KMC jacket, (e) A mother providing KMC to her twin babies. One baby is receiving oxygen by open tube; and
(fl KMC being practiced in a ventilated baby
Newborn Infants 1153-
Procedure
Kangaroo positioning: The baby should be placed between
the mother's breasts in an upright position (Fig. 9.31). The
head should be turned to one side and in a slightly
extended position. This slightly extended head position
keeps the airway open and allows eye-to-eye contact
between the mother and her baby. The hips should be
flexed and abducted in a 'frog' position; the arms should
also be flexed. Baby's abdomen should be at the level of
the mother's epigastrium. Mother's breathing stimulates
the baby, thus reducing the occurrence of apnea. Support
the baby's bottom with a sling or binder.
Monitoring: Babies receiving KMC should be monitored
carefully, especially during the initial stages. The baby's
neck position is neither too flexed nor too extended,
breathing is regular, color is pink and baby is maintaining
temperature.
Feeding: The mother should be explained how to
breastfeed while the baby is in KMC position. Holding
the baby near the breast stimulates milk production. She
may express milk while the baby is still in KMC position.
The baby could be fed with paladai, spoon or tube,
depending on the condition of the baby.
Privacy: The staff must respect mother's sensitivities in this
regard and ensure culturally acceptable privacy standards
in the nursery and the wards where KMC is practiced.
Duration: Skin-to-skin contact should start gradually in
the nursery, with a smooth transition from conventional
care to continuous KMC (Fig. 9.32). Sessions that last less
than one hour should be avoided because frequent
handling may be stressful for the baby. The length of skin
to-skin contact should be gradually increased up to
24 hours a day, interrupted only for changing diapers.
When the baby does not require intensive care, she should
be transferred to the postnatal ward where KMC should
be continued.
The mother can sleep with baby in KMC position in
reclined or semirecumbent position about 30 ° from
horizontal. This can be done with an adjustable bed or
with pillows on an ordinary bed. A comfortable chair
with an adjustable back may be used for resting during
the day.
FLUID AND ELECTROLYTE MANAGEMENT be 10% dextrose with no electrolytes in order to maintain
a glucose infusion rate of 4--6 mg/kg/min. As the infant
Transition from fetal to extrauterine life is accompanied
grows and receives enteral feeds, the solute load presented
by remarkable changes in body fluid composition.
to the kidneys increases and the infant requires more fluid
Neonates are born with an excess of total body water
to excrete the solute load. Water is also required for fecal
(TBW) primarily in the extracellular fluid (ECF)
losses and for growth purposes. Therefore, the fluid
compartment. This excess of TBW is normally lost by
requirements increase by 15 to 20 mL/kg/ day till a
diuresis during first week of life. Term neonates lose about
maximum of 150 mL/kg/day by the 7th day. Sodium and
7-10% of body weight during first 3 to 5 days of life.
potassium should be added to IV fluids after 48 hours.
Preterm neonates have proportionately higher TBW and,
therefore, may lose up to 10-15% of birth weight during Babies with birth weight <1500 g: The urine output in
first week of life. these babies is similar to a baby of 1500 g or more.
The heart, kidneys, the skin and the neuroendocrine However, the fluid requirement is higher due to increased
system regulate fluid and electrolyte balance in neonates. IWL. These babies need 80 mL/kg/day of 10% dextrose
In neonates, kidneys have a limited capacity to concentrate on day 1 of life (Table 9.9). The babies should ideally be
or dilute urine due to lower glomerular filtration rate and dressed including provision of caps and socks to reduce
reduced proximal and distal tubular sodium reabsorption. the IWL under the radiant warmer. As the skin matures,
In addition to water loss by the kidneys and the IWL progressively decreases and fluid requirement
gastrointestinal system, additional water losses occur due becomes similar to bigger babies. Fluids need to be
to evaporation from the skin and respiratory tract increased at 10-15 mL/kg/day up to a maximum of 150
(insensible water loss; IWL). IWL is higher in preterm mL/kg/day by 5th to 7th day. Sodium and potassium
infants owing to thin skin. Fever, increased respiratory should be added to IV fluids after 48 hours.
rate, radiant warmers and phototherapy increase IWL. Problems with IV fluid therapy include local and
systemic infection, phlebitis, fluid overload and extra
Guidelines for Fluid Therapy vasation. Because IV fluid therapy is a major risk factor
Healthy babies of 1200 g or more should be started on for nosocomial infection, all asepsis precautions must be
enteral feeding with breast milk. A baby of 1800 g or more followed during insertion of IV cannula or administering
would be able to breastfeed directly while a smaller baby fluids. Oral feeds should be started at the earliest possible
may require expressed breast milk fed by suitable alternate opportunity when clinical condition of neonate improves
route. and IV fluid should be stopped when oral feeds constitute
Intravenous (IV) fluid therapy: IV fluids are indicated about two-thirds of daily fluid requirement. IV sites
when baby is either small or sick. Babies less than <28 should be inspected frequently to timely detect
weeks should be started on IV fluids routinely. Sick babies extravasation.
(irrespective of weight or gestation) such as those with Calculation of fluids for a 1250 g baby:
respiratory distress, significant asphyxia, feed intolerance, • Day 1: 100 mL (80 mL/kg) to be infused at 4.2 mL/hr
hemodynamic instability, gastrointestinal malformations • Day 2: 120 mL (95 mL/kg) to be infused at 5.0 mL/hr
(like tracheoesophageal fistula, intestinal atresia, etc.) or
any other severe illness precluding oral feeding should Monitoring of Fluid and Electrolyte Status
be given IV fluids. Peripheral intravenous line is the most Fluid therapy should be monitored every 12 to 24 hours
common route used to provide fluids. Fluid requirement in a baby on IV fluids using following parameters:
is calculated based on birth weight, day of life and the Body weight: Serial weight measurements can be used as
current fluid balance. a guide to estimate the fluid deficit in newborns. Term
Babies with birth weight >1500 g: Infants on IV fluids neonates lose 1-3% of their birth weight daily with a
require to excrete a solute load of about 15 mOsm/kg/ cumulative loss of 5-10% in the first week of life. Preterm
day in the urine. To excrete this solute load at a urine neonates lose 2-3% of their birth weight daily with a
osmolarity of 300 mOsm/L, the infant would have to pass cumulative loss of 10-15% in the first week of life. Failure
a minimum of 50 mL/kg/day of urine. Allowing for an to lose weight in the first week of life may be an indicator
additional IWL of 20 mL/kg, the initial fluids should be of excessive fluid administration. However, excessive
60-80 mL/kg/day (Table 9.9). The initial fluids should weight loss (>3% in 24 hours) in the first 5-7 days or later
Table 9.9: Daily fluid requirements during first week of life (mUkg/day)
Birth weight Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 and onwards
would be non-physiological and would merit correction The appropriate method of feeding in an LBW infant is
with fluid therapy. decided by following factors:
Clinical examination: The usual physical signs of • Whether the infant is sick or not; and
dehydration are unreliable in neonates. Infants with 10% • Feeding ability of the infant
(100 mL/kg) dehydration may have sunken eyes and
fontanel, cold and clammy skin, poor skin turgor and Level of Sickness
oliguria. Infants with 15% (150 mL/kg) or more It is essential to categorize LBW infants into two major
dehydration would have signs of shock (hypotension, groups, sick and healthy, before deciding the initial
tachycardia and weak pulses). method of feeding.
Urine output: A well-hydrated baby would pass urine at Sick infants: This group constitutes infants experiencing
1 to 3 mL/kg/hr. various significant illnesses such as respiratory distress
requiring assisted ventilation, shock, seizures, etc. These
Suggested Reading infants generally require IV fluids. Enteral feeds are
• Chawla D, Agarwal R, Deorari AK, Paul VK. Fluid and electrolyte
initiated as soon as they reasonably recover from the
management in term and preterm neonates.Indian J Pediatr. illness and are hemodynamically stable. The choice of
2008;75:255-9. feeding method depends on the infants' gestation and
clinical condition.
Feeding of LBW Babies The enteral feeding is important for sick neonates and
Nutritional management influences immediate survival not be delayed without a valid reason. The infants with
as well as subsequent growth and development of LBW respiratory distress receiving mechanical ventilation can
infants. Early nutrition could also influence the long-term be fed enterally once the acute phase is over. Similarly,
neurodevelopmental outcomes. sepsis (unless associated with shock/sclerema/NEC) is
Term infants with normal birth weight require some not a contraindication for enteral feeding.
assistance for feeding in the immediate postnatal period, Healthy LBW infants: Enteral feeding should be initiated
but they are able to feed directly from mothers' breast. immediately after birth in healthy LBW infants with the
In contrast, feeding in LBW infants has following appropriate feeding method determined by their oral
limitations: feeding skills and gestation.
i. Over one-third of LBW infants are born at preterm with
inadequate feeding skills. They might not be able to Ability to Feed
breastfeed efficiently and require alternate methods Breastfeeding requires effective sucking, swallowing and
of feeding such as spoon or gastric tube feeding. a proper coordination between suck/ swallow and
ii. Many LBW babies have significant illnesses during breathing. These complex skills mature with increasing
first few days of life interfering enteral feeding. gestation. A robust sucking pattern is not present until
iii. Preterm infants have higher fluid requirements in the 32-34 weeks gestation. A coordination between sucking,
swallowing and breathing does not mature until 34 weeks
first few days of life due to higher insensible water
of gestation and it fully matures by 37 to 38 weeks of
loss.
gestation. The maturation of oral feeding skills and the
iv. Since intrauterine accretion of many nutrients occurs choice of initial feeding method at different gestational
mainly in third trimester, preterm infants (particularly ages are summarized in Table 9.10.
those born before 32 weeks of gestation) have lower Not all infants born at a particular gestation would have
body stores of these nutrients at birth, which same feeding skills. Hence, the feeding method in an infant
necessitates supplementation in the postnatal period. is individualized based on the feeding skills (Fig. 9.33).
v. Because of the gut immaturity, they are more likely to Stable LBW infants, irrespective of their initial feeding
experience feed intolerance necessitating adequate method, should be offered direct breastfeeding. This helps
monitoring and treatment. in faster acquisition of feeding skills of smaller preterm
infants and improves milk production in their mothers
Methods (non-nutritive sucking). Figure 9.34 shows the method of
Direct and exclusive breastfeeding is the goal of feeding paladai and gastric tube (gavage) feeding.
all LBW infants. However, because of the various
limitations, not all LBW infants would be able to accept Progression of Oral Feeds
breastfeeding at least during the initial a few days after All LBW infants, irrespective of their gestation and birth
birth. These infants have to be fed by either spoon/paladai weight, should ultimately be able to feed directly from
or gastric tube (gavage) feeding. The babies not able to the mothers' breast. For preterm LBW infants, the
receive any enteral feeding at all require intravenous (IV) progression to direct and exclusive breastfeeding is
fluids. summarized in Fig. 9.35.
156 Essential Pediatrics
Table 9.10: Maturation of oral feeding skills and the choice of initial feeding method in LBW infants
Gestational age, weeks Maturation of feeding skills Initial feeding method
<28 weeks Inadequate sucking efforts Intravenous fluids
Lack of propulsive gut motility
28-31 weeks Sucking bursts develop Orogastric or nasogastric tube feeding with
Lack of coordination between suck/ occasional spoon or paladai feeding
swallow and breathing
32-34 weeks Slightly mature sucking pattern Feeding by spoon or paladai
Coordination between breathing and
swallowing begins
>34 weeks Mature sucking pattern Breastfeeding
Coordination between breathing
and swallowing
>34 weeks
Initiate breastfeeding
Observe if:
Positioning and attachment are good
Able to suck effectively and long enough
(about 10-15 min) 32-34 weeks
Yes No
Breastfeeding Start feeds by spoon or paladai
Observe if:
Accepting well without spilling/coughing
Able to accept adequate amount 28-31 weeks
I I
Yes No
Spoon or paladai feeding Start feeds by orogastric or nasogastric tube
Observe if:
Vomiting or abdominal distension occurs
No
Infant on IV fluids
If hemodynamically stable
If accepting well
Fig. 9.35: Progression of oral feeding in preterm LBW infants. Term and near-term sick infants started on intravenous (IV) fluids can
be Initiated on breastfeeding once they are hemodynamlcally stable
milk can be stored for about 6 hours at room temperature Infants who are fed by spoonlpaladai or by intragastric
and for 24 hours in domestic refrigerator (2° to 8° C). tube: The daily fluid requirements of neonates have been
The steps of breast milk expression are given in Fig. 9.27. discussed in the section of fluids and electrolytes. VLBW
infants ( <1500 g) need about 80 mL/kg fluids on the first
Sick mothers/contraindication to breastfeeding: In these day of life. It needs to increased by 10-15 mL/kg/day to
rare circumstances, the options available are: a maximum of 160 mL/kg/day by the end of the first week
i. Formula feeds: of life. LBW infants >1500 g are usually given about
a. Preterm formula in VLBW infants, and 60 mL/kg fluids on the first day of life and fluid intake is
b. Term formula in infants weighing 1500 g or more increased by about 15-20 mL/kg/day to a maximum of
at birth 160 mL/kg/day by the end of the first week of life. The
ii. Animal milk, e.g. undiluted cow milk volume for an individual feed can be determined by diving
Once the mother's condition becomes stable (or the total fluid to be given divided by number of feeds planned
contraindication to breastfeeding no longer exists), these in 24 hours.
infants should be started on exclusive breastfeeding.
Nutritional Supplementation
How Much to Feed? Birth weight of 1500-2499 g: These infants are more likely
Infants who are breastfed: Infants who are able to suckle to be born at term or near term gestation (>34 weeks). They
effectively at the breast should be breastfed on demand. need vitamin D and iron (Table 9.11).
Small babies ( <2000 g) may not be relied on demand Birth weight <1500 g: Those infants who are usually born
feeding and be fed every 2-3 hours. before 32-34 weeks gestation have inadequate body stores
Table 9.11: Nutritional supplements for infants with birth weight between 1500 g and 2499 g
Nutrients Method of supplementation Dose Duration
Vitamin D Multivitamin drops or syrup 400 IU/day 2 weeks to 1 year of age
Iron Iron drops or syrup 2 mg/kg/day (maximum 15 mg) 6-8 weeks to 1 year of age
158 Essential Pediatrics
of most of the nutrients. Since EBM has inadequate Table 9.12: Causes of inadequate weight gain
amounts of protein, energy, calcium, phosphorus, trace
Inadequate intake
elements (iron, zinc) and vitamins D, E and K, it is often
not able to meet the daily requirement of these infants. Breastfed infants
Hence, these infants need multinutrient supplementation Incorrect feeding method (improper positioning or
till they reach term gestation (40 weeks, i.e. until the attachment)*
expected date of delivery). These nutrients can be Less frequent breastfeeding, not feeding in the night hours*
provided by fortification of expressed breast milk with Infants on spoon or paladai feeds
human milk fortifiers (HMF). Fortification increases the Incorrect method of feeding* (e.g. excess spilling)
nutrient content of the milk without compromising its Incorrect measurement or calculation
other beneficial effects. As HMF does not provide Infrequent feeding*
adequate iron, the same has to be given separately in form Not fortifying the milk in VLBW infants
of drops. Fortification or supplementation of minerals and
vitamins should be continued only till term gestation (40 Increased demands
weeks) in VLBW infants. After 40 weeks, only vitamin D Hypothermia or cold stress*
and iron needs to be supplemented (similar to infants with Chronic illnesses, bronchopulmonary dysplasia
birth weights of >1500 g). Medications such as corticosteroids
*Common causes
Growth Monitoring of LBW Infants
Regular growth monitoring helps in assessing the iv. Proper demonstration of the correct method of
nutritional status and adequacy of feeding in LBW infants; expression of milk and paladai feeding: It is important
it also identifies those infants with inadequate weight gain. to observe how the mother gives paladai feeds; the
All LBW infants should be weighed daily until the time technique and amount of spillage should be noted. This
of discharge. Length and head circumference should be should be followed by a practical demonstration of the
recorded weekly. proper procedure.
Both term and preterm LBW infants tend to lose weight v. Ensuring optimum thermal protection
(about 10% and 15%, respectively) in the first 7 days of
life; they regain their birth weight by 10-14 days. Jaundice
Thereafter, the weight gain should be at least 15-20 g/kg/ Problems
day till a weight of 2-2.5 kg is reached. After this, a gain • Larger RBC volume for body weight
of 20 to 40 g/day is considered appropriate.
• Immaturity of hepatic enzymes and hepatic excretory
Growth charts: Using a growth chart is a simple and capacity
effective way to monitor the growth. Serial plotting of • Immature blood-brain barrier-increased risk for
weight and other anthropometric indicators in the growth bilirubin encephalopathy
chart allows the individual infant's growth to be compared
with a reference standard. It helps in early identification Management: This has been discussed in section on
of growth faltering in these infants. jaundice.
followed by application of 0.5% gentian violet four disruption of skin integrity with needle pricks and use of
times a day till redness subsides would take care. intravenous fluids.
• Severe infection: When area of redness extends beyond
1 cm of surrounding tissue or there are signs of sepsis Clinical Features
local therapy plus systemic antibiotic should be started NNS often manifests with vague and ill-defined symptoms
as in management of septicemia. and, therefore, requires high index of suspicion for early
Oral thrush: White patchy lesions on the oral mucosa and diagnosis. An early but non-specific manifestation is
tongue can occur in healthy newborns. True oral thrush alteration in the established feeding behavior. The baby,
lesions are difficult to wipe off and leave hemorrhagic who had been active and sucking normally, refuses to suck
points when removed. Local nystatin or clotrimazole and becomes lethargic, or unresponsive. Poor cry,
application four times a day after feed is recommended. hypothermia, abdominal distension, vomiting and apneic
spells are other common manifestations. Diarrhea is
Conjunctivitis: Infection should be differentiated from uncommon. Fast breathing, chest retractions and grunt
sticky eyes and blocked nasolacrimal duct. Sticky eyes indicate pneumonia. Most cases of meningitis do not have
generally manifests as mucoid discharge without any signs any distinct clinical picture per se, making it mandatory
of inflammation and requires cleaning with saline. to suspect meningitis in all cases suspected of sepsis.
Conjunctivitis manifests as purulent discharge and signs Shock, bleeding, sclerema and renal failure are indicators
of inflammation and requires local instillation of of overwhelming sepsis.
antibiotics. Gonococcal conjunctivtis can result in Diagnosis of sepsis is fraught with poor specificity. A
blindness and requires timely systemic antibiotics therapy. host of conditions like hypothermia, hyperthermia,
Systemic Infections (Neonatal Sepsis)
hypoglycemia, hypoxia, late metabolic acidosis,
congestive heart failure and even simple conditions like
When pathogenic organisms gain access into the blood nasal block may mimic sepsis. A careful clinical
stream, it can result into neonatal sepsis, which may be examination and relevant investigations are necessary to
generalized and/or localized to the lungs (pneumonia), differentiate these conditions from NNS and avoid
the meninges (meningitis) or bones and joints unnecessary antibiotics therapy. Babies who are clinically
(osteomyelitis/arthritis). Systemic bacterial infections are stable can be observed, without admission and
known by the generic term neonatal sepsis (NNS), which intravenous antibodies, while providing good supportive
incorporates generalized sepsis, pneumonia, meningitis care (Fig. 9.36).
and bone-joint infections.
Investigations
Etiology No investigation is required to start treatment in a sick
Escherichia coli, Staphylococcus aureus and Klebsiella sp. are baby who has high probability of sepsis (Fig. 9.36). Blood
the predominant organisms. Organisms like Acinetobacter, culture provides definitive diagnosis of NNS and should
Pseudomonas and coagulase negative staphylococci are be taken before starting antimicrobial therapy. After
also important pathogens in healthcare associated cleaning the skin (with alcohol, povidone iodine and again
infections. alcohol), a specimen of 0.5 to 1.0 mL of blood can be taken
in a small culture media bottle containing 5 to 10 mL of the
Early Versus Late Sepsis liquid broth.
Early-onset sepsis (EOS) (up to 72 hours after birth) A panel of tests (sepsis screen) consisting of total leukocyte
infections are caused by organisms prevalent in the count (TLC; <5000/mm3), absolute neutrophil count (ANC;
maternal genital tract or in the delivery area. EOS occurs <1800/mm3), immature to total neutrophil ratio (I/T ratio;
in presence of perinatal risk factors namely spontaneous more than 20%), CRP (more than 1 mg/dL) and micro-ESR
onset of preterm labor, prolonged rupture of membranes, (15 mm or more in the first hour) constitute a useful sepsis
foul smelling liquor, multiple per vaginal examinations, screen for clinically doubtful cases. Sepsis screen is
maternal fever, and difficult or prolonged labor. EOS considered positive, if two of these parameters are positive.
frequently manifests as pneumonia and less commonly Lumbar puncture should be performed in all cases
as septicemia or meningitis. suspected of NNS except in asymptomatic babies being
Late-onset sepsis (LOS) (72 hours or later) infections investigated for maternal risk factors. Table 9.13 provides
are caused by the organisms thriving in the external gestation specific cut offs for values of various parameters
environment of the home or the hospital. The infection is in cerebrospinal fluid.
often transmitted through the hands of the care-providers.
The presentation is that of generalized sepsis, pneumonia Treatment
or meningitis. The predisposing factors include LBW, lack Institution of prompt treatment is essential for ensuring
of breastfeeding, poor cord care, superficial infections optimum outcome of neonates with sepsis who often reach
(pyoderma, umbilical sepsis), aspiration of feeds and the health care facilities late and in a critical condition.
Newborn Infants 161-
Table 9.13: Normal CSF examination in neonates, mean (range) over 5-10 minutes, if perfusion is poor. Repeat the same
Test Term Preterm 1-2 times over the next 30-45 minutes, if perfusion
Cells continues to be poor. Dopamine and dobutamine may be
Leukocytes 7 (0-32) 9 (0-29) required to maintain normal perfusion.
Polymorphonuclear cells 61% 57% • Insert intravenous line. If hypoglycemia is suspected,
infuse glucose (10%) 2 mL/kg stat. Do not use glucose
Protein (mg/dl) 90 (20-170) 115 (65-150)
boluses routinely. Provide maintenance fluid,
Glucose (mg/dl) 52 (34-119) 50 (24-63) electrolytes and glucose (4-6 mg/kg/min). Add
potassium to N fluids once normal flow of urine has
Supportive care and antibiotics are the two equally been documented.
important components of treatment. Antibiotics take at • Ensuring optimal nutrition is extremely helpful in sick
least 12 to 24 hours to show any effect, optimum suppor babies. Enteral feeds should be initiated early, if there
tive care improves the outcomes in sick septic babies. is no abdominal distension and baby is hemo
dynamically stable. Feed mother's milk.
Supportive care: Good supportive care requires meticulous
attention to various aspects: Specific care: Antimicrobial therapy constitutes the
• Provide warmth; ensure normal temperature (36.5 °- mainstay of treatment of sepsis. In a seriously sick neonate
37.5 0 C). suspected of sepsis, appropriate antibiotics therapy should
• Start oxygen by hood or mask, if the baby is cyanosed be initiated without any delay after obtaining blood
or grunting. Provide bag and mask ventilation, if samples for culture.
breathing is inadequate. Instilling normal saline drops Empiric therapy when etiologic agent is not known: The
in nostrils may help clear the nasal block. empiric therapy of NNS should cover the major causative
• Assess peripheral perfusion by palpating peripheral pulses, pathogens while awaiting reports of culture studies.
capillary refill time (normally <2-3 seconds) and skin color. Since the antimicrobial spectrum and susceptibility
Serial measurement of urine output is helpful for this profile is different in different settings, there cannot be a
purpose. Infuse normal saline or Ringer lactate 10 mL/kg universal policy of empiric regimen. Antibiotics are often
162 Essential Pediatrics
used in neonates on the slightest suspicion of sepsis outcomes. The reported mortality rates in neonatal sepsis
because of the grave and fulminant nature of neonatal in various studies from India ranges between 45 and 58%.
sepsis. But unbridled overuse of antibiotics is associated
with the serious risk of emergence of resistant strains of Necrotizing Enterocolitis
pathogens. Most newborn units in the country are facing Necrotizing enterocolitis (NEC) occurs among smaller
the problem of overwhelming antimicrobial resistance to premature infants, often those less than 32 weeks. The
practically all antibiotics. Rational use of antibiotics is, clinical picture mimics neonatal septicemia because of the
therefore, the responsibility of every physician. presence of abdominal distension, apnea, bradycardia,
Each treating unit should adopt a suitable policy. Based instability of temperature, cyanosis and lethargy.
on changes in the spectrum of etiologic agents and the Management
antibiotics sensitivity pattern, the choice of antibiotics
must be periodically reviewed and modified. Table 9.14 Oral feeding should be withheld. A nasogastric tube is
provides possible regimen of empiric antibiotics. inserted to relieve distension and to aspirate stomach
contents. Fluids and electrolytes in adequate quantities
Therapy after an etiologic agent is known: Antimicrobial should be administered. Parenteral nutrition may be
therapy can be made specific once a positive culture and administered. The baby is given antibiotics after taking
sensitivity report is available. However, this would be suitable cultures. Shock is managed by replacement of
known only after 2-3 days. Even in best institutions, only fluids and use of vasopressor agents. Plasma and platelet
approximately one-fourth of babies suspected of sepsis transfusion may be necessary to prevent bleeding tendency.
have positive blood culture.
Suggested Reading
Mode of Administration and Dosage • Sankar MJ, Agarwal R, Deorari AK, Paul VK. Sepsis in the
Antibiotics should preferably be administered parenterally. newborn.Indian J Pediatr. 2008 Mar; 75:261--6.
In a baby with septicemia or pneumonia (but not
meningitis), who has received intravenous ampicillin and PERINATAL ASPHYXIA
gentamicin initially and is clinically well after 3 days, the Perinatal asphyxia is an insult to the fetus or newborn
physician may consider an individual basis switching over due to a lack of oxygen (hypoxia) and/ or a lack of per
to oral amoxycillin along with single-dose intramuscular fusion (ischemia) to various organs. It is often associated
gentamicin therapy for the rest of the course. with tissue lactic acidosis and hypercarbia.
There is no universally accepted definition of perinatal
Monitoring
asphyxia. The American Academy of Pediatrics Committee
Intensive care and monitoring is the key determinant of on Fetus and Newborn has suggested essential criteria
improved survival of neonates. The elements of (Table 9.15) for defining perinatal asphyxia.
monitoring in sepsis are not different from those in other In the absence of such quantification, it is better to use
life-threatening conditions. Proper monitoring of sick the term 'neonatal depression', which refers to a condition
babies enables care providers detection of complications of the infant in the immediate postnatal period
at the earliest. The periodicity of documenting the various (approximately 1st hr) without making any association
parameters should be individualized. with objective evidence.
National Neonatology Forum of India (NNF) and WHO
Prognosis use an Apgar of 0-3 and 4-7, at 1 min, to define severe
The outcome depends upon weight and maturity of the and moderate birth asphyxia, respectively (1985). For the
infant, type of etiologic agent, its antibiotic sensitivity community settings, NNF defines asphyxia as absence of
pattern; and adequacy of specific and supportive therapy. cry at 1 min and severe asphyxia as absent or inadequate
The early-onset septicemia carries higher risk of adverse breathing at 5 minutes.
Newborn Infants 1163-
Table 9.15: Essential criteria for perinatal asphyxia Table 9.16: Neurological patterns of hypoxic-ischemic
encephalopathy
Prolonged metabolic or mixed acidemia (pH <7.0) on an
umbilical arterial blood sample Premature newborns
Persistence of Apgar score of 0-3 for >5 minutes Selective subcortical neuronal necrosis
Neurological manifestations, e.g. seizures, coma, hypotonia Periventricular leukomalacia
or hypoxic ischemic encephalopathy (HIE) in the immediate Focal and multifocal ischemic necrosis
neonatal period Periventricular hemorrhage or infarction
Evidence of multiorgan dysfunction in the immediate neonatal Term newborns
period
Selective cortical neuronal necrosis
Status marmoratus of basal ganglia and thalamus
Neuropathology
Parasagittal cerebral injury
These differ according to gestation (Table 9.16) and are of Focal and multifocal ischemic cerebral necrosis
the following main types:
Diagnosis and Approach
Term
Hypoxia is an evolving process that starts at the onset of
Selective neuronal necrosis involves cerebral cortex,
the insult and continues after resuscitation and thereafter
hippocampus, basal ganglia, cerebellum and anterior horn
manifests in form of sequelae. Management thus depends
cells of spinal cord. Seen predominantly in term infants on which point in this evolution it is detected; with the
and depending on site, this manifests clinically as preventive approach beginning in the prenatal period and
diminished consciousness, seizures and abnormalities of then continuing in the form of a long follow-up much after
feeding, breathing, etc. Parasagittal area is a watershed the stabilization of the initial condition.
area for many arteries and is vulnerable to ischemia A wide-spectrum of clinical manifestations is seen
resulting in proximal limb weakness (upper >lower) that depending on the severity of injury. These manifestations
later may develop into spastic quadriparesis. Status change over time and are clinically noted in babies of
marmoratus is a variant of selective neuronal necrosis gestational age more than 36 weeks by classification on
involving basal ganglia and thalamus, having long-term the basis of Levene stages of HIE (Table 9.17).
sequelae such as choreoathetosis, spastic quadriparesis HIE staging helps predict evolution of the disease and
and retardation. long-term outcome. Babies with stage 1 have uniformly
Preterm good prognosis. Adverse neurological outcomes are
present in 20% of babies with stage 2 HIE. In stage 3 HIE,
Selective neuronal necrosis is rare in preterms; half of the neonates die and remaining half tend to have
diencephalic neuronal necrosis restricted to thalamus and poor neuro-development outcomes.
brainstem with or without hypothalamus and lateral
geniculate body is seen. Hypoxia and acidosis followed Post-Resuscitation Management of an
by hyperoxia demonstrates a unique pattern of injury Asphyxiated Baby (Fig. 9.37)
involving pontine nucleus and subiculum of the i. Temperature: Maintain normal temperature of the baby
hippocampus. and avoid hyperthermia. In resourceful setting,
Periventricular leukomalacia (PVL) results from moderate induced hypothermia (core temperature of
hypoxic-ischemic insult leading to coagulative necrosis 33 ° to 34 ° C) reduces the death or severe neuro
and infarction of periventricular white matter that is the developmental handicap. However, the efficacy and
watershed area between various arteries. Long-term safety of therapeutic hypothermia has not been proved
sequelae of PVL include spastic diplegia and quadriplegia in resource restricted setting (in absence of intensive
(lower limbs >upper limbs) and visual impairment. care).
ii. Oxygen: Both hypoxia and hyperoxia can damage if neurological examination is normal and baby is feeding
neurons. Oxygen saturations are maintained between well on breast.
90 to 95%. CO2 concentration in ventilated babies
should be maintained between 40 and 50 mm Hg as Prognosis
hypocarbia as well as hypercarbia are detrimental to The following features predict a poor outcome:
brain. • Lack of spontaneous respiratory effort within 20-30
iii. Perfusion: Cerebral perfusion in asphyxiated babies is minutes of birth is associated with almost uniform
in 'pressure passive' state means there is loss of auto mortality
regulation and blood supply to the brain is entirely • HIE stage 3
dependant on BP; it decreases when BP falls and • Abnormal neurological findings persisting beyond the
increases when BP rises. Therefore, to maintain normal first 7-10 days of life
perfusion pressure, a systemic mean arterial pressure • Oliguria ( <1 mL/kg/day) during the first 36 hours
of 45-50 mm Hg (term), 35-40 (1-2 kg weight) and Thus all these babies should have regular follow-up
30-35 mm Hg ( <1 kg weight) is required. Judicious with monitoring of neurodevelopmental milestones to
use of fluid boluses and use of vasopressors help detect any deficits early and to intervene effectively.
maintain BP.
iv. Glucose: Levels between 75 and 100 mg/dL are recom Suggested Reading
mended. Hyperglycemia enhances cerebral edema and • Agarwal R, Jain A, Deorari AK, Paul VK. Post-resuscitation
compromises perfusion, while hypoglycemia poten management of asphyxiated neonates. Indian J Pediatr 2008;75:175-
tiates excitotoxic damage. Hypoglycemia is commonly 80.
seen in asphyxiated infants and the infant must be
regularly monitored. RESPIRATORY DISTRESS
v. Metabolic profile: Hypocalcemia and electrolyte Respiratory distress in the neonate is a common problem
disturbances should be regularly looked for until and it can be a serious neonatal emergency. Respiratory
stabilization of baby and corrected as indicated. distress is defined as presence of tachyp nea (RR >60/min)
vi. Seizures: 20-50% of infants with HIE develop seizures with lower chest retractions, grunting and cyanosis. It can
during day 1 or 2. Seizures are commonly subtle or be due to respiratory (Table 9.18) and non-respiratory
focal or multifocal. Metabolic disturbances such as causes (Table 9.19). Early recognition and prompt
hypoglycemia, hypocalcemia and hyponatremia must treatment is essential to improve the outcomes.
be ruled out. Seizures should be treated with anti
epileptic drugs (AEDs) such as phenobarbitone and
phenytoin. The seizures may be intractable initially but Approach
usually tend to burn out by 48 hours. Subtle seizures Respiratory distress in a neonate can be recognized by
lasting for brief duration need not be treated. the presence of varying combinations of tachypnea (RR
Once the baby is seizure-free for 3-4 days, AEDs are >60/min), chest retractions, grunting, flaring of alae nasi
stopped in the same order as they were started, except and cyanosis. The gestation, age at onset, severity of
phenobarbitone. Phenobarbitone is stopped at discharge, distress and presence of associated clinical features help
Newborn Infants l1ss-
Table 9.18: Pulmonary causes of respiratory distress
Cause Time of onset Remarks
Respiratory distress syndrome First 6 hours of life Common in preterm neonates
Meconium aspiration syndrome First few hours of life Common in term, post-term and small for date babies; history
of meconium-stained liquor
Pneumonia Any age Often bacterial
Transient tachypnea of newborn First 6 hours after birth Tachypnea with minimal distress; lasts for 48-72 hours
Pneumothorax Any age Sudden deterioration; usually during assisted ventilation
Tracheoesophageal fistula, Any age May show associated malformations; polyhydramnios in
diaphragmatic hernia esophageal atresia
Table 9.19: Non-pulmonary causes of rapid breathing Respiratory Distress Syndrome (RDS)
Cardiac Congestive heart failure; congenital heart RDS is common in preterm babies less than 34 weeks of
disease gestation. The overall incidence is 10-15% but can be as
Metabolic Hypothermia, hypoglycemia, metabolic high as 80% in neonates <28 weeks. In addition to
acidosis prematurity, asphyxia, acidosis, maternal diabetes and
Central nervous Asphyxia, cerebral edema, hemorrhage cesarean section can increase the risk of RDS.
system
Etiopathogenesis
Chest wall Asphyxiating thoracic dystrophy,
Werdnig-Hoffman disease In RDS, the basic abnormality is surfactant deficiency.
Surfactant is a lipoprotein-containing phospholipids like
phosphatidylcholine and phosphatidylglycerol and
in arriving at diagnosis. It should be noted that chest
proteins. Surfactant is produced by type II alveolar cells
retractions are mild or absent in respiratory distress due
of lungs and helps reduce surface tension in the alveoli.
to non-respiratory causes.
In the absence of surfactant, surface tension increases and
Respiratory causes: Conditions listed in Tables 9.18 and alveoli tend to collapse during expiration. During
9.19 can occur both in preterm and term babies. However, inspiration, more negative pressure is needed to keep
if a preterm baby has respiratory distress within the first alveoli patent. There is inadequate oxygenation and
few hours of life, the most likely cause is respiratory increased work of breathing. Hypoxemia and acidosis
distress syndrome (RDS). Similarly, if a term baby born result in pulmonary vasoconstriction and right to left
to a mother with meconium-stained liquor develops shunting across the foramen ovale. This worsens the
respiratory distress within the first 24 hours, the most hypoxemia and the neonate eventually goes into
likely cause is meconium aspiration syndrome (MAS). A respiratory failure. Ischemic damage to the alveoli causes
term baby with uncomplicated birth developing transudation of proteins into the alveoli that forms
tachypnea in the first few hours of birth is likely to have hyaline membrane. Surfactant production starts around
transient tachypnea of newborn. Presence of suprasternal 20 weeks of life and peaks at 35 weeks gestation.
recessions with or without stridor indicates upper airway Therefore, any neonate less than 35 weeks is prone to
obstruction. develop RDS.
Cardiac disease: Cardiac etiology for respiratory distress Clinical Features
should be suspected, if a neonate with distress has
Respiratory distress usually occurs within the first 6 hours
cyanosis or hepatomegaly. Congenital heart disease and
of life. Clinical features include tachypnea, retractions,
cardio-myopathies or rhythm disorders can present as
grunting, cyanosis and decreased air entry. Diagnosis can
congestive cardiac failure in the neonatal period.
be confirmed by chest X-ray. Radiological features include
Transposition of great vessels (TGV) and hypoplastic left
reticulogranular pattern, ground glass opacity, low lung
heart syndrome usually present on day one with
volume, air bronchogram (Fig. 9.38) and white out lungs
progressive distress. Most other cardiac conditions present
in severe disease.
after the first week of life. A preterm neonate having a
systolic murmur with tachypnea and hepatomegaly is Management
likely to have patent ductus arteriosus (PDA).
Mild to moderate RDS can be managed with continuous
Neurological causes: Neonates with birth asphyxia, positive airway pressure (CPAP). CPAP is a noninvasive
cerebral hemorrhage, or meningitis can present with modality of support where a continuous distending
tachypnea and respiratory distress. These neonates are pressure (5-7 cm H20) is applied at nostril level to keep
usually lethargic with poor neonatal reflexes. the alveoli open in a spontaneously breathing baby
166 Essential Pediatrics
+ +
Yes No
+
Yes No
breastfeed frequently and exclusively. Mother should be jaundice, extravasated blood (cephalohematoma), ongoing
told to bring the baby to the hospital, if the baby looks hemolytic disease, G6PD deficiency and hyp othyroidism.
deep yellow or palms and soles have yellow staining. One should rule out cholestasis by noting the urine and
There is no use to expose the baby to direct sunlight to stool color and checking the level of direct bilirubin. If the
reduce hyperbilirubinemia. baby has dark urine or significant jaundice, investigations
Any newborn discharged prior to 72 hours of life should should be initiated to rule out:
be evaluated again in the next 48 hours for assessment of i. Cholestasis (stool color, urine color, direct and indirect
adequacy of breastfeeding and progression of jaundice. bilirubin levels)
ii. Ongoing hemolysis, G6PD screen
Pathological Jaundice iii. Hypothyroidism
Term and near term neonates: The American Academy of iv. Urinary tract infection
Pediatrics (AAP) has laid down criteria for managing
I
babies with elevated serum bilirubin (Figs 9.44 for 25 25
phototherapy and 9.45 for exchange transfusion). Both the :::::, A
.s
Figs have age in hours on the X-axis and TSB levels on Y � 20 20
B
axis. There are three curves on each Fig. representing three C C
risk categories of babies defined by gestation and other :0 15 15 '6
� Cl
E
risk factors. Risk factors refer to hemolysis, asphyxia, :0
t t r 1
E 10 10
acidosis, low albumin level, G6PD deficiency, hypothemia
and sickness. ro 5 5
Preterm neonates: Table 9.21 provides cutoffs for exchange �
transfusion and phototherapy in preterm neonates below 0 0
Birth 24 h 48 h 72 h 96 h 5 days 6 days 7 days
35 weeks of gestation. Age
Prolonged Jaundice (Beyond 3 Weeks) Fig. 9.44: Guidelines for phototherapy in infants of 35 weeks'
gestation or more. (A) Infants at lower risk (>38 weeks and well);
This is defined as persistence of significant jaundice (B) Infants at medium risk (>38 weeks+ risk factors or 35-37 6/
(10 mg/dL) beyond three weeks in a term baby. The 7 week and well) and (C) Infants at higher risk (35-37 6/7 week
common causes include inadequate feeding, breast milk + risk factors)
Newborn Infants 1111-
� 20 -------------',_+20 =a,
c
_J
Photo oxidation: This is a minor reaction, where
E:::, photo-products are excreted in urine.
:!!. 15 15
Types of phototherapy lights: The phototherapy units
available in the market have a variety of light sources that
include fluorescent lamps of different colors (cool white,
10 10 blue, green, blue-green or turquoise) and shapes (straight
Birth 24 h 48 h 72 h 96 h 5 days 6 days 7 days
Age or U-shaped commonly referred as compact fluorescent
Fig. 9.45: Guidelines for exchange transfusion in infants 35 lamps, i.e. CPL), halogen bulbs, high intensity light
weeks' gestation or more. (A) Infants at lower risk (>38 weeks emitting diodes (LED) and fibroptic light sources.
and well); (BJ Infants at medium risk (>38 weeks+ risk factors or With the easy availability and low cost in India, CPL
35-37 6/7 week and well) and (CJ Infants at higher risk (35-37 6/ phototherapy is being most commonly used device. Often,
7 week+ risk factors) (Adapted from MP 2004) CPL devices have four blue and two white (for exami
nation purpose) CFLs but this combination can be replaced
Table 9.21: Suggested TSB cut-offs for phototherapy and with 6-blue CFLs in order to increase the irradiance output.
exchange transfusion in preterm infants <35 weeks In last couple of years, blue LED is making inroads in
Gestation (completed Phototherapy Exchange transfusion neonatal practice and has been found to equally effective.
weeks) LED has advantage of long life (up to 50,000 hours) and is
capable of delivering higher irradiance than CPL lamps.
<28 5-6 11-14
28 to 29 6-8 12-14 Maximizing the efficacy of phototherapy: The irradiance
13-16
of phototherapy lights should be periodically measured
30 to 31 8-10
and a minimum level of 30 microW / cm2 / nm in the wave
32 to 33 10-12 15-18 length range of 460 to 490 nm must be ensured. The lamps
34 12-14 17-19 should be changed, if the lamps are flickering or ends are
Use postmenstrual age (for phototherapy for example, when a 29 week blackened, if irradiance falls below the specified level or
infant is 7 days old, use the TSB level for 30 weeks). as per the recommendation of manufacturers.
(Adapted with permission from Maisels et al, Jour Perinatol, 2012)
Expose maximal surface area of the baby (Fig. 9.46).
Avoid blocking the lights by any equipment (e.g. radiant
Phototherapy warmer), a large diaper or eye patch, a cap or hat, tape,
Phototherapy remains the mainstay of treating dressing or electrode, etc. Ensure good hydration and
hyperbilirubinemia in neonates. Phototherapy is highly nutrition of the baby. Make sure that light falls on the baby
effective and carries an excellent safety track record of over perpendicularly, if the baby is in incubator. Minimize
50 years. It acts by converting insoluble bilirubin interruption of phototherapy during feeding sessions or
(unconjugated) into soluble isomers that can be excreted procedures.
in urine and feces. Many review articles have provided
detailed discussion on phototherapy-related issues. The
bilirubin molecule isomerizes to harmless forms under
blue-green light (460-490 nm); and the light sources
having high irradiance in this particular wavelength range
are more effective than the others.
For phototherapy to be effective, bilirubin needs to be
present in skin so there is no role for prophylactic
phototherapy. Phototherapy acts by several ways:
• Configurational isomerization: Here the Z-isomers of
bilirubin are converted into E-isomers. The reaction is
instantaneous upon exposure to light but reversible as
bilirubin reaches into the bile duct. After exposure of 8-
12 hours of phototherapy, this constitutes about 25% of
TSB, which is nontoxic. Since this is excreted slowly from
body, this is not a major mechanism for decrease in TSB.
• Structural isomerization: This is an irreversible reaction Fig. 9.46: A jaundiced baby receiving phototherapy with two
where the bilirubin is converted into lumirubin. The overhead units and biliblanket pad (arrow)
172 Essential Pediatrics
Management
The baby should be nursed supine or in an upright
position and esophageal pouch should be gently sucked
every 5 minutes, or continuously using a slow suction
device. Intravenous fluids should be administered and
infection, if any, should be treated. Surgical repair should
be undertaken as early as possible.
Anorectal Malformation
A variety of anorectal anomalies have been described
(Fig. 9.48b). These may be anatomically classified as high,
intermediate or low. The position is determined by the
relation of terminal part of bowel to the puborectalis sling.
High or intermediate lesions are more common in males.
An X-ray film of the abdomen is obtained 12-24 hours
after birth, with the baby being kept in an inverted
position. A lateral picture of the pelvis should be obtained
to define whether the rectal pouch is above or below a
Fig. 9.47: Esophageal atresia with tracheoesophageal fistula. line drawn from the pubis to the coccyx.
Note the radiopaque catheter at T4 level (arrow). There is a Treatment is surgical. Prognosis is better with low
double gas bubble sign indicating presence of concomitant defects. About 80 to 90% of patients become continents
dueodenal atresia. after surgery for low defects. More than two-thirds of
patients are incontinent after surgery of high defects.
Fig. 9.48: Various congenital malformations: (a) Congenital hydrocephalus; (b) Anorectal malformation; (c) Tuft of hair overlying
with underlying neural tube defect; (d) Meningocele
174 Essential Pediatrics
TRANSPORT OF NEONATES
Transport is an important component of sick newborn
care. It requires careful attention to vital parameters,
temperature and blood glucose levels as well as
coordination with the receiving hospital (Fig. 9.51).
If the birth of an at-risk neonate is anticipated, the
mother should be transported (in utero transport) to a
facility with optimum maternal and neonatal care before
delivery (in utero transfer). However, if referral of a
neonate is unavoidable, efforts should be made to do the
Fig. 9.49: Unilateral cleft lip and cleft palate best possible job.
Newborn Infants 175-
Determine the indication* to transport the baby to higher noted, if supplemental feeding is given. It is also
health facility important to record the duration of exclusive
Birth weight <1200 g or gestation <30 weeks breastfeeding. If mentation can be considered.
Sickness: Severe respiratory distress, shock, severe jaundice, major
•
malformations requiring surgery, refractory seizures
Complementary feeding should be started at 6 months
corrected age. Initially, semisolids should be advised
in accordance with the local cultural practices.
Prepare for transport
Baby ii. Growth monitoring: Growth (including weight, head
Stabilize (temperature, airway, breathing, circulation and blood sugar) circumference, midarm circumference and length)
Secure IV line and give necessary treatment before transfer should be monitored and plotted on an appropriate
Logistics
Counsel the parents and family before transport growth chart at each visit.
Communicate with referral facility. Provide a brief note iii. Developmental assessment: Assessment of developmental
•
Arrange supplies, equipment and transport vehicle
milestones should be done according to the corrected
age. The milestones should be assessed in four
Care during transport domains-gross motor, fine motor, language and
Monitor frequently (temperature, airway and breathing, circulation,
IV cannula and infusions) personal-social. Infants who lag behind in any
Ensure that the baby receives feeds or fluid domain should undergo a formal developmental
Stop the vehicle, if necessary, to manage problems evaluation. Age appropriate stimulation should be
+ provided to these babies.
Feedback after transport
Communicate with referral team for condition at arrival and outcome iv. Immunization: Immunization should be ensured
according to chronological age.
* Indications may vary as per the facility v. Ongoing problems: Ongoing morbidities, such as
Fig. 9 .51 : Transport of sick neonates diarrhea, pneumonia, occur more frequently in these
babies and should require appropriate treatment.
FOLLOW-UP OF HIGH-RISK NEONATES vi. Neurological assessment: Muscle tone should be
Improved perinatal and neonatal care has resulted in assessed, any asymmetry between the extremities
improved survival of many sick and small neonates who should also be recorded. Any history of seizures or
are at-risk for long-term morbidities such as growth involuntary movements should also be recorded.
failure, developmental delay and visual/hearing vii. Hearing and vision evaluation: High-risk infants have
problems. A proper and appropriate follow-up program higher incidence of moderate to profound hearing
would help in prevention, early detection and appropriate loss (2.5-5% versus 1%). Since clinical screening is
management of these problems, thereby ensuring often unreliable, brainstem auditory evoked
disability and morbidity free survival. responses (BAER/BERA) should be performed
between 40 weeks PMA and 3 months postnatal age.
Who Needs Follow-up Care? Vision of the baby should be checked at 9 months.
Table 9.22 lists the cohort of high-risk infants who require
followup services. METABOLIC DISORDERS
Hypoglycemia
What should be Done at Follow-up?
Hypoglycemia is defined as a blood glucose value of less
i. Assessment of feeding and dietary counseling: Parents
than 40 mg/dL (plasma glucose less than 45 mg/dL).
should be asked about the infants' diet and offered
dietary counseling at each visit. Breastfeeding Screening for hypoglycemia is recommended in high
frequency and adequacy should be assessed. The risk situations (Table 9.23). These babies should be
amount, dilution and mode of feeding should be screened for hypoglycemia at 2, 6, 12, 24, 48 and 72 hours
after birth with reagent strips (dextrostix). Babies showing
Table 9.22: Common newborn conditions requiring high-risk blood sugar value of less than 40 mg/dL on reagent strip
follow-up care should be treated for hypoglycemia but should have
Birth weight <1500 g and/or gestation <32 weeks confirmation of hypoglycemia by a lab test as reagent
Perinatal asphyxia: Apgar score �3 at 5 min and/or hypoxic
ischemic encephalopathy Table 9.23: Common causes of hypoglycemia
Mechanical ventilation for >24 hours Inadequate substrate: Small for gestational age (weight for
Metabolic problems: Symptomatic hypoglycemia and gestation <3rd percentile), gestation <35 weeks, birth weight
hypocalcemia <2000 g
Infections: Meningitis and/or culture positive sepsis Relative hyperinsulinemia: Infants of diabetic mother, large for
Hyperbilirubinemia >20 mg/dl or requirement of exchange date baby (weight for gestation >97th percentile).
transfusion Sickness: Hypothermia, sepsis, asphyxia
176 Essential Pediatrics
strips have high false positive rates. Appropriate for i. Fetus may die suddenly during the last trimester of
gestational age babies who are breastfeeding adequately pregnancy
do not require any screening for hypoglycemia. ii. Macrosomia or large size of the body (Fig. 9.52) and
its attending risks during delivery such as birth trauma,
Clinical Features asphyxia and increased possibilities of cesarean section
Clinically, the hypoglycemia may be asymptomatic or may iii. Higher risk of congenital anomalies. (Infants of
manifest with a range of clinical features like stupor, mothers with diabetes are 20 times more at risk to
tremors, apathy, cyanosis, convulsions, apneic spells, develop cardiovascular defects.)
tachyp nea, weak and high-pitched cry, lethargy, difficulty iv. Neonatal respiratory distress
in feeding, eye rolling, episodes of sweating, sudden v. Metabolic problems such as hypoglycemia and
pallor, hypothermia and rarely, cardiac arrest. hypocalcemia
vi. Polycythemia, increased viscosity of blood and
Management of Hypoglycemia hyperbilirubinemia
Prevention of hypoglycemia: All high-risk babies should
receive proper breastfeeding, counseling and support. Pathogenesis
Adequacy of breastfeeding should be assessed and small Maternal hyp erglycemia leads to fetal hyperglycemia and
babies not able to suck effectively on the breast, should that in turn leads to fetal hyperinsulinemia (Pederson
receive expressed breast milk by alternate methods. hypothesis). Insulin is an anabolic hormone and promotes
Asymptomatic babies: If the blood sugar is more than growth. Excess maternal glucose and amino acids provide
20 mg/dL in an asymptomatic baby, a trial of oral feeds is the substrate for increased synthesis of protein, lipids and
given and blood sugar be tested after 30-45 minutes. If glycogen in the fetus. Large fetal size is mostly due to the
repeat blood sugars values are above 40 mg/dL, frequent accumulation of fat.
feeding is ensured with 6 hourly monitoring of blood
sugar for 48 hours. However, if blood sugar values persist
below 40 mg/dL, baby should receive IV glucose infusion.
If the initial blood sugar value is less than 20 mg/dL,
then intravenous glucose infusion is started.
Symptomatic babies: A bolus of 2 mL/kg of 10% dextrose
should be given, followed immediately by glucose
infusion at an initial rate of 6 mg/kg/min. Blood sugar is
checked after 30-45 minutes and then 6 hourly. Repeat
hypoglycemic episodes may be treated by increasing the
glucose infusion rate by 2 mg/kg/min until a maximum
of 12 mg/kg/min. If two or more consecutive values are
>50 mg/dL after 24 hours of parenteral therapy, the
infusion can be tapered off at the rate of 2 mg/kg/min
every 6 hours, with glucose monitoring. Tapering has to
be accompanied by concomitant increase in oral feeds.
Diabetes Mellitus
Diabetes is one of the most common endocrine disorders
affecting women during pregnancy. The following Fig. 9.52: (a) Infant of diabetic mother. Note the large size of
complications are likely to occur during pregnancy of a the baby with broad shoulders and torso and a relatively smaller
diabetic mother. head; (bl Hairy pinna of the baby
Newborn Infants 1111-
10 Immunization and
Immunodeficiency
Aditi Sinha • Surjit Singh
Table 10.1: Causes of secondary immunodeficiency Table 10.2: Work-up for suspected immunodeficiency
Human immunodeficiency virus infection Screening investigations
Following measles Total and differential leukocyte counts, leukocyte morphology,
Severe malnutrition platelet count and size
HIV serology; X-ray chest
Nephrotic syndrome
Lymphoreticular malignancies Specific investigations
Severe burns Quantitative immunoglobulins: lgG, and subclasses: lgA; lgM;
lgE
Drugs: Glucocorticoids, cyclophosphamide, azathioprine,
diphenylhydentoin Blood group isohemagglutinins (for functional lgM)
Anti-diphtheria and anti-tetanus antibodies (functional lgG)
Severe, chronic infections
CD3, CD4, CD8, CD19, CD16, CD56 by flow cytometry
clinically important causes of secondary immuno CD18, flow cytometry (leukocyte adhesion defect)
deficiency. Bruton tyrosine kinase protein; Wiskott-Aldrich syndrome
Primary immunodeficiency disorders can affect any of (WAS) protein
the major components of immune system, including T Mitogen stimulation tests (e.g. response to phytohemagglutinin)
and/ or B lymphocytes, antibody production, phagocyte Nitroblue tetrazolium dye reduction test, and dihydrorhodamine
number or function and complement components. The assay on flow cytometry, CGD
condition should be suspected in patients presenting with CH50, and AH50 assays and levels of complement component
� of the following 10 warning signs: (i) �4 new infections Mannan binding lectin assay
in a year; (ii) � serious sinus infections in a year; (iii) �2 Enzyme assays, e.g. adenosine deaminase, purine nucleoside
cases of pneumonia in a year; (iv) �2 months of antibiotics phosphorylase
without effect; (v) failure of an infant to gain weight or Delayed skin tests ( Candida, Tetanus toxoid)
grow normally; (vi) recurrent deep skin infections or organ AH50: Alternate pathway complement hemolytic assay; CD: Cluster
abscesses; (vii) persistent oral thrush, or candidiasis differentiation; CGD: Chronic granulomatous disease; CH50: Total
elsewhere beyond infancy; (viii) need for IV antibiotics to hemolytic complement assay; HIV: Human immunodeficiency virus
clear infections; (ix) �2 deep-seated infections (e.g.
meningitis, cellulitis); and (x) family history of ranging from mildly increased susceptibility to infections
immunodeficiency. to severe disease requiring thymic or hematopoietic stem
Tables 10.2 and 10.3 outline the workup and clinical cell transplant.
findings in various disorders. Conditions that mimic Wiskott-Aldrich syndrome (WAS): This X-linked recessive
immunodeficiency (e.g. gastroesophageal reflux, disorder is caused by mutations at Xpll.22-23, encoding
Kartagener syndrome, cystic fibrosis) should be excluded. the WAS protein in the cytoplasm of lymphocytes and
platelets. Eczema begins in early infancy and may mimic
Cellular and/or Combined Immunodeficiency atopic dermatitis. Thrombocytopenia is associated with
Severe combined immunodeficiency (SCID): Children with small-sized platelets. Due to impaired responses to
SCIO present in early infancy with severe infections due polysaccharide antigens, patients are susceptible to
to viruses, fungi (e.g. Pneumocystis jirovecii) or intracellular infections with pneumococci, meningococci and
pathogens (e.g. Mycobacteria). Tonsillar tissue is usually Haemophilus influenzae. The clinical phenotype varies; some
absent and lymph nodes are not palpable. Left untreated, children have a fulminant course with repeated severe
such babies do not live for more than a few months. infections (WAS spectrum), while others present later,
Profound lymphopenia is characteristic. The most predominantly with bleeding manifestations (X-linked
common form of SCIO is X-linked and is caused by thrombocytopenia spectrum). The risk of lymphoreticular
mutations in the common gamma chain [of interleukin malignancies is increased. There is severe IgM deficiency
2 (y)]; approximately one-fourth cases have adenosine in addition to defective T cell signaling, secondary to
deaminase deficiency. SCIO due to purine nucleoside deficient expression of CD43 in lymphocytes.
phosphorylase deficiency may present later in childhood
with milder features. Ataxia-telangiectasia: This autosomal recessive disorder
is characterized by progressive ataxia (beginning during
DiGeorge anomaly: This disorder arises from defects in infancy), telangiectasia (initially on bulbar conjunctiva),
embryogenesis of third and fourth pharyngeal pouches. sinopulmonary infections, chromosomal breakage and
It is characterized clinically by an unusual fades increased sensitivity to ionizing radiation. The gene is
(hypertelorism, antimongoloid slant, low set ears, localized to chromosome llq22-23; its product regulates
micrognathia, short philtrum, bifid uvula), hypocalcemic the cell cycle. The degree of immunodeficiency is less
tetany, aortic arch anomalies and absent thymus. In profound than in Wiskott-Aldrich syndrome. Serum IgA,
addition, 20-30% patients show a variable T cell defect, IgG2 subclass and IgE levels are usually reduced;
180 Essential Pediatrics
lymphocyte proliferative responses are decreased and the may be responsible: Inducible costimulator (ICOS); CD19;
number of yo-positive T cells is increased. CD20; CD81; B cell-activating factor of tumor necrosis
Hyper-IgM syndrome: This syndrome can result from factor family receptor (BAFF-R), tumor necrosis factor
multiple causes, the most common being a CD40 ligand receptor superfamily member 13B or transmembrane
defect. Affected children have a profound immuno activator (TNFRSF13B, TACI) or TNFRSF13C. Autoimmune
deficiency characterized by low levels of IgG but normal disorders (leukopenia, thrombocytopenia, hemolytic
or raised IgM. There is increased susceptibility to anemia and arthritis) are associated. Patients require
infections with Pneumocystis jirovecii. Some patients may monitoring for lymphoreticular malignancies.
have associated autoimmune disorders. IgA deficiency: This is one of the most common causes of
primary immunodeficiency. Affected individuals usually
Humoral Immunodeficiency
do not have a clinically significant immunodeficiency and
X-linked (Bruton) agammaglobulinemia: This X-linked may remain entirely asymptomatic or have recurrent mild
recessive disorder is caused by mutation in the gene for respiratory infections, especially if IgG subclass deficiency
tyrosine kinase (Bruton tyrosine kinase, Btk). Affected is also present. These patients may occasionally evolve to
boys present in second half of infancy with pyogenic common variable immunodeficiency later.
infections; later presentation is also described. Tonsils and
lymph nodes are usually atrophic. B cells (CD19+) are IgG subclass deficiency: IgGl provides protection against
absent in peripheral blood but T cells (CD3+) are normal bacterial pathogens (e.g. diphtheria, tetanus), IgG2
in number and function. protects against capsular polysaccharide antigens (e.g.
pneumococcus, Haemophilus influenzae), IgG3 has antiviral
Common variable immunodeficiency: This term refers to properties, while IgG4 has antiparasitic activity. Children
heterogeneous conditions characterized by hypogamma with deficiency of one of the subclasses may have normal,
globulinemia and variable defects in T cell number and or sometimes even elevated, total IgG levels.
function. Presentation is later in childhood and, unlike
X-linked agammaglobulinemia, affected children show Transient hypogammaglobulinemia of infancy: Infants
marked lymphadenopathy and hepatosplenomegaly. B show physiological hypogammaglobulinemia between
cell number (CD19) is usually normal. Low levels of 3 and 6 months of age, when transplacentally acquired
lymphocyte proliferation following mitogen stimulation maternal IgG has been catabolized, and immunoglobulin
may be demonstrated. Mutations in the following genes production has not begun. In some infants, the physiological
Immunization and Immunodeficiency 1101-
hypogammaglobulinemia is prolonged to 18-24 months, cotrimoxazole) is required for some children with IgGl
resulting in transient hypogammaglobulinemia of infancy. and IgG3 subclass deficiency.
Serum IgG levels in infancy and early childhood should Long-term cotrimoxazole and itraconazole prophylaxis has
be interpreted in context of age-related nomograms. improved the management of chronic granulomatous disease.
Unlike X-linked agammaglobulinemia, B cell numbers are Interferon-y is used for treatment of life-threatening
normal. These children recover over time and long-term infections. Hematopoietic stem cell transplantation is
prognosis is excellent. increasingly used in patients with the disease.
Plasma infusions may be useful in patients with
Disorders of Nonspecific Immunity complement deficiencies. In Cl esterase inhibitor
Cellular Immunodeficiency deficiency, prophylactic therapy with tranexamic acid,
danazol or stanozolol result in significant improvement.
Chronic granulomatous disease refers to disorders with reduced
Injections of synthetic Cl esterase inhibitor are required, if
activity of nicotinamide adenine dinucleotide phosphate
there is laryngeal involvement with airway compromise.
(NADPH) oxidase leading to impaired generation of
Gene therapy has been successfully used in patients with
superoxide radical. The disease is X-linked in -50% patients,
X-linked SCIO, chronic granulomatous disease and
secondary to mutations in the gene encoding gp91-phox;
Wiskott-Aldrich syndrome.
others have autosomal recessive inheritance with mutations
in the gene encoding p47-phox, p67-phox or p22-phox. Intravenous lmmunoglobulin
Children present with recurrent life-threatening infections,
starting in early infancy. Infections are chiefly caused by Intravenous immunoglobulin (IVIg) is pooled normal
catalase-positive bacteria (Staphylococcus aureus, Serratia) and intact polyspecific IgG derived from plasma of healthy
fungi (Aspergillus). Findings include persistent pneumonia, donors, subjected to strict screening procedures. Each
prominent lymphadenitis, multiple liver abscesses and batch of IVIg represents a donor pool of several thousand
osteomyelitis of small bones of hands and feet. The diagnosis individuals such that the repertoire of antibodies is
is suggested by screening on nitroblue tetrazolium dye representative of the population. Most preparations
reduction test (NBT) and confirmed by dihydrorhodamine contain >90% monomeric IgG with only small amounts
assay on flow cytometry. of IgA and IgM. The IgG subclass distribution depends
on the manufacturing process; some IVIg preparations do
Miscellaneous not contain adequate quantities of IgG3.
Complement component deficiency: Individuals with IVIg is therapy of choice for Kawasaki disease,
deficiencies of the early complement components (C2-C4) idiopathic thrombocytopenic purpura and autoimmune
may present with recurrent bacterial infections, while demyelinating polyradiculoneuropathy, dose being 2 g/kg
those with deficiency of the later components (CS-C9) given in single or divided doses. IVIg is also replacement
have predilection for Neisseria infections. Systemic lupus therapy in various forms of hypogammaglobulinemia, the
erythematosus may occur in those with C2/C4 or Clq dose being 0.4-0.6 g/kg every 3-4 weeks. Use of IVIg is
deficiency. Deficiency of Cl esterase inhibitor is associated considered in severe myasthenia, lupus crisis, autoimmune
with hereditary angioneurotic edema, characterized by neutropenia, neonatal alloimmune and autoimmune
onset of recurrent non-itchy swellings in the body. thrombocytopenia, dermatomyositis not responding to
steroid therapy, and certain vasculitides. IVIg has been
Hyper-IgE syndrome: Mutations in STAT 3 gene result in used for prophylaxis and treatment of neonatal sepsis in
recurrent'cold' staphylococcal abscesses, pneumonia with low birth weight babies, with equivocal results.
pneumatoceles, retained primary dentition and markedly Administration of IVIg may be associated with adverse
elevated serum IgE concentration (>2000 IU /mL). effects, including anaphylactoid and anaphylactic (lgE
Inheritance is usually autosomal dominant. mediated) reactions. IVIg infusion must be started slowly
and the child monitored closely; infusion rate is slowed
Treatment of Primary Immunodeficiency Disorders or discontinued, if the child develops chills or rigors. The
Hematopoietic stem cell transplantation is the treatment risk of acute kidney injury is negligible with current iso
of choice for most forms of significant cellular immuno osmolar preparations. Long-term risks include transmission
deficiency (e.g. SCIO, Wiskott-Aldrich syndrome, hyper of hepatitis C infection.
IgM syndrome). The procedure should be done in early
infancy. Children with X-linked agammaglobulinemia, Suggested Reading
IgG2 subclass deficiency and common variable immuno • Gupta S, Madkaikar M, Singh S, Sehgal S. Primary immuno
deficiency require administration of intravenous deficiencies in India: A perspective. Ann N Y Acad Sci 2012;
immunoglobulin (IVlg) every 3-4 weeks. Though expensive, 1250:73-9.
• Singh S. Approach to a patient with suspected primary
therapy with IVIg results in satisfactory quality of life. immunodeficiency disorder. API Textbook of Medicine, 10th edn.
Patients with IgA deficiency do not require any specific Eds. Munjal YP, Sharma SK. Jaypee Brothers, New Delhi, 2015,
therapy. Prophylactic therapy with antimicrobials (usually pp. 249-55.
182 Essential Pediatrics
the chief reservoir (tetanus). Herd effect is a strategy for prolonged protection. Most killed bacterial and some viral
eradication of poliovirus, and measles epidemics. Herd vaccines (e.g. influenza) are associated with significant
immunity refers to the proportion of immune individuals local and systemic reactions.
in a population. The minimum proportion of population Toxoids are modified and purified toxins that are not
that must be immunized to eliminate disease is called the injurious to recipients. Primary immunization is provided
herd immunity threshold. as multiple divided doses in order to decrease adverse
Epidemiological shift refers to a significant change in the effects at each administration and to elicit high antibody
pattern of disease in a population following immunization. titers. Booster doses are required to sustain the protection.
Immunization with trivalent OPV caused selective
Subunit vaccines, including viral or bacterial antigens, are
extinction of type 2 poliovirus, due to higher efficacy
produced using recombinant DNA technology or genetic
against that subtype. Following partial immunization
engineering (Table 10.5).
coverage, some diseases (hepatitis A, varicella, rubella)
affect older individuals with more severe disease. Vaccination Route
Types of Vaccines Locations for intramuscular (IM) administration (22-25
guage needle) include the anterolateral aspect of the thigh
A good vaccine is easy to administer, induces permanent
in infants and deltoid in upper arm in older children and
immunity, is free of toxic substances, has minimal side
adults (Fig. 10.1). Gluteal administration is avoided to
effects and is stable for prolonged time (Table 10.4). Timing
reduce risk of injuring the sciatic nerve. Hepatitis B vaccine
of administration depends on the ability to mount immune
is particularly not given in the gluteal region as this has
response, age at which the disease is anticipated and
reduced efficacy. If required, two vaccines may be given
feasibility.
in the same thigh, but separated by 1 inch. Separate sites
Live vaccines infect the recipient and replicate to elicit are used when administering a vaccine and an
cellular and humoral immune responses. They mimic immunoglobulin. Preferred locations for subcutaneous
natural infection but do not cause disease, except rarely vaccines (25-27 guage needle) include the anterolateral
in immunocompromised hosts. While a single dose is thigh in infants and upper outer aspect of triceps in older
usually sufficient to induce immunity, OPV may need children. Intradermal injection (25-27 gauge needle) is
multiple doses to infect the intestinal mucosa. Residual given in skin overlying the deltoid.
maternal antibody in infant blood may neutralize the
organism before infection occurs, interrupting immune Principles of Immunization
response. Hence, vaccines like measles and measles, Compliance with the recommended dose and route of
mumps and rubella (MMR) are given after 9 months of vaccination is essential to retain efficacy and limit adverse
age. Maternally derived antibodies do not interfere with events. Important considerations are shown in Box 10.1.
vaccine response to BCG that induces cell-mediated Vaccines available as lyophilized powder are reconstituted
immunity, and OPV that infects gut mucosa. Live vaccines in: (i) sterile or distilled water, e.g. vaccines against
may confer herd immunity. Storage and transportation measles, mumps, rubella, meningococcus MPSV4, rabies
conditions are important in maintaining their potency. and varicella; (ii) normal saline, e.g. Hib vaccine; or (iii)
Killed vaccines, prepared by growing organisms in media another vaccine, e.g. combined vaccination with separately
followed by heat or chemical (formalin) inactivation, do available DTaP, inactivated polio and Hib vaccines. The
not cause infection but elicit protective immune response. maximum time allowed between reconstitution and use
Interference by maternal antibodies is less significant. varies from 30 minutes (DTaP-IPV-Hib, MMRV, Hib with
However, multiple doses are required since the organism MenCY, rabies, varicella and zoster), to 8 hours (MMR,
cannot replicate in the vaccinee. The immunity is not meningococcal) or 24 hours (Hib, rotavirus vaccines).
permanent; booster doses are necessary to ensure Reconstituted vaccines are not used, if there is
Fig. l 0.1: Routes of vaccination. (a) Oral: Poliovirus (attenuated), rotavirus; (bl Intranasal: Influenza virus (live-attenuated);
(c) lntradermal: BCG, inactivated poliovirus (fractionated dose) and rabies; (d) Subcutaneous: Measles, mumps, rubella, varicella,
yellow fever, Japanese encephalitis, meningococcal and pneumococcal polysaccharide, and inactivated poliovirus;
(e) Intramuscular: Most vaccines, including hepatitis A and B; diphtheria, tetanus and pertussis, H. influenzae b, pneumococcal
polysaccharide, inactivated polio and influenza
discoloration, particulate matter and inability to suspend young children with BCG, diphtheria and tetanus toxoids
the lyophilized powder. and whole cell pertussis (DTP or DTwP) and OPV
vaccines, and chiefly covered urban areas. The Universal
Vaccination Schedules and Immunization Programs Immunization Programme (UIP, 1985) improved nationwide
The choice of vaccines in national immunization schedules coverage of immunization and also included measles
is based on considerations of disease burden, vaccine vaccine. The Pulse Polio Immunization Programme (1995)
availability and cost-effectiveness, and program coverage enabled polio control. UIP has remained a key component
and sustainability. The Expanded Programme ofImmunization of the Child Survival and Safe Motherhood Programme
(EPI), introduced by the World Health Organization (1992), the Reproductive and Child Health Programme
(1974), was the first global immunization initiative. (1997) and National Rural Health Mission (NHRM, 2005).
Adopted by India in 1978, the EPI focused on vaccinating Efforts of UIP are supported by Child Vaccine Initiative
Immunization and Immunodeficiency 185-
Table 10.6: Immunization schedule in India before and after phased introduction of new vaccines
Age Schedule in 2010 Schedule in 2017
At birth BCG, OPV-0, HBV-0 BCG, bOPV-0, HBV-0
6 weeks OPV-1, DTP-1, HBV-1 bOPV-1, Pentavalent-1, Rota-1*, flPV-1, PCV-1*
10 weeks OPV-2, DTP-2, HBV-2 bOPV-2, Pentavalent-2, Rota-2*
14 weeks OPV-3, DTP-3, HBV-3 bOPV-3, Pentavalent-3, Rota-3*, flPV-2, PCV-2*
9 months Measles-1, JE-1* MR-1*, JE-1*, PCV-3*
16-24 months Measles-2, DTP-81, OPV-8 DTP-81, bOPV-8, JE-2*, MR-2*
5-6 years DTP-82 DTP-82
11-13 years HPV-1, HPV-2*
B: Booster; BCG: Bacillus Calmette-Guerin; bOPV: Bivalent oral poliovirus; DTP: diphtheria, pertussis, tetanus; flPV: Fractionated inactivated
poliovirus; HBV: Hepatitis B virus; HPV: Human papillomavirus; JE: Japanese encephalitis; MR: Measles, rubella; PCV: Pneumococcal conjugate
vaccine; Pentavalent: DTP+HBV+ Haemophilus influenzae b; Rota: Rotavirus
*Where implemented
Table 10.7: Immunization schedule recommended by the Box 10.3: Bacillus Calmette-Guerin (BCG) vaccine
Indian Academy of Pediatrics Dose, route 0.1 mL; intradermal
A
Age Schedule Site Left upper arm at insertion of deltoid
At birth BCG, bOPV-0*, HBV-1 Schedule
6 weeks IPV-1*, HBV-2*, DTP-1, Hib-1, Rota-1, PCV-1 National program At birth; catch up till 1-yr (if missed)
10 weeks IPV-2*, DTP-2, Hib-2, Rota-2, PCV-2 IAP 2016 At birth; catch up till 5-yr
14 weeks IPV-3*, DTP-3, Hib-3, Rota-3, PCV-3 Adverse reactions Local ulceration; discharging sinus;
6 months bOPV-1*, HBV-3* axillary lymphadenitis
9 months bOPV-2*, MMR-1, Typhoid (conjugate), JE-1$ If immunodeficient, disseminated
12 months IPV-81*, Hib-81, PCV-81, HAV-1* infection, osteomyelitis; scrofuloderma
15 months DTP-81, MMR-2,Varicella-1, JE-2$ Contraindication Cellular immunodeficiency; sympto
18 months HAV-2* matic HIV
2-3 years Typhoid (conjugate)-B Storage 2-8 ° C; sensitive to heat and light;
discard reconstituted vaccine after 4 hr
4--6 years bOPV-3*, DTP-82, MMR-3, Varicella-2
11-12 year Tdap; HPV-1 & HPV-2* rates are lower in developing compared to developed
B: Booster; BCG: Bacillus Calmette-Guerin; bOPV: Bivalent oral poliovirus; countries.
DTP: Diphtheria pertussis, tetanus; HAV: Hepatitis A virus; HBV: Hepatitis Each dose (2 drops) of trivalent OPV contained 105-106
B virus; Hib: Haemophilus influenzae b; HPV: Human papillomavirus; IPV:
Inactivated poliovirus; JE: Japanese encephalitis; MMR: Mumps, measles,
median cell culture infectious doses of each serotype 1, 2
rubella; PCV: Pneumococcal conjugate; Rota: Rotavirus and 3. Type-specific immunity was associated with highest
·Preferred schedule detailed under respective vaccines, particularly seroconversion rates for OPV type 2, leading to eradication
where indicated by; of wild type OPV2 in 1999. Since this serotype inhibits take
*Influenza vaccine recommended annually and vaccination in high-risk of OPVl and OPV3, and most cases of vaccine-derived
groups not shown poliomyelitis (VDPV) are due to OPV2, as part of Polio
$Qnly in endemic areas
Eradication and Endgame Strategic Plan 2013-18, trivalent
enteroviruses, concomitant diarrhea and interruptions in vaccine has been replaced by bivalent OPV (bOPV); OPV2
the vaccine cold chain. Vaccine 'take' and seroconversion use was globally discontinued in April 2016.
Vaccine Age Birth 6wk 10wk 14wk 6 mo 9 mo 12 mo 15-18 mo 2 yr 4-6 yr 10-13 yr 15-18 yr
BCG 1
Oral polio virus OPVO OPV1 OPV2 OPV3 OPVB1 OPVB2
Injectable polio vaccine OPVO flPV 1 flPV2 or lPV IPV12; OPV1 OPV2 IPVB1 OPV3
Alternative IAP schedule OPVO IPV1 IPV2 IPV3 OPV1 OPV2 IPVB1 OPV3
DPT 1 2 3 B1 B2 B3
HepatitisB 0 1 2 3or 2 3
Hemophilus influenza 1 2 3 B1
TT 1 2
Measles or Measles rubell, 1 2 3
MMR 1 2 3
Pneumococcal conjugate 1 2 3 B1
Rotavirus 1 2 3
JapaneseB encephalitis 1 1 2
Human papilloma virus 1&2 1, 2 & 3
Typhoid conjugate C or C1 C2/P1 P2
polysaccharide P
Varicella 1 2
Influenza Annually
Hepatitis A vaccine 1 2
Rabies At any age, 3 doses one week apart
KEY
Schedule Recommended age Catch up immunization
BCG Bacillus Calmette-Guerin; DTP diphtheria, pertussis, tetanus;
Universal Immunization Program only IPV inactivated poliovirus; MMR mumps, measles, rubella; OPV
Indian Academy of Pediatrics only oral poliovirus; TT tetanus toxoid
Both Schedules *Boosters (B) as either whole cell or acellular vaccine; B3 as
tetanus with reduced diphtheria and reduced pertussis (Tdap)
Only in selected areas in UIP Red font
Fig. 10.3: Vaccinations scheduled in Universal Immunization Program and Indian Academy of Pediatrics (2016). Details are under
respective vaccines
188 Essential Pediatrics
Box l 0.4: Bivalent oral poliovirus (bOPV) and inactivated poliovirus (IPV) vaccines
Bivalent oral poliovirus vaccine Inactivated poliovirus vaccine
Dose, route Two drops; oral 0.5 mL, IM or SC; 0.1 mL, intradermal
Schedule
National program Dose at birth or <2 weeks (zero dose); 0.1 mL intradermal (fractional dose) at 6 and
(OPV and IPV) 3 doses at 6, 10 and 14 weeks; two 14 weeks; or one full IM dose at 14 weeks
booster doses at 15-18 months and
5 years
IAP 2016 At birth, 6 months, 9 months and 5 years 3 doses of IPV at 6, 10 and 14 weeks; or 2 doses
(OPV and IPV)* at 8 and 16 weeks (primary) and one dose
at 15-18 months (booster)
Catch up Up to 5 years: Three doses 4 weeks apart Up to 5 years: 3 doses at 0, 2 and 6 months
Adverse reactions Vaccine-derived poliovirus; vaccine Local pain, swelling
associated paralytic poliomyelitis
Contraindications Inherited or acquired immunodeficiency; Known allergy
symptomatic HIV
Storage 2-8°C; sensitive to heat; use vaccine 2-8°C; sensitive to light and heat; use vaccine
vial monitor vial monitor
*IAP recommends above as ideal, but no child should go unimmunized at any time point when polio vaccine is indicated, and should receive OPV
if IPV cannot be given due to shortage/non-availability.
UIP intradermal (ID) fractionated dose IPV schedule is moderately effective; one intramuscular (IM) dose is given 2':8 weeks after second ID-fIPV
dose; if one dose of ID-fIPV was given, two IM doses are given at 8 week intervals.
retain the birth dose of OPV; this dose is necessary in areas hydroxide, the adjuvant. This is the most commonly used
with continued risk of wild virus transmission, and is vaccine. The quantity of toxoid in the vaccine, expressed
unlikely to cause VAPP in presence of maternally as limit of flocculation (Lf) content is 20-30 Lf of DT, 5-25
transmitted antibodies. Lf of tetanus toxoid (TT) and >4 IU of whole cell killed
pertussis.
Polio Eradication and Maternal antibodies protect the infant against disease
Endgame Strategic Plan 2013-2018 and interfere with immune responses to DPT vaccination,
This is a comprehensive strategy to deliver a polio-free particularly against pertussis. Protection requires that
world, developed by the Global Polio Eradication Initiative vaccination is begun within a few weeks of life and
in consultation with health authorities, experts and other multiple doses are given. Primary immunization with 3
stakeholders. The plan addresses the eradication of all polio doses of the vaccine, given 4-8 weeks apart, induces
disease, caused by wild or circulating vaccine- derived satisfactory immune response to DT and TT in 95-100%
poliovirus. Its objectives are: (i) Detect and interrupt all infants. Protective efficacy against pertussis is lower, at
poliovirus transmission; (ii) strengthen immunization -70-90%, and wanes over 6-12 years. Immunization does
systems and withdraw OPV; (iii) contain poliovirus and not eliminate C. diphtheriae from the skin or nasopharynx.
certify interruption of transmission; and (iv) plan post-polio Booster doses are required to sustain a protective antibody
legacy (Fig. 10.4). A midterm review suggests that certain titer of 0.1 IU /mL and protect from disease in the first
activities require focus, including: (i) strengthening disease decade of life. Natural infections and immunization
surveillance; (ii) improving quality of immunization against pertussis induce immunity lasting 4-12 years,
campaigns; (iii) building capacity to respond to outbreaks. making boosters necessary to prevent infection in
A post-certification strategy is being developed to maintain adolescence. Box 10.5 indicates the schedule for
a polio-free world. Its goals are: (i) Contain poliovirus administration of DTwP or DTaP, containing DT, TT and
sources by ensuring that they are properly controlled or acellular pertussis.
removed; (ii) protect populations by withdrawing OPV and DTwP vaccine is commonly associated with local (pain
immunizing with IPV against possible re-emergence of any and redness) and systemic (fever) reactions, chiefly
poliovirus; and (iii) detect and respond promptly to any attributed to the pertussis component. The incidence of
poliovirus reintroduction. these adverse effects increases with the number of doses
administered; hence the vaccine should not be used
Diphtheria, Pertussis and Tetanus Vaccine beyond 5 doses or beyond 7 years of age. DTP is also
Diphtheria vaccine contains diphtheria toxin (DT) incriminated in rarely inducing of serious neurological
inactivated by formalin and adsorbed on aluminum complications, though conclusive evidence is lacking
-190 Essential Pediatrics
Objectives Strategies
Wild
Virus detection and
poliovirus Outbreak response especially cVDPV
interruption
interruption
Strengthen
immunization;
Routine immunization IPV and OPV
address pre Introduce IPV
strengthening and in routine
requisites for Withdraw OPV2
OPV withdrawal immunization
OPV
withdrawal
Consultation and
Legacy planning Implementation of legacy plan
strategic plan
Timeline
A
Aug
2016
2017
A
Last wild Global
•
2018 2019
bOPV
£
OPV2 use poliovirus certification cessation
Fig. l 0.4: Polio Eradication and Endgame Strategic Plan 2013-18. There are four major objectives with corresponding areas of
work. The bottom panel outlines the timeline of wild type and vaccine-derived poliovirus elimination
(Box 10.5). The vaccine is contraindicated in children with complete the immunization schedule with OT that
progressive neurological disease; children with stable contains the same doses of OT and TT as DTP, but is
neurological diseases (e.g. developmental delay, cerebral devoid of the pertussis component. OT is recommended
palsy and idiopathic epilepsy) may receive the vaccine. up to the age of 7 years, beyond which Td must be used.
Absolute contraindications to administration of the
vaccine and adverse events that require precaution are
Ace/lular Pertussis Vaccine {DTaP]
listed in Box 10.5, if an event listed as precaution recurs
with a subsequent dose, further doses are contraindicated. The suspicion that the active pertussis toxin and endotoxin
Individuals in which DTP is contraindicated should cause the adverse events associated with DTwP led to the
Box l 0.5: Diphtheria toxoid, tetanus toxoid and killed whole cell pertussis (DTwP] or acellular pertussis (DTaP] vaccine
Dose, route 0.5 mL; intramuscular
Site Anterolateral aspect of mid-thigh (gluteal region: sciatic nerve injury; inadequate response)
Schedule
National program DTwP at 6, 10 and 14 weeks (primary); at 15-18 months and 5 years (boosters)
IAP 2016 (see footnote) DTwP for primary and DTaP or DTwP for booster in schedule as above; Tdap/Td at 10-12
years; Td every 10 years
Catch up (IAP 2016) <7 years: DTwP (preferred) or DTaP at 0, 1 and 6 months
7-10 years: Tdap at O month; Td at 1 and 6 months
>11 years: One dose of Tdap; one dose of Td every 10 years
Adverse reactions Common: Local pain, swelling, fever (DTwP>DTaP)
Rare: Hypotonic hyporesponsive episodes, inconsolable cry; fever >40.5 ° C; seizures;
encephalopathy (DTwP=DTaP)
Contraindications (i) Progressive neurological disease (administer DT or dT instead); (ii) anaphylaxis after previous
dose; (iii) encephalopathy within 7 days of previous dose
Precautions: Previous dose associated with (i) fever >40.5 °C within 48 hours; (ii) hyp otonic
hyporesponsive episode <48 hours; (iii) persistent inconsolable crying for >3 hours, <48 hours;
(iv) seizures <72 hours
Storage 2-8 ° C; sensitive to light
IAP recommmendations:
DTwP should be used in primary immunization; DTaP vaccine should be used only in children with severe adverse effects after previous dose of
DTwP or children with neurologic disorders; Either DTwP or DTaP may be used for booster doses; DTaP used should have� or more pertussis
components; Tdap should not replace the second booster of DTwP or DTaP
Immunization and Immunodeficiency 1191-
development of various types of purified acellular vaccines in India contain 5 Lf of tetanus toxoid, 2 Lf of
pertussis vaccines, or DTaP. These vaccines contain diphtheria toxoid and three acellular pertussis components
inactivated pertussis toxin and one or more additional (pertussis toxoid 8 µg, filamentous hemagglutinin 8 µg
pertussis antigens, like filamentous hemagglutinin (FHA), and pertactin 2.5 µg). Contraindications to Tdap are the
pertactin, fimbrial protein and a nonfimbrial protein. same as those listed for DTaP or DTwP. Tdap may also be
Approved vaccines have at least three pathogenic used as replacement for Td/tetanus toxoid (TT) booster
pertussis antigens, at least 4 IU of inactivated pertussis in children above 10 years and adults of any age, if they
toxin and 6.7-25 Lf of DT. While the efficacy of these have not received Tdap in the past and 5 years have
vaccines is similar to DTwP, the risk of systemic and local elapsed since the receipt of previous TT/Td vaccine.
side effects is lower. The DTaP vaccine is not included in
the National Program due to its prohibitive cost. The IAP Tetanus Vaccine
previously recommended that the vaccine be offered to Extensive routine immunization of pregnant women has
all children who can afford, in view of the advantage of led to decline in the incidence of neonatal tetanus.
fewer side effects, or following an adverse effect with Immunizing pregnant women with two doses, with the
DTwP. Since recent studies suggest that the efficacy of second dose administered at least 4 weeks prior to
DTaP vaccines, when used for primary immunization, is delivery, provides passive immunity to the baby due to
lower (46-92%) than with DTwP (61-89%) particullarly the transplacental passage oflgG antibodies. Tetanus toxin
for perfussis, the IAP thus recommends that only DTwP is inactivated by formalin and adsorbed onto aluminum
(and not DTaP) be used for primary immunization. salts to enhance immunogenicity. Each dose of the vaccine
Boosters at 16-24 months and at 5 years may be with either contains 5 Lf of toxoid. The vaccine is heat stable and
DTwP or DTaP (Box 10.5). Contraindications for DTaP remains potent for a few weeks even at 37 °C. The efficacy
vaccine are similar and the vaccine should not be given, if of TT vaccine varies between 80 and 100%. While antitoxin
a previous dose of DTwP or DTaP was associated with a level of 0.01 IU/mL is considered protective, the level of
contraindication; these children should complete protection available also depends on the toxin load. Since
immunization with DT instead of DTwP or DTaP. tetanus may occur at any age, primary immunization
should begin in early infancy. Tetanus toxoid is given with
Reduced Antigen Acellular Pertussis Vaccine (Tdap) DT and pertussis vaccine in DTP. DT, Td and TT may be
and Reduced Antigen Diphtheria used as boosters at 10 and 16 years of age and for wound
Toxoid Vaccine (Td) prophylaxis (Table 10.8). Children who have not received
As natural immunity to diphtheria and pertussis is primary immunization, should receive 2 doses of TT
acquired through apparent or inapparent infections 1 month apart.
(Chapter 11), a large proportion of adults especially in
developed countries, are susceptible through lack of Measles-containing Vaccines
natural boosting and waning of immunity. In nonendemic Measles vaccine, derived from the Edmonston-Zagreb
countries, revaccination against diphtheria every 10 years strain, is available as a monovalent preparation, or in
may be necessary to sustain immunity among adults, combination with rubella (MR), mumps (MMR) and
particularly healthcare workers. Vaccines useful in such varicella (MMR-V). Both cellular and humoral responses
situations include diphtheria and tetanus toxoids (DT) and are elicited. Since infants are protected by maternal
combinations with reduced toxoid content (Td, Tdap). antibodies till 6-9 months of age, administering the
While standard dose DT is recommended for primary vaccine at 9 months in endemic countries balances the
immunization against diphtheria because of its superior need for early protection with the ability to ensure
immunogenicity and minimal reactogenicity, the seroconversion. However, interference by maternal
reactogenicity of the vaccine increases with age. If given antibodies causes primary vaccine failure in 15%, making
beyond 7 years of age, primary immunization or booster a second dose necessary at 15 months. During outbreaks,
doses should be in the form of Tdap or Td, which contain the vaccine may be given even earlier (-6 months) with a
smaller amounts of diphtheria toxoid (2 Lf) and acellular repeat dose at 12-15 months. Each vaccine dose contains
pertussis vaccine than DTP, and is adequately immuno at least 1000 infective units of the attenuated virus. Measles
genic even in adults. To promote immunity against vaccine loses potency rapidly after reconstitution; unused
diphtheria, this vaccine may be used whenever TT is vaccine should be discarded after 4-6 hours since
indicated in children above 7 years of age. contamination may lead to staphylococcal sepsis and toxic
Similarly, Tdap offers the prospect of reducing pertussis shock syndrome.
incidence in adults and adolescents, and also reduces the The two doses of measles vaccine at 9-12 and 15-24
risk of their transmitting disease to young children. Its months (Box 10.6) in the national immunization program
reduced antigen content causes less severe adverse effects are being replaced by the MR vaccine in a phased manner.
while being sufficient to induce protective response in This follows the nationwide 'measles rubella' program
previously immunized (booster effect). The available Tdap (launched February 2017) in which one dose of the vaccine
192 Essential Pediatrics
is given to all children 9 months to 15 years of age, for mumps and >95% for rubella. While prolonged
irrespective of their immunization status. Recognizing the immunity is seen, rubella and mumps infections are
significant morbidity associated with mumps infections, reported beyond 5 years, confirming the need for a booster
the IAP recommends MMR instead of MR at 9- and 16-24 dose at 4-6 years. The vaccine is safe, but should be
months. IAP also recommends a third dose of MMR at avoided in pregnancy and immunodeficiency. Adverse
4-6 years, chiefly in order to boost anamnestic response. effects are mild (Box 10.6).
Post-exposure prophylaxis with immunoglobulin is The vaccine is dispensed as a lyophilized preparation
considered for immunocompromised contacts and 6-12- that should be used within 4 hours of reconstitution.
month-old infants within 6 days of exposure (see Passive Haphazard use of MMR vaccine without ensuring optimal
Immunization). Unimmunized immunocompetent (>80%) immunization coverage may result in an
contacts older than 12 months should receive measles or epidemiological shift of disease with more cases in
MMR vaccine within 72 hours of exposure. adulthood and a paradoxical increase in congenital rubella
syndrome. The latter was observed in Greece in 1990s
Measles Mumps Rubella [MMRJ Vaccine following incomplete MMR coverage in the 1970s.
While childhood mumps is often subclinical or causes
benign parotitis, infections in adolescents and adults may Hepatitis B Vaccine
be associated with oophoritis or meningitis. Rubella is a Hepatitis B virus (HBV) vaccine contains the surface
benign illness with rash and transient arthritis; vaccination antigen HBsAg, produced by recombinant DNA
aims at preventing congenital rubella syndrome with fetal technology in yeast, adsorbed on aluminum salt as
growth retardation, heart disease, hearing defects, adjuvant. While immunization at birth, 1 and 6 months
microcephaly and hepatosplenomegaly. Most developed has better immunological efficacy than the regime advised
countries use MMR rather than measles vaccine for in the National Program (Box 10.7), the latter integrates
primary immunization. HBV vaccination into the existing schedule without
The rubella component is the RA 27 /3 strain and the increasing visits and ensures compliance. Since
mumps component contains the live-attenuated Jeryl immunization at birth prevents horizontal transmission,
Lynn strain, both grown in human diploid or chick embryo vaccination must begin at birth, if the mother's HBsAg
cell cultures. Each dose contains 1000, 5000 and 1000 status is not known. If the mother is known to be HBsAg
TCID50 of live-attenuated measles, mumps and rubella positive, the child should receive the vaccine within a few
viruses, respectively. Mucosal and systemic humoral and hours of birth, and hepatitis B immunoglobulin (HBIG)
cellular responses are elicited following vaccination. within the first 24 hours at separate sites (see Passive
Seroconversion rates following a single dose are 86-100% Immunization). Subsequently, any of the schedules
incorporating a birth dose of the vaccine can be used. If is now part of the Universal Immunization Program,
HBIG is not administered, the baby should be immunized introduced as a pentavalent vaccine (DTP, HBV and
in an accelerated schedule at 0, 1 and 2 months, and an HibPRP-T vaccines) in 2015.
additional dose at 9-12 months. Combined passive and
active immunization with use of HBIG and HBV vaccine Pneumococcal Vaccine
results in 90% reduced risk of HBV transmission in S. pneumoniae causes 15-50% of community-acquired
patients with needle stick injuries, sexual exposure or use pneumonia, 30-50% of acute otitis media and 50% of
of blood product not screened for HBV. deaths due to pneumonia. Pneumococcal pneumonia is
Seroconversion rates exceed 95% after three HBV doses: the leading single cause of vaccine-preventable deaths,
Antibody titer >10 mIU/mL is protective. Vaccination globally and in India. Twenty of 90 known serotypes
usually induces long-term immunity, and booster doses account for 80% of invasive pneumococcal disease, and 13
are not routinely recommended. Double dose of vaccine serotypes cause 75% of invasive disease in young children.
and boosters may be required in patients with chronic Children below two years of age are particularly
kidney disease or immunodeficiency, in whom titers may susceptible to invasive pneumococcal disease. Children
wane. at high risk of disease, regardless of age, include: (i)
primary immunodeficiency, HIV, immunosuppressive
Hemophilus Vaccine therapy and organ transplant recipients; (ii) sickle cell
Haemophilus influenzae b (Hib) causes invasive infections disease, asplenia or hyposplenia; (iii) chronic cardiac, liver
such as pneumonia, meningitis and bacteremia, especially or pulmonary disease; (iv) chronic kidney disease and
in children <2-year-old. Vaccination prevents 33% of nephrotic syndrome; (v) diabetes mellitus; and (vi) children
pneumonia and 90% meningitis related to Hib. The chief with cerebrospinal fistula or cochlear implants.
antigen is Hib capsular polysaccharide, polyribosylribitol Two kinds of vaccines are available. Unconjugated
phosphate (PRP), which is conjugated to tetanus toxoid polysaccharide vaccine has 25 µg capsular polysaccharide
(PRP-T), mutant diphtheria toxin CRM-197 (Hib-OC) or of each of the 23 serotypes termed PPV23. Since
meningococcal outer membrane protein (PRP-OMP). Both polysaccharides stimulate B cells independent of T cells,
monovalent and combination (with DTP and hepatitis B the vaccine is poorly immunogenic <2 years and
or IPV) vaccines are safe and immunogenic, with efficacy immunological memory is low. This vaccine does not
of 85-95%. The vaccination schedule depends on age of reduce nasopharyngeal pneumococcal carriage or provide
the child at immunization (Box 10.8). A booster is required herd immunity. Its efficacy in preventing invasive
in the second year to sustain protection. As Hib infections pneumococcal disease in high-risk categories is <70%;
chiefly affect preschool children, IAP recommends that more than 2 doses are not recommended.
the vaccine be given to all children up to the age of 5 years; The pneumococcal conjugate vaccine has the
older children need vaccination, only if planned for polysaccharide of 13 most commonly pathogenic serotypes
splenectomy or if having sickle cell disease. Hib vaccine linked to a diphtheria carrier protein (PCV13); another is
194 Essential Pediatrics
a 10-valent conjugate vaccine (PCVlO) combined with non on G9Pll or 116E strain, manufactured in India. The
typeable H. influenzae vaccine. Apart from robust immune vaccine has 49-54% efficacy against rotaviral diarrhea in
response and immunological memory, conjugated the first 2 years of life; it is inexpensive and safe with a
vaccines reduce nasopharyngeal bacterial carriage low risk of intussusception.
resulting in significant herd effect. The protective efficacy All three rotavirus vaccines may be given with OPV
is 95-99% for invasive pneumococcal disease covered by without compromising efficacy of either vaccine.
included serotypes. Vaccination is avoided during acute gastroenteritis, as it
Since pneumococcal infections cause significant might compromise vaccine take. While none of the
morbidity and mortality in children <2 years of age, IAP vaccines increases the risk of intussusception, caution is
recommends using the conjugate vaccine (Box 10.9). Since necessary in infants at risk of intussusception, e.g. those
the risk of invasive infections decreases with age, with chronic gastrointestinal disease and gut malforma
vaccination beyond 5 years is not necessary except in high tions. Immunization should be completed by 8 months of
risk categories; the latter should additionally receive the age. Studies suggest that vaccine efficacy may be lower in
polysaccharide vaccine. An additional dose of the vaccine countries with high infection rates and competition for
may be given in high-risk categories 3-5 years later. Given intestinal infection by other pathogens. The vaccine has
its public health importance, pneumococcal vaccination reasonable potential for preventing diarrhea related
was launched in three states in May 2017. Vaccination will morbidity and mortality in developing countries. Given
be extended to the entire country in a phased manner. its importance, rotavirus vaccination was introduced in
the UIP in 2016 in selected districts in four states (Andhra
Rotavirus Vaccine Pradesh, Himachal Pradesh, Haryana and Odisha) using
Rotavirus is the chief cause of diarrhea in infants and the Rotavac vaccine.
toddlers, accounting for 6-45% of diarrhea-related
hospitalization in Indian children. Natural infection does Human Papillomavirus (HPV) Vaccine
not protect against reinfection or severe disease. The first Cervical cancer, the second most common cancer in
licensed vaccine (Rotashield), a live oral tetravalent women, is almost always due to infection with oncogenic
vaccine, was withdrawn following an association with HPV belonging to 20 of 100 known serotypes. Serotypes
intussusception. Two live-attenuated oral vaccines are 16 and 18 cause majority of invasive cervical cancer;
currently used worldwide (Box 10.10). Rotarix is a oncogenic serotypes also cause anal, vulvar, vaginal,
monovalent vaccine containing at least 106 median cell penile and oropharyngeal cancer. Nononcogenic serotypes
culture infective doses of rotavirus strain G1P8 attenuated 6 and 11 cause 90% of anogenital warts.
in Vero cell culture. RotaTeq is a pentavalent vaccine with HPV vaccines contain self-assembling virus like
2-116 million infectious units each of the 5 strains [Gl-4 particles containing recombinant Ll, a major capsid
and P8] reassorted between bovine and human WC3 protein. These vaccines protect against 90% of infections
rotaviruses, and attenuated by Vero cell culture. Both with included serotypes, but do not provide cross
vaccines have 85-98% efficacy against severe rotaviral protection against other strains. The quadrivalent vaccine
gastroenteritis. Rotavac is an indigenous monovalent Gardasil (HPV4) protects against strains 6, 11, 16 and 18,
human-bovine recombinant live-attenuated vaccine based while bivalent Cervarix (HPV2) targets HPV 16 and 18.
Both vaccines prevent cervical in situ neoplasia grade 2 Box l 0.11: Human papillomavirus vaccine
and 3, and adenocarcinoma in situ. Gardasil also prevents
serotype-related genital warts and vaginal and vulvar Dose, route 0.5 mL, intramuscular
intraepithelial neoplasia. Both vaccines are most Site Upper arm (deltoid)
immunogenic at 9-14 years of age and protection persists Schedule
for at least 5 years. The ideal age at vaccination and need National program In some states: Two doses 6-12 months
of booster doses, if any, is not determined. apart in girls 11-13 years
WHO; IAP 2016 Girls 9-14 years old: 2 doses of HPV4;
Governments of Delhi and Punjab have initiated school or HPV2 �6 months apart
based programs for girls aged 11-13 years old since 2016. Girls �15 years, immunocompromised:
Elsewhere, IAP recommends that the vaccine should be 3 doses [HPV4: 0, 2 and 6 months; or
offered to all girls prior to sexual debut (Box 10.11). HPV2: 0, 1 and 6 months]
Immunization carries the risk of complacency regarding Catch up Up to 45 years (IAP); preferably before
routine screening for cancer; which together with initiation of sexual activity
incomplete immunization coverage might paradoxically Adverse reactions Local pain, swelling, erythema; fever
raise cervical cancer-related mortality. There are no serious Syncope (due to injection, not vaccine)
adverse events of HPV vaccine. Contraindication Anaphylaxis after previous dose
Storage 2-8 ° C; protect from light
Japanese B Encephalitis Vaccine
Japanese encephalitis (JE) is an important cause of viral is highly immunogenic in children, with seroconversion
encephalitis in India and is associated with high fatality. >90% with two doses. The risk of adverse effects is lower
Vaccination as a control measure is recommended for all than live-attenuated vaccine. The inactivated purified Vero
children and adults residing in highly endemic areas and cell derived vaccine (based on Kolar strain) is safe and
for individuals visiting endemic areas for longer than 4 effective, with serocoversion in 93-98%.
weeks. Previously available vaccines, discontinued in
2005, included inactivated mouse brain-derived vaccine Typhoid Vaccine
(Nakayama or Beijing-I strains) and primary hamster Typhoid vaccine is currently not part of the national
kidney cell culture vaccine (Beijing-3 strain). Three of the program, but is recommended by IAP for families who
four second generation vaccines are licensed for use in India can afford (Box 10.13). The whole cell-inactivated typhoid
(Box 10.12). vaccine containing heat-killed phenol-preserved or
The live-attenuated cell culture vaccine is used in the acetone-inactivated whole cell S. typhi and S. paratyphi A
national program in hyperendemic districts of Uttar and B is no longer used. Two doses of the vaccine,
Pradesh, West Bengal, Assam and Kamataka. It is based administered SC 4 weeks apart, induced humoral
on SA-14-14-2, a genetically stable neuro-attenuated JE antibodies that were 50-80% effective in preventing
strain that is unlikely to show neurovirulence (Box 10.12). typhoid. Adverse effects (chiefly fever, local pain and
While a single dose has protective efficacy of 85-99%, two headache) were common (10-35%) and revaccination was
doses are recommended to provide complete and sustained required every 2-3 years.
protection. In endemic districts, a strategy of mass An oral vaccine, not marketed in India, contains 2-6
immunization followed by routine vaccination is practised. million live-attenuated lyophilized bacteria of Ty21a
The purified formalin inactivated SA-14-14-2 is a whole mutant strain of S. typhi. The mutation is genetically stable
virus vaccine derived from Vero cell culture. The vaccine and unlikely to revert to virulent form. The vaccine is
196 Essential Pediatrics
supplied as an enteric coated capsule that induces coupled to diphtheria toxoid or its mutant toxin CRM197
intestinal mucosal immunity, with an efficacy of 50--60% are not licensed in India. Conjugate vaccines are preferred
within 7 days of completing the schedule. To avoid to polysaccharide vaccine, since they generate strong
bacterial inactivation by gastric acidity, capsules are anamnestic response and show prolonged immunological
swallowed intact, making the vaccine unsuitable for young memory.
children. Antibiotics are avoided for 3 days before to
7 days after vaccination to avoid interference with Varicella Vaccine
response. Vaccination is repeated every 3 years. Varicella is a benign self-limiting illness, but complications
The Vi capsular polysaccharide vaccine contains the are common in adults and in immunocompromised
purified Vi capsular antigen of S. typhi strain Ty2. Children patients. Each dose of varicella vaccine has at least 1000
older than 2 years, administered one vaccine dose, develop plaque-forming units of the live virus of Oka strain
anti-Vi IgG antibodies with protective efficacy of 50-75%. attenuated in human diploid cell culture. Both cellular and
Since polysaccharide vaccines lack memory responses, humoral immune responses are elicited, providing 95-99%
revaccination is essential every 3 years (Box 10.13). Two protective efficacy. Following onedose, seroconversion is
typhoid conjugate vaccines are approved for use in India seen in 95% young children and 80% of those >12 years;
and recommended by IAP for children >9 months old. two doses seroconvert 90% of the latter. If breakthrough
Here, the Vi antigen is coupled to a carrier protein such infection occurs, it is usually a mild afebrile illness with a
as tetanus toxoid (PedaTyph® and Typbar-TCV®); vaccines few lesions and predominance of papules over vesicles.
Varicella vaccine is not included in the National elderly and immunocompromised, and those with chronic
Immunization Program because the illness is not a public illnesses. Since available vaccines elicit a strain-specific
health priority, the vaccine is expensive, and high rates of humoral response with protective efficacy of 30-90%, their
immunization coverage are necessary to prevent an composition is annually reviewed by the WHO for
epidemiological shift to affect older individuals, causing changes in component antigens.
severe disease. The IAP recommends the vaccine for Inactivated influenza vaccines: These tri- or quadrivalent
children if it is afforded (Box 10.14). Two doses are vaccines, containing two influenza A and one or two
recommended to reduce the risk of breakthrough influenza B strains, are derived from viruses grown in
infections with waning immunity. Internationally chick embryos or cell culture. Whole virus vaccines,
available monovalent preparations (Varilrix® and associated with significant adverse effects, are no longer
Variped®) and its combination with MMR (MMR-V, used. Current vaccines are either split product, produced
Priorix-Tetra®) show similar immunogenicity and from detergent-treated purified viruses, or surface antigen
efficacy. Other monovalent preparations (Nexipox®, subunit vaccines, containing purified hemagglutinin and
Biovac-V® and Varivax®) are also immunogenic, but neuraminidase. These are highly immunogenic and
information on their efficacy is limited. Since MMR-V is associated with minimal adverse events. Newer virosome
associated with higher rate of adverse events (fever, rash, adjuvated vaccines stimulate strong antibody responses
seizures) in patients 12-23 months old than MMR and and activate Thl/Th2 and cytotoxic T cells. Inactivated
varicella administered separately, the IAP cautions against vaccine is recommended in high-risk groups (Box 10.15).
the use of MMR-V in this age group; older patients may
safely receive MMR-V. Live-attenuated intranasal vaccine: These trivalent or
Vaccination is indicated for the following high-risk quadrivalent vaccines are developed by repeated passage
groups: (i) chronic cardiac or lung disease; (ii) of viruses at low temperature, to form a temperature
asymptomatic HIV infection with CD4 >15%; (iii) leukemia sensitive variant that grows well at 25 ° C but does not
in remission and off chemotherapy >3 months; (iv) replicate at 37-39 ° C. The vaccine is recommended for
anticipated prolonged immunosuppression (before healthy children older than 2 years, and is more
transplantation; periods off immunosuppression in immunogenic than the inactivated vaccines. Live vaccines
nephrotic syndrome); (v) prolonged aspirin therapy are avoided in high-risk categories. Healthy children, >2-
(discontinue aspirin for 6 weeks after). Vaccination should year-old, may receive either the live or inactivated vaccine.
also be considered for unimmunized household contacts Following reports of unsatisfactory efficacy of the former,
of immunocompromised patients, and adolescents and the WHO has recommended the use of only inactivated
adults without history of varicella, particularly in vaccines during 2016-2018.
institutional settings (school, hospital or army). When
recommended for post-exposure prophylaxis (within Rabies Vaccine
72 hours of contact), its protective efficacy is -70%. India is endemic for rabies, accounting for 50% of global
deaths. Nerve tissue vaccines are not recommended due
Influenza Vaccine to poor efficacy and high incidence of adverse effects.
Influenza virus has three antigenic types (A to C) and Tissue/cell culture vaccines are available as lyophilized
several subtypes based on the surface antigens preparations that are reconstituted to provide at least 2.5
hemagglutinin, and neuraminidase. Mutations due to IU per intramuscular dose, and include: (i) Purified duck
antigenic drifts and shifts result in frequent changes in embryo vaccine (Vaxirab); (ii) purified chick embryo cell
circulating strains. Influenza viruses (A, B) cause global vaccine (Rabipur, Vaxirab-N); (iii) human diploid cell
flu epidemics with severe disease in young children, the vaccine (Rabivax); and (iv) purified Vero cell vaccine
(Indirab, Verorab, Abhayrab, Verovax-R). These vaccines remaining immunoglobulin is administered intra
have comparable efficacy and, since they lack myelin basic muscularly at a site away from vaccination site, usually
protein, are relatively safe. the deltoid or anterolateral thigh. Local tenderness and
stiffness and fever are common. Currently available equine
Post-exposure prophylaxis: An animal bite/wound is immunoglobulins are potent and overall safe, but adverse
characterized as follows: Category I: Animal touch or lick effects are common and usually require prior skin testing.
on intact skin; Category II: Minor scratches or abrasions While preferred, human immunoglobulin is expensive
without bleeding, licks on broken skin or nibbling of and not available readily.
uncovered skin; and Category III: Single or multiple
Vaccination is usually planned using the Essen or WHO
transdermal bites, abrasions that bleed, scratches or
schedule, in which 5 doses are given on days 0, 3, 7, 14 and
contamination of mucous membranes with saliva/licks.
28; an additional dose on day 90 is advised in immuno
Individuals with category II or III wounds need wound
compromised or severely malnourished individuals. The
management and rabies vaccine (Box 10.16). Patients with
Updated Thai Red Cross Schedule involves administering
wound category III, and immunocompromised patients
two intradermal doses each on days 0, 3, 7 and 30.
with wound category II, should also receive rabies
Abbreviated and effective alternate schedules include:
immunoglobulin. Patients who have received pre- or post
Zagreb (two IM doses on day O; one dose each on days 7
exposure prophylaxis with rabies vaccine in the past do not
and 14); abbreviated multisite (similar to Zagreb, except
require immunoglobulin.
that last dose is on day 21), reduced four dose (IM dose
Wound management includes immediate irrigation on 0, 3, 7 and 14 days), and eight site (8 intradermal doses
with running water for 10 minutes, thorough cleaning with on day 0, four doses on day 7, and one each on day 28 and
soap and water, and application of povidone iodine, 70% 90). Following re-exposure, patients who have previously
alcohol or tincture iodine. Tetanus toxoid and antibiotics completed pre-exposure prophylaxis should receive two
are administered as indicated. Wound suturing is doses on days O and 3.
avoided; if necessary, it is performed after administering
immunoglobulin. Pre-exposure prophylaxis: This is offered to individuals
Rabies immunoglobulin provides passive immunity by at high risk of rabies, such as laboratory staff handling
neutralizing rabies viruses; dose is 20 U/kg for human virus or infected material, care providers to patients with
immunoglobulin (ImogenRab, KamRab, BeriRab-P; rabies, veterinarians, animal handlers and catchers,
maximum 1500 U) and 40 U/kg for equine preparations taxidermists, wildlife workers, wardens, quarantine
(anti-rabies serum, Equirab, Vinrig; maximum 3000 U). officers, municipal workers, postmen and travelers to
This is infiltrated in and around the wound as soon as endemic areas. Three IM doses are given on days 0, 7
possible and not later than day 7 of injury. For large or and 21 or 28. A booster dose is required after 1-yr and
multiple wounds, immunoglobulin is diluted with normal every 5 years thereafter; boosters are required annually,
saline to infiltrate the entire wounded region. Any if using the intradermal schedule. Antibody titers are
Immunization and Immunodeficiency 199-
monitored 6-12 monthly and boosters given to maintain titer administration to all children. High-risk categories in
>0.5 U/mL. which vaccination must be considered include: (i) patients
with chronic liver disease; (ii) seronegative travelers to
Hepatitis A Vaccine endemic areas; (iii) children attending creches and
India is endemic for hepatitis A; 50% children are daycare; (iv) seronegative adolescents; and (v) liver and
seropositive by 5 years of age, following infection usually kidney transplant recipients. The vaccine is effective as
with minor manifestations. Disease severity, complications postexposure prophylaxis, if administered to unimmunized
and mortality are higher in adolescents, adults and household or institutional contacts of symptomatic
children with underlying chronic liver disease. Two types patients within 10 days of exposure.
of vaccines are available. Formalin inactivated viral
vaccines usually have aluminium hydroxide or a virosome Meningococcal Vaccine
adjuvant. The vaccine is available either singly or in Neisseria meningitidis accounts for 30-40% cases of
combination with hepatitis B. Two doses, administered bacterial meningitis in children, with high case fatality.
6-12 months apart, provide protective efficacy of 95%, if Invasive infections are caused by serogroups A, B, C, Y
administered at >1 year age; maternal antibody may and W135. While serogroup A (and sometimes C) cause
interfere with immune responses in infancy (Box 10.17). epidemics, endemic disease in India is due to sero-group
Two live vaccines are based on H2 and L-A-1 strains of B. Two types of vaccines are available. Unconjugated
hepatitis A virus, attenuated through repeated cell culture vaccines contain group specific capsular polysaccharides,
and grown on human diploid lung fibroblasts. A single which are T cell independent, do not induce immuno
dose of the vaccine is irnmunogenic and safe (Box 10.17). logical memory and are poorly irnmunogenic below 2 years
While hepatitis A vaccination is not a public health of age. These are available as bivalent (containing groups
priority, improving hygiene has resulted in increaseded A and C) and tetravalent (groups A, C, Y and W135)
age at infection, and serious infections including fulminant vaccines. Conjugate vaccines are preferred over
hepatic failure may occur. Hence, IAP recommends its polysaccharide vaccines due to higher immunogenicity,
prolonged efficacy and potential for herd effect, especially vaccines). This is distinct from simultaneous administration
in childhood. Two types of polysaccharide-protein of multiple separate vaccines at the same time at separate
conjugate vaccines are available in India (Box 10.18). The sites. The immune system of an infant can respond to a
quadrivalent conjugated vaccine (groups A, C, Y and large number of antigens simultaneously, and the efficacy
W135; Menactra®) uses diphtheria toxin as carrier protein, of most vaccines is not altered by concurrent administra
while the monovalent (serogroup A) vaccine uses tetanus tion. With the requirement of vaccination against several
toxoid as carrier protein. infections, a child needs to be administered more than 20
antigens in the first 2 years. Combining vaccines have
Yellow Fever Vaccine several benefits. Fewer injections at each visit and fewer
The yellow fever vaccine is a live-attenuated vaccine of visits increase compliance. The immunization program
either 170-204 or 1700 strain that is effective against all also benefits from decreased expenditure on packaging,
known strains of yellow fever. Neutralizing antibodies storage and transportation and enhanced immunization
develop in 90% vaccinees by 10 days and in 100% by coverage.
3 weeks, and persist for three decades. A single dose Development of combination vaccines is challenging.
should be administered at least 10 days before planned The antigens should be compatible and not interfere with
travel to endemic areas (Africa; South or Central America). each other's immunological 'take' (relevant for live viral
Adverse effects are common (Box 10.19); administration vaccines) and be indicated at the same time. Some antigens
in young infants and pregnant women is avoided. may require an adjuvant to be present in the combination.
The total volume of the vaccine should not be excessive
Combination Vaccines and the product should be stable for at least a year. Their
A combination vaccine consists of multiple immunogens efficacy is evaluated and cost benefit analyses are done
physically combined in a single preparation, including before licensing. Common combination vaccines include
antigens or serotypes of the same pathogen (trivalent polio pentavalent, DTwP, DTaP, OT, dT, OPV, IPV, MMR, MR
vaccine) or different pathogens (pentavalent or DTP and influenza (Table 10.9).
Table 10.9: Combination vaccines for use in children and infants ii. Distraction techniques (playing music, pretending to
Vaccine Examples
blow away the pain, deep breathing)
iii. Breastfeeding or ingestion of sweet liquids during
DTwP-HB-Hib Pentavalent vaccine; Pentavac PFS®,
Comvac-5®, ComBE Five®, Shan-5®
vaccination
May combine in same syringe, e.g. Qvac® iv. Stroking skin near injection site
+ HibPro®, Hiberix® + Tritanrix® v. Administering IM injections rapidly without
DTwP Tripvac® , Triple antigen®, Comvac3® aspiration; and
DTaP-HB-Hib Easy-5® iv. Topical analgesia (5% lidocaine or prilocaine emulsion
DTaP-Hib-lPV Pentaxim® or spray).
DTaP lnfanrix®, Boostrix®, Tripacel® Older children are less anxious, if the procedure is
Tdap Boostrix®, Adacel® explained, and by vaccinating in sitting rather than lying
DTwP-HB Shantetra ®, Q-VAC ® , Tritanrix-HB ® , down position.
Tripvac-HB®, Comvac-4-HB® Immediate allergic reactions are rare and difficult to
DTaP-Hib May combine Tripacel® + ActHib®, lnfanrix® predict. Severe reactions (anaphylaxis) are usually caused
+ Hiberix® by vaccine constituents, rather than by microbial
DTwP-Hib Easy-4®, Quadrovax®, Shan-4®, Tetract contamination. While anaphylaxis is rare (1 per million
Hib®; Triple antigen® + HibPro® doses) and may follow any vaccination, yellow fever,
HepA-HepB Twinrix® MMR and tetanus vaccines are most commonly
MMR-V Priorix tetra® , Proquad® implicated. Each patient must be observed for at least 15
Meningococcal A, C, Y and 135 (Mencevax ACWY®); A, minutes after vaccination. Anaphylaxis might need to be
C, Y and 135 DT conjugate (Menactra®) differentiated from vasovagal reaction. Components
Pneumococcal 1 O or 13-valent (Prevnar®>, 23-valent implicated in allergic reactions include:
(Pneumo23®>, polyvalent polysaccharide
(Pneumovax®) i. Egg protein: Yellow fever, measles, MMR, rabies PCEV,
influenza (killed injectable and live-attenuated)
aP: Acellular pertussis; ap: Acellular pertussis reduced dose; D/DT:
diphtheria toxoid; d/dT: Diphtheria toxoid reduced dose; HB: Hepatitis B;
vaccines
HepA: Hepatitis A; Hib: Haemophilus influenzae b; MMR: Measles, ii. Gelatin: Influenza, measles, MMR, rabies, varicella,
mumps, rubella; T/TT: Tetanus toxoid; V: Varicella; wP: Whole cell pertussis yellow fever and zoster vaccines
iii. Latex in the vaccine vial stopper or syringe plunger
iv. Casein: DTaP vaccine
Adverse Events following Vaccination
v. Saccharomyces cerevisiae: Hepatitis B, HPV vaccines.
Untoward events after vaccination are categorized as Trace amounts of neomycin may cause allergic reactions.
follows: Thiomersal, aluminum and phenoxyethanol, added as
i. Vaccine induced: Event caused or precipitated by an preservatives, may cause delayed type hypersensitivity
active component of vaccine, e.g. anaphylaxis after or contact dermatitis. The use of thiomersal, an
measles vaccine, vaccine associated paralytic polio organomercury compound with bacteriostatic properties,
myelitis, BCG related adenitis, pertussis encephalopathy is being minimized due to risks of mercury toxicity.
ii. Vaccine potentiated: Event precipitated by vaccination Reportable events are:
but may have occurred without vaccination, e.g. first i. Anaphylaxis or anaphylactic shock �7 days
febrile seizure
ii. Adverse effects listed as contraindications to vaccination
iii. Injection reaction: Event from anxiety, pain due to the
injection (rather than the vaccine), e.g. syncope after iii. Any serious or unusual event; and
vaccination iv. Any sequelae of reportable events.
iv. Program error: Event due to error in vaccine pre Vaccine-specific events include:
paration, handling or administration, e.g. toxic shock i. Oral polio: Paralytic polio or vaccine strain polio within
syndrome due to contaminated measles vaccine, 1--6 months of vaccine administration
abscess at injection site; and ii. Measles: Thrombocytopenic purpura within 7-30 days;
iv. Coincidental: Temporally linked, by chance or due to measles infection in an immunodeficient recipient
unrelated illness, e.g. gastroenteritis after MMR �6 months
injection.
iii. Measles, mumps and/or rubella: Encephalopathy or
Minor reactions are common, and include fever, encephalitis <15 days
irritability, malaise and pain, and swelling or redness at
the injection site. These are self-limiting or settle following iv. Tetanus: Brachial neuritis �28 days
cold compresses and paracetamol. Strategies to reduce v. Pertussis: Encephalopathy or encephalitis �7 days
pain and anxiety include: vi. Rotavirus: Intussusception �O days; and
i. Antipyretics vii.Rubella: Chronic arthritis <6 weeks.
-202 Essential Pediatrics
Other serious vaccine specific events include: Table 10.10 lists specific equipment used at various sites
i. DTP: Hypotensive hyporesponsive epidose in the cold chain system. Temperatures are monitored to
ii. DTP: Inconsolable cry ensure that the cold chain system is maintained.
iii. Measles (S. aureus contamination): Toxic shock syndrome Vaccine vial monitors comprise of a tag, present on the
label of liquid vaccines or cap of freeze-dried vaccines that
iv. BCG: Axillary lymphadenitis. There is no causal contains a heat sensitive material, which changes color in
relationship between MMR vaccine and autism or response to cumulative heat exposure (Fig. 10.6).
inflammatory bowel disease.
Immunization in Special Circumstances
Vaccine Storage and Cold Chain
In addition to routine immunizatiuon, certain high-risk
Maintenance of temperature is critical to the viability and categories need additional vaccines.
potency of a vaccine. Vaccines such as OPV, measles and
BCG (especially after reconstitution) are sensitive to heat Chronic diseases: Patients with chronic illnesses
but may be frozen without harm (Fig. 10.5). In contrast, (Table 10.11) are at risk of serious infections and should
vaccines like hepatitis B, DTP, penatavalent vaccine and preferably receive pneumococcal, inactivated influenza,
tetanus toxoid are less sensitive to heat and are damaged varicella, hepatitis A and rotavirus vaccines. Pneumococcal
by freezing. Certain vaccines lose their potency if exposed and inactivated influenza vaccines are particularly
to bright light, and are, therefore, packaged in dark brown important in patients with cardiac or pulmonary disease
glass (BCG, MMR, measles and rubella vaccine). Within and hepatitis A and B vaccines in liver disease.
the refrigerator, OPV vials are stored in the freezer Prematurity: Most preterm and low birth weight babies
compartment (0 to-4°C). BCG, measles and MMR vaccines mount adequate immune responses, with serocoversion
are kept in the top racks of the main compartment (4-10° C) rates comparable to term newborns. They should receive
(just below the freezer); DTP, DT, TT, hepatitis A and immunization at the same chronological age, at the same
typhoid are stored in the middle racks; and hepatitis B, doses, and according to the same schedule as for full term
varicella and diluents are stored in the lower racks. infants. Since seroconversion rates for hepatitis B vaccine
Hepatitis B; Pentavalent
Human papillomavirus
Inactivated poliovirus
Hepatitis B
Diphtheria toxoid Diphtheria toxoid
Hemophilus Tetanus toxoid
Fig. 10.5: Heat and freeze sensitivity of various vaccines. BCG Bacillus Calmette-Guerin
@@@@@O@@
----------- Usable Unusable ----
Fig. l 0.6: Vaccine vial monitor (WM) comprises an inner lighter square within an outer dark circle. The inner circle darkens gradually
and irreversibly following exposure to heat in a time dependent manner. The vaccine is usable as long as the inner square is lighter
than the outer circle, and should be discarded if the color of the square matches to or is darker than the circle. Time to color
change varies with the vaccine type; e.g. two days for OPV and 14 days for the DTP-hepatitis B combination.
Table 10.11: High-risk conditions in which certain vaccines Patients are considered significantly immuno
may be necessary suppressed, if the dose of prednisolone (or its equivalent)
Circumstances that increase risk of acquiring certain infections
is ;?:2 mg/kg/day or 20 mg/day for 14 days or more. These
children should not receive live vaccines until after
Congenital or acquired immunodeficiency
4 weeks of stopping corticosteroid therapy. Live vaccines
Chronic cardiac, pulmonary, renal, liver or hematologic disease;
diabetes mellitus
may be given, if corticosteroids are given for <14 days, in
Prolonged immunosuppression with steroids or other agents
lower doses, on alternate days, or by inhaled, topical or
Radiation therapy
intra-articular routes. Wherever possible, vaccination
Cerebrospinal fluid leak, cochlear implantation should be completed prior to initiation of chemotherapy,
Malignancies immunosuppressive drugs or radiation. Live vaccines are
Functional/anatomic asplenia/hyposplenia not given for 3 months after such treatment; inactivated
During disease outbreaks vaccines during therapy might need to be repeated.
Travelers to endemic areas Children infected with HIV are susceptible to severe
Vaccines that may be necessary for high-risk conditions and/ or recurrent infections with usual or unusual
pathogens. Efficacy and safety of vaccines in such children
Influenza vaccine
Meningococcal vaccine
depends on the degree of immunodeficiency. Most
Travel to endemic area
vaccines are safe and effective in early infancy when
Japanese encephalitis vaccine immune functions are relatively intact, but efficacy
Cholera vaccine declines and immune responses wane as disease advances.
Rabies vaccine Live vaccines are unsafe in advanced HIV disease.
Yellow fever vaccine Symptomatic infants should not receive BCG. The neonate
Pneumococcal vaccine of an HIV positive mother with indeterminate HIV status
should receive initial vaccination as per schedule; IPV is
are lower for preterm neonates weighing <2 kg, the initial preferred over OPV, if feasible. Measles, MMR and
may be postponed by 1-month, if the mother is known to varicella vaccines are administered, if CD4 count >15%
be HBsAg negative. Preterm or low birth weight newborns for age after counseling regarding anticipated benefits
of HBsAg positive mothers or mothers with unknown versus risks.
status should receive the vaccine and hepatitis B
Splenectomy: Children with splenectomy or anatomical or
immunoglobulin within 12 hours of birth.
functional asplenia (sickle cell disease) are at an increased
Primary or secondary immunodeficiency: Immunodeficiency risk of infections with encapsulated organisms
may be primary or secondary to malignancy, HIV infection, (pneumococci, meningococci, H. infiuenzae). Where feasible,
corticosteroids and immunosuppressive therapy. The risk of vaccines against these organisms should be administered
certain infections and severity of most vaccine preventable at least two weeks before elective splenectomy.
diseases is increased compared to immunocompetent
children. These patients should receive pneumococcal and Miscellaneous: Minor illnesses are not a contraindication
inactivated influenza vaccines. Live vaccines (BCG, OPV, to immunization. Immunization is deferred during
measles, MMR, varicella) are contraindicated. Since moderate to severe sickness, since it might inhibit immune
household contacts may transmit OPV to immuno response. If permitted, children with bleeding or
compromised children, siblings of such patients should coagulation defects should receive vaccine by subcutaneous
ideally receive IPV. Toxoid and killed vaccines can be given rather than IM route. Live vaccines (except OPV, yellow
safely, but their efficacy may be compromised; seroconversion fever) should be avoided for 3 months after administration
should be documented and antibody titers monitored to of blood product(s); blood products are preferably not given
decide on need for additional doses. for 2 weeks following live vaccination.
204 Essential Pediatrics
Lapsed immunization: Table 10.12 suggests schedules for • CDC The Pink Book. https://www.cdc.gov/vaccines/pubs/
children who have missed routine immunization. For pinkbook/index.html
vaccines with multiple doses, the entire schedule need not • GOI. Immunization Handbook for Medical Officers. New Delhi:
be repeated and only limited doses are given. The vaccination Department of Health and Family Welfare; 2016
schedule for adolescents is discussed in Chapter 5. • Guide to introducing Inactivated Poliomyelitis Vaccine based on
the Polio Eradication & Endgame Strategic Plan 2013-2018.
Passive Immunization Available at http:/ /www.who.int/immunization/diseases/
Passive immunity is resistance based on antibodies, poliomyelitis/endgame_objective2/inactivated_polio_vaccine/
preformed in another host. Thus, preformed antibodies to • Indian Academy of Pediatrics, Advisory Committee on Vaccines
varicella and hepatitis B can be injected during the and Immunization Practices (ACVIP). IAP recommended
incubation period to limit viral multiplication (Table 10.13). immunization schedule for children aged O through 18 years, 2016,
Normal human immunoglobulin serves the same purpose, and updates on immunization. Available at http://www.acvip.
if specific immunoglobulin is not available, e.g. to protect org/files/lAP-immunization-schedule-2016-IP-2016-Epub.pdf
from hepatitis A or measles. • Mission Indradhanush. Available at http:/ /www.mission
indradhanush.in/
Suggested Reading • National Immunization Schedule for infants, children and pregnant
• AAP Red Book. Available at www.aapredbook. aappublications. women. Available at https://mohfw.gov.in/sites/default/files/
org/site/resources 245453521061489663873.pdf
Chapter
11
Infections and Infestations
Tanu Singhal • Rakesh Lodha • Sushil K Kabra
significant is unknown. However, fever may be associated visits. The overwhelming majority are due to viral
with adverse effects such as paradoxical suppression of infections. Of greater concern are fevers without localizing
immune response, increased insensible water losses, signs/without focus in children below the age of 3 years
cardiopulmonary stress and triggering febrile seizures in (especially below 3 months) as they may indicate an
predisposed patients. underlying serious bacterial infection. Since H. influenzae
Reduction of fever should be a priority in patients with and S. pneumoniae are important causes of serious bacterial
past/family history of febrile seizures, those critically ill, infection, the algorithms suggested here may change with
those with cardiorespiratory failure, those with disturbed increasing immunization with H. influenzae and
fluid and electrolyte balance, or with temperature S. pneumoniae vaccines.
exceeding 40° C (104 °F). For the rest, treatment should be
individualized; parental counseling is important. Fever without Focus in < 1 Month
The two commonly used drugs for antipyresis in Fever in a neonate ( <1 month of age) is generally a medical
children are paracetamol and ibuprofen. Other agents such emergency. This is because of (i) 5-15% risk of serious
as aspirin, nimesulide and mefenamic acid are associated bacterial infection such as sepsis, bacteremia, urinary tract
with high incidence of adverse effects and are better infections, pneumonia, enteritis and bacterial meningitis,
avoided. Ibuprofen decreases fever at the same rate as (ii) neonates may look well and still have serious bacterial
paracetamol, the nadir with ibuprofen is slightly lower infection and (iii) the implications of missing or delaying
and duration of action is longer (6 hours) as compared to diagnosis of sepsis are serious.
paracetamol (4 hours). However, the risk of side effects Sometimes neonates get fever due to over clothing and
such as acute renal failure and gastrointestinal bleeding warm weather ('dehydration fever') in which the baby
is theoretically higher with ibuprofen, though not looks well and active. This only warrants frequent feeding
substantiated by observational studies. Conversely, the and nursing in less warm environment. The infant is kept
consequences of paracetamol overdose (hepatic failure) under observation for other signs of sepsis and
are more sinister than those with ibuprofen. Considering investigated if in doubt.
all factors, it is reasonable to use paracetamol at a dose of A detailed clinical assessment should be performed for
15 mg/kg every 4 hours (max. 5-6 doses/day) as the first a febrile neonate (Fig. 11.1). A toxic neonate is at high risk
line drug for fever management. It is suggested to shift to of serious bacterial infections and should be treated
ibuprofen in patients who do not adequately responded aggressively. The patient should be hospitalized to
to paracetamol, at a dose of 10 mg/kg every 6 hours. There undergo a complete sepsis work up and administered anti
is some evidence to suggest a marginal benefit on biotics (3rd generation cephalosporin such as cefotaxime
amelioration of fever by combining paracetamol and or ceftriaxone with or without an aminoglycoside) without
ibuprofen as compared to using either drug alone. Tepid awaiting the results of investigations. Other supportive
water sponging may be used as a complementary method therapy should be instituted, if required.
to drug therapy in bringing down fever quickly in some Management of a well appearing febrile neonate is
children. controversial. If fever is thought to be due to over bundling
Heat illness is a medical emergency. The high then repeat temperature assessment should be done after
temperatures can cause irreversible organ damage and 15-30 minutes. Most guidelines recommend hospitaliza
should be brought down quickly. Since the hypothalamic tion of well looking febrile infants less than 1 month of
set point is not altered, non-steroidal anti-inflammatory age as they may have serious infections. These infants
drugs, which act by reducing prostaglandin production,
are ineffective. External cooling is needed with ice water Fever >38 ° C in less than 90 days age, no focus
sponging, cooling blankets, cold water enemas and gastric
washes. At the same time, measures should be taken to
correct the underlying condition.
should undergo basic evaluation including blood counts fever. If the count is less than 15,000/cu mm, observation
and C-reactive protein. Cultures should be sent if is continued and if fever persists beyond 48 hours without
available. If the septic screen is positive, IV antibiotics development of a focus, a complete evaluation including
should be started after doing a lumbar puncture and complete blood counts, malarial parasite, C-reactive
cerebrospinal fluid examination. If the screen is negative protein, urinalysis and blood culture is indicated.
the baby should be observed, and a repeat screen sent
6-12 hours later. If repeat screen is also negative, Fever of Unknown Origin
observation of the neonate should continue till the baby Definition
is afebrile and culture reports are available. By this time,
The definition of fever of unknown origin (FUO) is fever
in most babies, the fever would have subsided or a focus
>101° C lasting for 3 weeks or more for which no cause is
would have developed.
apparent after 1 week of outpatient investigation. A prac
Fever without Focus in Infants 1-3 Months Old tical definition of FUO is simply fever >101° F measured
on several occasions over a 7-day period with normal
Infants in this age group like those aged less than 1 month preliminary investigations including at least complete
are at high risk of serious bacterial disease (10%, with blood counts, malarial smear, urinalysis and culture, blood
2-3% risk of bacteremia). Also, they may look well and culture, chest X-ray and ultrasound abdomen.
still have bacterial disease. The algorithm for management
of these babies is fairly similar to those less than 1 month Causes
(Fig. 11.1). A detailed clinical assessment should be
The principal causes of FUO are listed in Table 11.1;
performed. A history of recent immunization should be
infections account for most causes (60-70%). Most
obtained as fever may be related to the immunization.
common among infectious causes are enteric fever,
All toxic/ill-appearing babies should be managed as malaria, pulmonary or extrapulmonary tuberculosis and
an infant less than 1 month (discussed earlier). A well urinary tract infections. Bacterial sinusitis may be a
looking infant 1-3 months of age should undergo a common cause of FUO even without the classical
complete sepsis evaluation while in the outpatient symptoms of upper respiratory infections. Malignancies
department including leukocyte and platelet counts, band including leukemia and lymphoma and autoimmune
cell count, C-reactive protein, urinalysis, urine and blood diseases chiefly systemic onset juvenile rheumatoid
cultures and if indicated smear for malarial parasite, and arthritis are important. Other causes include drug fever,
chest X-ray. CSP examination may be undertaken, if no temperature dysregulation, diabetes insipidus,
other clue to focus of infection is found. If the screen is sarcoidosis, ectodermal dysplasia and sensory autonomic
positive, the patient is hospitalized and treated with neuropathies. Even with extensive investigations the cause
antibiotics. A well-looking infant with no clinical focus of of FUO remains undiagnosed in 10-20% of the cases.
infection and a negative screen (leukocyte count <15,000/
cu mm, band count <20%, C-reactive protein negative, Approach to FUO
urine white cells <10/HPF) can be observed at home
without antibiotics, provided the care takers are reliable The first step is to identify sick patients who need
and agree to bring the infant for reassessment 24 hours stabilization and urgent referral to a tertiary care centre.
and 48 hours later. All attempts are made to reach an etiologic diagnosis. A
detailed history is important, and includes:
Fever without Focus in Children Aged 3-36 Months • Whether and how fever was documented
The risk of serious bacterial infections decreases with
advancing age and in this age group it is 5%. A child Table 11.1: Causes of fever of unknown origin
presenting with fever without focus should be assessed Infectious causes
completely. Detailed history is taken about vaccination, Enteric fever, malaria, urinary tract infections, tuberculosis,
history of sick contacts in family and the condition of the sinusitis, infectious mononucleosis, human immunodeficiency
child when fever is down. If the patient looks toxic, he virus, rickettsial infections, hidden abscesses (liver, pelvic),
should be hospitalized and undergo appropriate mastoiditis, osteomyelitis, chronic meningitis, infective
evaluation and treatment. In a non-toxic child with fever endocarditis, brucellosis, cytomegalovirus, toxoplasmosis,
less than 39 ° C, one can merely observe. In children with kala-azar
fever more than 39 ° C, the risk of bacteremia is higher and Autoimmune causes
it is recommended to do a leukocyte count and examine Systemic onset juvenile rheumatoid arthritis, Kawasaki disease,
smear for malarial parasite. If the leukocyte count is systemic lupus erythematosus, inflammatory bowel disease,
>15,000/cu mm, blood culture should be sent and the polyarteritis nodosa, Kikuchi disease
patient administered IV ceftriaxone on either an inpatient Malignant causes
or outpatient basis. A count less than 5000/cu mm should
Leukemia, lymphoma, hemophagocytic lymphohistiocytosis
make one suspect viral infections, dengue and enteric
208 Essential Pediatrics
• Duration and pattern of fever (distinguish from It should be possible to make a diagnosis of the etiology
recurrent fever) of FUO in most cases. In a small number of cases, it may
• Symptoms referable to all organ systems, weight loss not be possible to arrive at the etiologic diagnosis. In such
• History of recurrent infections, oral thrush; joint pain, cases, periodic reassessments should be done as the
rash, photosensitivity disease may finally surface (e.g. lymphoma, systemic onset
• History of contact with tuberculosis and animals juvenile rheumatoid arthritis). Some cases of FUO may
(brucellosis) self-resolve over time. Empirical antitubercular therapy
• Travel to endemic zones (kala-azar, rickettsia) with four drugs for four weeks may be tried, if it is not
• Drug history particularly anticholinergics (drug fever) possible to arrive at an etiologic diagnosis after exhaustive
work up and if the patient is sick. Empirical use of steroids
History is followed by a complete physical examination.
should be avoided.
Documentation of fever is necessary, followed by
assessment of general activity, nutritional status and vitals. Suggested Reading
A head to toe examination, after removing all clothes, is
• Antoon JW, Potisek NM, Lohr JA, Pediatric fever of unknown
vital. The physical examination should be repeated on origin. Pediat Rev 2015; 36:380-91.
daily basis as new findings may emerge that provide a • Chien YL. Clinical approach to fever of unknown origin in children.
clue to the etiology. One must keep Kawasaki disease in J Microbiol Irnmunol Infect 2017; 50:893-98.
mind since diagnosis before the 10th day of fever is crucial
to prevent coronary complications (Fig. 11.2). Fever with Rash
Preliminary investigations, which should be done in Fever with rash is a common problem that might signify
all patients with FUO include complete blood counts, a serious disorder (dengue hemorrhagic fever,
peripheral smear, malarial parasite, C-reactive protein, meningococcemia) or conversely a minor drug allergy.
ESR, blood culture, Widal test, chest X-ray, tuberculin test, There are a number of infectious and non-infectious causes
urinalysis and culture, liver function tests, serum of fever with rash (Table 11.2).
creatinine and abdominal ultrasound. Specialized
investigations are done, depending on clinical clues. Evaluation
If a diagnosis is established on the basis of the above The most important factor that helps determine the
approach, appropriate treatment should be instituted. If etiology of an exanthematous febrile illness is the nature
no diagnosis is made, clinical reassessment and further of rash. Rashes may be macular, maculopapular, vesicular,
investigations are merited. While second line investiga
tions are being planned and executed, treatment with Table 11.2: Common exanthematous illnesses seen in children*
intravenous ceftriaxone may be considered as enteric fever Macular/ maculopapular rash
is an important cause of FUO in our country, especially in Measles, rubella, dengue, roseola infantum, erythema
those with negative clinical and preliminary investiga infectiosum, drug rash, infectious mononucleosis,
tions. chikungunya, HIV, adenoviral and enteroviral infections,
Second-line investigations include HIV ELISA, contrast Mycoplasma pneumoniae, secondary syphilis, brucellosis,
enhanced CT of chest and abdomen, CT of the paranasal scrub typhus, chronic hepatitis B, CMV, lupus, systemic JRA
sinuses, 2D echocardiogram, complement level, Diffuse erythema with peeling or desquamation
antinuclear antibodies and rheumatoid factors, and if Scarlet fever, Stevens-Johnson syndrome, toxic epidermolysis,
indicated bone marrow histology and cultures and tissue staphylococcal and streptococcal toxic shock syndrome,
biopsies. Other serologic tests include brucella and Kawasaki disease
Epstein-Barr virus serology and hepatitis B surface Vesicular rash
antigen. Tests that are of limited value include quantiferon
gold and serology for M. tuberculosis. Varicella, herpes simplex, zoster, enteroviral infections (hand
foot-and-mouth disease), papulonecrotic TB
Petechial and/or purpuric rash
Meningococcemia, dengue hemorrhagic fever, Indian
spotted fever, gonococcemia, hemorrhagic measles and
chickenpox, cutaneous vasculitis, Henoch-Schonlein purpura
Urticaria/ rash
Scabies, cutaneous larva migrans, strongyloides, insect bites,
pediculosis
Nodular rash
Molluscum contagiosum, disseminated histoplasmosis,
Fig. 11.2: Kawasaki disease: (a) Red and cracked lips; (bl Palmer cryptococcosis, erythema nodosum
rash and swelling *Common and serious conditions are in bold
Infections and Infestations 1209-
Etiopathogenesis
Measles is caused by an RNA virus belonging to the
paramyxovirus family. The virus is transmitted by droplet
spread from the secretions of the nose and throat usually
4 days before and 5 days after the rash. The disease is
highly contagious with secondary attack rates in
susceptible household contacts exceeding 90%. The portal
of entry is the respiratory tract where the virus multiplies
in the respiratory epithelium. Primary viremia occurs
resulting in infection of the reticuloendothelial system
followed by secondary viremia, which results in systemic
symptoms. The incubation period is around 10 days.
Clinical Features
The disease is common in preschool children; infants are
protected by transplacental antibodies, which decline by
Fig. 11.3: Diffuse erythematous rash in a patient with dengue 9 months (hence the rationale for vaccination at this age).
The prodromal phase is characterized by fever, rhinorrhea,
nodular, urticaria! or purpuric (Table 11.2); overlap may conjunctiva! congestion and a dry hacking cough. Koplik
occur with one etiology having varying presentations. spots, considered pathognomonic of measles, appear on
Other factors that help in diagnosis are epidemiology, the 2nd or 3rd day of the illness as gray /white grains of
season, history of exposure, incubation period, age, sand-like lesions with surrounding erythema opposite the
vaccination status, prodromal symptoms and relation of lower second molars on the buccal mucosa. The rash
rash with fever, distribution and progression of rash, usually appears on the fourth day with rise in fever as
involvement of mucous membranes and history of drug faint reddish macules behind the ears, along the hairline
intake. Examination includes nature of the rash and and on the posterior aspects of the cheeks (Fig. 11.4). The
distribution, involvement of palms and soles (dengue, rash rapidly becomes maculopapular and spreads to the
Fig. 11.3; spotted fever; Kawasaki disease; Stevens-Johnson face, the neck, chest, arms, trunk, thighs and legs in that
syndrome), involvement of mucous membranes, adeno order over the next 2-3 days. It then starts fading in the
pathy, organomegaly and signs of meningeal irritation. same order that it appeared, and leaving behind branny
Investigations that assist in diagnosis include complete desquamation and brownish discoloration that fades over
blood counts, C-reactive protein, blood cultures and the next 10 days.
serology, and sometimes biopsy. Modified measles seen in partially immune individuals
is a much milder and shorter illness. Hemorrhagic measles
Management
is characterized by a purpuric rash and bleeding from the
All efforts are made to diagnose the serious entities first nose, mouth or bowel.
and institute treatment; a specific diagnosis is often not
possible. In this situation, symptomatic therapy, close
observation, explanation of danger signs to parents and
staying away from school until the rash resolves is
recommended. Often drugs and antibiotics are given to a
child with fever and rash. Distinguishing this viral
exanthem from drug-related rash is difficult; intense
itching is common with the latter. Withholding the drug,
symptomatic therapy and observation is recommended.
Rechallenge with the medication may be permitted, if the
rash was mild.
Treatment
Management is symptomatic and includes antipyretics
(aspirin is contraindicated due to risk of Reye syndrome
and ibuprofen due to risk of necrotizing fasciitis),
: ... :·:.,,.,· antipruritic agents and good hygiene. The child should
ti'·�� not attend school until no new lesions appear and all
� �.·
-: -.
lesions have crusted. Administration of oral acyclovir
(20 mg/kg/dose four times a day for 5 days) within
I
24 hours of onset of rash in healthy children reduces the
duration of rash by one day and lesions by 25%. There
Fig. 11.5: The polymorphic rash of chickenpox
may be some benefit even if started within 24-48 hours of
the rash but none beyond 48 hours. IV acyclovir (10 mg/
Complications
kg every 8 hours for 14 days) is recommended for patients
Secondary bacterial infections of the skin lesions may with complicated varicella and illness of any severity in
occasionally result in necrotizing fasciitis; usual organisms high-risk patients such as neonates and immuno
are S. aureus and S. pyogenes. Neurologic complications compromised children.
include meningoencephalitis, acute cerebellar ataxia,
transverse myelitis, LGB syndrome and optic neuritis. Prevention
Other complications include purpura fulminans due to
Prevention against varicella with varicella vaccine and use
antibodies against protein C, CNS vasculitis leading to
of varicella zoster immune globulin (VZIG) for post
stroke, autoimmune thrombocytopenic purpura, cold exposure prophylaxis are detailed in Chapter 10. VZIG is
antibody-mediated immune hemolytic anemia and Reye
fairly expensive and not always available. Other options,
syndrome. which may be used are intravenous immunoglobulin and
The progressive varicella syndrome is a dreaded oral acyclovir.
complication of chickenpox in the immunocompromised,
neonates, pregnant women and sometimes even healthy Suggested Reading
children, adolescents and adults. This syndrome is • English R. Varicella. Pediatr Rev 2003;24:372-79.
characterized by continued development of lesions, • Gershon AA, Breuer J, Cohen JI, et al. Varicell zoster virus
hemorrhagic lesions, coagulopathy and visceral organ infections. Nature Rev Dis Primers 2015; 1: 15016; doi:10.1038/
involvement including hepatitis, pneumonia and nrdp.2015.16.
encephalitis; mortality rates are high despite therapy. • Wutzler P, Bonanni P, Burgess M, et al. Varicella vaccination
Chickenpox in pregnancy is associated with increased global experience. Expert Rev Vaccines 2017;16:833-843.
risk of severe disease in the mother. Congenital varicella
syndrome may occur following infection in the first and Infectious Mononucleosis
second trimester at a frequency of 0.4-2% and is Infectious mononucleosis (IM), a syndrome characterized
characterized by skin scarring, malformed extremities, by fever, fatigue, sore throat and lymphadenopathy, is
cataracts and brain abnormalities (e.g. aplasia, most often caused by a herpes virus, Epstein-Barr virus
calcifications). Finally, if the disease occurs in the mother (EBY). Infectious mononucleosis-like illness can also be
5 days before and 2 days after delivery, severe and often caused by toxoplasma, CMV, adenoviruses and primary
fatal neonatal disease may result. HIV infection.
Herpes zoster in children is characterized by a mild
vesicular rash with dermatomal distribution; unlike adults Epidemiology
pain is less and post-herpetic neuralgia unusual. The risk The EBY virus, a DNA virus of the herpes virus family, is
of herpes zoster is more in children who acquire chicken shed in oral secretions and transmitted by close intimate
pox in infancy, those whose mothers developed varicella contact like kissing or exchange of saliva. The virus
in the third trimester and in the immunocompromised. replicates in the oral epithelial cells then spreads to
salivary glands travels in the B lymphocytes in the blood
Diagnosis to the lymphoreticular system including lymph nodes,
The diagnosis is clinical and usually not difficult. Chicken liver and spleen. The CD8 lymphocytes proliferate to check
pox should be differentiated from other vesicular this replication of virus in the B lymphocytes and represent
-212 Essential Pediatrics
the atypical lymphocytes seen in EBV infection. Like other enlarged adenoids. There is no clear role of acyclovir in
herpes viruses, EBV establishes lifelong latent infection _ treatment of EBV in the immunocompetent.
after the primary infection with frequent asymptomatic
reactivations. Other Manifestations of EBV Infections
The epidemiology of IM is related to the age of primary EBV has oncogenic potential and has been causally
acquisition of EBV infection. In developing countries, most associated with aggressive proliferative disorders such as
EBV infection occurs in infancy and early childhood when virus associated hemophagocytic syndrome, oral hairy
it is either asymptomatic or similar to other childhood leukoplakia and lymphoid interstitial pneumonitis in
infections. For this reason, IM is uncommonly seen or patients with AIDS, nasopharyngeal carcinoma, Burkitt
reported in India. In developed countries, the age of lymphoma, Hodgkin disease and tumors in i�mui:io
acquisition of EBV infection shifts upwards and thus IM .
compromised patients (e.g. X-lmked lymphoprohferahve
is seen more commonly. disease, leiomyosarcoma, CNS lymphoma).
Clinical Features
Suggested Reading
Symptomatic EBV infections in older children and adults
are characterized by insidious onset with symptoms such • Dunmire SK, Verghese PS, Balfour HH JR. Epstein-Barr virus
infection. J Clin Virol 2018;102:84-92.
as malaise, fatigue, fever, headache, nausea, sore throat, • Stanfield BA, Luftig MA, Recent advances in understanding E-B
abdominal pain and myalgia. Examination shows virus. FlOOORes 2017;6:386.
pharyngeal inflammation with exudates and petechi�e at
the junction of soft and hard palate, generalized Roseola lnfantum
lymphadenopathy (cervical, less often axillary and Roseola infantum (exanthem subitum, sixth disease) is a
inguinal), mild splenomegaly (50%) and hepatomegaly common childhood exanthematous illness caused most
(10%). Maculopapular rashes are seen in 3-15% and in commonly by a DNA human herpes virus-6 (HHV-6) and
30% of those who have received ampicillin or amoxicillin. less commonly by HHV-7 and echovirus 16. HHV-6 and
Complications are rare and include splenic rupture HHV-7 target the CD4 T cells and like other herpes viruses
following minor trauma, airway obstruction due to can remain latent in the body for several years after acute
enlargement of oropharyngeal lymphoid tissue, infection.
meningitis, seizures, ataxia, myocarditis, hemolytic
The peak age for roseola is between 6 months and
anemia, thrombocytopenia, neutropenia, aplastic anemia,
3 years. The prodromal period is characterized by upper
interstitial pneumonitis and pancreatitis.
respiratory signs such as rhinorrhea, pharyngeal
Diagnosis inflammation, conjunctiva! redness, mild cervical and
occipital adenopathy and sometimes palpebral edema.
Most patients show leukocytosis and absolute lympho The classic clinical illness is heralded by high fever ranging
cytosis, with presence of atypical ly�phocyte�. The from 38 ° C to 40 ° C associated with febrile seizures in
platelet counts are mildly low and hepatic transammases 5-10% and lasting for 3-4 days. Fever declines abruptly
elevated in 50% patients. The Paul-Bunnell test (hetero and is followed by development of a rash within
phile antibody test) is used for screening. This test is bas�d 12-24 hours. The rash is discrete erythematous and
on agglutination of sheep/horse red cells by heterophile maculopapular which first appears on the trunk and then
antibodies present in the serum of patients with EBV spreads to the face, neck and proximal extremitie�. It is
infection. This test may have false negative rates of 10% nonpruritic, rarely becomes confluent and fades m 3-4
and remains positive for a few months to 2 years after days. Infectiousness is low and outbreaks have not
infection. IgM antibody to viral capsid antigen (IgM VCA) occurred. Roseola should be differentiated from childhood
is confirmatory for diagnosing acute infection. illnesses such as rubella, measles, enteroviruses and drug
IM should be differentiated from other causes of hypersensitivity. Treatment is symptomatic and prognosis
mononucleosis enumerated earlier, streptococcal excellent.
pharyngitis and acute leukemia.
Suggested Reading
Treatment
• Agut H, Bonnafous P, Gautheret- Dejean A. Update on infections
Rest and symptomatic therapy are mainstays of manage with human herpes viruses 6A, 6B and 7. Med Mal Infect
ment. Participation in strenuous activities and contact 2017;47:83-91.
sports should be prohibited in the first 2-3 weeks of illness • Stone RC, Micali GA, Schwartz RA. Roseola infantum and its causal
due to risk of splenic rupture. Treatment with prednisolone human herpes viruses. Int J Dermatol 2014;53:397-403.
(1 mg/kg/ day for 7 days) is advised for complications
such as hemolytic anemia, airway obstruction, meningitis Erythema lnfectiosum
and thrombocytopenia with bleeding. Intranasal steroids Erythema infectiosum (fifth disease) is a common
may be used to relieve nasal obstruction caused by exanthematous illness of childhood caused by a small
Infections and Infestations 1213-
Etiopathogenesis
Most cases occur between 5 and 15 years of age; infants
are rarely affected due to the presence of transplacentally
acquired maternal antibodies. Man is the only reservoir
of infection; a carrier state does not exist. The incidence is
high in winter and spring; infections occur by direct
contact, airborne droplets and fomites contaminated by
saliva and urine. The virus proliferates in the respiratory
epithelium and enters the circulation; it then gets localized
to the glandular and neural tissue. The virus has been
isolated from saliva as long as 6 days before and 9 days
after appearance of salivary gland swelling. Secondary
infection rates vary from 40 to 80%. Mumps infection or
immunization is believed to confer lifelong immunity.
Clinical Features
Fig. 11.6: The "slapped cheek" rash of erythema infectiosum Following an incubation period of 2-4 weeks, the
symptoms begin acutely with fever, malaise and headache.
DNA virus Parvovirus B19. This virus has tropism for cells Mumps infection is characterized by unilateral or bilateral
of the erythroid lineage at the pronormoblast stage. parotitis. This presents as earache, jaw tenderness while
The peak age for erythema infectiosum is between chewing, dryness of mouth and swelling at the angle of
5-15 years. Transmission of infection is by the respiratory jaw. The ear lobe may appear to be pushed upwards and
route and the incubation period is 4-28 days (mean outwards. The defervescence and resolution takes about
16-17 days). The prodromal phase is mild and consists of a week Occasionally other salivary glands including the
low-grade fever, headache and symptoms of mild upper submaxillary and sublingual glands are affected.
respiratory tract infection. The characteristic rash first The occurrence of epididymo-orchitis is common in
appears as erythematous flushing on the face in what is a adolescent boys or postpubertal men (unilateral in 85%
slapped cheek appearance (Fig. 11.6). It spreads rapidly cases) and occurs 1-2 weeks after parotitis. The testes are
to trunk and proximal extremities as a diffuse erythe enlarged and tender. Some degree of atrophy develops in
matous macular rash that rapidly undergoes central the affected testes; sterility is rare.
clearing to give it a lacy or reticulated pattern. The rash CNS involvement in the form of aseptic meningitis is
gradually fades over a 1-3 weeks period. Complications seen in -1-10% patients with parotitis. Recovery is
include arthropathy, idiopathic thrombocytopenic generally uneventful. Mumps is one of the commonest
purpura and aseptic meningitis. Fifth disease should be causes of aseptic meningitis in children. The risk of
differentiated from measles, roseola, rubella and drug encephalitis is between 0.02 and 0.3%, with satisfactory
rash. Treatment is symptomatic. prognosis and of <2%. Other manifestations include
Other serious manifestations of parvovirus B19 auditory nerve damage with deafness, cerebellar ataxia,
infection include arthralgia and arthropathy in adolescents facial neuritis, transverse myelitis and Guillain-Barre
and adults, transient aplastic crises in patients with chronic syndrome. Uncommon presentations include pancreatitis
hemolytic anemia, chronic anemia, pancytopenia or (5% may trigger insulin-dependent diabetes mellitus),
marrow suppression, virus associated hemophagocytic mastitis, oophoritis, nephritis and myocarditis.
syndrome in the immunocompromised, hydrops fetalis
in pregnant women and rare episodes of myocarditis in Diagnosis
healthy children and adults. The diagnosis is based on clinical features. Serum amylase
is elevated in almost 90% patients. The diagnosis may be
Suggested Reading
confirmed by serum IgM ELISA. Mumps parotitis needs
• Ramdass P, Mullick S, Farber HF. Viral skin diseases. Prim Care to be differentiated from suppurative parotitis, sub
2015; 42:517-67
• Servant-Delmas A, Morinet F. Update of the human parvovirus B
mandibular lymphadenitis, juvenile parotitis, calculus in
19 biology. Transfus Clin Biol 2016;23:5-12 Stensen duct and other infectious causes, e.g. coxsackie A
and cytomegalovirus.
Mumps
Mumps is an acute viral infection characterized by painful Treatment
enlargement of salivary, most commonly the parotid Symptomatic treatment is given in the form of antipyretics
glands. Mumps is caused by an RNA virus of genus and warm saline mouthwashes. Orchitis is treated by bed
Paramyxovirus; only one serotype is known. rest and local support. Aseptic meningitis responds well
214 Essential Pediatrics
Diagnosis
The diagnosis is based on history and characteristic clinical
features of asymmetric flaccid paralysis. Stool examination
is recommended in every case of acute flaccid paralysis
(AFP). Virus can be detected from onset to 8 or more weeks
after paralysis; the highest probability of detection being
in the first 2 weeks after onset of paralysis. Examination
of cerebrospinal fluid (cell count, Gram stain, protein and
glucose) is useful in eliminating other conditions that
cause AFP. Current serologic tests cannot differentiate
between wild and vaccine virus strains. Collection of blood
specimens for culture or serology is not recommended.
Differential Diagnosis
It is not possible to clinically differentiate between wild
and vaccine-associated paralytic polio (VAPP). The two Fig. 11.7: Vesicular rash of hand-foot-and-mouth disease
diseases most commonly confused with polio are Guillain
Barre syndrome and transverse myelitis. Other conditions Clinical Features
with a presentation similar to those of paralytic polio
myelitis include traumatic neuritis, rabies, meningitis/ The onset is with a prodrome characterized by low grade
encephalitis, and illnesses due to toxins (diphtheria, fever, feeling of being unwell, sore throat. This is followed
botulism) (Chapter 19). by development of ulcers/ blisters in the oral cavity mostly
on the posterior aspect, papulovesicular skin rash on the
Treatment palms and soles and less commonly on buttocks, knees,
elbows and genital area (Fig. 11.7). All manifestations may
Treatment should be early and appropriate to the stage not be present in all patients. The illness resolves quickly
and degree of paralysis. Children with bulbospinal polio over the 4-5 days in most patients.
and respiratory paralysis require hospitalization. Children
Complications include loss of toe nails or finger nails
with isolated limb paralysis can be managed at home. As
4 weeks after onset of disease which is temporary. Rare
the acute phase of illness subsides, recovery in muscle
complications include aseptic meningitis, encephalitis,
power is helped by physiotherapy, ambulation and
polio-like paralysis, myocarditis and respiratory distress
prevention of deformities. Some children require orthosis
syndrome. Mortality is reported in HFMD outbreaks
at some stage for ambulation. Others with fixed
particularly due to enterovirus 71 with neurologic
deformities and contractures require orthopedic
complications, from China, Vietnam, Taiwan and
intervention.
Malaysia. Some experts believe that HFMD enteroviruses
are occupying the ecologic niche created by eradication
Prevention
of polioviruses.
The available vaccines and the recommended schedule
are discussed in Chapter 10. Diagnosis
Suggested Reading Diagnosis is clinical and the disease should be differen
tiated from other illnesses causing oral ulcers such as
• Polio Global Eradication Initiative. www.polioeradication.org
• World Health Organization. Poliomyelitis. www.who.int herpangina, herpetic gingivostomatitis and aphthous
ulcers and also from chicken pox and insect bite allergy.
Hand-Foot-and-Mouth Disease (HFMD)
HFMD is a common viral illness affecting primarily
Treatment and Prevention
children below the age of 5 years. The illness is caused by Treatment is symptomatic with analgesics and soft diet.
viruses of the enterovirus genus, belonging to family Isolation of affected children at home and promotion of
Picornaviridae. This genus includes other infection hand hygiene is important. There is no vaccine available
causing viruses, including poliovirus, ECHO virus, against HFMD.
Coxsackie virus and enteroviruses. Though many viruses
can cause HFMD, Coxsackie virus A16 and enterovirus Suggested Reading
71 are the most common. The disease commonly presents • Hand-foot-and-mouth disease. www.mayoclinic.org
as outbreaks often in preschools and transmission is • Koh WM, Badaruddin H, La H, et al. Severity and burden of
by direct contact with an affected patient or infected hand-foot-and-mouth disease in Asia. BMJ Glob Health 2018; 3(1):
fomites. e000442
216 Essential Pediatrics
(above 16 years), telbivudine (above 16 years) and more coinfection with HIV) and receipt of blood transfusions
recently tenofovir (above 12 years) (see Chapter 12). prior to the period when HCV testing became routine.
HCV is not transmitted by breastfeeding. Transmission
lmmunoprophylaxis by unsafe injections, drug abuse, tattooing are other routes
Hepatitis B immunoglobulin (HBIG) is used in the post for disease transmission. Unlike HBV, HCV is not
exposure prophylaxis of newborns of HBV-infected transmitted to household contacts and sexual transmission
women. It is administered intramuscularly as soon as is infrequent.
possible after birth and should be given concurrently with
Clinical Features
HBV vaccine, at a different site. The dose for infants is 0.5
mL. Combination of HBIG and HBV vaccination in infants In adults, 85% of patients exposed to HCV will develop
born to HBsAg positive mothers prevents transmission chronic infection, of which approximately 10-20%
in approximately 95% of those at risk (see Chapter 10). develops cirrhosis and some hepatocellular carcinoma.
Chronic HCV is a common indication for liver transplant
Suggested Reading in the developed nations. However, the prognosis of
• Nelson NP, Easterbrook PJ, McMahan BJ. Epidemiology of hepatitis childhood HCV infection is generally good. A significant
B virus infections and impact of vaccination on disease. Clin Liver percentage (-40%) of vertically infected children
Dis 2016; 20:607-28. spontaneously clears HCV over a few years. The rate of
spontaneous clearance reduces as age of acquisition of
Hepatitis D
infection advances. Even chronically infected children
Hepatitis delta virus (HOV) was first detected as a new remain asymptomatic; most have normal liver enzymes
nuclear antigen in the hepatocytes of patients infected with and a few changes on liver biopsy. Progression to chronic
hepatitis B virus (HBV) and was frequently associated with disease, hepatic failure and carcinoma are rare in children.
severe acute or chronic hepatitis. Transmission of HOV
requires either co-infection with HBV or superinfection Diagnosis
in individuals who are HBV carriers. Although HDV The diagnosis of HCV infection is based on detection of
infection is closely associated with HBV, HDV clearly antibodies against recombinant HCV antigens by enzyme
belongs to a distinct virus group. Currently, HOV is immunoassay or rapid immunoblot assays or by detection
assigned a floating genus, Deltavirus. of HCV RNA using nucleic acid tests. Enzyme immuno
assays are fairly sensitive but less specific especially with
Hepatitis C
false positive results in patients with elevated globulin
Hepatitis C virus (HCV) was recognized in 1989 as a major levels such as those with autoimmune hepatitis. Recom
cause of non-A, non-B hepatitis. HCV is an enveloped, binant immunoblot/immunochromatographic assays are
single-stranded, positive-sense ribonucleic acid (RNA) less sensitive but more specific than enzyme immunoassay
virus, classified as an independent genus (Hepacivirus) in detecting anti-HCV antibodies. Hence the EIAs are
within the Flavivirus family. recommended as screening tests and the recombinant
immunoblot assay as confirmatory tests. Patients with
Viral Variants positive EIA and negative immunoblot assays are labeled
The HCV RNA-dependent RNA polymerase lacks proof as indeterminate and repeating tests after 4-6 weeks in
reading ability, which results in HCV being genetically such a setting is recommended. Antibodies against HCV
heterogeneous. Based on analysis of HCV sequences, six are non protective and may last for life even if the patient
major HCV genotypes are recognized. HCV genotypes has cleared HCV from the body. Diagnosis of perinatal
1 and 2 are the most prevalent worldwide. HCV infection, early infection (in the first 4-8 weeks) or active
genotype 3 is most common in Australia and the Indian infection is by performing the HCV RNA PCR.
subcontinent. The viral genotypic distribution in children
generally parallel that reported regionally in adults. HCV Therapy
genotype 1 correlates with higher serum viral levels and Most childhood HCV infections do not need specific
a less favorable response to antiviral treatment. therapy. Treatment is indicated only in children with
persistently elevated liver enzymes and abnormalities on
Epidemiology liver biopsy. Standard treatment in these children includes
The worldwide prevalence of HCV infection is approxi interferon 2a (preferably pegylated) with or without
mately 3%, which represents an estimated 170 million ribavirin for 24-48 weeks depending on the genotype. A
infected persons. Infection occurs due to contact with number of new anti-viral medications (sofosbuvir,
blood and body fluids of infected people. The primary velpatasvir, ledipasvir, simprevir) have been approved for
modes of infection in children are vertical transmission use in patients with hepatitis C, including those with
from infected mothers (rates ranging from 2 to 10% compensated cirrhosis, HIV co-infection or severe kidney
depending on the level of maternal viremia and disease (see Chapter 12).
Infections and Infestations 1219-
same time as fever. Aedes mosquitoes may acquire the usually seen in older children, adolescents and adults and
virus when feeding on an individual. can be described under three phases: Febrile, critical and
recovery.
Pathophysiology
Febrile phase: Characterized by sudden onset of high
The major pathophysiology that differentiates severe grade fever that may last for 2-7 days, there is facial
dengue from dengue fever is plasma leakage and flushing, skin erythema, bodyache, myalgia, arthralgia,
abnormal hemostasis leading to rising hematocrit values, headache, anorexia, nausea and vomiting. Occasionally
moderate to marked thrombocytopenia and varying the child may have sore throat, injected pharynx and
degrees of bleeding. The cause of abnormal leakage of conjunctiva! injection. A positive tourniquet test and
plasma is not entirely understood. However, rapid minor hemorrhagic manifestations (petechiae, mucosal
recovery without residual abnormality in vessels suggests bleeding from nose and gums) may be seen in some
it to be the result of release and interaction of biological patients. Liver may be enlarged and tender from 2 to 5 days
mediators, capable of producing severe illness with and indicates risk for developing severe illness. There is
minimal structural injury. progressive decrease in total white cell count and platelet
The pathogenesis of dengue and severe dengue count.
infection is not clear. It is observed that sequential infection
with any two of the four serotypes of dengue virus results Critical phase: During defervescence, 3-7 days from onset
in DHF/DSS in an endemic area. It is suggested that of fever, the patient may show bleeding and shock with
antibodies produced during the first infection are able to fall in platelet count and increase in packed cell volume
neutralize a second viral infection with the same serotype. (PCV). Some children show organ dysfunction with severe
However, when no neutralizing antibodies are present (i.e. hepatitis, encephalitis or myocarditis and/ or severe
infection due to another serotype), the second infection is bleeding, even in the absence of plasma leakage or shock.
under the influence of enhancing antibodies and the
Recovery phase: After 24-48 hours in critical phase, a
resulting infection and disease are severe. It is proposed
that serotype cross-reactive antibodies generated from gradual reabsorption of extravascular compartment fluid
previous infection with a particular dengue virus serotype takes place in next 48-72 hours. The general well-being
are not specific for other serotypes. Hence, they bind to improves, appetite returns, gastrointestinal symptoms
the virions but do not neutralize them, and instead abate, hemodynamic status stabilizes and diuresis ensues.
increase their uptake by antigen presenting cells (tissue Some patients may have a rash of 'isles of white in the sea
dendritic cells, monocytes, macrophages). Enhanced of red.' Others exhibit pruritus, bradycardia and
antigen presentation by these cells results in activation electrocardiographic changes; respiratory distress due to
and proliferation of memory T cells, and release of pulmonary edema is uncommon. PCV stabilizes or may
cytokines that contribute to the pathogenesis of DHF/DSS. be lower due to dilution. While leukocyte counts rise after
defervescence, recovery of thrombocytopenia may take
Endothelial cell dysfunction manifests as increased longer.
capillary permeability with microvascular leak,
hemoconcentration and circulatory insufficiency. The Unusual features: A few patients may present with
transient nature of plasma leakage suggests that this might persistent thrombocytopenia mimicking idiopathic
be mediated by a soluble mediator. Dengue viral infection thrombocytopenia, hemophagocytic lymphohistiocytosis
is commonly associated with thrombocytopenia, due to and an extended course of illness in form of multi-organ
molecular mimicry between dengue virus proteins dysfunction (extended dengue syndrome). Dengue in
(especially NSl) and endogenous self-proteins. There is immunocompromised children shows higher incidence
activation of blood clotting and fibrinolytic pathways. of organ dysfunction and longer time for platelet
Mild disseminated intravascular coagulation, liver injury recovery.
and thrombocytopenia contribute to hemorrhage. Liver
may show diffuse hepatitis with focal necrosis and Differential Diagnosis
steatosis; viral antigen may be detected on immuno
Differential diagnosis includes other hemorrhagic fever,
histochemistry. Central nervous system involvement is
chikungunya infection, influenza, malaria, enteric fever,
attributed to direct neurotropic effect of the virus.
leptospirosis and less commonly meningococcemia and
rickettsiosis. Malaria, leptospirosis, flu, enteric fever and
Clinical Manifestations chikungunya infections may be coinfected with dengue.
Dengue infection has varying clinical presentations and The features of chikungunya infection are similar to
often with unpredictable clinical evolution and outcome. dengue. However, fever is of shorter duration, and
Incubation period varies between 3 and 7 days. Infants thrombocytopenia and bleeding are less frequent. Patients
and young children may present with an undifferentiated with chikungunya often have skin eruptions, mucosal
febrile illness. The classic presentation of dengue fever is lesions, polyarthralgia and encephalopathy.
Infections and Infestations 1221-
Following clinical and laboratory features suggest Antibody determination needs careful interpretation.
presence of severe dengue infection: Following primary dengue infection, 80% patients show
Clinical criteria: Acute onset high-grade fever, detectable IgM antibodies by day 5, 99% by day 10 that
hemorrhagic manifestations (positive tourniquet test), peak by day 14 and are undetectable by 2-3 months. IgG
tender hepatomegaly, effusion in body cavities and/ antibodies rise later, peak to levels lower than IgM, decline
shock. slowly and remain detectable at low levels for life.
Diagnosis of primary dengue infection is thus based on
Laboratory criteria: Thrombocytopenia (:s;lOO 000 cells per elevated IgM antibodies.
mm 3; <1-2 platelets per oil immersion field), rising
hematocrit Management
Tourniquet test: This test is part of the WHO case Undifferentiated fever: Patients have non-specific symp
definition for dengue, and a marker of capillary toms. Treatment consists of paracetamol for fever and
fragility. The test is done by inflating the blood pressure regular monitoring for development of any complications.
cuff to a point midway between the systolic and
diastolic blood pressure for 5 minutes. The cuff is Dengue infection without warning signs: Patients with
deflated and removed. After waiting for 2 minutes, the fever, bodyache, rashes or minor bleeding may be treated
number of petechiae is counted in the antecubital fossa. symptomatically. Fever and bodyache are best treated
The presence of 10 or more petechiae per 1 square inch with paracetamol. Salicylates and other non-steroidal, anti
indicates a positive finding. This finding is present in inflammatory drugs should be avoided as these may
more than 50% of cases. predispose to mucosal bleeds. Child should be encouraged
to drink plenty of fluids. In epidemic situations, the
primary care physician or health worker should monitor
Laboratory Investigations
for warning signs (see below) along with hematocrit (PCV)
Children with severe dengue infection show increasing and platelet count, if possible.
PCV and low platelet and leukocyte counts with
lymphocyte predominance. A low leukocyte count in a Dengue with warning signs: Children with suspected
child with febrile illness during the endemic season dengue infection who have any of the following need
suggests possible dengue infection. While malaria and hospitalization: (i) abdominal pain or tenderness,
enteric fever may have low white cell counts, leukopenia (ii) persistent vomiting, (iii) clinical fluid accumulation,
is more severe in dengue. (iv) mucosal bleeding, (v) lethargy, restlessness, (vi) liver
Blood levels of total protein and albumin are reduced, enlarged >2 cm, (vi) increase in PCV with concurrent or
more marked in patients with shock. Levels of rapid decrease in platelet count.
transaminases are raised; higher increase in SGOT than These patients should be admitted in hospital and need
SGPT suggests dengue rather than other virus infection. intravenous fluids. Crystalloids are the preferred fluids.
Patients with severe dengue may show hyponatremia and In the hospital, all children without hypotension should
acidosis, with increase in urea and creatinine. X-ray chest be given Ringer lactate or normal saline infusion at a rate
or ultrasound examination may show varying degrees of of 7 mL/kg over one hour. After one hour, if PCV has
pleural effusion that is more common on the right, but decreased and vital parameters are improving; fluid
occasionally bilateral. Ultrasound examination of infusion rate should be decreased to 5 mL/kg over next
abdomen may show ascites and enlarged gallbladder. hour and to 3 mL/kg/hour for 24-48 hours with frequent
monitoring of PCV and vital parameters. When the patient
Confirmation of diagnosis of dengue is established by the is stable as indicated by normal blood pressure, good oral
following: intake and urine output, the child can be discharged
Direct methods: Virus isolation by culture; genome (Fig. 11.9).
detection by PCR; NSl antigen detection. If at 1 hour, the PCV is rising and vital parameters do
Indirect methods: IgM detection; IgG detection. not show improvement, the infusion rate is increased to
10 mL/kg over next hour. In case of no improvement, fluid
Virus isolation or PCR requires the sample to be infusion rate may further be increased to 15 mL/kg in the
obtained within the first 5 days of fever, is technically 3rd hour. If no improvement is observed in vital parameters
demanding, not universally available and hence of limited and PCV at end of 3 hours, colloids are given at 10 mL/kg.
practical use. NSl antigen is a highly conserved Once PCV and vital parameters are stable, the infusion rate
glycoprotein of dengue virus and secreted during the is gradually reduced and stopped over 24-48 hours.
initial phase of illness. It disappears as antibodies appear
and hence declines as illness advances and in secondary Severe dengue: Children having any of the following:
dengue infections. The specificity is -100% and sensitivity (i) Severe plasma leakage leading to shock or fluid
in the first 4 days of illness is 90% in primary dengue and accumulation with respiratory distress; (ii) Severe
70% in secondary dengue infection. bleeding; (iii) Severe organ involvement: high AST, ALT
222 Essential Pediatrics
Colloids 10 ml/kg/hr
Improved No improvement
No improvement
Look for anemia, acidosis, mycardial; treat accordingly
Look for anemia, acidosis
and myocardial dysfunction;
treat accordingly Fig. 11. l 0: Management of severe dengue fever
fluid overload, shock and low PCV may have occult and its employees is crucial for the success of control
hemorrhage should receive careful fresh whole blood program. A live-attenuated quadruple vaccine has been
transfusion. Patients in shock and high PCV should receive approved for use in some countries between 9 and 45 years
repeated small boluses of colloids. of age.
Other supportive care: Organ dysfunction (liver, kidney) Suggested Reading
should be managed using standard guidelines. There is
• Dengue Guidelines for Diagnosis, Treatment, Prevention and
no role of therapy with corticosteroids, intravenous Control. Joint publication of the World Health Organization (WHO)
immunoglobulins or activated factor VIL Broad-spectrum and the Special Program for Research and Training in Tropical
antibiotics are indicated in case of superadded bacterial Diseases, 2009.
infection. Blood transfusion (20 mL/kg) is indicated when • Gan VC. Dengue: Moving from current standard of care to state
shock persists despite declining PCV (which indicates of-the-art treatment. Curr Treat Options Infect Dis 2014;6:208-226.
• Lodha R, Kabra SK. Dengue infection: Challenges and way forward.
adequate fluid replacement). All children with Indian J Pediatr 2015; 82:1077-9.
hyp otension should receive oxygen inhalation by nasal • Royal College Physician of Thailand. Practical guideline for
cannula/face mask or oxygen hood. management of Dengue in adults. Southeast Asian J Trop Med
Public Health 2015;46 Suppl 1:169-85.
Monitoring
Monitoring of the patient is crucial in the first few hours Chikungunya
of illness. Heart rate, respiratory rate, blood pressure and Chikungunya, an acute disease with fever, arthritis and
pulse pressure is monitored every 30 minutes till the skin rash, is caused by an enveloped RNA virus. Because
patient is stable, then every 2-4 hours as long as the child of severe arthritic symptoms, the disease was given the
is in the hospital. In critically ill children, central venous Swahili name of chikungunya (that which bends up).
pressure and accurate urine output with an indwelling Outbreaks of the disease have been reported from Tanzania,
urinary catheter should be monitored. Absolute platelet South Africa, India and Philippines. Chikungunya re
counts should be checked once a day till there is a rising emerged in India during 2005--06, causing 1.3 million cases
trend. in 13 states, chiefly Andhra Pradesh and Karnataka.
Prognosis Epidemiology
Dengue fever is a self-limited disease but mortality in The rural cycle of chikungunya transmission involves
severe dengue may be as high as 20-30%, if untreated. Aedes africans, A. fancifer, and wild primates, while the
Early recognition of illness, careful monitoring and urban cycle involves A. aegypti and humans. In rural cycle
appropriate fluid therapy has resulted in considerable (seen in Africa), the disease is endemic with a small
reduction of case fatality rate to <1%. Early recognition of number of cases occurring in most years. In urban areas,
shock is of paramount importance as the outcome of a the outbreaks are sporadic and explosive with infection
patient with DSS depends on the duration of shock. If of a large population within weeks. In Asia, the virus may
shock is identified when pulse pressure starts getting be maintained in urban cycle, with A. aegypti or require
narrow and IV fluids are administered at this stage, the reinoculation before onset of epidemic. Outbreaks occur
outcome is excellent. during the rainy season, associated with the population
density of the mosquito vector, which breeds in household
Prevention containers and puddles with peak activity in mid-morning
Preventive measures are directed towards elimination of and late afternoon. After an epidemic, the disease wanes
adult mosquitoes and their larvae. During epidemics, for years because a large proportion of the population is
aerial spraying/fogging with malathion is recommended immune.
for adult mosquitoes. Larval control measures by source
reduction and use of larvicides are even more crucial. Clinical Features
Mesocyclops, the shell fish are credited to eat and The disease has sudden onset, with incubation period of
effectively eliminate larvae of Aedes. The strategy has been 2-12 days. Infection is characterized by fever, headache,
used with success by Australian scientists working in fatigue, nausea, vomiting, rash and muscle and joint pain.
Vietnam by growing shell fish in ponds and water traps. Fever rises abruptly to 103-104 ° F and is accompanied by
A. aegypti breed in and around human dwellings and rigors that last for 2-3 days. Joint pain appears suddenly
flourish in fresh water. Special drives must be launched and is severe in intensity; the arthralgia and arthritis is
during and soon after the rainy season to interrupt their polyarticular, migratory, and chiefly affects small joints
breeding. There should be no stagnation of water in the of hands, wrist, ankle and feet with less involvement of
bathroom, kitchen, terrace, lawn and other open places; larger joints. The joint pains may continue for months after
stored water should be covered. Cooperation from every the illness. Headache is present in 80% of cases in the acute
house owner, public establishment and the government stage. Photophobia and retro-orbital pain may also occur.
224 Essential Pediatrics
An itchy, transient maculopapular rash appears 4-8 days Cambodia. There has been considerable progress in
later affecting the trunk and limbs. Inguinal lymph nodes improving access to antiretroviral therapy. Without access
may be enlarged. Fatalities are rare and associated with to such therapy, 20% of vertically infected children will
young age, shock and thrombocytopenia. Rarely progress to AIDS or death in their first year of life and
encephalopathy may occur in infants and young children. more than half of HIV-infected children will die before
their fifth birthday.
Diagnosis
Chikungunya should be suspected in patients who HIV- l , HIV-2
presents with the characteristic triad of fever, rash and HIV-1 and HIV-2 are members of the Retroviridae family
arthritis. Viremia is present in most patients during the and belong to the Lentivirus genus. The HIV-1 genome is
initial 2--4 days of disease and may be isolated in cell single-stranded RNA that is 9.2 kb in size. The genome
cultures. Polymerase chain reaction can be used to confirm has three major sections: The gag region, which encodes
the infection. Virus specific IgM antibodies may be the viral core proteins (p24, pl7, p9, p6; these are derived
detected by capture ELISA and hemagglutination from the precursor p55), the pol region, which encodes
inhibition assays by 5-7 days of illness. the viral enzymes (reverse transcriptase [p51], protease
[plO], and integrase [p32]); and the env region, which
Treatment encodes the viral envelope proteins (gp120 and gp41). The
Symptomatic treatment in the form of rest, fluids, and major external viral protein of HIV-1 is a heavily
ibuprofen, naproxen, acetaminophen, or paracetamol may glycosylated gp120 protein which contains the binding
relieve symptoms. Aspirin should be avoided during acute site for the CD4 molecule, the most common T lymphocyte
phase of illness. surface receptor for HIV.
Following viral attachment, gp120 and the CD4
Prevention molecules undergo conformational changes, allowing
Strategies for control include breaking the transmission gp41 to interact with the fusion receptor on the cell surface.
cycle of A. aegypti and by holding the mosquito population Viral fusion with the cell membrane allows entry of viral
at extremely low levels. A live-attenuated vaccine, RNA into the cell cytoplasm. Viral DNA copies are then
developed recently, which induces long-term production transcribed from the virion RNA through viral reverse
of neutralizing antibodies, is being examined. transcriptase enzyme activity, and duplication of the DNA
copies produces double-stranded circular DNA. Because
Suggested Reading the HIV-1 reverse transcriptase is error-prone, many
• WHO. Chikungunya. http:/ /www.who.int/mediacentre/ mutations arise, creating wide genetic variation in HIV-1
factsheets/ fs327/en/ isolates even within an individual patient. The circular
• Raghavendhar BS, Ray P, Ratagiri VH, et al. Evaluation o f DNA is transported into the cell nucleus where it is
chikungunya virus infection in children from India during 2009- integrated into chromosomal DNA; this is called as the
2010: A cross sectional observational study. J Med Virol 2016; 88:
923-30.
provirus. The provirus can remain dormant for extended
• Guaraldo L, Wakimoto MD, Ferreira H, et al. Treatment o f periods. HIV-1 transcription is followed by translation. A
chikungunya musculoskeletal disorders: a systematic review. capsid polyprotein is cleaved to produce, among other
Expert Rev Anti Infect Ther. 2018 Mar 13. doi:10.1080/ products, the virus-specific protease (plO). This enzyme
l 4787210.2018.1450629. is critical for HIV-1 assembly. The RNA genome is then
incorporated into the newly formed viral capsid. As the
HIV INFECTION, ACQUIRED
new virus is formed, it buds through the cell membrane
IMMUNODEFICIENCY SYNDROME
and is released.
HIV infection has become an important contributor to HIV-2 is a rare cause of infection in children, more
childhood morbidity and mortality, especially in prevalent in western and southern Africa. If HIV-2 is
developing countries and has undone many of the major suspected, a specific test that detects antibody to HIV-2
gains in child health. peptides should be used.
Epidemiology Transmission
It is estimated that more than 36 million persons Transmission of HIV-1 occurs via sexual contact,
worldwide were living with HIV infection at the end of parenteral exposure to blood, or vertical transmission from
2016; 2.lmillion of these were children under 15 years of mother to child. The primary route of infection in the
age. More than 90% of HIV-infected individuals live in pediatric population is vertical transmission. Most large
developing nations. Sub-Saharan Africa accounts for studies in the United States and Europe have documented
nearly 90% of the world population of HIV-infected mother-to-child transmission rates in untreated women
children. India and Thailand dominate the epidemic in between 12 and 30%. In contrast, transmission rates in
Southeast Asia, with expansion into Vietnam, China, and Africa and Asia are higher, up to 50%.
Infections and Infestations 1225-
Vertical transmission of HIV can occur during the normally have a relative lymphocytosis. Therefore, for
intrauterine or intrapartum periods, or through breast example, a value of 1500 CD4 cells/mm3 in children
feeding. Up to 30% of infected newborns are infected in <1 year of age is indicative of severe CD4 depletion and
utero. The highest percentages of HIV-infected children is comparable to <200 CD4 cells/mm 3 in adults.
acquire the virus intrapartum. Breastfeeding is an Lymphopenia is relatively rare in perinatally infected
important route of transmission, especially in the children and is usually only seen in older children or those
developing countries. The risk factors for vertical with end-stage disease.
transmission include preterm delivery ( <34 weeks B cell activation occurs in most children, as evidenced
gestation), a low maternal antenatal CD4 count, use of by hypergammaglobulinemia with high levels of anti
illicit drugs during pregnancy, >4 hours duration of HIV-1 antibody. This response may reflect both
ruptured membranes and birth weight <2500 g. dysregulation of T cell suppression of B-cell antibody
Transfusions of infected blood or blood products have synthesis and active CD4 enhancement of B lymphocyte
accounted for a proportion of pediatric AIDS cases. Heat humoral responses.
treatment of factor VIII concentrate and HIV antibody CD4 depletion and inadequate antibody responses lead
screening of donors have virtually eliminated HIV to increased susceptibility to various infections and clinical
transmission to children with hemophilia. Blood donor features vary with the severity of immunodeficiency.
screening has dramatically reduced, but not eliminated,
the risk of transfusion-associated HIV infection. Sexual Clinical Features
contact is a major route of transmission in adolescents. The clinical manifestations of HIV infection vary widely
among infants, children and adolescents. In most infants,
Natural History physical examination at birth is normal. Initial signs and
Before highly active antiretroviral therapy (HAART) was symptoms may be subtle and non-specific, such as
available, three distinct patterns of disease were described lymphadenopathy, hepatosplenomegaly, failure to thrive,
in children. Approximately 10-20% of HIV-infected chronic or recurrent diarrhea, interstitial pneumonia or
newborns in developed countries presented with a rapid oral thrush and may be distinguishable from other causes
disease course, with onset of AIDS and symptoms during only by their persistence. While systemic and pulmonary
the first few months of life; if untreated, these patients findings are common in the United States and Europe,
died from complications by 4 years of age. In resource chronic diarrhea, wasting, and severe malnutrition
poor countries, >85% of the HIV-infected newborns may predominate in Africa. Symptoms more common in
have such a rapidly progressing disease. children than adults include recurrent bacterial infections,
chronic parotid swelling, lymphocytic interstitial
It has been suggested that if intrauterine infection
pneumonitis (LIP), and early onset of progressive
coincides with the period of rapid expansion of CD4 cells
neurologic deterioration.
in the fetus, it could effectively infect the majority of the
body's immunocompetent cells. Most children in this Pediatric HIV disease is staged using two parameters:
group have a positive HIV-1 culture and/or detectable Clinical status (Table 11.3) and degree of immunologic
virus in the plasma in the first 48 hours of life. This early impairment (Table 11.4).
evidence of viral presence suggests that the newborn was
infected in utero. In contrast to the viral load in adults, Opportunistic Infections
the viral load in infants stays high for at least the first Children with HIV infection and advanced or severe
2 years of life. immunosuppression are susceptible to develop various
Majority of perinatally infected newborns (60-80%) opportunistic infections. The important pathogens
present with the second pattern: Slower progression of include: Pneumocystis jirovecii, Cryptosporidium, Crypto
disease with a median survival of 6 years. Many patients coccus, Isospora and CMV.
in this group have a negative viral culture or PCR in the
first week of life and are, therefore, considered to be Respiratory Diseases Complicating HIV Infection
infected intrapartum. In a typical patient, the viral load P. jirovecii (previously P. carinii) pneumonia is the
rapidly increases by 2-3 months of age, and then slowly opportunistic infection that led to the initial description
over 24 months. The third pattern (i.e. long-term survivors) of AIDS. This is one of the commonest AIDS defining
occurs in a small percentage ( <5%) of perinatally infected illnesses in children in the US and Europe; most cases
children who have minimal or no progression of disease occur between 3rd and 6th months of life. Even if a child
with relatively normal CD4 counts and very low viral develops the illness while on prophylaxis, therapy may
loads for longer than 8 years. be started with cotrimoxazole. With the use of appropriate
HIV-infected children have changes in the immune therapy, the mortality decreases to less than 10%. Risk
system that are similar to those in HIV-infected adults. factors for mortality are severity of the episode and
CD4 cell depletion may be less dramatic because infants severity of the immunosuppression.
226 Essential Pediatrics
Table 11.3: WHO clinical staging of HIV/ AIDS for children with confirmed HIV infection
Clinical stage 1
Asymptomatic
Persistent generalized lymphadenopathy
Clinical stage 2
Unexplained8 persistent hepatosplenomegaly
Papular pruritic eruptions
Fungal nail infection
Angular cheilitis
Lineal gingival erythema
Extensive wart virus infection
Extensive molluscum contagiosum
Recurrent oral ulceration
Unexplained8 persistent parotid enlargement
Herpes zoster
Recurrent or chronic upper respiratory tract infections (otitis media, otorrhea, sinusitis, tonsillitis)
Clinical stage 3
Unexplained8 moderate malnutrition or wasting not adequately responding to standard therapy
Unexplained8 persistent diarrhea (14 days or more)
Unexplained8 persistent fever (above 37.5 ° C intermittent or constant, for longer than one month)
Persistent oral candidiasis (after the first 6-8 weeks of life)
Oral hairy leukoplakia
Acute necrotizing ulcerative gingivitis/periodontitis
Lymph node TB
Pulmonary TB
Severe recurrent bacterial pneumonia
Symptomatic lymphoid interstitial pneumonitis
Chronic HIV-associated lung disease including bronchiectasis
Unexplained anemia (<8 g/dl), neutropenia (<0.5 x 109/L) or chronic thrombocytopenia (<50 x 109/L)
Clinical stage 4b
Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy
Pneumocystis pneumonia
Recurrent severe bacterial infections (empyema, pyomyositis, bone, joint infection, meningitis; excluding pneumonia)
Chronic herpes simplex infection (orolabial or cutaneous for >1 month duration; visceral at any site)
Esophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
Extrapulmonary/disseminated TB
Kaposi sarcoma
Cytomegalovirus infection (retinitis or CMV infection affecting another organ, with onset at age >1 month)
Central nervous system toxoplasmosis (after one month of life)
Extrapulmonary cryptococcosis (including meningitis)
HIV encephalopathy
Disseminated endemic mycosis (extrapulmonary histoplasmosis, coccidioidomycosis)
Disseminated non-tuberculous mycobacterial infection
Chronic cryptosporidiosis (with diarrhea)
Chronic isosporiasis
Cerebral or B cell non-Hodgkin lymphoma
Progressive multifocal leukoencephalopathy
Symptomatic HIV (associated nephropathy or cardiomyopathy)
•unexplained refers to where the condition is not explained by other causes
bAdditional specific conditions may be included in the regional classifications (e.g. reactivation of American trypanosomiasis, meningoencephalitis
and/or myocarditis in Americas region, penicilliosis in Asia and HIV-associated rectovaginal fistula in Africa)
Infections and Infestations 1221-
Table 11.4: Classification of immune suppression in children (CD4 levels in relation to severity of immune suppression)
HIV-associated Age-related CD4 cell values
immunodeficiency < 11 months 12-35 months 36-59 months '2:.5 years
Not significant >35% >30% >25% >500 cells/mm3
(normal CD4 cells)
Mild 30-35% 25-30% 20-25% 350-499 cells/mm3
Advanced 25-30% 20-25% 15-20% 200-349 cells/mm3
Severe <25% <20% <15% <15%
<1500 cells/mm3 <750 cells/mm3 <350 cells/mm3 200 cells/mm3
Recurrent bacterial pneumonia may be present in up to 90% Fungal infections present as a part of disseminated disease
HIV-infected children. Initial episodes often occur before in immunocompromised children. Primary pulmonary
the development of significant immunosuppression. As fungal infections are uncommon.
the immunosuppression increases the frequency increases. Lymphoid interstitial pneumonitis (LIP) has been recognized
The common pathogens for community-acquired as a distinctive marker for pediatric HIV infection and is
pneumonia are S. pneumoniae, H. influenzae and S. aureus. considered in the criteria for AIDS in children. In absence
In children with severe immunosuppression and hospital of antiretroviral therapy, nearly 20% of HIV-infected
acquired infections, gram-negative organisms, such as, children developed LIP. The etiology and pathogenesis
Pseudomonas aeruginosa gain importance. Clinical features of LIP are not well understood, but include: Exaggerated
in HIV-infected children are similar to those in other immune response to inhaled or circulating antigens, and/
children. However, in severely immunocompromised or primary infection of the lung with HIV, Epstein-Barr
children, the signs may be subtle. Often, the response to virus (EBV), or both. LIP is characterized by nodule
therapy is slow and the relapse rates are high. Bacteremia formation and diffuse infiltration of the alveolar septa by
may be more common, seen in up to 50%. lymphocytes, plasmacytoid lymphocytes, plasma cells and
Choice of antibiotics is based on local patterns of immunoblasts. There is no involvement of the blood
etiologies and susceptibilities. An appropriate choice is vessels or destruction of the lung tissue. Children with
the combination of a broad-spectrum cephalosporin and LIP have a relatively good prognosis.
an aminoglycoside. In areas with large proportion of LIP is usually diagnosed in children with perinatally
MRSA, vancomycin, clindamycin, linezolid or other drugs acquired HIV infection when they are older than 1 year of
may be used. Children with non-severe pneumonia can age. Most children with LIP are asymptomatic. Tachypnea,
be managed as out-patients using a second or a third cough, wheezing and hypoxemia are in children with
generation cephalosporin or coamoxiclav. Since P. jirovecii severe features; crepitations are uncommon. Clubbing is
pneumonia cannot be excluded in most children with present in advanced disease. These patients can progress
severe respiratory symptoms, cotrimoxazole is also used to chronic respiratory failure. Long-standing LIP may be
unless another diagnosis has been made. associated with bronchiectasis. The presence of a
Tuberculosis is a common medical concern. Co-existent TB reticulonodular pattern, with or without hilar
and HIV infections accelerate the progression of both lymphadenopathy, that persists on chest radiograph for
diseases. HIV-infected children are more likely to have 2 months or greater and that is unresponsive to
extrapulmonary and disseminated tuberculosis; the course antimicrobial therapy is considered presumptive evidence
is also likely to be more rapid. The overall risk of active TB of LIP. A definitive diagnosis is made by histopathology.
in children infected with HIV is at least 5- to 10-fold higher Early disease is managed conservatively. The effect of
than in children not infected with HIV. The duration of antiretroviral agents is limited. Steroids are indicated, if
antitubercular therapy in patients is same as that for not children with LIP have symptoms and signs of chronic
HIV infected; a few children may need prolongation of pulmonary disease, clubbing and/or hypoxemia.
treatment to 9-12 months. Close follow-up is essential to Treatment includes an initial 4- to 12-week course of
diagnose non-response or drug resistance. Rifampicin may prednisolone (2 mg/kg/d) followed by tapering to low
show drug interactions with some antiretroviral agents dose medication, using oxygen saturation and clinical state
(nevirapine, protease inhibitors). as guide to improvement.
Viral infections, chiefly respiratory syncytial virus,
influenza and parainfluenza viruses, often result in Gastrointestinal Diseases
symptomatic disease. Infections with adenovirus and Multiple microbes can cause gastrointestinal disease,
measles virus might result in serious sequelae. including bacteria (Salmonella, Campylobacter,Mycobacterium
Disseminated CMV is a known opportunistic infection, avium intracellulare complex), protozoa (Giardia, Isospora,
but pneumonia caused by the virus is rare. Cryptosporidium, microsporidia), viruses (CMV, HSV,
228 Essential Pediatrics
rotavirus) and fungi (Candida). Protozoa! infections are manifestation; polyuria, oliguria, and hematuria have also
severe and can be protracted in children. Children with been observed. Hypertension is unusual.
Cryptosporidium infestation can have severe diarrhea
leading to hypovolemic shock. AIDS enteropathy, a Diagnosis
syndrome of malabsorption with partial villous atrophy All infants born to HIV-infected mothers test antibody
not associated with specific pathogens, is the result of positive at birth because of passive transfer of maternal
direct HIV infection of the gut. HIV antibody across the placenta. Most uninfected infants
Chronic liver inflammation is relatively common in lose maternal antibody between 6 and 12 months of age.
HIV- infected children. In some children, hepatitis caused As a small proportion of uninfected infants continue to
by CMV, hepatitis B or C viruses, or MAC may lead to have maternal HIV antibody in the blood up to 18 months
liver failure and portal hypertension. It is important to of age, positive IgG antibody tests cannot be used to make
recognize that several of the antiretroviral drugs such as a diagnosis of HIV infection in infants up to this age. In
didanosine, and protease inhibitors may also cause children > 18 months old, demonstration of IgG antibody
reversible elevation of transaminases. to HIV by a two or three reactive enzyme immunoassay
Pancreatitis is uncommon in HIV-infected children. (EIA) and confirmatory test (e.g. Western blot or
This may be the result of drug therapy, e.g. didanosine, immunofluorescence assay) can establish the diagnosis of
lamivudine, nevirapine, or pentamidine. Rarely, opportu HIV infection. While serologic tests were commonly used
nistic infections, such as MAC or CMV, may be responsible in the past, tests that allow for earlier definitive diagnosis
for acute pancreatitis. have replaced antibody assays as the tests of choice for
the diagnosis of HIV infection in infants.
Neurologic Diseases Specific diagnostic assays, such as HIV proviral DNA
The incidence of central nervous system (CNS) involve or RNA PCR, HIV culture, or HIV p24 antigen are useful
ment in perinatally infected children may be more than for diagnosis of young infants born to HIV-infected
50% in developing countries but lower in developed mothers (Fig. 11.11). By 6 months of age, the HIV culture
countries, with a median onset at about one and a half and/ or PCR identifies all infected infants, who are not
years of age. The most common presentation is progressive having continued exposure due to breastfeeding. HIV
encephalopathy with loss or plateau of developmental RNA PCR is the preferred virological assay in developed
milestones, cognitive deterioration, impaired brain growth countries. HIV culture has similar sensitivity to HIV RNA
resulting in acquired microcephaly, and symmetric motor PCR; however, it is more technically complex and
dysfunction. CNS infections: Meningitis due to bacterial expensive, and results are often not available for 2-4
pathogens, fungi such as Cryptococcus and a number of weeks. The p24 antigen assay is less sensitive than the
viruses may be responsible for the clinical features. CNS other virological tests. Fig. 11.11 shows the algorithm for
toxoplasmosis is exceedingly rare in young infants, but diagnosis of HIV infection in infants. The national program
may occur in HIV-infected adolescents; the overwhelming (Early Infant Diagnosis) now uses HIV total nucleic acid
majority has serum IgG antitoxoplasma antibodies. (RNA + proviral DNA) PCR test on dried blood spot
samples; positive tests need confirmation with HIV PCR
Cardiovascular Involvement test on another sample.
Cardiac abnormalities in HIV-infected children are
common, persistent, and often progressive; the majority Management
is subclinical. Left ventricular structure and function The management of HIV-infected child includes
progressively may deteriorate in the first 3 years of life, antiretroviral therapy, prophylaxis and treatment of
resulting in subsequent persistent cardiac dysfunction and opportunistic and common infections, adequate nutrition
increased left ventricular mass. Children with encephalo and immunization. Decisions about antiretroviral therapy
pathy or other AIDS-defining conditions have the highest (ART) for HIV-infected patients were earlier based on the
rate of adverse cardiac outcomes. Resting sinus tachy magnitude of viral replication (i.e. viral load), CD4
cardia has been reported in up to nearly two-thirds and lymphocyte count or percentage and clinical condition.
marked sinus arrhythmia in one-fifth of HIV-infected The current World Health Organization guidelines
children. Gallop rhythm with tachypnea and hepato recommend ART for all children irrespective of the
splenomegaly appear to be the best clinical indicators of immunologic or clinical stage.
congestive heart failure; anticongestive therapy is Availability of antiretroviral therapy has transformed
generally very effective, especially when initiated early. HIV infection from a uniformly fatal condition to a chronic
infection, where children can lead a near normal life.
Renal Involvement Current therapy does not eradicate the virus and cure the
Nephropathy is an unusual presenting symptom of HIV child; it rather suppresses the virus replication for
infection, more commonly occurring in older symptomatic extended periods of time. The three main groups of drugs
children. Nephrotic syndrome is the most common are nucleoside reverse transcriptase inhibitors (NRTI),
Infections and Infestations 229-
Positive Negative
+
Send whole blood sample -
+
Continue cotrimoxazole; stop
.-- -
DBS for HIV-1 PCR nevirapine at 6 weeks
1
Positive Negative
l
continue breastfeeding is symptomatic
Positive Negative
i
Repeat HIV-1 PCR by DBS test 6 Cotrimoxazole till HIV is excluded
weeks after cessation of breast milk feeding or breastfeeding till 1 year followed
if the child develops symptoms of HIV infection by gradual stoppage over 1 month
+ +
I Establish definitive diagnosis at 18 months, by HIV antibody tests (3 rapid tests) I
*Following infants are at higher risk of acquiring infection:
Mothers receiving <4 weeks of antiretroviral therapy at the time of delivery
Mothers having high viral load (RNA >1000 copies/ml) within 4 weeks before delivery
Mothers acquiring infection during pregnancy or breastfeeding
Mother first identified during postpartum period with or without a negative HIV test prenatally
Fig. 11.11: HIV diagnosis in children < 18 months with DNA-PCR. DBS dried blood spot
non-nucleoside reverse transcriptase inhibitors (NNRTI) All infants documented to be living with HIV should
and protease inhibitors (PI). Highly active antiretroviral receive cotrimoxazole prophylaxis regardless of symptoms
therapy (HAART) is a combination of 2 NRTI with a PI or or CD4 percentage. After one year of age, cotrimoxazole
an NNRTI. The National Program for management of prophylaxis is given to symptomatic children (WHO clinical
HIV-infected children recommends combination of stages 2, 3 or 4 for HIV disease) or children with CD4 <25%.
zidovudine or abacavir + lamivudine + efavirenz as first-line All children who begin cotrimoxazole prophylaxis
therapy; for children less than 3 years of age, a protease (irrespective of age) should continue until the age of 5 years,
inhibitor is used instead of NNRTI (Table 11.5). Pediatric when they can be reassessed.
fixed dose combinations (FDC) have also been developed.
lsoniazid Prophylaxis
Cotrimoxazole Prophylaxis Current NACO guidelines recommend administration of
In resource-limited settings, cotrimoxazole prophylaxis isoniazid prophylaxis to all HIV-infected children who do
is recommended for all HIV-exposed infants starting at not have evidence of active tuberculosis.
4-6 weeks of age (or at first encounter with the health care
system) and continued until HIV infection can be excluded. Nutrition
Cotrimoxazole is recommended for HIV-exposed HIV-infected children often show failure to thrive and
breastfeeding children of all ages; prophylaxis should be require nutritional rehabilitation.
continued until HIV infection is excluded by antibody
testing (beyond 18 months of age) or virological testing Immunization
(before 18 months of age), at least 6 weeks after cessation Vaccines recommended in the national schedule can be
of breastfeeding. administered to HIV-infected children, except that
230 Essential Pediatrics
symptomatic HIV-infected children should not be given to the onset of labor and rupture of membranes), and
OPV and BCG. complete avoidance of breastfeeding.
Prevention of Mother-to-Child Transmission (MTCT) Antiretroviral Drug Regimens for Pregnant Women
The risk of MTCT can be reduced to under 2% by For all HIV-infected pregnant women, antiretroviral
interventions that include antiretroviral therapy given to therapy is indicated. The recommended regimen is a
women during pregnancy and labor and antiretroviral combination of zidovudine (AZT), lamivudine (3TC) and
prophylaxis to the infant in the first week of life, obstetrical nevirapine (NVP) or efavirenz (EFV) during antepartum,
interventions including elective cesarean delivery (prior intrapartum and postpartum period; EFV-based regimens
Infections and Infestations l2a1-
should not be newly-initiated during the first trimester of leads to frequent antigenic drifts" (seen in both A and B)
II
pregnancy. The ART regimen should be started as early when there is minor change in antigenicity and "shifts"
as possible. (seen only in A) where there is major change in
antigenicity. The phenomena of antigenic change lead to
Antiretroviral Regimens for Infants Born to evolution of new viruses, which result in annual outbreaks
HIV-Infected Mothers and occasionally pandemics. The novel HlNl pandemic
If mother received triple drug ART during pregnancy and occurred due to emergence of a new swine origin influenza
entire breastfeeding, the infant should receive daily AZT virus HlNl which was pathogenic to humans and capable
or NVP from birth until 6 weeks of age (irrespective of of rapid human-to-human transmission and to which there
feeding). was no pre-existing immunity. It is estimated that the
novel HlNl pandemic between 2009 and 2010 caused
lntrapartum Interventions 18,000 deaths globally (2000 in India) with case fatality
Artificial rupture of membranes should be avoided, unless rates ranging from 0.0004% to 1.5% (0.83% in India). The
medically indicated. Delivery should be by elective pandemic strain then became endemic and caused another
cesarean section at 38 weeks before onset of labor and epidemic in 2015 in India with 30000 cases and 2000
rupture of membranes. Procedures increasing exposure deaths. The currently circulating influenza virus strains
of child to maternal blood should be avoided. are H3N2, pandemic HlNl and influenza B.
Avian HSNl commonly referred as bird flu is a highly
Breastfeeding pathogenic strain of influenza virus that infects and kills
The risk of HIV infection via breastfeeding is highest in humans in close contact with diseased birds but has not
the early months of breastfeeding. Factors that increase acquired pandemic potential due to limited human-to
likelihood of transmission include detectable levels of HIV human transmissibility.
in breast milk, presence of mastitis and low maternal CD4+ Influenza is transmitted from person to person through
T cell count. Exclusive breastfeeding has been reported to airborne droplet spread or through contact. The portal of
carry a lower risk of HIV transmission than mixed feeding entry is the respiratory tract and the virus attaches itself
and risk of mortality in non-breastfed infants in resource to the respiratory epithelium through hemagglutinin, the
limited settings is increased. Currently, exclusive main virulence factor. The incubation period is 1-3 days
breastfeeding is recommended during the first months of and the period of infectivity is usually 7 days after illness
life. WHO recommends that the transition between onset and sometimes longer in those with severe disease.
exclusive breastfeeding and early cessation of The attack rates are highest in children and young adults.
breastfeeding should be gradual and not an early and II
In temperate climates, there is a clear defined influenza
abrupt cessation". season in fall and winters, but in tropical countries like
India, it occurs throughout the year with peak during the
Suggested Reading monsoons.
• WHO/UNAIDS. AIDS epidemic update Dec 2016.
• World Health Organization. Consolidated guidelines on the use
Clinical Features
of antiretroviral drugs for treating and preventing HIV infection, In most individuals, influenza is a minor illness charac
2nd edn. WHO, Geneva, 2016. terized by a combination of fever, runny nose, sore throat,
• NACO. Pediatric antiretroviral therapy guidelines, 2013 http://
naco.gov.in/sites/default/files/Pediatric_14-03-2014.pdf.
cough, body ache, headache, abdominal pain, diarrhea and
vomiting. The illness may have a biphasic course.
Influenza Recovery usually occurs within a week. It is sometimes
difficult to differentiate from common cold. Asymptomatic
The influenza virus is capable of causing disease in and subclinical infections are also very common.
humans, birds and animals. Influenza has recently gained A small proportion of individuals (less than 1%) can
more prominence owing to the 2009 novel HlNl have complications and severe disease. The risk of
pandemic. complications is higher at extremes of age (children below
2 and the elderly), pregnant women and those who have
Epidemiology just delivered, those with underlying comorbidities such
The influenza virus is an RNA virus of the Orthomyxo as any chronic neurologic/metabolic/cardiac/
viridae family. Influenza A and B are the two types that pulmonary/renal disease, those who are immuno
cause human disease. Influenza A is further classified into compromised and those with severe asthma. In the novel
subtypes based on the two surface proteins-hemagglutinin HlNl epidemic, the elderly were spared due to pre
(H) and neuraminidase (N). Influenza B is classified into existent immunity and morbid obesity emerged as an
two distinct lineages-Yamagata and Victoria but not into important risk factor.
subtypes. Influenza has a highly segmented genome that The most dreaded complication of influenza is
is prone to frequent mutations and reassortment. This pneumonia with acute respiratory distress syndrome,
232 Essential Pediatrics
respiratory failure and sometimes shock and renal failure. For patients who present with symptoms of severe
As many as 30% of these patients have bacterial coinfection illness or who have complications, antiviral treatment with
with S. pneumoniae and S. aureus. Progression is very rapid oseltamivir should be started without delay. An effort
and most patients require ventilator support over the next should be made to rule out other illnesses with similar
24 hours. Occasionally, other complications such as symptomatology. In patients with signs of lower
encephalitis, seizures, quadriparesis and myocarditis have respiratory involvement, antibiotics like coamoxyclav or
been reported. Complications usually set in by day 4 or 5 cephalosporins (cefuroxime, ceftriaxone or cefpodoxime)
of illness. The red flag symptoms are persistent high fever should be used as bacterial coinfections are common.
of more than 3 days duration, reappearance of fever after
initial defervescence, breathlessness, dyspnea, tachypnea, Prevention
hemoptysis in older children and adolescents, extreme Vaccination is the most effective preventive strategy and
weakness, poor oral intake and altered sensorium. is discussed further in Chapter 10. Chemoprophylaxis
with oseltamivir is also effective in preventing influenza
Diagnosis but is not routinely recommended due to risk of resistance.
Influenza is primarily a clinical diagnosis. The complete Household transmission can be reduced by good
blood count may show leukopenia and thrombocytopenia. ventilation in the room, proper hand hygiene and
Diagnosis is confirmed by antigen detection or PCR on adherence to cough etiquettes by the index case. School
throat or nasopharyngeal swabs. PCR-based tests are fairly children show one of the highest infection rates and
sensitive and very specific but are of limited use in routine outbreaks are common in school. For reducing
clinical practice. Specific therapy may thus begin before transmission in schools, the classrooms should be kept
results become available. If the test is negative, therapy well ventilated, children should be trained in hand
cannot be discontinued as sensitivity is only 60-70% and hygiene and cough etiquettes and sick children should be
even lower, if the sample is not properly collected. prohibited from attending school till they are afebrile.
Molecular diagnosis of influenza should be restricted to Temporary school closure may be considered during a
hospitalized patients with severe disease when a definitive massive pandemic. In order to prevent nosocomial
diagnosis helps in tracking the severity of the outbreak. transmission, standard infection control precautions
Since the symptoms and lab findings of severe flu including droplet isolation and routine immunization of
overlap those of other infections such as malaria, dengue, health care workers are recommended.
enteric fever, viral hepatitis and leptospirosis, it is
important to conduct appropriate laboratory tests to Suggested Reading
exclude these illnesses. • World Health Organization. Influenza update. www.who.int
• Kumar B, Asha K, Khanna M, et al. The emerging influenza virus
Treatment threat: Arch Virol 2018; 163:831-44.
Definitive treatment of influenza is with M2 inhibitors Zika Virus
(amantadine, rimantidine) or neuraminidase inhibitor
drugs (oseltamivir, zanamivir). The duration of therapy is Zika is an RNA flavivirus closely related to the dengue
5 days. These drugs reduce duration of symptoms, risk of and chikungunya viruses which has recently assumed
complications and death. Though they are most effective, if prominence due to its association with newborn
given within first 48 hours, they are useful even if given microcephaly.
later. The pandemic HlNl strain and most current seasonal
flu strains are resistant to the M2 inhibitors. Oseltamivir is Epidemiology
the first-line drug and zanamivir is used in those with The virus was first identified in a rhesus monkey in the
oseltamivir-resistant virus. Oseltamivir is well tolerated Zika forest of Uganda in 1947 with only 13 human cases
with occasional GI and neurological side effects. diagnosed till 2007. Since then, large outbreaks have
For any patient presenting with influenza-like illness, happened in the Pacific islands of Micronesia, French
the treatment strategy depends on two factors: The Polynesia and New Caledonia. A very large outbreak was
severity of illness and the likelihood of complications. In reported in Brazil in 2015 with almost a million cases. The
patients with mild disease who are not at risk for virus has since spread worldwide including Asia. The
complications, only symptomatic treatment is indicated. WHO has declared it as a public health emergency of
Antibiotics and antivirals should not be prescribed. International Concern. No cases have been reported in
Patients should be counselled about the red flag signs and India as yet; but India is at high risk for introduction of
asked to seek medical care in the event these occur. These the virus due to presence of the Aedes aegypti mosquito.
patients should be asked to stay at home till they are The virus is transmitted primarily by the bite of Aedes
afebrile to prevent disease transmission to others. Patients aegypti. Other routes of transmission include vertical
who are at high risk for complications should be started transmission from mother to child, sexual and possibly
on antiviral therapy irrespective of the severity of disease. through blood transfusion.
Infections and Infestations 1233-
Clinical Features and Complications weakness, nausea, vomiting, abdominal pain and joint and
Many infections are asymptomatic. Clinical disease is muscle aches. This is followed by bleeding from multiple
characterized by low grade fever with arthralgia, myalgia, sites and multiorgan failure, with fatality of 60%.
rash, conjunctivitis and lymphadenopathy. Sympto Diagnosis and Treatment
matology resembles dengue and chikungunya except that
rash and conjunctivitis are more prominent than the other There is leukopenia and thrombocytopenia. Definitive
two illnesses. diagnosis is by antigen detection, IgM ELISA, polymerase
There are two major complications of zika infection. chain reaction and viral isolation. Treatment is supportive
The first is acute neurologic syndromes such as Guillain and symptomatic. Several novel therapies including
Barre syndrome, myelitis and meningoencephalitis. serum of infected patients who have recovered from
However, more importantly are the teratogenic effects disease and nucleic acid-based therapies are under
with an incidence of 30% in some cohort studies in Brazil. evaluation.
Infections in the first trimester and sometimes in the Prevention
second trimester are associated with abortions,
intrauterine deaths and stillbirths, microcephaly (13%) and Prevention centers around strict isolation of infected cases,
ocular abnormalities. safe burial practices and avoiding consumption of bush
meat. Candidate vaccines are undergoing trials.
Diagnosis
Suggested Reading
Diagnosis in the first seven days is by performing an RT
• Richards GA, Baker T, Amin P, et al. Ebola virus disease. J Crit
PCR in blood and after seven days is by IgM MAC ELISA. Care 2018; 43:352-55.
ELISA can demonstrate cross-reactivity with other
flaviviruses. Emerging Viruses in India
Nipah virus, an important cause of encephalitis, has been 1:160 or 1: 320) are considered diagnostic. Common
increasingly reported from West Bengal. Its natural differential diagnoses include tuberculosis, enteric fever,
asymptomatic hosts are fruit bats who can transmit chronic malaria, HIV, sarcoidosis and lymphoproliferative
infection and disease to pigs and humans. Human-to disorders.
human transmission has also been reported. Clinical
features in humans are fever followed by features of Treatment
encephalitis and sometimes pneumonia and respiratory Treatment consists of the combination of doxycycline and
distress. Mortality is as high as 70% and there are residual rifampicin for 6 weeks supplemented with intramuscular
sequelae in survivors. Treatment is symptomatic and streptomycin or gentamicin for the first 1-2 weeks. For
supportive. Prevention centers around limiting human children less than 8 years of age, combinations containing
exposure to raw date palm juice contaminated by fruit rifampicin and cotrimoxazole for 6 weeks with or without
bat excreta and infected pigs. aminoglycosides are recommended. Treatment may need
to be prolonged for endocarditis and neurobrucellosis.
Chandipura virus, a rhabdovirus, is implicated as a cause
of epidemic viral encephalitis in children in several states Suggested Reading
in India. It is transmitted by bite of infected sandflies and
• Dean AS, Crump L, Greter H, et al. Clinical manifestations of
is associated with high mortality and neurologic sequelae. human brucellosis. PLoS Neg! Trop Dis 2012; 6: e1929.
meningitis. It is estimated that for every 1000 cases of otitis Suggested Reading
media, there is 1 case of meningitis. Other less common • Global pneumococcal disease and vaccine, www.cdc.gov/
invasive diseases due to pneumococci are osteomyelitis, pneumococcal/ global.html
septic arthritis, cellulitis and peritonitis. • Maraga NF. Pneumococcal infections. Pediatr Rev 2014; 35:299-310.
Pneumococcus is responsible for 30% of all acute Diphtheria
bacterial meningitis and is associated with high rate of
complications like subdural empyema, morbidity and Diphtheria is an acute bacterial infection caused by gram
mortality. Pneumococcal bacteremia presents usually as positive bacillus Corynebacterium diphtheriae. Though the
fever without focus in infants and children below 3 years, incidence of diphtheria has decreased remarkably
and needs aggressive therapy. Pneumococcal pneumonia following increasing immunization, cases do occur in
has a lobar distribution with necrosis and empyema being unvaccinated children and adults who have lost their
common complications. immunity.
Etiopathogenesis
Diagnosis
The secretions and discharges from infected person or
The gold standard for diagnosis is culture. Low culture carrier are the main source of infection. The infection is
yields are responsible for under recognition of pneumo transmitted by contact or via droplets of secretion. The
coccus as a common pathogen. Pneumococcus unlike portal of entry is commonly the respiratory tract. The
Salmonella is difficult to culture, especially if antibiotics incubation period of the disease is 2-5 days. C. diphtheriae
have been administered. Special media containing sheep proliferates and liberates powerful exotoxin which is the
blood are required and delays in transportation and principal cause of systemic and local lesions. The exotoxin
improper storage further reduce recovery. In pneumonia, causes necrosis of the epithelial cells and liberates serous
isolation rates from blood are low, and the ideal sample and fibrinous material which forms a grayish white
of lung aspirate cannot be obtained in routine clinical pseudomembrane which bleeds on being dislodged. The
practice. Other tests useful in diagnosis are Gram stain surrounding tissue is inflamed and edematous. The organs
(Fig. 11.13), latex agglutination tests in CSF and pleural principally affected by the exotoxin include the heart,
fluids and recently PCR. kidney and myocardium.
Treatment Clinical Features
Penicillin and its derivatives such as ampicillin and The onset is generally acute with fever, malaise and
amoxicillin are the drugs of choice for treatment of headache. The child has a toxic look. The clinical features
pneumococcal infections; ceftriaxone is a satisfactory depend on the site of involvement. The commonest form
alternative. Like many other bacteria, resistance in is faucial or tonsillopharyngeal diphtheria in which there
pneumococcus is being increasingly reported (more from is redness and swelling over the fauces. The exudates
the West and relatively less from India). Resistance to beta coalesce to form a grayish white pseudomembrane, which
lactams is due to altered penicillin-binding protein that extends to surrounding areas. The cervical lymph nodes
may be intermediate or high level. Intermediate resistance are enlarged leading to a bull neck appearance. Sore throat,
can be overcome by using higher doses of penicillin or dysphagia and muffled voice are frequently present. In
amoxicillin, but high level resistance requires use of nasal diphtheria, there is unilateral or bilateral
alternative drugs like fluoroquinolones, vancomycin, or serosanguineous discharge from the nose and excoriation
teicoplanin. of upper lip. In laryngotracheal diphtheria, the membrane
over the larynx leads to brassy cough, stridor and
respiratory distress. Diphtheritic lesions may occasionally
also be found in skin and conjunctiva.
The commonest complication is respiratory failure due
to occlusion of the airways by the membrane. Myocarditis
generally occurs by second week of illness and can lead
to symptoms of congestive cardiac failure, arrhythmias
and sudden death. Neurological complications include:
(i) Palatal palsy, which occurs in second week and is
clinically manifested by nasal twang and nasal
regurgitation; (ii) ocular palsy in third week; (iii) loss of
accommodation, manifested by visual blurring and
inability to read; (iv) generalized polyneuritis occurs by
Fig. 11.13: Gram stain of pus showing abundant gram-positive third to sixth weeks of illness. Renal complications include
diplococci, pneumococci oliguria and proteinuria.
Infections and Infestations 1237-
cold liquids. In infants <3 months, this stage may be Suggested Reading
considerably prolonged. • Yeung KHT, Duclos P, Nelson EAS, Hutubessy RCW. An update
In the convalescent phase, the intensity and paroxysms of the global burden of pertussis in children younger than 5 years.
of cough decrease gradually over 1--4 weeks. The vomiting Lancet Infect Dis 2017; 17:974-80.
becomes less frequent. Appetite, general condition and Enteric Fever
health gradually improve.
The term enteric fever includes typhoid fever caused by
Complications Salmonella enterica var typhi and paratyphoid fever caused
by S. enterica var paratyphi A, B or C. Paratyphoid infections
• Young infants show apnea, leukocytosis and constitute about 20% of all cases of enteric fever
pulmonary hypertension and high mortality worldwide. As enteric fever is a disease transmitted by
• Respiratory complications: Otitis media, pneumonia, the feco-oral route, its greatest burden is in resource
atelectasis, emphysema, bronchiectasis, pneumothorax limited countries where water supply and sanitary
and pneumomediastinum conditions are poor. In a community based study in urban
• Neurological complications: Seizures and encephalopathy slums of Delhi, the incidence was estimated to be 980/
(2-7%) 100,000 population with 44% of the cases occurring in
• Bleeding episodes: Epistaxis, retinal or subconjunctival children below 5 years.
bleeds, intracranial hemorrhage. Enteric fever is one of the commonest causes of fever
lasting for more than 7 days in clinical practice in India.
• Inguinal hernia, rectal prolapse
• Malnutrition due to persistent vomiting and Etiopathogenesis
disinclination to eat S. enterica serotype typhi/paratyphi is a gram-negative, non
• Flare up of tuberculosis lactose fermenting, flagellate bacterium. The somatic or
0 antigen is shared among various salmonellae; the
Diagnosis flagellar or H antigen is specific to the serovar. S. enterica
The diagnosis of whooping cough is based on clinical var typhi also possesses a Vi polysaccharide capsule.
features. There may be a lymphocytic leukocytosis and The infective dose of typhoid/paratyphoid bacillus
low ESR. Specific diagnosis depends on isolation of the varies from 103 to 106 organisms. The organism must
organism from nasopharyngeal swab or cough plate survive the gastric barrier to reach the small intestine;
cultured on Bordet-Gengou medium. Culture positivity conditions which reduce gastric acidity, such as antacids,
declines with advancing illness and administration of H2 receptor blockers and proton pump inhibitors reduce
antibiotics. Other diagnostic tests including serology and the infective dose. On reaching the small intestine, the
PCR in throat swab are not routinely available. Differen organism penetrates the mucosa and infects lymphoid
tials for pertussis include adenoviral infections, follicles and subsequently the draining mesenteric nodes
endobronchial tuberculosis, extrinsic compression of and the liver and spleen. It multiplies in the reticulo
airways by lymph nodes, inhaled foreign body and endothelial system and after incubation period varying
reactive airway disease. from 7-14 days spills into the bloodstream and is widely
disseminated, especially to liver, spleen, bone marrow,
Management gallbladder and Peyer patches of the terminal ileum. This
marks the onset of clinical manifestations of enteric fever.
General measures include providing adequate nutrition Infection leads to local and systemic immune responses,
and hydration and avoiding factors aggravating cough. which are, however, inadequate to prevent relapse or
Macrolides including erythromycin, azithromycin or reinfection.
clarithromycin are the drugs of choice. Antibiotics
terminate the respiratory tract carriage of B. pertussis thus Clinical Features
reducing the period of communicability but do not shorten There is no appreciable difference between the manifesta
the course of illness. Nebulization with salbutamol is tions of typhoid and paratyphoid fever. The hallmark of
sometimes effective in reducing bronchospasm and enteric fever is fever which starts as a low grade fever
controlling bouts of cough. Cough suppressants and and then shows stepwise increase peaking to as high as
antihistaminic agents should be avoided. 103-104 ° C by the end of the first week. This pattern
differentiates it from viral fever where the peak is usually
Prevention at the onset of fever. With fever, there is associated malaise,
Chemoprophylaxis with erythromycin is recommended dull headache, anorexia, nausea, poorly localized
for close family contacts especially children <2 years of abdominal discomfort, mild cough and malaise. There
age. Non-immunized and partially immunized contacts may be diarrhea; constipation in children is rare. Physical
should be vaccinated (Chapter 10). findings are unremarkable with the exception of a coated
Infections and Infestations 1239-
tongue, tumid abdomen and sometimes hepatospleno drops to 40% in the 4th week. Its overall sensitivity is 60%,
megaly. The rash described in Western textbooks is seldom which reduces to 20-40% after antibiotics. Salmonella is
or never seen in Indian subjects. Infants and young an easy organism to culture and use of bile broth media
children with enteric fever may have diarrhea as a pre and automated culture systems such as BACTEC improve
dominant manifestation or a short-lasting undifferentiated recovery. Sufficient blood should be collected (10 mL in
febrile illness. In the absence of treatment, fever may adults and 5 mL in children) and a blood: media ratio of
continue for 3-4 weeks followed by natural remission or 1:5 should be maintained. The use of clot culture methods
by development of complications. does not significantly improve recovery rates. Bone
marrow cultures have higher yield as compared to
Complications peripheral blood cultures as Salmonella is a pathogen of
The commonest intestinal complications are bleeding or the reticuloendothelial system and should be sent, if a bone
perforation seen in the 2nd or 3rd week of illness in marrow examination is done as part of work-up for
10-15% adult patients, but less frequently in children. pyrexia of unknown origin. Owing to very low recovery
Bleeding is due to erosion of a necrotic Peyers patch rates, stool cultures and urine cultures are not
through the wall of a vessel and is usually mild but can, recommended. Antimicrobial susceptibility testing of the
sometimes, be life-threatening. Perforation is a dreaded isolate is important in the era of multidrug resistance.
complication manifesting as acute abdomen, with high The Widal test detects presence of IgG and IgM
mortality unless appropriately treated. antibodies to H (flagellar antigen) of S. enterica var typhi
The term severe or complicated enteric fever is used and paratyphi A and B, and O (somatic antigen) common
for patients presenting with neurological complications to typhi and paratyphi A and B. Anti-0 titers are both
such as delirium, coma, obtundation, stupor or shock and IgG and IgM that rise and decline early, while anti-H is
is associated with mortality rates as high as 50%. Other primarily IgG that rise and decline late in course of the
complications of include hepatic and splenic abscesses, disease. The conventional method of interpretation of the
hepatitis, cholecystitis, pneumonia, disseminated Widal test has been to demonstrate fourfold rise in
intravascular coagulation, psychosis, ataxia or meningitis. antibody titers in two samples. Since this is often not
The case fatality rate is less than 1% in appropriately practical, a single titer of at least 1:160 for both O and His
treated cases but may be 10-20% in inadequately treated considered positive. Even with this compromise, the Widal
or complicated cases. test has several limitations. Sensitivity is low in the first
week of illness and in patients treated with prior
Relapse: Relapse may occur in 5-15% of treated cases,
antibiotics. Specificity is low owing to anamnestic
usually due to the organism with the same susceptibility
reactions, prior vaccination, cross-reactivity with other
as the original attack and is relatively a milder illness. Rate
Enterobacteriaceae and subclinical infections in endemic
of relapse is dependent on choice of drug therapy. It is
areas.
higher with beta lactams such as cefixime or ceftriaxone
as compared to quinolones and azithromycin.
Treatment
Carrier state: Although 5-10% adult patients may shed
Indications for inpatient treatment: Most cases of enteric
Salmonella in stool following an acute attack for up to
fever can be managed at home with oral antibiotics and
3 months, only 1-4% excrete bacilli for more than 1 year.
advice to seek medical follow-up in case of failure to
These individuals are potential sources of infection for
respond to therapy or development of complications.
family members and contacts and for the community, if
Children with persistent vomiting, poor oral intake, severe
they are in occupations that involve food processing. There
diarrhea or abdominal distension usually require
is no data on carrier prevalence in children; routine
intravenous (IV) antibiotics and IV fluids, necessitating
examination of stool following recovery from enteric fever
admission to hospital.
is not recommended.
Antimicrobial susceptibility: The antimicrobial sensitivity
Diagnosis
of S. typhi/paratyphi has shown changes over the decades.
Leukocyte counts may be normal to low with absolute Though resistance to chloramphenicol was first noted soon
eosinopenia and neutrophilic predominance. Anemia and after its first use in 1940s, it was not until 1972 that
thrombocytopenia may occur in advanced illness. There chloramphenicol-resistant typhoid fever became a major
may be mild elevation of transaminases to 2-3 times problem. Multidrug-resistant typhoid fever (MDRTF)
normal (SGOT being higher than SGPT). A very high C became a common occurrence by the end of 1990s, with
reactive protein sometimes helps to differentiate enteric emergence of S. typhi simultaneously resistant to all the
from viral fevers, especially dengue. Ultrasound abdomen drugs that were used as first-line treatment (chloram
shows mesenteric adenitis with splenomegaly. phenicol, trimethoprim, sulfamethoxazole and ampicillin).
The gold standard for diagnosis is blood culture. The Fluoroquinolones were introduced in the late 1980s and
sensitivity is greatest in the first week at around 90% but early 1990s and produced very good results initially, but
240 Essential Pediatrics
the past decade has seen a progressive increase in the cefixime) especially if shorter duration of therapy is used.
minimum inhibitory concentrations (MIC) of ciprofloxacin Although relapses may be satisfactorily treated with the
in S. typhi and paratyphi and resistance rates to same drug as used for primary therapy, azithromycin is
fluoroquinolones/nalidixic acid now approach 90%. the preferred drug since it is associated with very low
Alongside the rise in resistance to quinolones, there has relapse rates.
been return in sensitivity to first-line antibiotics such as
chloramphenicol, cotrimoxazole and ampicillin. However, Prevention
concerns of toxicity and inconsistent reports of sensitivity The most effective and desirable method for preventing
preclude their widespread use. There are recent sporadic enteric fever is by improving hygiene and sanitation. This
reports of resistance to ceftriaxone due to production of will yield additional dividends of reduction in the burden
novel type of beta lactamases. Salmonel la may show in vitro of other water-borne illnesses as well. Vaccination as the
susceptibility to aminoglycosides and second-generation other major preventive strategy, is discussed in Chapter 10.
cephalosporins, but these are not effective in vivo, and
should not for treatment. Suggested Reading
• Kumar P, Kumar R. Enteric fever. Indian J Pediatr 2017; 84:227-30.
Choice for empirical therapy: Where enteric fever is
• Kundu R, Ganguly N, Ghosh TK, Yewale VN, Shah RC, Shah NK;
clinically suspected but cultures have not been sent for, IAP Task Force. Report: management of enteric fever in children.
reports are awaited or are sterile, empirical therapy may Indian Pediatr 2006; 43:884-7.
be started. Choice for empirical therapy is guided by • Kundu R, Ganguly N, Ghosh TK, Yewale VN, Shah RC, Shah NK;
various factors including the severity of the illness, IAP Task Force. Report: diagnosis of enteric fever in children.
Indian Pediatr 2006; 43:875---83.
inpatient/outpatient therapy, presence of complications
and local sensitivity patterns. Leptospirosis
For uncomplicated enteric fever, oral cefixime at a dose
of 20 mg/kg/day (ceiling dose of 1200 mg) is the drug of Leptospirosis is a zoonotic disease with worldwide
choice. Azithromycin (10-20 mg/kg/day) is a good second distribution, caused by spirochetes of the genus Leptospira.
choice agent; chloramphenicol (50 mg/kg/ day), Most cases occur in tropical and subtropical countries.
amoxicillin and cotrimoxazole are other second-line While rats are the principal source of human infection,
agents. Clinical efficacy is more or less the same with all dogs, cats, livestock and wild animals are other important
these drugs with each drug having its own advantages animal reservoirs. Infected animals may excrete the
and limitations. The choice of medication depends on spirochete in urine for several weeks. The survival of
individual preference, experience, and level of comfort excreted organisms depends on the moisture content and
and cost considerations. Once culture results are available, temperature of the soil. Humans acquire infection after
therapy can be modified. There is no data at present to being exposed to water or soil contaminated with rat urine.
support use of combination therapy in enteric fever. Agricultural workers, sewage workers, veterinarians,
meat handlers, rodent control workers and laboratory
For severe illness and where complications are present,
personnel are at risk of getting infected because of
intravenous ceftriaxone and cefotaxime are used a dose
occupational exposure. Infection is also common in the
of 100 mg/kg/day and 200 mg/kg/day, respectively. In
monsoons and during flooding.
patients with history of penicillin or cephalosporin allergy,
aztreonam, chloramphenicol (in higher than usual doses) Pathogenesis
and cotrimoxazole (in higher than usual doses) are used
as second-line agents. Parenteral treatment is continued Leptospira enter the body through abrasions and cuts in
until defervescence has occurred, oral intake has improved skin or through mucous membranes, and spread to all
and complications resolved. Thereafter, therapy can be organs hematogenously. The organisms damage the
switched to oral cefixime to complete a total duration of endothelial lining of small blood vessels, with leakage and
14 days. Other oral drugs that may be used for switch extravasation of blood cells, hemorrhage, and ischemic
over therapy include azithromycin, cotrimoxazole and damage to various organs including liver, kidneys,
amoxicillin. meninges and muscles.
In culture proven enteric fever, if defervescence does Clinical Features
not occur by day 7, causes such as drug fever, thrombo
phlebitis, hepatic or splenic abscesses, hemophagocytic Human infection with Leptospira may range from
syndrome and coinfections need to be excluded. If cultures asymptomatic infection to severe and often fatal
are negative and defervescence has not occurred by day multiorgan involvement. Symptomatic infection presents
7, a thorough search for alternative etiology for fever as a relatively mild anicteric febrile illness in over 70% of
should be made and ceftriaxone continued. patients, aseptic meningitis in about 20%; severe
leptospirosis with hepatorenal dysfunction (Weil's
Therapy of relapses: Relapse rates vary with the type of disease) develops in 5-10% individuals. The incubation
drug and are most common with beta lactams (ceftriaxone, period is usually 1-2 weeks.
Infections and Infestations 1241-
The illness is often biphasic. In the initial or septicemic by dark field microscopy or immunofluorescence and
phase lasting 2-7 days, the onset is abrupt with high grade cultures are not routinely available. However, it is now
fever with rigors and chills, lethargy, severe myalgia, possible to diagnose the illness in the first few days by
headache, nausea, vomiting. Patient may have PCR in blood.
conjunctiva! suffusion with photophobia and orbital pain, Leptospirosis should be differentiated from other
generalized lymphadenopathy and hepatosplenomegaly. febrile illnesses commonly seen in the monsoon season
Transient maculopapular erythematous rash may be seen such as malaria, dengue, enteric fever, acute viral hepatitis
in <10% cases. Hypotension with bradycardia and and hanta virus infections.
circulatory collapse is rarely seen. Some patients develop
acute respiratory distress syndrome with respiratory Treatment
failure. Most patients become asymptomatic within one Treatment should be initiated as early as possible. For
week. severe leptospirosis, parenteral penicillin G (6-8 million
In some patients, after a brief asymptomatic phase, U/m2/24 hr q 4 hr N for 7 days) is the drug of choice.
the second phase, called the immune or leptospiruric Ceftriaxone and IV tetracycline are also acceptable
phase, becomes manifest wherein Leptospira localize to alternatives. For oral treatment, amoxicillin and in children
various tissues to cause tissue specific signs and above 8 years, doxycycline are preferred.
symptoms. In this phase, circulating autoantibodies to
Leptospira are present; organisms can no more be isolated Prevention
from blood or CSF but persist in tissues like kidneys and Prevention entails avoidance of exposure to contaminated
aqueous humor. During the immune phase, some water. Single dose doxycycline or amoxicillin following
children may develop aseptic meningitis or uveitis with exposure can also prevent illness.
recurrence of fever. Encephalitis, cranial nerve palsies,
paralysis and papilledema are rare manifestations. Suggested Reading
Central nervous system abnormalities usually normalize • Rajapakse S, Rodrigo C, Balaji K, et al. Atypical manifestations of
within one week; mortality is rare. leptospirosis. Trans R Soc Trop Med Hyg 2015; 109:294-302.
In icteric leptospirosis (Weil's syndrome) after the initial • Tullu MS, Karande S. Leptospirosis in children: a review for family
phase of fever, patients develop severe hepatic and renal physicians. Indian J Med Sci 2009; 63:368-78.
dysfunction. Jaundice, hepatomegaly and tenderness in
right upper quadrant are usually detected. Splenomegaly Tetanus
found in 20% of cases. Non-oliguric renal failure with Tetanus is caused by the bacterium Clostridium tetani, a
azotemia may develop, often during the second week of spore-forming, anaerobic, gram-positive, motile bacillus,
illness. All patients have abnormal urinary finding on found in human and animal feces. These spores are
urinalysis in the form of hematuria, proteinuria and casts. widespread in the environment. From an estimated
Hemorrhagic manifestations are rare but when present, 80,000 deaths from neonatal tetanus in India in 1990, less
may include epistaxis, hemoptysis and gastrointestinal than 500 cases were reported in 2015 thus certifying India
and adrenal hemorrhage. Transient thrombocytopenia as free of maternal/neonatal tetanus. Elimination of
may occur. Mortality is 5-15%. neonatal tetanus has been defined as less than 1 case of
neonatal tetanus per 1000 live births in every district of
Diagnosis the country.
Complete blood count shows anemia, leukocytosis with
polymorph predominance and thrombocytopenia. The Pathogenesis
CRP is elevated and liver enzymes are mildly elevated C. tetani is a non-invasive organism. The spores of the
with SGOT more than SGPT; CPK levels are high. In organism remain nonpathogenic in soil or contaminated
patients with Weil's disease, there is elevated serum tissues until conditions are favorable for transformation
creatinine, deranged coagulation parameters and direct into vegetative form. Transformation occurs in the
hyperbilirubinemia with elevated transaminases. presence of locally decreased oxygen reduction potential,
Specific diagnosis is established by serologic testing, typically in devitalized tissue, in the presence of a foreign
microscopic demonstration of the organism, culture or body, trauma and crush injury and suppurative infections.
PCR. Serologic diagnosis is possible after 5 days of illness. Two types of toxins are produced by the organism,
The gold standard for serologic diagnosis is the tetanolysin and tetanospasmin. Tetanospasmin is the main
microscopic agglutination test (MAT), which is only toxin responsible for the manifestations of the disease. It
available in reference centers. Commercial kits for binds to the neuromuscular junction at the site of injury,
serologic diagnosis include rapid tests and IgM ELISA but and undergoes retrograde axonal transport to reach the
these tests are often associated with cross-reactivity and presynaptic nerve terminal where it prevents the release
false positivity with other infections such as enteric fever of inhibitory neurotransmitters glycine and GABA leading
and malaria. Demonstration of organism in tissues or urine to uncontrolled contraction of muscles.
242 Essential Pediatrics
Clinical Features
Tetanus mainly affects the unimmunized and partly
immunized individuals. The disease may occur in various
forms: Neonatal, generalized, localized, and cephalic. The
most common forms are generalized and neonatal
tetanus.
Generalized tetanus has an incubation period of
approximately 8 days (range 2-14 days). However, the
disease may occur months after the initial injury. The
incubation period depends on the distance of the site of
injury from the central nervous system. The faster is the
onset of symptoms, the poorer is the prognosis.
Characteristically, there is descending paralysis, with
initial involvement of the jaw muscles. There is spasm of
the masseters leading to trismus or lockjaw. Subsequent Fig. 11.14: Neonatal tetanus (Courtesy: Dr Amarjeet Mehta,
involvement of the neck, back and abdominal muscles Jaipur)
occurs, soon involving the whole body. As the disease
progresses, minimal stimuli may lead to generalized Treatment
spasms, the hallmark of the disease and contribute to Most patients require intensive care management and
serious complications and eventually death. Typically, the good supportive care. The aims of treatment are airway
sensorium of the patient is preserved. There is difficulty maintenance, prevention of further toxin absorption,
in swallowing. Autonomic instability may occur, with relieving clinical features, e.g. spasms, controlling auto
blood pressure fluctuations in the form of hyp ertension nomic instability and antibiotics. Airway management
or hypotension, diaphoresis and arrhythmias. Recovery may require intubation and mechanical ventilation,
usually begins after 3 weeks and approximately takes four especially in severe cases and if the infant gets frequent
weeks. Recovery from tetanus occurs by sprouting new episodes of largyngeal spasms, apneic attacks or central
nerve terminals in the spinal cord leading to relaxation of respiratory failure. Neutralization of free toxin is done by
the contracted muscles. administering human tetanus immunoglobulin; however,
antitoxin cannot dislodge the toxin already fixed to the
Neonatal tetanus is a major cause of mortality in nerve roots. The route of administration is intramuscular
developing countries. Pregnant women who are not or intrathecal. The usual dose is 500 to 1000 IU. Antibiotic
immunized against tetanus do not pass on protective therapy is needed to abolish the bacteria from the wound
antibodies to their babies. Infection results from unhygienic site; commonly used agents are crystalline penicillin or
birth practices, most commonly when the umbilical cord is metronidazole.
contaminated at the time of cutting. Symptoms usually Spasms are precipitated by minimal stimuli, therefore,
appear by the third day after birth, never in the first two efforts should be made to avoid noxious stimuli including
days of life and rarely after the age of two weeks. Excessive bright lights, pain and loud noises. Relief of spasms is done
unexplained crying followed by refusal of feeds and apathy using benzodiazepines. The most commonly used agent
are the common initial symptoms. The baby develops is diazepam, either as an intermittent IV bolus or as
progressive feeding difficulty, becomes rigid, develops continuous infusion. Diazepam prevents further spasms
paralysis, and may develop opisthotonic posturing and by causing GABA-mediated central inhibition. It also
experience painful spasms. The mouth is kept slightly open helps by reducing anxiety and promoting muscle
due to pull and spasm of the neck (Fig. 11.14). There is relaxation. Other agents used for severe spasms include
generalized rigidity and opisthotonus in extension. Spasms pancuronium bromide. Autonomic instability is controlled
of larynx and respiratory muscles are characteristically with the use of alpha and beta adrenergic blockers, and
induced by stimuli such as touch, noise and bright light, IV magnesium.
resulting in episodes of apnea and cyanosis. The case fatality
All patients should receive a complete course of
is high (70-100%).
immunization with tetanus toxoid once recovered, as the
Localized tetanus is less severe in comparison, and is disease does not induce protective antibodies.
characterized by rigidity and pain confined to the muscles
adjacent to the wound. It may lead to generalized tetanus Prognosis
later. In patients with isolated localized tetanus, the The disease has high mortality rate in spite of adequate
mortality is less than 1%. Cephalic tetanus is a form of local supportive care, which may reach up to 50% in severe
tetanus, which occurs due to injury of the bulbar muscles, generalized tetanus and 90% in neonatal form. The
has a poor prognosis. outcome depends on the incubation period, the site of
Infections and Infestations 1243-
absorbed and the caseous area inspissated. Healing occurs unrecognized. Asymptomatic infection is defined as
by fibrosis and calcification. When the cell-mediated immune infection associated with tuberculin hypersensitivity and
response is weak, the bacilli continue to multiply and the a positive tuberculin test, without significant clinical or
inflammatory process extends to the contiguous areas. radiological findings.
Progressive primary disease is a serious complication Symptoms in children with PPC include mild fever,
of the pulmonary primary complex (PPC) in which the anorexia and weight loss; occasionally PPC are detected
PPC, instead of resolving/ calcifying, enlarges steadily and during evaluation of intercurrent infection. Cough is
develops a large caseous center. The center liquefies and inconsistent and may be absent even in advanced disease.
may empty into an adjacent bronchus leading to formation Irritating dry cough can be a symptom of bronchial and
of a cavity, which characteristically is associated with large tracheal compression due to enlarged lymph nodes.
numbers of tubercle bacilli. Next, the bacilli may spread Lymph nodes may continue to enlarge even after
to other parts of the lobe or the entire lung, resulting in resolution of parenchymal infiltrates, and lead to
lobar consolidation or bronchopneumonia. Cavitary compression of neighboring bronchi.
disease is uncommon in young children. The enlarged Progressive primary disease (PPD) is the result of the
lymph nodes may compress the neighboring airway. Ball progression of primary disease. Children with PPD
valve effect due to incomplete obstruction may lead to
present with high-grade fever and cough. Expectoration
trapping of air distal to obstruction (emphysema).
of sputum and hemoptysis are associated with advanced
Enlarged paratracheal nodes may cause stridor and
respiratory distress, and subcarinal nodes impinge on the disease and development of cavity or ulceration of
esophagus and cause dysphagia. If obstruction of the bronchi. Cavitating pulmonary tuberculosis is uncommon
bronchus is complete, atelectasis may occur. in childhood. Children with endobronchial tuberculosis
usually present with fever, troublesome cough (with or
Outcome of Bronchial Obstruction without expectoration). Dyspnea, wheezing and cyanosis
may be present. Partial compression of the airway can lead
i. Complete expansion and resolution of chest X-ray
findings to emphysema; features of collapse are seen with large
airway compression.
ii. Disappearance of the segmental lesions
Miliary tuberculosis, characterized by hematogenous
iii. Scarring and progressive compression of the lobe or
segment leading to bronchiectasis spread and multiple systemic foci, is common in infants
and young children. The onset of illness is sudden and
A caseated lymph node may erode through the wall of
the bronchus, leading to tuberculous bronchitis or clinical features depend on the number of disseminated
endobronchial tuberculosis. Fibrosis and bronchiectatic organisms and involved organs. Unlike other forms of
changes may supervene. Discharge of bacteria into the tuberculosis, the child shows high-grade fever; dyspnea,
lumen may lead to their bronchial dissemination. cyanosis and altered sensorium are associated. There are
Hematogenous dissemination from infected lymph hardly any pulmonary findings, but fine crepitations and
nodes occurs early in course, resulting in foci of infection rhonchi may be present. Patients often show lymphadeno
in various organs (e.g. Simon focus in apex of the lungs). pathy and hepatosplenomegaly. Choroid tubercles may
If the host immunity is good, these foci are contained and be seen in -50% and meningitis in 20-30%.
disease does not occur. Lowered host immunity, as in Pleural effusion follows the rupture of a subpleural
infants, severely malnourished children and immuno focus into pleural cavity, but may also occur following
deficiency, may lead to activation of these metastatic foci hematogenous spread from the primary focus. The
and occurrence of disease. Massive hematogenous seeding effusion occurs because of hypersensitivity to tubercular
with M. tuberculosis, usually within 3-6 months after initial proteins. Minor effusions are usually asymptomatic.
infection, leads to miliary tuberculosis where all lesions Tuberculous effusion is uncommon in children younger
are of similar size. than 5 years of age, and is rarely associated with segmental
Pulmonary tuberculosis resulting from endogenous lesion and miliary tuberculosis. The onset may be
reactivation of foci of infection is uncommon in children; insidious or acute with fever, cough, dyspnea, pain and a
but may be seen in adolescents. The commonest site for pleural rub. Increase in effusion may make breathing
this type of disease is the apex of the lung (Puhl lesion), shallow and difficult. Early signs include decreased chest
because blood flow is sluggish at apex. Regional lymph wall movement, impaired percussion note and reduced
nodes are usually not involved. Miliary and meningeal air entry on affected side. As fluid collection increases,
tuberculosis usually occur within 1 year of the primary signs of pleural effusion are more definite.
lesion.
Extrathoracic Tuberculosis
Clinical Features The most common forms of extrathoracic disease in
The incubation period varies between 4 and 8 weeks. The children include tuberculosis of the superficial lymph
onset of symptoms is insidious, but may be acute in miliary nodes (scrofula) and the central nervous system. Other
tuberculosis. Primary infection usually passes off rare forms of extrathoracic disease include osteoarticular,
Infections and Infestations 1245-
abdominal, gastrointestinal, genitourinary, cutaneous and and history of contact with adult patients. Clinical features
congenital disease. may be nonspecific and chest radiograph and tuberculin
Tuberculosis of superficial lymph nodes may be test are difficult to interpret. In addition, these do not give
associated with drinking unpasteurized cow milk or conclusive evidence for the disease. While demonstration
extension of primary lesions of upper lung or abdomen of mycobacterium in various clinical specimens is the gold
leading to involvement of the supraclavicular, anterior standard, this is often not possible in children due to the
cervical, tonsillar and submandibular nodes. Although paucibacillary nature of the illness.
lymph nodes may become fixed to surrounding tissues, History of contact: A contact is defined as a child who
low grade fever may be the only systemic symptom. A lives in a household with an adult taking antitubercular
primary focus is visible radiologically in 30 to 70% therapy or having taken such therapy in the past 2 years.
patients; tuberculin test is usually reactive. Although A history of contact is available in less than one-third of
spontaneous resolution may occur, untreated lympha the patients. Contacts can often be traced to a maid servant,
denitis frequently progresses to caseating necrosis, cook, domestic aid or gardener in case of patients from
capsular rupture, and spread to adjacent nodes and well-to-do families with healthy parents. Tracing of
overlying skin, resulting in a draining sinus tract. contact is useful for confirming the diagnosis, as well as
Central nervous system disease is the most serious protection of other susceptible children from the disease.
complication of tuberculosis and arises from formation of
a caseous lesion in the cerebral cortex or meninges, due to Laboratory Tests
occult lymphohematogenous spread. Infants and young Diagnostic tests for pulmonary tuberculosis can be divided
children are likely to experience rapid progression to into 2 categories based on demonstration of: (i) M.
hydrocephalus, seizures and raised intracranial pressure. tuberculosis or one of its components; (ii) host response to
In older children, signs and symptoms progress over M. tuberculosis.
several weeks, beginning with fever, headache, irritability Tubercle bacteria can be demonstrated by (i) Ziehl
and drowsiness. The disease advances with lethargy, Neelsen (acid-fast) staining, (ii) special stains, (iii) cultures,
vomiting, nuchal rigidity, seizures, hypertonia and focal and (iv) cartridge-based nucleic acid amplification test.
signs. The final stage of disease is marked by coma, The above methods can be used on sputum, induced
hypertension, decerebrate and decorticate posturing and sputum, gastric or bronchoscopic lavage fluid, or pleural
death. Rapid confirmation of the diagnosis can be difficult fluid. The best specimen for demonstration of M.
because of variable cerebrospinal characteristics, tuberculosis in children is the early morning gastric aspirate
nonreactive tuberculin tests (40%) and normal chest obtained by using a nasogastric tube. For better results, at
radiographs (50%). Since better outcomes are associated least two specimens of gastric aspirates are recommended.
with early institution of therapy, the diagnosis should be Fluorescence microscopy (using auramine-rhodamine
considered in any child with basilar meningitis, stains) may improve yield further. In young children who
hydrocephalus or cranial nerve involvement. are not able to provide sputum, that can be induced by
Tuberculosis of abdomen is due to hematogenous nebulized hypertonic saline (3-5%). Older children may
spread from the lungs. It may, however, be secondary to provide expectoration at end of the procedure. In young
swallowing of the infected sputum by a patient with children, a nasopharyngeal aspirate is collected and
pulmonary lesions. Patients with abdominal tuberculosis processed like sputum for smear and culture.
may remain asymptomatic initially. Symptomatic patients
show toxemia and have colicky abdominal pain, vomiting Culture: Lowenstein-Jensen (LJ) medium is the most
and constipation. The abdomen feels characteristically widely used medium for determination of characteristic
doughy; abdominal wall is not rigid but tense. The rolled features of colonial morphology, growth rate and pigment
up omentum and enlarged lymph nodes appear as production. Though the culture technique is simple, 7-10
irregular nodular masses with ascites; liver and spleen are weeks of incubation is necessary for detection of
often enlarged. organisms. Microscopic examination of thin layer culture
Children may rarely present with hemophagocytic plate may lead to detection of microcolonies of M.
lymphohistiocytosis (HLH), immune hemolytic anemia, tuberculosis as early as after 7 days. The yield of culture of
superior mediastinal syndrome, pneumothorax and gastric aspirate varies from 30-50% in children with
immune reconstitution inflammatory syndrome (IRIS) in tuberculosis. In view of the excessively long period for
form of paradoxical worsening of symptoms after starting isolation of M. tuberculosis by conventional culture, LJ
antituberculous drugs, especially in children with immune media has been replaced by mycobacterial growth
deficiency. indicator tube (MGIT) system. In this system, culture is
positive in majority by end of 2 weeks, though final result
Diagnosis is available by the end of 6 weeks.
The diagnosis of tuberculosis in children is based on Cartridge-based nucleic acid amplification test (CBNAAT):
clinical features, chest roentgenogram, tuberculin testing The test, based on real-time polymerase chain reaction, is
246 Essential Pediatrics
preferred for diagnosis of pulmonary tuberculosis; results Table 11.6: Causes of false positive and false negative
are available in less than 2 hours. CBNAAT identifies tuberculin skin test (Mantoux test)
presence of M. tuberculosis and provides information on False negative results False positive results
rifampicin resistance. The sensitivity and specificity of two Infections due to atypical
Infections
gastric aspirates for diagnosing pulmonary tuberculosis in Viral (measles, mumps, chickenpox, mycobacteria
children ranges between 60-70% and 90-100%, respectively. HIV) BCG vaccination
Its utility in extrapulmonary tuberculosis is lower. Bacterial (enteric fever, typhus, leprosy, Infection at the site of
Serodiagnosis: ELISA has been used to detect antibodies pertussis, severe TB) test
to various antigens of the bacillus. Despite a number of Live vaccines (measles, mumps, polio,
studies, current techniques have no role for the diagnosis varicella)
of tuberculosis in children. Chronic renal failure, liver failure
Hodgkin disease, lymphoma, chronic
Methods to diagnose latent infection: Till date, tuberculin leukemia, sarcoidosis
skin test was the only method to diagnose latent Corticosteroids, immunosuppressive
tuberculosis infection. Recently, a new test based on agents
interferon gamma release assay (IGRA) has been developed. Newborn, elderly patients
This in vitro test estimates a component of cell-mediated
immunity to M. tuberculosis, based on quantitation of Factors related to tuberculin
interferon-gamma (IFN-y) released from sensitized Exposure to light, heat, chemicals;
lymphocytes in whole blood incubated overnight with contamination
antigens specific for the bacterial species. Two tests are Improper dilution; adsorption
available: QuantiFERON® gold TB test (QFT) and ELISPOT. Factors related to technique
In countries with high prevalence of tuberculosis, it is Injection of too little antigen
recommended to continue using tuberculin skin test that is Subcutaneous injection
considerably less expensive than IGRA. Delayed administration after drawing
into syringe
Tuberculin skin test: The tuberculin or Mantoux test is
Injection close to other skin tests
commonly used to make the diagnosis of tuberculosis in
Inexperienced reader; errors in recording
children. Although currently available test antigens are
not 100% sensitive or specific, no better diagnostic test is test is based on risk of infection and progression to disease
widely available. Infection with M. tuberculosis produces (Table 11.7).
a delayed hypersensitivity reaction to its specific antigenic
components. All purified protein derivative (PPD) lots are BCG test: An accelerated response after injection of the
bioassayed to demonstrate equal potency. The standard vaccine is observed in individuals suffering from
test dose of a preparation is defined as dose of that product tuberculosis. Induration of more than 5-6 mm after 3 days
that is biologically equivalent to 5 TU of PPD-S or 2 TU of of BCG vaccine is considered a positive reaction. However,
tuberculin PPD RT23. The reaction to tuberculin typically due to high antigen load, there are higher chances of false
begins 5-6 hours after the intradermal injection and positive results and this test is not recommended.
reaches maximal induration at 48-72 hours; vesiculation Radiology: Chest radiograph has an important role in
and necrosis are rare.
diagnosis of pulmonary tuberculosis. In extrapulmonary
Variability of the tuberculin test may be reduced by tuberculosis, presence of lesions on chest radiograph
attention to administration and reading. A 26-gauge supports diagnosis. The typical chest X-ray appearance
needle and tuberculin syringe are used to inject 0.1 mL of of a pulmonary primary complex (PPC) is that of a
PPD intradermally into the volar aspect of the forearm. consolidation of variable size, usually unifocal and
Forty-eight to 72 hours later, the diameter of induration homogenous (Fig. 11.15). Enlarged lymph nodes are seen
is measured transversely to the long axis of forearm and in the hila and right paratracheal region. Adenopathy
recorded in millimeters. A non-reactive tuberculin test
does not exclude latent or active tuberculosis. Numerous Table 11.7: Interpretation of Mantoux test
factors can diminish tuberculin reactivity, resulting in a Size of induration Interpretation
false negative reaction (Table 11.6). Because some antigens
<10 mm Negative; no active disease
in PPD are shared with other mycobacteria and Bacillus
Calmette-Guerin (BCG), false-positive reactions can occur 5-10 mm Borderline; consider positive in immuno
in those infected with other mycobacteria or following compromised host; contact with adult
patient with sputum AFB positive tuber
vaccination. Although BCG vaccination of older children
culosis
or adults results in greater initial and more persistent
cross-reactivity, most individuals lose cross-reactivity >10 mm Positive; suggests disease in presence
of clinical features
within 10 years of vaccination. Interpretation of the skin
Infections and Infestations 1247-
alone may be the sole feature of primary tuberculosis. detected on computed tomography. CT features such as
Consolidation in progressive primary disease (PPD) is low attenuation lymph nodes with peripheral enhance
usually heterogeneous, with poorly marginated predilec ment, lymph node calcification, branching centrilobular
tion for apical or posterior segments of upper lobe or nodules and miliary nodules are helpful in suggesting the
superior segment of lower lobe (Fig. 11.16). There may be diagnosis where the radiograph is normal or equivocal.
features of collapse (Fig. 11.17). Bronchiectasis may occur Contrast MRI is useful for CNS tuberculosis, since it
because of (i) destruction and fibrosis of lung parenchyma demonstrates localized lesions, meningeal enhancement,
resulting in retraction and irreversible bronchial dilatation, brainstem lesions and ventricular dilatation.
and (ii) cicatricial bronchostenosis secondary to localized
endobronchial infection resulting in obstructive pneumo Histopathology: Lymph nodes, liver and other tissues
nitis and distal bronchiectasis. In children, cavitary disease may be examined for histological evidence of tuberculosis
is uncommon. by fine needle aspiration cytology.
Pleural effusion may occur with or without lung lesions
(Fig. 11.18). In miliary tuberculosis, there are multiple Diagnostic Algorithm for Tuberculosis
lesions of size 2-5 mm (Fig. 11.19). Occasionally, the chest The diagnosis of tuberculosis disease in children is
radiograph may be normal and lymphadenopathy is challenging. Even in advanced nations, the diagnosis is
,91� '� R
Fig. 11.15: Pulmonary primary complex (PPC) showing left hilar Fig. 11.16: Progressive pulmonary disease showing consoli
adenopathy with ill-defined parenchymal lesion dation
Fig. 11.17: Collapse with consolidation of right upper lobe Fig. 11.18: Massive pleural effusion on left side, with mediastinal shift
-248 Essential Pediatrics
Drug Regimens
Changes have occurred in the therapeutic approach to
childhood tuberculosis. Short course therapy, with
treatment duration of 6 months, is now standard
practice.
The major problem in inclusion of children in Directly
Observed Treatment Short course (DOTS) program has been
a difficulty in demonstration of AFB and classification of
different manifestations according to categories described
for adults. A joint statement of the Indian Academy of
Pediatrics and Revised National Tuberculosis Control
Program (RNTCP) has proposed to classify children into
two categories. Table 11.9 gives the categories of
tuberculosis, as defined by WHO, along with suggested
clinical condition in children. In view of increasing INH
resistance, use of three drugs (INH, rifampicin and
ethambutol) instead of two (INH and rifampicin) is
Fig. 11.19: Miliary shadows with right paratracheal adenopathy suggested during the continuation phase.
made by combination of a positive tuberculin test, chest Corticosteroids
radiograph, physical examination and history of contact
Additional therapy with these agents is useful in treating
with a patient (Fig. 11.20). Newer diagnostic methods,
patients with CNS and rarely pulmonary tuberculosis,
such as CBNAAT, have improved the yield of micro especially when host inflammatory reaction contributes
biologically confirmed tuberculosis. to tissue damage. Short courses of corticosteroids are
indicated in children with endobronchial tuberculosis
Treatment
(with localized emphysema, segmental pulmonary
The principles of therapy in children with tuberculosis lesions or respiratory distress) and severe miliary
are similar to that of adults. Medications used for treat tuberculosis (if alveolocapillary block is suspected).
ment of tuberculosis in children are given in Table 11.8. Significant improvement in symptoms is seen in children
Suspected pulmonary TB
• Fever and/or cough >2 weeks
• ± Loss of weight or no weight gain
• History of contact with suspected or diagnosed active TB
Look for alternative cause for symptoms
X-ray suggestive of TB
+
X-ray not suggestive of TB
Antibiotics for 7-10 days, if has not already received
Symptoms persist
Gastric aspirate (GA), induced sputum: Smear, geneXpert, MGIT
•
Smear, MGIT, geneXpert
Sputum or GA positive Negative or not feasible
l
Assign to a category
Symptoms persist
Repeat chest X-ray
Sputum positive Sputum negative
Table 11.9: Standardized clinical categories for tuberculosis (TB) and clinical conditions
Categories Suggested by WHO Suggested conditions (for adults) Suggested regimens" in children
Category I New sputum positive PPC, PPD, TBL 2HRZE + 4HRE
Pulmonary TB Pleural effusion
Serious extrapulmonary TB Abdominal TB
Osteoarticular TB
Genitourinary TB
Central nervous system TB
Pericardia! TB
Category II Relapse Relapse 2SHRZE + 1HRZE + 5HRE
Treatment failure Treatment failure
Return after default Interrupted treatment
PPC: Pulmonary primary complex; PPD: Progressive primary disease; TB: Tuberculosis; TBL: Tubercular lymphadenitis
H isonizid, R rifampicin, Z pyrizinamide, E ethambutol, S streptomycin
#Numerical denotes months for which the drug is to be given; e.g. 4HR is 4 months of INH and rifampicin
All children in household of an adult patient with sputum positive tuberculosis should be screened for evidence of infection. Children exposed to
adults with sputum positive illness should receive 6 months of isoniazid prophylaxis.
with tuberculous pericardia! effusion, but not pleural Management of a Child in Contact
effusion. The medication used is prednisolone, at doses with an Adult with Tuberculosis
of 1-2 mg/kg/day for 4-6 weeks. One-third of children with adult contacts with active
tuberculosis show features of infection. Infection is more
Infant born to Mother with Tuberculosis common in younger children, and those with severe mal
nutrition, absence of BCG vaccination, sputum positive
Congenital tuberculosis is rare, the fetus infected either
contacts and exposure to tobacco smoke. Children <5-year
hematogenously (through umbilical vessels) or by old who are in contact with adult patients with pulmonary
ingestion of infected amniotic fluid. In the former, the tuberculosis should receive INH prophylaxis (10 mg/kg/
primary focus is in the liver and in latter, the lungs. It is day for 6 months) after excluding presence of disease.
often difficult to differentiate between congenital and
postnatally acquired tuberculosis. Infants born to mothers Monitoring of Therapy
with active tuberculosis should be screened for disease Response to treatment is judged by clinical, radiological,
by examination, tuberculin test and X-ray chest. If bacteriological and laboratory assessment.
examination and investigations are negative for the disease,
the infant should receive INH prophylaxis (10 mg/kg/ Clinical Criteria
day for 6 months). The infant is examined regularly for Clinical improvement judges the response of therapy. The
features suggestive of tuberculosis. Infants with congenital child should be seen every 2-4 weeks initially, then every
tuberculosis are treated with 4 medications (INH, 4-8 weeks. Most children show improvement in symptoms
rifampicin, pyrazinamide, ethambutol) in intensive phase (fever, cough, appetite, well being) within a few weeks. The
for 2 months, followed by 3 drugs (isoniazid, rifampicin, child is examined for weight gain and improvement in chest
ethambutol) during maintenance for 4 months. findings. Compliance to therapy should be ensured.
250 Essential Pediatrics
In presence of unsatisfactory response or worsening of • Jenum S, Dhanasekaran S, Lodha R, et al. Approaching a diagnostic
features, the initial basis of diagnosis is reviewed, point-of-care test for pediatric tuberculosis through evaluation of
immune biomarkers across the clinical disease spectrum. Sci Rep
especially if there are no issues with compliance. The 2016; 6:18520.
possibility of drug resistant tuberculosis should be • Lodha R, Mukherjee A, Saini D, et al; Delhi TB Study Group. Role
considered. Following completion of therapy, patients are of the QuantiFERON®-TB Gold in-Tube test in the diagnosis of
reviewed every 3-6 months for 2 years. intrathoracic childhood tuberculosis. Int J Tuberc Lung Dis 2013;
11:1383-8 .
Radiological Criteria • Mukherjee A, Singh S, Lodha R, et al; Delhi Pediatric TB Study
Clinical improvement precedes radiological clearance. The Group. Ambulatory gastric lavages provide better yields of
first chest X-ray is done after 8 weeks' therapy, i.e. at the Mycobacterium tuberculosis than induced sputum in children with
intrathoracic tuberculosis. Pediatr Infect Dis J 2013; 32:1313-7.
end of intensive phase. In patients who show increase or
• Seth V, Kabra SK (Eds). Essentials of tuberculosis in children, 3rd
little change in radiological features coupled with delayed edn. New Delhi, Jaypee Publishers; 2010.
clinical response, prolongation of intensive phase by one
month is suggested. Further films are taken after 4 weeks
Mycobacteria Other than Tuberculosis (MOTT)
and child, if better, should be shifted to continuation
phase; else the patient is investigated for failure of Atypical mycobacteria or non-tuberculous mycobacteria
treatment and drug resistance. The degree of radiological (NTM) or mycobacteria other than tuberculosis (MOTT)
clearance is graded as: (i) complete, (ii) moderate ( Yi -�rd are environmental pathogens that are being increasingly
clearance), (iii) mild (�rd decrease in size), or (iv) no recognized as cause of human disease. These bacteria are
clearance or appearance of new lesion(s). One need not classified depending on the rapidity of growth in media
treat till complete radiological clearance, since improve as rapid growers which grow within 7 days and slow
ment may continue even after stoppage of therapy. growers, as those which take longer to grow. Acquisition
is through contact with the environment; human-to
Microbiological Criteria human or animal-to-human transmission almost never
Childhood tuberculosis is paucibacillary. In children, occurs. Though asymptomatic infection can occur, there
where isolation of M. tuberculosis was possible at the time is no recognized latent infection or reactivation disease.
of diagnosis, efforts are made to document disappearance NTM infections may occur in previously healthy or those
of bacilli during therapy. If smear was positive initially, with underlying immunodeficiency, like HIV.
repeat sampling is done at 2 and 6 months. Lymphatic disease is the most common manifestation
of NTM disease in children. It usually presents as painless
Suspecting Drug-Resistant Tuberculosis cervical adenitis in children aged 1-5 years with no
Children in the following categories are at risk of develop systemic symptoms. The main differential is tuberculous
ing drug resistant tuberculosis: Contact with adult patients lymphadenitis. The definitive diagnosis is by culture; the
with proven drug resistance; irregular treatment or recent usual causative organisms are MAC (Mycobacterium avium
death due to tuberculosis; children not responding to intracellulare), M. scrofulaceum and M. hemophilium.
standard antitubercular therapy; children who respond Treatment is complete excision of the lymph nodes.
initially but later show deterioration. Appearance of new Pulmonary disease due to NTM occurs in adults with
lymph nodes on treatment, and persistence or isolated underlying pulmonary problems and is usually due to
non-clearance of radiologic shadows are not considered MAC, M. kansasii and M. abscessus. Disseminated NTM
indicators of drug resistant tuberculosis. disease, mainly in adults and less commonly children with
Drug-Resistant Tuberculosis advanced HIV infection, is usually due to MAC and
presents as fever, weight loss, night sweats, abdominal
Clinicians should neither miss nor overdiagnose the pain, diarrhea and anemia. Blood cultures are positive.
disease. Problems with overdiagnosis of drug-resistant Skin and soft tissue infections are usually a consequence
tuberculosis are multiple: Second-line drugs are less of trauma or health care procedures. These are usually
effective; they have more side effects; and are expensive. due to M. abscessus, M. chelonae, M. fortuitum, M. ulcerans
A physician may suspect drug resistance based on the and M. marinum. They have been implicated in infections
above criteria, but before making a diagnosis, all attempts following injections, central lines, peritoneal dialysis
are made to demonstrate AFB from appropriate samples catheters, laparoscopy, liposuction, cosmetic procedures,
and obtain culture and sensitivity. If the diagnosis is implants and prosthesis, LASIK and surgery. These
confirmed or not established, these patients must be mycobacteria species are usually hardy, resist the
referred to centers treating patients with drug resistance. commonly used disinfectants and hence occur when
Suggested Reading surgical (chiefly laparoscopic) equipment is rinsed with
• Dhooria S, Madan K, Pattabhiraman V, et al. A multicenter study
tap water and inadequately disinfected. Usually these
on the utility and safety of EBUS-TBNA and EUS-B-FNA in infections present as indolent abscesses that do not
children. Pediatr Pulmonol 2016; 51:1031-39. respond to the usual antibiotics.
Infections and Infestations l2s1-
Microbiologic diagnosis of NTM infections is possible in India. Cases have been reported from all states chiefly
in specialized laboratories where identification and from rural and forested areas and occasionally also urban
speciation is done by advanced biochemical or molecular areas.
methods. Treatment depends on the causative organism Scrub typhus is transmitted by bite of the trombiculid
and its sensitivity. MAC is usually treated with combina mite and Indian spotted fever by ticks. Rickettsial disease
tion therapy consisting of a macrolide (clarithromycin/ is due to invasion of the endothelial region of the
azithromycin), rifampicin, ethambutol and during initial vasculature and subsequent microvasculitis. This process
stages with an aminoglycoside for 12-18 months. especially affects the brain, cardiac and skeletal muscle,
Treatment of the rapidly growing mycobacteria (M. skin, liver, lungs and kidneys.
abscessus, M. chelonae, M. fortuitum) includes a combination
of clarithromycin, quinolones, aminoglycosides, Clinical Manifestations
tobramycin, amikacin, imipenem, minocycline, linezolid Incubation period varies from 2 to 14 days. A history of
and clofazimine. exposure to ticks, history of origin from an endemic area
or a similar illness in family members may be forthcoming.
Suggested Reading Severity of manifestations varies from a mild, self-limiting
• ATS/IDSA Statement: Diagnosis, treatment and prevention of illness to a life-threatening disease.
nontuberculous mycobacterial diseases. Am J Respir Crit Care Med
2007; 175:367-416.
Initially, the illness appears to be nonspecific and patients
• BTS Guidel ines for the management of non-tuberculous present with unrelenting headache, very high fever,
mycobacterial pulmonary disease. Thorax 2017; 72:969-10. anorexia, myalgias, restlessness, calf muscle pain and
tenderness. Gastrointestinal symptoms include abdominal
RICKETTSIAL AND MVCOPLASMA INFECTIONS pain, nausea, vomiting, and diarrhea. Skin rash is usually
not present until after 2-4 days of illness. The typical triad
Rickettsial Infections
of fever, headache and rash is observed in only half of the
Rickettsial diseases are a group of febrile illnesses caused patients. In spotted fever, rash is initially discrete pale rose
by obligate intracellular gram-negative bacilli and red blanching macules or maculopapules on the extremities.
transmitted to man by arthropod vectors. Rickettsial Later, the rash spreads to involve the entire body including
diseases are often under diagnosed due to poor awareness. palms and soles and may be petechial or present as palpable
purpura (Fig. 11.21). In severe form of the disease, petechiae
Epidemiology may enlarge into ecchymosis, which can become necrotic.
Rickettsia are a group of motile, gram-negative, nonspore Severe vaso-occlusive disease secondary to rickettsial
forming, highly pleomorphic bacteria that present as cocci, vasculitis and thrombosis is infrequent but can result in
rods or thread-like obligate, intracellular parasites. gangrene of the digits, toes, earlobes, scrotum, nose or entire
Rickettsia are classified on basis of clinical features and limbs (Fig. 11.21). In scrub typhus, rash is seen initially on
epidemiology into the typhus group (epidemic typhus, trunk or may not be present at all. Painless eschar, the tache
endemic typhus and scrub typhus), the spotted fever noire, at the initial site of tick attachment is seen in scrub
group (Rocky mountain spotted fever, Indian spotted typhus.
fever), Q fever, trench fever and ehrlichiosis. Scrub typhus Complications may involve any organ system and
caused by R. tsutsugamushi, Indian spotted fever caused include encephalopathy, pulmonary edema, myocarditis,
by R. conorii and Q fever caused by C. burnetii are prevalent hepatic failure, acute renal failure and vascular collapse.
I I I I
///I/ I 111 \ \ ......,C __ .....I
Fig. 11.21: Spotted fever showing: (a) Maculopapular rash on the soles; (bl Necrotic rash chiefly in gluteal region and legs;and
(c) Gangrene of digits of hand, earlobe (Courtesy: Dr Atul Kulkarni, Sholapur)
252 Essential Pediatrics
available. Most multiplex PCR kits for diagnosis of parenteral nutrition especially intralipids, neutropenia,
respiratory infections include Mycoplasma. central venous catheters, etc. Commonest form of
invasive candidiasis is bloodstream infection and less
Treatment commonly meningitis, endocarditis, osteomyelitis and
Since Mycoplasma lack cell walls, all cell wall active septic arthritis. Clinical features are similar as bacterial
antibiotics including beta lactams are inactive. Macrolides sepsis and outcomes are poor, if therapy is not initiated
are the drugs of choice; recommended regimens include early.
azithromycin 10 mg/kg in one dose on the first day and Diagnosis is primarily by fungal blood cultures which
5 mg/kg in one dose for four days, clarithromycin 15 mg/ are only 50% sensitive. It is, therefore, important to have
kg/ day in two divided doses for 10 days, or erythromycin a high index of suspicion so that empirical therapy may
30 to 40 mg/kg/day in four divided doses for 10 days. In be started early in patients with high likelihood of
children older than 8 years, tetracycline 20 to 50 mg/kg/ infection.
day in four divided doses (maximum daily dose 1 to 2 g) Fluconazole is the drug of choice especially because of
and doxycycline 2 to 4 mg/kg/day in one or two divided low cost, ease of administration and availability of oral
doses (maximum daily dose 100 to 200 mg) for 10 days switchover. However, there has been a recent increase in
are also effective. incidence of infection by fluconazole-resistant Candida for
The role of anti-Mycoplasma therapy in improving the which treatment with drugs like amphotericin B,
outcome of mycoplasma pneumonia is controversial. echinocandins may be required. At the same time,
Nonetheless, empiric treatment for Mycoplasma should be isolation of Candida from non-sterile sites like tracheal
considered in children older than 5 years presenting with secretions, urine and stool is common in critically sick
suspected mycoplasma pneumonia, those who are not children and should not be treated unless other features
responding to standard beta lactam therapy and possibly favoring invasive infection are present.
those with severe/very severe pneumonia.
Aspergillosis
Extrapulmonary Mycoplasma infection is often immune
mediated and may need additional therapeutic modalities Aspergillus is a ubiquitously distributed filamented
including steroids and plasmapheresis. fungus; the two common species causing human infection
are A. fumigatus and A. niger. Aspergillus causes certain
Suggested Reading non-invasive infections like otomycosis, sinusitis,
• Colin AA, Yousef S, Forno E, Korppi M. Treatment of Mycaplasma
aspergilloma and allergic bronchopulmonary aspergillosis.
pneumoniae in pediatric lower respiratory infection. Pediatrics 2014; More sinister is invasive aspergillosis which can have
133:1124-5. mortality as high as 50%. Invasive aspergillosis always
occurs in the immunocompromised; common pre
FUNGAL INFECTIONS disposing factors include patients with cancer undergoing
chemotherapy and resultant neutropenia, stem cell
Fungi have become an increasingly common cause of transplant recipients and patients on other immuno
disease in humans. Superficial fungal infections are suppressive drugs. Common sites of involvement are the
detailed in Chapter 26. We discuss some of the serious lungs (Fig. 11.22) and sinuses. Clinical symptoms and signs
invasive fungal infections, including invasive candidiasis, depend on the site of involvement. Diagnosis is primarily
aspergillosis, mucormycosis and cryptococcosis. by radiology and histopathologic demonstration of the
invasive hyphae in biopsy samples and finally by culture.
Invasive Candidiasis Estimation of galactomannan in serum/bronchoalveolar
The major infection causing species of Candida are lavage samples has emerged as a non-invasive diagnostic
C. albicans, C. tropicalis, C. parapsilosis, C. krusei and test. Treatment should be aggressive. The drug of choice
C. glabrata. It commonly causes superficial infections such is voriconazole. Other options are amphotericin Band caspo
as thrush, vaginitis, paronychia, etc. Colonization with fungin. Fluconazole has no activity against Aspergillus.
Candida at mucosal sites in patients on antibiotic therapy Surgical resection may be required in non-responding cases.
is also common. Invasive infections with Candida usually
happen as nosocomial infections in individuals with Mucormycosis
impaired defenses such as preterm neonates in the Mucormycosis refers to infection with the filamented fungi
neonatal intensive care unit, critically sick children in of the genus Mucor and Rhizopus. The hyphae are broad
the pediatric intensive care unit and children with cancer and aseptate unlike those of Aspergillus that are narrow
on chemotherapy or following stem cell transplant. The and septate. Mucormycosis is an invasive infection that
usual risk factors for invasive candidiasis include primarily occurs in patients with risk factors such as
prolonged intensive stay, broad-spectrum antibiotic diabetic ketoacidosis, cancer chemotherapy, transplant
therapy, renal failure, corticosteroid and other recipients, iron overload and receipt of immuno
immunosuppressive therapy, renal failure, use of total suppressive drugs. Sites of involvement are mainly the
254 Essential Pediatrics
Suggested Reading
• Dadar M, Tiwari R, Karthik K, et al. Candida albicans-Biology,
molecular characterization, pathogenicity and advances in
diagnosis and control. Microb Pathog 2018; 117:128-38.
• Steinbach WJ. Antifungal agents in children. Pediatr Clin North
Am. 2005; 52:895-915.
PROTOZOAL INFECTIONS
Malaria
Malaria the most important protozoa! disease of man is
caused by the genus Plasmodium. There are four species
pathogenic to man, P. vivax, P. falciparum, P. malariae and
P. ovale of which the first two occur in India. Most of the
malaria deaths are attributable to P. falciparum.
Epidemiology
Malaria is an important tropical disease, afflicting
350- 500 million patients annually with over one million
deaths. Of regions endemic for malaria, >70% cases are in
Sub-Saharan Africa. Malaria is also an important cause of
morbidity and mortality in South Asia including India.
Fig. 11.22: Multiple air space opacities with irregular borders The National Vector-Borne Disease Control Program
and internal cavitation suggestive of invasive aspergillosis reported around 0.8 million cases of malaria in India in
2014 with some 300 deaths; 60% of the cases were due to
nasal sinuses and less commonly pulmonary, gastro P. faciparum. Large number of cases are reported from
intestinal and skin/soft tissue. Infection can sometimes Orissa, Chhattisgarh, West Bengal, Karnataka, Jharkhand,
occur due to direct inoculation in traumatic/surgical Madhya Pradesh, Uttar Pradesh, Assam, Gujarat and
wounds and injection sites. Clinical features depend on Rajasthan. About 10% cases are reported from the urban
the site involved; in the nasal form pain, swelling, bloody areas, due to construction activities, population migration,
discharge and presence of blackish eschars on nasal and inappropriate water storage and disposal.
examination are common. Confirmation of diagnosis is by
demonstration of the characteristic hyphae on histopatho Transmission
logy and fungal cultures. Treatment includes radical surgical The infectious stage of the parasite, the sporozoite, is
debridement, antifungal therapy with amphotericin B and transmitted to the host by the bite of the female Anopheles
correction of underlying predisposing factors. mosquito. Six species of anopheline mosquitoes are
important in the transmission of the disease, namely
Cryptococcosis Anopheles culicifacies (rural), A. fluvitalis, A. stephensi
Infection with Cryptococcus neoformans is commonly seen (urban), A. minimus, A. philippinesis and A. sundaicus. To
in HIV-infected individuals with advanced immuno enable development of parasites in the vector's body and
suppression and less commonly in other immuno make it capable of transmitting the disease, the vector must
compromised patients such as those on long-term be susceptible, feed on human blood and live at least for
steroids, or those with CD4 lymphocytopenia. Rarely, it 10-12 days after an infective blood meal. The vector should
may occur in the immunocompetent (usually due to C. be present in large number or sufficient density to be of
gattii). The disease most often affects the central nervous importance. Resting habits of the mosquito are important
system; pulmonary and disseminated forms are less for planning control measures. Mosquitoes usually breed
common. Clinical symptoms include headache, vomiting, in edges of streams, water tanks, pits, cisterns and over
altered sensorium, signs of meningism and less head tanks. A. stephensi breed in wells, cisterns, fountains
commonly neurologic deficits. CSF is usually under and overhead tanks, A. fluviatilis in moving water and A.
increased pressure and has high protein with pleocytosis. sundaicus in brackish water. Breeding sites such as
The diagnosis is confirmed by demonstrating cryptococci burrowed pits, pools, ponds, marshy areas and unregulated
in the CSF by India ink, cryptococcal antigen testing and irrigation channels are conducive to mosquito breeding
finally culture. Treatment includes antifungal therapy and spread of malaria. Mosquitoes thrive best in
with amphotericin B and flucytosine for 2 weeks followed temperature between 20 and 30° C, relative humidity 60%
by fluconazole for prolonged periods. Reduction of and in areas with good rainfall. The peak transmission
elevated pressure by serial lumbar punctures is also season of malaria is between July and November. Malaria
crucial. is uncommon at altitudes over 2000 m above sea level.
Infections and Infestations l2ss-
Efficient vectors are those that bite humans in
preference to cattle, have high biting rates and where the
duration of sporogony is shorter and who are long lived
(hence they outlive sporogony). More efficient the vector,
greater the burden of malaria; A. gambiae the vector in Sub
Saharan Africa is a very efficient vector and is largely
responsible for the huge burden of malaria in that area.
phagocytosis of the RBC in spleen. Malarial immunity in Table 11.10: Criteria for severe malaria
endemic areas increases with age and disappears when Clinical findings
the individual leaves the endemic area; a phenomenon
known as premunition. Impaired consciousness or unarousable coma
Prostration; generalized weakness; patient unable walk or sit
up without assistance
Clinical Features
Failure to feed
The clinical manifestations and severity of malaria depend Multiple convulsions-more than two episodes in 24 hours
largely on the species of the parasite and endemicity of Deep breathing, respiratory distress; acidotic breathing
disease. Most cases of severe or complicated malaria are Circulatory collapse or shock; systolic pressure <70 mm Hg
due to P.falciparum; there are increasing number of reports (adults) and <50 mm Hg (children)
due to severe disease by P. vivax. In highly endemic areas Clinical jaundice and evidence of other vital organ dysfunction
with"stable malaria" such as Sub-Saharan Africa, children Hemoglobinuria
below 5 years and pregnant women are most affected with Abnormal spontaneous bleeding
severe anemia and cerebral malaria being prominent Pulmonary edema
manifestations. In areas of lower endemicity including Laboratory findings
most areas of India, all ages including children and young Hypoglycemia (blood glucose <40 mg/dl)
adults are affected. Metabolic acidosis (plasma bicarbonate <15 mEq/L)
The incubation period of malaria varies between 9 and Severe normocytic anemia (Hb <5 g/dl, packed cell volume
30 days, being the least for P. falciparum and longest for P. <15%)
malariae infections. The onset of the disease is sudden with Hemog/obinuria
fever, headache, loss of appetite, lassitude and pain in the Hyperparasitemia (>2% or 100 000/µL in low intensity
limbs. The fever may be continuous or remittent for several transmission areas; >5% or 250 000/µL with high stable malaria
days before it becomes classically intermittent. The illness, transmission intensity)
then, is characterized by a cold stage (chills and rigors with Hyperlactatemia (lactate >5 mmol/L)
headache, nausea, malaise and anorexia); hot stage (dry Renal impairment (serum creatinine >3 mg/dl)
flushed skin, rapid respiration and marked thirst); and
sweating stage (temperature falls by crisis). In most recommended, if the clinical suspicion for malaria is high
children, the classic intermittent fever is not seen. and the initial smear is negative.
On basis of severity, malaria is classified as Rapid diagnostic tests (RDTs) have revolutionalized the
"complicated or severe" and uncomplicated malaria. diagnosis of malaria and obviated other methods such as
Severe malaria can affect virtually every organ system and quantitative buffy coat (QBC) and acridine orange stains.
has a mortality rate of approximately 20%. The criteria These tests detect malaria antigens (PfHRP2/PMA/
for severe malaria are listed in Table 11.10. Presence of pLDH/aldolase) from asexual and/or sexual forms of the
any of the criteria with asexual parasitemia with P. parasite as color changes on antibody coated lines on the
falciparum or P. vivax classifies malaria as severe and strips (Fig. 11.24) In general, these are quick and simple
should be treated as such. Presence of thrombocytopenia to use, distinguish between the major forms of human
alone is not a criteria for defining severe malaria. malaria, and are useful when reliable microscopy is not
available. Disadvantages include cost, lower sensitivity
Diagnosis than microscopy (detect 100-200 parasites/µL), variation
Specific diagnosis: The gold standard for diagnosis of in quality from batch-to-batch and need for rigorous
malaria is careful examination of a properly prepared thick storage conditions. In addition, they do not give informa
film. Thick smears have sensitivity of detecting tion on the parasite load and cannot be used to monitor
5-10 parasites/µL. Thin smears have a lower sensitivity response. The OptiMAL test based on detection of parasite
of 200 parasites/µL but enable species identification. LDH and tests based on plasmodium aldolase are superior
I
Microscopy also provides information about the parasite
load (number of infected red cells/total red cells), Negative
prognosis (mature schizonts and pigmented neutrophils
indicating a poor prognosis) and tracks response to
therapy. Additionally peripheral smears are cheap and I I P vivax
I I I
readily available. The main drawback is need for expertise
and that they are time consuming (careful examination of P falciparum
100 fields needs 20 minutes). Sometimes peripheral smears
may be negative due to partial antimalarial treatment or Fig. 11.24: OptiMAL test for ra pid diagn osis of malaria.
sequestration of parasitized cells in deep vascular beds. Expected reaction patterns on the OptiMAL test strip for a
Repeating smears every 6-8 hourly at least three times is negative patient, and patients with vivax and falciparum malaria
Infections and Infestations 1257-
to the Parasight F test, which is based on detection of HRP2 brought down before giving chloroquine to reduce the
antigen of P. falciparum as the latter is positive even in past risk of vomiting. Radical therapy with primaquine is
infection and cannot be used to diagnose P. vivax malaria. indicated for vivax malaria to eliminate the exoerythro
cytic stages in liver and reduce risk of relapses. Prirnaquine
Polymerase chain reaction (PCR) has been found to be
(0.25--0.3 mg/kg/day for 14 days) also has schizonticidal
highly sensitive and specific for detecting all species of
effect and is given as combination therapy for vivax
malaria, particularly in cases of low level parasiternia but
malaria with chloroquine. G6PD level should be checked
is not available commercially and hence of limited
prior to administering primaquine. For patients who
practical utility.
relapse despite standard primaquine, higher doses (0.5-
Test usefulfor disease management and assessing severity: 0.75 mg/kg) can be used. Primaquine is contraindicated
These include complete blood counts, prothrombin time; in those with severe G6PD deficiency, infants, pregnant
blood levels of glucose, electrolytes, pH, bicarbonate, and breastfeeding women. In patients with mild G6PD
anion gap, lactate, bilirubin transaminases and creatinine. deficiency, 0.75 mg/kg can be given weekly for 8 weeks.
A chest X-ray is done in patients with respiratory distress; For patients who cannot be given primaquine, relapses
urinalysis is also required. Blood cultures should be sent may be prevented by administering chloroquine as
in patients presenting with shock. Repeated assessments suppressive therapy at a dose of 10 mg/kg weekly for 3-6
of blood glucose are important. months.
Quinine and pyrimetharnine sulfadoxine do not have
Differential Diagnosis adequate activity against vivax malaria and should not
Common differentials include other tropical and monsoon be used for treatment. The combination of artemether with
infections like typhoid fever, leptospirosis, dengue, viral lumefantrine is associated with higher risk of relapse in
hepatitis, influenza, chikungunya and rickettsial vivax malaria as compared to chloroquine; new combina
infections. Cerebral malaria should be differentiated from tions of dihydroartemisinin piperaquine or arterolane
other causes of acute febrile encephalopathy such as piperaquine are better.
meningitis and encephalitis. Patients with algid malaria
(those in shock) mimic meningococcemia and gram Uncomplicated falciparum malaria: Falciparum malaria
negative shock. should always be treated with combination therapy, in
view of its efficacy and lower risk of emergence of
Treatment of Uncomplicated Malaria resistance. Both agents should have an independent mode
of action and should be effective in the area where they
In a setting of suspected uncomplicated malaria,
are used. Pyrimethamine sulfadoxine is not combination
establishing a lab diagnosis is a must before giving
therapy as both partner drugs have similar mechanism
empirical therapy. This is to prevent irrational therapy
of action. Similarly, if an area has resistance to
and consequent drug resistance and also to avoid missing
pyrimethamine sulfadoxine and mefloquine, then these
other causes of febrile illness.
should not be used as part of combination therapy.
Vivax malaria: The drug of choice for managing vivax Artemisinin-based combination therapy (ACT) is the
malaria is chloroquine. Resistance to chloroquine has been treatment of choice for falciparum malaria (Table 11.9).
rarely reported in India. The total dose is 25 mg/kg; first Artemisinin (qinghaosu) is the antimalarial extract isolated
dose is 10 mg/kg, followed by 10 mg/kg after 24 hours from Artemisia annua. Artemisinin and its derivatives
and 5 mg/kg at 48 hours (Table 11.11). Fever should be (artemether, artesunate, arteether) are the most rapidly
acting of all antimalarials; they also have wide spectrum is administered (see above). A single dose of primaquine
antimalarial effect from ring forms to mature trophozoites 0.75 mg/kg should be used to reduce risk of transmission.
(like chloroquine and unlike quinine that acts only on Artemisinin derivatives have a good safety profile. Local
mature forms). Artemether lumefantrine is the most reactions after intramuscular administration are rare and
commonly used oral ACT. Other drugs such as meflo much less frequent as compared to IM quinine.
quine, amodiaquine and pyrimethamine-sulfadoxine may Cardiotoxic effects in the form of prolongation of the QT
be used in combination with artesunate in areas where interval in patients receiving high dose artemether have
resistance to these drugs is uncommon. Arterolane maleate been reported. Artemisinins should not be combined with
plus piperaquine phosphate is also an affective ACT. Oral other cardiotoxic drugs such as quinine and halofantrine.
quinine with clindamycin or doxycycline (in children >8- Physicians should be aware about reports of neurotoxicity,
year-old) for 7 days is an alternate treatment, but is especially with repeated use, and unregulated therapy.
associated with poor tolerability of oral quinine and need
for prolonged therapy. Quinine-based therapy: Quinine acts principally on the
Chloroquine should not be used for treatment for mature trophozoite stage of parasite development; it does
falciparum malaria unless there is demonstrable not prevent sequestration or further development of
sensitivity to the medication; similarly mefloquine and formed meronts and does not kill the pre-erythrocytic or
pyrimethamine sulfadoxine monotherapy is not sexual stage of Plasmodium falciparum. Parenteral quinine
recommended. At the end of antimalarial therapy, a is available as dihydrochloride salt in concentrations of
single gametocidal dose of primaquine (0.75 mg/kg) is 300 mg/mL. Quinine must always be given by rate
recommended to reduce community transmission of controlled intravenous infusion and never by bolus or
malaria. push injection. It is recommended to administer a loading
dose of quinine, i.e. 20 mg salt/kg diluted in 10 mL/kg of
Uncomplicated mixed malaria: Uncomplicated mixed normal saline/ dextrose over a period of 4 hours. The
malaria should be treated as P. falciparum malaria with objective of loading dose is to provide therapeutic levels
ACT. The preferred ACT, if available, for mixed malaria as early as possible in the course of treatment, without
is either dihydroartemisinin with piperaquine or overshoot to toxic levels. The loading dose should be
arterolane with piperaquine. Primaquine should be used avoided if there is reliable evidence that the patient has
as mentioned above. received quinine/halofantrine/mefloquine in the past
24 hours (halofantrine and mefloqune produce additive
Treatment of Complicated Malaria
cardiac toxicity). After the loading dose, quinine is
The treatment of severe malaria is an emergency as it is continued at a dose of 10 mg salt/kg as infusion over
associated with high mortality approaching 20%. If the 2 hours every 8 hours. Intramuscular quinine is another
suspicion of malaria is strong then treatment should be alternative for initial therapy if facilities for controlled IV
initiated without waiting for confirmation of diagnosis. quinine administration are not available; subcutaneous
Severe malaria whether due to falciparum or vivax should adminstration may cause skin necrosis.
be treated similarly. Supportive care and treatment of The parasite counts start declining only after 24 hours,
complications are as important as antimalarial therapy. slower than artemisinin derivatives. The patient is
Broad spectrum antibiotics are administered if patient is switched to therapy with oral quinine as soon as possible.
in shock or secondary infection is suspected. If parenteral quinine is continued beyond 48 hours or if
Treatment should be parenteral as most patients are renal failure supervenes, the maintenance dose should be
not able to take orally and the bioavailability of oral drugs reduced to 5-7 mg/kg to avoid quinine toxicity. Total
is unpredictable. Artemisinin-based therapy is considered duration of therapy is 7 days. A second drug such as
superior to quinine in reducing mortality. pyrimethamine sulphadoxine, doxycycline or clindamycin
Artemisinin-based therapy: Parenteral formulations of should be added. A single dose of primaquine 0.75 mg/kg
artesunate, artemether and arteether are commercially is given on completion of quinine therapy to eradicate
available; artesunate is preferred. Artesunate is available gametocytes and prevent transmission.
as a dry powder which is reconstituted with sodium The only contraindication to use of quinine is evidence
bicarbonate and given as a bolus injection. Artemether of severe quinine allergy and G6PD deficiency. Thrombo
and arteether are given by the intramuscular route. The cytopenia, jaundice, renal failure, hypotension are not
dose of artesunate is 3 mg/kg in children with weight less contraindications for quinine administration. Minor side
than 20 kg, and 2.4 mg/kg in patients weighing >20 kg. effects including tinnitus, deafness, headache, nausea and
For artemether the dose is 3.2 mg/kg stat and then visual disturbances (cinchonism) are common in conscious
repeated after 12 and 24 hours and then daily. Parasite patients but do not warrant dose reduction. Serious side
counts start declining 5-6 hours after institution of effects with parenteral quinine are rare, if it is administered
therapy; asexual parasitemia disappears after mean of 72 properly. Quinine produces prolongation of the QTc
hours. Once the patient is better, a full course of oral ACT interval on the ECG but significant conduction or
Infections and Infestations 259-
repolarization abnormalities are rare. Routine ECG National Vector Borne Disease Control Prcgramme (NVBDCP)
monitoring during quinine infusion is not required, if there The NVBDCP strategies are two folds: Early case detection
is no evidence of preexisting heart disease. Frequent blood and prompt treatment and vector control. It has laid out
glucose monitoring is necessary during therapy. Quinine guidelines for detection and management of malaria.
can cause marked intravascular hemolysis (blackwater NVBDCP recommends treatment of uncomplicated vivax
fever); change of therapy to artemisinin derivatives may malaria with chloroquine and falciparum malaria with
be required. Quinine can cause immune-mediated ACT. Artemisinin monotherapy is banned in India and is
thrombocytopenia, which is suspected, if platelet counts marketed only as combinations. Strategies for vector
fail to recover despite clinical improvement. control include source control, elimination of breeding
places, biologic control with use of larvivorous fish in
Treatment Failures, Recrudescence and Relapse
water bodies, and finally chemical vector control by indoor
An optimal response to therapy is defined as counts which residual spray, space fogging and use of chemical
on day 1 are less than day 0, counts on day 3 are <25% of larvicides like abate in water bodies.
count on day 0, no parasites are seen in peripheral blood
72 hours after starting therapy and up to 28 days and there Suggested Reading
is no fever after 72 hours. • National Vector Borne Disease Control Program, Ministry of Health
Patients with parasitologically confirmed malaria who and Family Welfare, Government of India. Malaria. http://
continue to have fever 72 hours after starting therapy are www.nvbdcp.gov.in/iec.htrnl
occasionally seen in clinical practice. If peripheral smear • WHO. Guidelines for the treatment of malaria. 3rd edn, 2015;
for malaria is negative, the causes include IV thrombo 1-317. www.who.int/malaria/docs/TreatrnentGuidelines2015.pdf
phlebitis, secondary bacterial infections, coinfections such • WHO. Malaria. http://www.who.int/malaria/areas/treatrnent/
overview/en/
as typhoid or rarely immune phenomena. If drug
resistance is suspected than treatment should be changed Leishmaniasis
to either ACT combination or quinine.
Reappearance of asexual parasites within 28 days of Leishmaniasis is a disease caused by parasites of the genus
treatment is defined as recrudescence or late treatment Leishmania, which are transmitted by bites of female
failure. Causes for recrudescence include choice of wrong sandflies. There are three major clinical forms: Visceral
drug, wrong dose, poor compliance or drug resistance. leishmaniasis (VL), cutaneous leishmaniasis, and muco
Recrudescence is fairly common in falciparum malaria, if cutaneous leishmaniasis (espundia). VL and cutaneous
artemisinin monotherapy is used; and in vivax malaria, if forms of the disease seen in India are caused by Leishmania
ACT is used. Treatment of recrudescence includes donovani. Kala azar, the Indian term for VL, denotes
optimizing drug therapy or change to an alternative regime. hyperpigmentation seen in these patients; -200000 cases
are reported annually, most often from Bihar and eastern
Control and Prevention of Malaria UP.
Control and prevention of malaria is based on elimination
of the vector by strategies like insecticide spraying, use of Transmission and Etiopathogenesis
insecticide treated bed nets and elimination of breeding The parasite exists in the human or animal reservoir as
places. The latest malaria vaccine RTS, S/ASOl acts against amastigotes (non-flagellated, oval Leishman-Donovan
P. falciparum. Phase 3 trials on African children, aged bodies) and in the sandfly and culture medium as
6 weeks to 17 months, show efficacy ranging from 18- flagellated promastigotes. In India and Sudan, humans
39%. In holoendemic areas like Africa, chemoprophylaxis are the chief reservoir (anthroponotic cycle). The female
with pyrimethamine sulfadoxine administered twice sandfly (genus Phlebotomus) ingests the amastigotes, which
during pregnancy to reduce prevalence of maternal develop into promastigotes in its digestive tract, migrates
anemia and low birth weight is practised. to the proboscis (salivary glands) and is injected into the
Chemoprophylaxis against malaria is recommended for susceptible host when the sandfly takes its next feed.
travelers from non-endemic areas to endemic areas. Drugs Within the host, promastigotes infect macrophages and
used include weekly chloroquine (for areas that are develop into amastigotes. Amastigotes multiply in cells
chloroquine sensitive), weekly mefloquine, weekly of the mononuclear phagocyte system (monocytes, macro
chloroquine and daily proguanil, daily doxycycline and phages, histiocytes, Kupffer cells and reticuloendothelial
daily atovaquone-proguanil (expensive but safest). cells in spleen and lymphoid tissue).
Prophylaxis should be started at least 1-2 weeks before Children aged 1-4 years are considered more
departure and continued for 4 weeks after return (except susceptible to the disease. The protective response is
atovaquone-proguanil where it can be started on the day primarily cell mediated immunity that results in
of departure). For travelers to India, prophylaxis with subclinical infection and spontaneous cure in most cases.
either weekly mefloquine 5 mg/kg or daily atovaquone Failure of immunity results in illness, such that for every
proguanil is advised. case of VL, there are about 30 subclinical infections.
260 Essential Pediatrics
Malnutrition and HIV infection also predispose to clinical Immunochromatographic strip and ELISA for
disease. leishmanial anti-K39 antibody has been used successfully
for serodiagnosis with high sensitivity (>90%) and
Clinical Features specificity (-90%). Antibody titers to K39 decrease
Visceral leishmaniasis: The incubation period is generally following successful therapy, and increase during relapse
3 to 8 months. Features include high grade fever, weight making it a useful test to recognize treatment failure.
loss, hepatosplenomegaly and abdominal discomfort. Newer methods with high sensitivity and specificity
There are no rigors and the patient does not appear toxic. include the detection of Leishmania antigen and antibody
Splenohepatomegaly, with spleen larger than the liver, is in the urine.
usual. Spleen is huge, firm, smooth and nontender and
palpable by end of first month of illness; moderate Treatment
hepatomegaly is seen in -80%. Unlike African VL, Drugs available for treatment of VL in India include
lymphadenopathy is infrequent in Indian VL ( <5%). sodium stibogluconate, amphotericin B, lipid formulation
Hyperpigmentation of skin is a feature of Indian VL, seen amphotericin B and miltefosine. Sodium stibogluconate
in about two-thirds of patients and affecting the face, was considered first line therapy for VL in India. However,
hands and upper trunk. Progressive emaciation occurs in need for prolonged therapy, adverse effects and increasing
all cases, though appetite is preserved. Cough and resistance are its major limitations. In certain areas of
diarrhea are common. Bleeding manifestations in the form Bihar, the resistance rates exceed 50%.
of petechial hemorrhages, epistaxis and gum bleeding may The National Vector Borne Disease Control Programme
be seen. Pedal edema may occur due to hypoalbuminemia, recommends that in areas where stibogluconate resistance
however, jaundice is uncommon. Diminished cell rates are more than 10%, amphotericin B deoxycholate be
mediated immunity may account for a high incidence of used. Side effects of amphotericin include fever, chills,
secondary infections. Pancytopenia and hypergamma hypokalemia and nephrotoxicity. Liposomal amphotericin
globulinemia are characteristic. B dosed as 1 mg/kg/day over 3-5 days or a single dose of
The disease may begin insidiously and be asympto 5 mg/kg is highly efficacious with fewer adverse effects.
matic initially, but usually runs a chronic course that may Indigenous lipid formulations of amphotericin B (2 mg/
be fatal without or despite treatment. Death usually occurs kg) mixed with 100 mL of 20% fat emulsion and dosed for
within 2 years in 75-95% cases, because of severe 5 doses approaches success rates more than 90% and at
secondary bacterial infections or gastrointestinal bleeding considerably lower cost, compared to liposomal
in advanced disease. amphotericin B and even stibogluconate.
Post-kala-azar dermal leishmaniasis (PKDL): A small Miltefosine is an orally active agent. Treatment with
proportion of patients in Africa and India may show PKDL this drug for 3-4 weeks results in cure rates of 95-100%,
that develops 1-10 years after resolution of VL. Hypo comparable to that with amphotericin. Mild gastro
pigmented macular, maculopapular or nodular skin intestinal side effects may be seen. Other effective drugs
lesions are seen first in the perioral area, chin and lips, used for treating leishmaniasis include pentamidine and
and later appear over the neck, extensor surfaces of the paromomycin. Recommended treatment regimens are
arms, trunk, and legs. Lesions spare the scalp, palms, soles, summarized in Table 11.12.
axillae and perineum. Lepromatous leprosy is a close Severe anemia and thrombocytopenia may necessitate
differential, but peripheral nerves are spared. Skin lesions packed cell and platelet transfusions. The child should
may persist for up to 20 years. These patients may act as receive a nutritious diet, and coexisting nutritional
chronic reservoir of infection. deficiencies should be corrected. Concurrent infections
should be treated using appropriate antimicrobial agents.
Diagnosis
There is pancytopenia, mild elevation of liver enzymes Response to treatment: Fever, spleen size, hemoglobin,
and hypergammaglobulinemia with reversal of albumin blood cell counts, serum albumin, and body weight are
globulin ratio. The aldehyde test has poor sensitivity and monitored for response to therapy. In most patients, the
specificity and is no longer used. fever subsides within 7 days, blood counts and hemoglobin
Definitive diagnosis of VL is usually based on micro levels rise, the patient feels better, and spleen becomes
scopic detection of amastigotes in smears of tissue smaller within 2 weeks. Parasitological cure should be
aspirates or biopsy samples. Bone marrow aspirate or documented at the end of therapy by splenic or bone
biopsy is frequently the tissue of choice with sensitivity marrow aspiration. As relapses are common in this disease,
between 55 and 97%. Lymph node aspirate or biopsy patient should be followed for at least 6 months before
(sensitivity 60%), liver biopsy (sensitivity 85%) and splenic considering a definite cure. The spleen may take
aspirates (sensitivity 97%) may also be used. PCR methods 6-12 months to regress completely. Relapse is suggested
on tissue samples and peripheral blood with very high by an increase of spleen size, a fall in hemoglobin levels
sensitivities have been developed. and should be confirmed by the demonstration of parasites.
Infections and Infestations 261-
Table 11.12: Treatment of visceral leishmaniasis Amebic dysentery and extraintestinal amebiasis is
Drug Dose Duration associated with high morbidity and mortality and is a
major public health problem globally, especially in adults
Sodium stibogluconate 20 mg/kg/day IM or IV 28 days
in developing countries. It is less common in children and
Amphotericin B 1 mg/kg alternate day 28 days some estimates suggest that it is responsible for less than
Liposomal amphotericin B 1 mg/kg/day IV 5 days 3% diarrhea in children <5 years.
Miltefosine 2.5 mg/kg/day oral 28 days
Pentamidine 4 mg/kg IV/IM thrice 8 weeks Etiopathogenesis
weekly The organism exists in nature as a cyst or trophozoite. Each
Paramomycin (aminosidine) 16-20 mg/kg/day IV/IM 21 days ingested cyst excysts in the small intestine to produce eight
trophozoites that colonize the mucosa of the large
PKDL: Treatment is indicated only for those who have intestine. Trophozoites may cause tissue invasion and
severe and prolonged disease. Pentavalent antimonials destruction through several virulence factors, with little
(2-month course) and liposomal amphotericin Bare both or no local inflammation, resulting in characteristic flask
effective. shaped ulcers, seen commonly in cecum, transverse colon
and sigmoid colon. Extraintestinal complications occur
Prevention and Control when trophozoites invade the bloodstream and migrate
Control of leishmaniasis involves controlling the source through the portal circulation, to lodge, usually in the liver.
of infection and eradicating the vector. Where sand flies
are mostly endophilic (rest mostly indoors after feeding), Clinical Features
spraying houses with insecticide is effective; use of treated Asymptomatic cyst passage is the most common
and untreated bed nets is effective where sand flies are manifestation of E. histolytica, in most cases, the infection
endophagic (feed mainly indoors). Insecticide treatment resolves spontaneously, but uncommonly, these
of dogs and dog collars is useful where canines are individuals may later present with amebic dysentery and
important reservoirs. In India, where anthroponotic other invasive manifestations.
transmission is important, effective treatment of patients,
especially those with PKDL (who act as long-term After a variable incubaton period of weeks to months,
about 10% individuals colonized with E. histolytica develop
reservoirs), has been found to be effective in controlling
symptomatic disease, in form of colitis or extraintestinal
transmission when combined with vector control. There
is no effective vaccine for prevention of leishmaniasis. disease. Amebic colitis presents as abdominal pain or
tenderness (-80%), with watery, bloody or mucous
Suggested Reading diarrhea. Some may have only intermittent diarrhea
alternating with constipation. Fever is unusual.
• WHO. Leishmaniasis. http://www.who.int/leishmaniasis/en/
Occasionally fulminant amebic colitis may occur, with
• National Vector Borne Disease Control Program, Ministry of Health
and Family Welfare, Government of India. Operational guidelines profuse bloody diarrhea, fever, widespread abdominal
on kala-azar (visceral leishmaniasis) elimination In India-2015. pain, diffuse tenderness and pronounced leukocytosis.
http:/ /www.nvbdcp.gov.in/Doc/opertional-guideline-KA- Toxic megacolon, ameboma, cutaneous amebiasis and
2015.pdf rectovaginal fistulae can occur as complications of
• Aronson N, Herwaldt BL, Libman M, et al. Diagnosis and treatment intestinal amebiasis.
of leishmaniasis: Clinical Practice Guidelines by the Infectious
Diseases Society of America (IDSA) and the American Society of Amebic liver abscess is seen in about 1 % of infected
Tropical Medicine and Hygiene. Am. J. Trop. Med. Hyg 2017; 96(1): individuals and may occur months to years after infection.
24-45. While some individuals may have concurrent amebic colitis,
more commonly there are no bowel symptoms. The child
Amebiasis usually presents with fever with chills and rigors and right
Amebiasis is defined as infection with Entamoeba upper quadrant pain of acute onset (<10 days). Examination
histolytica. Clinical features of amebiasis due to E. reveals toxic appearance, right upper quadrant tenderness
histolytica range from asymptomatic colonization to and hepatomegaly; jaundice is unusual (10-15%). Cough,
amebic dysentery and invasive extraintestinal amebiasis. along with dullness or crepitations in the right lung base
may be present. Complications include rupture into the
Epidemiology pleura, which has a relatively good prognosis, and rupture
E. histolytica is thought to infect 10% of the world into the pericardium and superinfection with bacteria,
population, and 2-55% Indians. However, these are which are more serious.
overestimates, because two morphologically identical,
genetically distinct but apparently nonpathogenic species, Diagnosis
namely E. dispar and E. moshkovskii, are now recognized Diagnosis of amoebic colitis is established by demonstra
as causing most asymptomatic cases. tion of motile trophozoites by direct microscopic examina-
262 Essential Pediatrics
tion of fresh fecal sample. At least 3 stool specimens taken abdominal pain after 4 days of treatment), individuals
on consecutive days should be examined because the test with large left lobe abscesses (risk of rupture into the
has poor sensitivity (<60%; -90% with 3 fresh samples). pericardium), size more than 8-10 cm (suggesting
Stool contains plenty of erythrocytes but few leukocytes impending rupture) and severely ill patients with
unlike bacillary dysentery where leukocytes are plentiful. accelerated clinical course and large abscesses (suggesting
Presence of ingested erythrocytes within trophozoites is imminent rupture). Aspiration, percutaneous catheter
pathognomonic for E. histolytica. Presence of cysts of E. drainage, or both, improve outcomes in the treatment of
histolytica in stool samples is of no clinical significance and amebic empyema after liver abscess rupture, and
should not be treated. percutaneous catheter (or, if necessary, surgical) drainage
Serological tests are routinely employed for diagnosis could be lifesaving in the treatment of amebic pericarditis.
of extra intestinal disease with E. histolytica especially for
differentiating amebic from pyogenic liver abscess. Suggested Reading
Commonly used serologic tests in clinical practice are • Cope JR. Amebiasis. Center for Disease Control and Prevention.
ELISA, IHA and IFA. They are positive in 70-80% patients Yellow Book 2018. https:/ /wwwnc.cdc.gov /travel/yellowbook/
with invasive disease at presentation, and in >90% cases 2018/infectious-diseases-related-to-travel/amebiasis
beyond first week of symptoms. However, they can persist • Fotedar R, Stark D, Beebe N, Marriott D, Ellis J, Harkness J.
for years and thus are of limited utility in endemic areas. Laboratory diagnostic techniques for Entamoeba species. Clin
Microbiol Rev. 2007; 20:511-32.
Thus a negative test is more useful than a positive test in • Stanley SL. Amoebiasis. The Lancet 2003; 361:1025-1034.
ruling out infection.
In case of liver abscess, chest radiograph shows elevated Giardiasis
diaphragm and pleural reaction on the right side.
Ultrasound, CT, MRI, or isotope scan can localize the Giardiasis, caused by Giardia lamblia (also known as G.
abscess in most cases. Leukocytosis without eosinophilia, intestinalis or G. duodenalis), is a prominent cause of
mild anemia, raised alkaline phosphatase and high diarrhea in children and in travelers.
erythrocyte sedimentation rate are common findings in
these patients. Epidemiology
The infection is endemic in developing countries with poor
Treatment sanitation. Breast milk protects against giardiasis by virtue
The practice of giving antiamebic drugs for all children of the glycoconjugates and secretory IgA. Individuals with
presenting with diarrhea should be strongly discouraged malnutrition, humoral immunodeficiencies and cystic
since amebiasis is relatively uncommon in young children. fibrosis are particularly susceptible. Children appear to
Metronidazole is the drug of choice for treating amebic be more severely affected than adults.
colitis (dosed at 30 mg/kg/day in 3 divided doses for
7-10 days). Alternatives include tinidazole (50 mg/kg/ Etiopathogenesis
day for 3 days), ornidazole and secnidazole. Since Giardia exists in two stages, cysts and trophozoites.
metronidazole does not destroy the cysts, a luminal agent Outside human body it exists as cysts, which are hardy,
such as diloxanide furoate (20 mg/kg/day in 3 divided capable of surviving in cool moist environments for up to
doses for 10 days) should be used to eradicate colonization. 2 months and in chlorinated water, but are destroyed by
When possible, fulminant amebic colitis, even with boiling for 10 minutes. Transmission of infection is
perforation, is managed conservatively, with the addition through cysts, which may be ingested in contaminated
of antibiotics to deal with bowel flora. Radiographic water or food or spread by person to person contact.
monitoring of the abdomen by CT scan, coupled with the Ingestion of 10-100 cysts is sufficient for causing infection.
judicious use of percutaneous catheter drainage to obtain Low pH of the duodenum facilitates excystation and
suspect fluid, might aid in management. release of trophozoites. Trophozoites colonize the
Most amebic liver-abscesses, even large ones, can be duodenum and proximal jejunum of the host, where they
cured without drainage with IV metronidazole (50 mg/ attach to the intestinal brush border. Unlike amebiasis,
kg/day in three divided doses for 7-10 days). Most there are no invasive or locally destructive lesions. It is
patients show response to treatment (reduced fever and believed that the infection causes diarrhea, via a combina
abdominal pain) within 72-96 hours. Individuals with tion of intestinal malabsorption and hypersecretion. These
amebic liver abscess should also receive a luminal agent effects cause malabsorption and maldigestion and, in
to eliminate intestinal colonization. Abscess cavity addition, facilitate the development of chronic enteric
resolves slowly over a period of several months. disorders, including inflammatory bowel disease, irritable
Aspiration is reserved for individuals in whom bowel syndrome and allergies. Steatorrhea is attributed
diagnosis is uncertain (where pyogenic abscess or bacterial to pancreatic involvement, or bacterial overgrowth in the
superinfection is a concern), those who have not duodenum and upper jejunum, and deconjugation of bile
responded to metronidazole therapy (persistent fever or salts with release of free bile acids.
Infections and Infestations 263-
Suggested Reading
• Shet A. Congenital and perinatal infections: throwing new light
with an old TORCH. Indian J Pediatr. 2011; 78:88-95.
• Adachi K, Nielsen-Saines K. Zika clinical updates. Curr Opin
Pediatr 2018; 30:105-116.
Fig. 11.25: Classical periventricular calcification of CMV
HELMINTHIC INFESTATIONS
The diagnosis of congenital CMV is confirmed by a
positive IgM in the first two weeks of life. The sensitivity Helminthic infestations contribute to significant disease
is low and a negative IgM does not rule out CMV. The burden in children in developing countries. Helminthiasis
detection of CMV by PCR on urine or blood is more sensi is caused by three groups of worms, nematodes
tive. A positive CMV IgM or PCR after the first 2 weeks of (roundworms), cestodes (tapeworms) and trematodes
life can also occur due to postnatal transmission and is (flukes). Nematodes may be further classified as intestinal
not specific for diagnosis of congenital CMV. Antiviral treat nematodes and tissue nematodes. All these groups differ
ment with ganciclovir is available, but indicated only in significantly in life cycle, mode of infection, pathogenesis
patients with progressive neurologic disease and deafness. and clinical manifestations.
heart, then the lungs, trachea, pharynx and finally mature enterobiasis, the eggs are present on the perianal skin from
into adult worms in the intestines. Strongyloides is unique which they can be lifted using the scotch tape method. In
among the intestinal nematodes in several respects: Larvae strongyloidiasis, fresh stool should be examined for larvae
divide parthenogenetically in the small intestine, as eggs are rarely present; wet mount examination of
development of the eggs into infective larvae occurs within centrifuged CSF and bronchoalveolar lavage may also
the intestine leading to autoinfections and retroinfections. help. Peripheral blood examination may reveal eosino
philia (striking in Strongyloides, visceral larva migrans).
Clinical Features In ascariasis, the worms may be incidentally observed in
Clinical features depend on the worm burden and vary the biliary or pancreatic ducts by ultrasound or in the
from asymptomatic infection to severe morbidity. intestines during contrast studies of the gastrointestinal
Penetration of the skin by the larvae of Ancylostoma, tract. Serology may also be used to diagnose Strongyloides.
Necator and Strongyloides may cause a maculopapular itchy
rash. Migration of the larvae through the lungs in case of Treatment
ascaris and hookworm may cause Loeffler syndrome All family members should be treated. Antiparasitic drugs
characterized by fever, cough, dyspnea, wheeze, urticaria, available for nematode infections including albendazole
eosinophilia and lung infiltrates. Other causes of Loeffler (200 mg for children aged 1-2 years and 400 mg for those
syndrome include filarial infection, visceral larva migrans, aged 2 years and above, taken with a fatty meal),
schistosomiasis and allergic bronchopulmonary mebendazole (100 mg twice daily for 3 days or 500 mg
aspergillosis. Visceral larva migrans refers to infection by single dose), pyrantel pamoate (11 mg/kg, max dose
dog/ cat ascaris where the larva have an aberrant life cycle 1 gm), ivermectin in a daily dose of 150-200 µg/kg.
and cause prominent visceral manifestations such as fever, Nitazoxanide is a new drug (100 mg for children aged 1-
eosinophilia, bronchospasm and hepatosplenomegaly. 3 years, 200 µg for children aged 4-11 years and 500 mg
Cutaneous larva migrans characterized by an erythe for older children adolescents) dosed twice daily for 3 days
matous, serpiginous, pruritic eruption refers to infection (Table 11.13). For pinworm, it is essential to stress on
by non-human hookworms where the larva migrate personal hygiene, keep nails clipped short, clean bed linen
through the epidermis and are unable to mature. thoroughly and ensure hand washing before meals.
Ascaris being the largest worm has the most prominent
intestinal manifestations. Heavy infestation can lead to Prevention
vague abdominal discomfort, abdominal distension, Eradication of nematodes is possible only with improved
vomiting, irritability, poor growth and nutritional defi hygiene and sanitation and appropriate sewage disposal.
ciencies. A large mass of worms may cause bowel There is limited rationale for periodic deworming in
obstruction and migration of the worms can result in healthy children.
cholecystitis, cholangitis, pancreatitis and rarely
intrahepatic abscess. Tissue Nematodes
Hookworms (Ankylostoma, Necator) suck blood from the
intestine and lead to iron deficiency anemia, hypo Tissue nematodes of significance in India include
albuminemia and edema. The severity of anemia varies Wuchereria bancrofti, Brugia malayi (causes of lymphatic
and with heavy infestations, transfusion may be needed. filariasis) and Dracunculus medinensis (guinea worm).
Heavy infestation with Trichuris may cause dysentery, Lymphatic filariasis is endemic in several Indian states,
anemia, rectal prolapse, abdominal pain, distension, chiefly Bihar and Kerala.
hypoproteinemia and growth retardation. Manifestations
of enterobiasis include perianal or vulval itching caused
Life Cycle
by migration of the gravid females to the perianal skin to Humans are infected by bite of the vector which in most
lay eggs. Strongyloides is associated with abdominal pain, instances in India is the Culex mosquito. The bite releases
vomiting, diarrhea, bleeding, steatorrhea and weight loss. the infective larvae which migrate to the lymphatics and
Ulceration and strictures of the duodenum may occur. grow into adult males and females in about one year. They
Hyperinfection syndrome due to Strongyloides occurs mate and release thousands of larvae termed as micro
in the immunocompromised (high dose steroids, filaria which stay in the lung arterioles during the day
chemotherapy, transplant, HIV) and is characterized by and emerge in the systemic circulation at night. They are
dissemination of massive numbers of larvae into various then taken up the insect vector where they develop further
body organs (pulmonary infiltrates, meningitis) gram and become infective to humans. The life span of the adult
negative sepsis and high mortality. worms is usually 5-10 years but can be up to 40 years.
(Fig. 11.26). In around 0.5% of infected patients a distinct depends on the feeding habits of vector. In case of W.
immunologic reaction to the microfilaria results in an bancrofti, night time collection is preferred. Diethyl
entity called tropical pulmonary eosinophilia. Features of carbamazine (DEC) can be used as a provocative agent
this condition include cough that worsens at night, to facilitate day time collections. The filarial antigen can
wheezing, low grade fever, enlarged neck nodes, also be detected by immunochromatography-based card
interstitial infiltrates on chest X-ray marked peripheral tests.
blood eosinophilia (more than 3000/cu mm) and very high
serum IgE levels. This syndrome can also result from the Treatment
pulmonary phase of ascariasis and hookworms, visceral Most of the symptoms are due to the adult worms but
larvae migrans due to zoonotic ascaris and strongyloides paradoxically treatment suppresses or reduces microfilaria
infections. Chronic manifestations of lymphatic filiariasis but does not affect the adult worms. Treatment is usually
seen usually in adults include hydrocele, lymphedema with a single dose of DEC (6 mg/kg) or ivermectin
and elephantiasis. 200 µg/kg and albendazole 400 mg. Corticosteroids may
need to be used to manage allergic reactions of dying
Diagnosis microfilaria. Treatment may need to be repeated every
This is largely clinical and confirmed by demonstrating 6-12 months for reappearing microfilaria till the adult
the microfilaria in Geimsa stained thin and thick blood worms spontaneously die. For tropical pulmonary
smears obtained from finger pricks. The time of collection eosinophilia, treatment with DEC at a dose of 6 mg/kg/
Fig. 11.26: (a) Filariasis manifestating as an erythematous swelling on the chest of a 2-year-old child; and (b) Ultrasound showing
the convoluted worm in the soft tissue
-268 Essential Pediatrics
day for 12-21 days is recommended. Chronic complica When ingested by pigs or cattle, these eggs develop into
tions need surgical treatment. larvae that invade the intestinal wall, enter the blood
stream and lodge in various tissues to develop into cysts.
Prevention The eggs of beef tapeworm are not infectious to
Since lymphatic filariasis causes considerable morbidity, humans. Humans may ingest T. solium eggs, usually by
the National Vector Borne Disease Control Programme feco-oral transmission (contamination of food by food
(NVBDCP) has envisaged elimination of lymphatic handlers with poor hand hygiene, or ingestion of raw
filariasis by 2015. The strategy employed is mass drug fruits or vegetables fertilized with contaminated human
administration of single dose of DEC with/without waste), or sometimes through autoinfection (reflux of eggs
albendazole annually to all residents of an endemic district from intestine into the stomach by reverse peristalsis).
for 5 years. Vector control is also important. Thus humans become dead-end hosts of the larval stage
of the parasite, and develop cysticercosis in various body
Suggested Reading tissues. Ingestion of encysted pork does not directly cause
• Raju K, Jambulingam P, Sabesan S, Vanamail P. Lymphatic filariasis cysticercosis; rather, it causes an intestinal infection with
in India: epidemiology and control measures. J Postgrad Med. 2010;
56(3):232-8.
the adult tapeworm and a human reservoir for T. solium
• Guideline. Alternative mass drug administration regimens to eggs. Cysticercosis can therefore occur in persons who do
eliminate lymphatic filariasis. Geneva: World Health Organization; not eat pork.
2017. Initially the larvae become encysted, which helps viable
cysts avoid initial host reaction and destruction by the host.
Cestodes
This phase that may last for 5-10 years is often clinically
The cestodes that infect humans include giant tapeworms silent except when cyst location or size causes signs or
like Taenia saginata, T. solium and Diphyllobothriurn latum, symptoms. Degenerating cysts release larval antigens that
dwarf tapeworms like Hymenolepis nana and zoonotic produce a vigorous host response with release of
cestodes like Echinococcus granulosus and E. multilocularis. inflammatory mediators and surrounding edema. After
Infection with T. saginata and T. solium is acquired through this phase, the encysted larvae degenerate entirely, die
ingestion of cysticerca in contaminated food, while and often calcify.
Echinococcus infection is through ingestion of eggs, and
D. latum infection is carried to man by ingestion of cysts Clinical Features
in freshwater fish.
Infection with adult worm is mostly symptomatic, but
Teniasis and Cysticercosis some children may have non-specific symptoms like
nausea, abdominal pain and diarrhea. These patients may
Two species of tapeworms infest humans, Taenia solium
also develop cysticercosis through auto-infection.
or the pork tapeworm and T. saginata or beef tapeworm,
the names reflecting the principal intermediate hosts for The clinical features of cysticercosis depend on the
each of them. Man is the only definitive host for both the location of the cysts and overall cyst burden. In about
parasites. While the pork tapeworm has a scolex with 2 months, the larvae mature into cysticerci of about 2 mm
suckers and hooks that aid its attachment to the intestinal to 2 cm size. Cysts can lodge in the brain, skeletal muscle,
wall, hooks are absent in T. saginata. Taeniasis refers to subcutaneous tissues, spinal column and eyes. The two
intestinal infection by the adult tapeworm, and sites associated with high morbidity are the brain, the most
cysticercosis results from larval lodging in various sites. common (60-90%) location for cysts, and the eye, the least
common site (1-3%). Cysts in the brain parenchyma
Epidemiology (parenchymal neurocysticercosis) cause focal or
Cysticercosis is the most common parasitic disease generalized seizures and, less commonly, headache, focal
worldwide, with an estimated prevalence of more than neurologic deficits, or behavioral abnormality. Heavy cyst
50 million persons. Neurocysticercosis, the neurologic burden can cause encephalopathy with fever, headache,
manifestation of cysticercosis, is the most prevalent nausea, vomiting, altered mental status and seizures. Cysts
infection of the brain worldwide. in the subarachnoid or ventricular spaces may cause
meningeal signs and symptoms, obstructive hydro
Pathogenesis cephalus or cranial nerve palsies (by nerve entrapment);
The life cycle of T. solium and T. saginata begins as a larva those located in the spinal column can cause radicular pain
in pigs/cattle, and human infection is acquired by or paresthesias. Ocular cysts in the subretinal space or
ingestion of these larvae in undercooked pork or beef. The vitreous humor can impair vision by inflammation or
larvae attach to the human gut and grow into adult through retinal detachment, while those in the extraocular
tapeworms. The adult tapeworm sheds proglottids muscles may limit the range of eye movements and
containing hundreds of tapeworm eggs into human feces. those in the subconjunctival tissue present as a nodular
Infections and Infestations 1269-
• Zammarchi L, Bonati M, Strohmeyer M, et al. Screening, diagnosis are multilocular that proliferate exogenously and also
and management of human cysticercosis and taeniasis: Technical metastasize.
recommendations COHEMI project study group. Trop Med Int
Health 2017; 22:881-94.
Clinical Features
Hymenolepiasis Symptoms depend on the target organ involved. Very
Infection with Hymenolepis nana, also known as the dwarf often, liver cysts may regress spontaneously without
tapeworm, is very common in developing countries. Man becoming symptomatic. Otherwise, cysts may become
acts as both definitive and intermediate host because the symptomatic after several years when significant mass
entire life cycle may be completed in human host; effect results in abdominal pain vomiting, increase in
however, rodents, ticks and fleas may serve as the abdominal girth and a palpable mass; jaundice is rare.
intermediate host. The infestation usually results from Alveolar cysts have a more malignant course. Direct
poor hygiene. The adult worm lives in the jejunum. spread of infected tissue may result in cysts in the
Transmission is mainly feco-oral, but autoinfection may peritoneal cavity, kidneys, adrenal gland or bones. Lung
also occur, such that one host may harbor upto thousands cyst may present with chest pain, cough, hemoptysis and
of adult worms. Symptoms are usually non-specific, breathlessness. Involvement of the genitourinary tract may
including mild abdominal discomfort, poor appetite and manifest as passage of cysts in the urine (hydatiduria) and
cosmophilia, some show growth retardation. The infection hematuria. Rupture or leakage from a hydatid cyst may
is a major cause of eosinophilia. The diagnosis is based cause anaphylaxis, manifest as fever, itching and rash, and
on the demonstration of characteristic eggs in stools. results in dissemination of infectious scolices. Rare but
Treatment is with praziquantel (25 mg/kg once) or potentially serious complications include compression of
niclosamide (50 mg/kg once, maximum 2 g). important structures in the central nervous system, bone,
heart, eyes or genitourinary tract.
Echinococcosis (Hydatid Disease)
Diagnosis
Human echinococcosis is an infestation caused by larval
stages of members of the genus Echinococcus, and is Physical examination may reveal a palpable mass, hepato
characterized by production of unilocular or multilocular megaly or subcutaneous nodules. Ultrasonography is the
cysts in the lung and liver. Echinococcosis is endemic in most valuable tool in diagnosing echinococcal cysts. Lung
most continents of the world, with hyperendemic areas hydatids may be visible on plain X ray. MRI and CT may
in Western China, North Africa, West Asia and areas of be used for further delineation (Fig. 11.28). Diagnostic
South America. aspiration is generally contraindicated because of risk of
infection and anaphylaxis. Antibody detection by ELISA
Pathogenesis is more sensitive but less specific. The test uses partially
purified antigens that cross-reacts with other parasites
Hydatidosis is a zoonosis caused by two Echinococcus
such as cysticercosis and schistosomiasis.
species, E. granulosus and E. mulilocularis. The parasite eggs
are transmitted from members of the canine family like
Management
dogs and wolves, to various wild and domestic animals
like sheep, cattle and goats, which act as intermediate Treatment depends on the stage and location of the lesion,
hosts. Humans are accidental hosts. Eggs from the adult and importantly the experience of the treating center and
worm are passed in the stools that may contaminate the includes albendazole, surgical excision or PAIR
water and soil, and also the fur coats of dogs. Ingestion of (percutaneous aspiration, instillation of hypertonic saline
food or water contaminated with eggs or direct contact or another scolicidal agent; and reaspiration after
with infected dogs may result in humans being infected 15 minutes).
accidentally. Eggs hatch in the intestines to release larvae
that penetrate the intestinal mucosa, and traverse the Suggested Reading
venous or lymphatic system to reach the liver, lungs and, • Czemak BV, Akhan 0, Hiemetzberger R, et al. Echinococcosis of
less commonly, other target organs. the liver Abdom Imaging 2008; 33:133-43.
• Nabarro LE, Amin Z, Chiodini PL. Current management of cystic
In the target organs, larvae develop into characteristic
echinococcosis. Clin Infect Dis 2015; 60:721---8.
multiloculated fluid-filled cysts, called hydatid cysts. In
children, lung cysts are common, whereas in adults, cysts
are more commonly seen in the right lobe of the liver. RATIONAL ANTIMICROBIAL THERAPY
Other tissues that may be involved include bone, brain, AND ANTIMICROBIAL RESISTANCE
genitourinary tract, intestines and subcutaneous tissue. Rational antimicrobial therapy refers to using anti
The cyst may keep on expanding over several years. microbials only when indicated; the right drug for the right
Life cycle of E. multilocularis is the same except that duration through the right route and in the right dose.
rodents and mice serve as intermediate hosts, and the cysts Irrational use of antibiotics compromises treatment
Infections and Infestations 271-
Solutions
• Education of medical practitioners about rational
antimicrobial practices from the undergraduate level
through postgraduation and for practicing doctors.
• Development of evidence-based guidelines to treat
common infections and ensuring that they are
implemented.
• Educating the public and parents about the hazards of
overuse of antibiotics
• Legislation to prevent over the counter availability of
antimicrobials and licensing of irrational fixed drug
Fig. 11.28: Large hydatid cyst of the liver
combinations
• Preventing overuse of antimicrobials in the veterinary
outcomes, increases adverse effects and cost of therapy. industry
Irrational use of antimicrobials is the biggest driver for • Establishing antimicrobial stewardship programs in
antimicrobial resistance. Rising antimicrobial resistance hospitals targeting use of antimicrobials in inpatients
is responsible for increasing morbidity, mortality and especially intensive care units.
treatment cost of infections.
The most important antimicrobial resistance challenges Suggested Reading
are: • Marston HD, Dixon DM, Knisely JM. Antimicrobial resistance.
• Resistance in gram-negative bacilli due to production JAMA 2016; 316:1193-1204.
of extended spectrum beta-lactamases and carba
penemases (New Delhi metallo-beta-lactamase) HEALTHCARE-ASSOCIATED INFECTIONS
• Multidrug-resistant tuberculosis AND INFECTION CONTROL
• Chloroquine-resistant falciparum malaria
Healthcare-associated infections (HAis) are termed as
• Resistance in HIV. those infections that occur in hospitalized patients and
Examples of Irrational Therapy were neither present nor incubating at the time of
admission. They include those infections that occur as a
• Prescribing antimicrobials when not indicated, e.g. result of hospital visit (varicella following exposure in the
using antibiotics to treat viral upper respiratory tract emergency room or outpatient visit), or in hospitalized
infections and viral gastroenteritis patients (diarrhea) or health care personnel (see Chapter 28).
• Prescribing multiple antimicrobials at the same time,
irrational combinations and changing them frequently Types of HAis
• Using high end antimicrobials such as carbapenems to These may range from minor infections such as viral upper
treat community acquired infections and using drugs respiratory tract infections, diarrhea to serious infections.
for MRSA such as vancomycin when not indicated. Immunocompromised children, those in the intensive care
• Using fewer drugs than indicated for diseases such as unit and those who undergo surgery are at the greatest
tuberculosis, HIV, malaria. risk for serious infections. These infections include central
line-associated bloodstream infections (CLABSI), health
Causes care-associated pneumonia (HAP), catheter associated
• Practitioner errors due to inadequate knowledge about urinary tract infections (CAUTis), surgical site infections
microbial etiology and resistance patterns. Other (SSis) and C. difficile associated diarrhea.
reasons are fear of missing a diagnosis, in order to
circumvent investigations and sometimes due to Etiology of HAis
pressure from parents. The wrong belief that use of The etiology of health care associated infections in India is
newer and multiple antimicrobials is beneficial also predominantly resistant gram-negative bacilli including
drives practitioners to over use antibiotics. ESBL (extended spectrum beta-lactamase), AmpC beta
• Self medication by parents and as per pharmacist lactamases and now even carbapenamase producing E. coli,
recommendations Klebsiella, Pseudomonas and Acinetobacter spp. Gram- positive
• Aggressive marketing of antimicrobials by pharma pathogens including S. aureus and enterococcus are less
ceutical companies common. Candida is emerging as an important pathogen.
272 Essential Pediatrics
12 Diseases of Gastrointestinal
System and Liver
Anshu Srivastava • Barath Jagadisan • Surender K Yachha
5 episodes in all or 3 episodes during a 6-month period. 24 hours ambulatory esophageal pH monitoring is a
Typically, the attacks begin in early morning with validated method for quantitative measurement of
symptoms of autonomic surge, e.g. lethargy, pallor, mild esophageal acid exposure (Fig. 12.3). It is also used to
fever, headache, tachycardia, hypertension, diarrhea and evaluate the efficacy of anti-secretory therapy and to
abdominal pain. Most subjects have onset in preschool or correlate symptoms (e.g. cough, chest pain) with acid
school age. Family history of migraine and/or motion reflux episodes.
sickness is noted in 30-40% cases. Symptoms may overlap
Combined 24 hours multiple intraluminal impedance and
with abdominal migraine.
pH monitoring detects acid, weakly acid and nonacid
Management: Known precipitants of the episodes should reflux episodes. It is thus superior to pH monitoring alone
be avoided. Management of an attack includes providing which detects only acid reflux episodes. Its main utility is
a quiet environment, administration of intravenous fluids, to evaluate the temporal relationship between symptoms
use of serotonin 5-HT3 antagonists such as ondansetron and GER episodes.
(0.34l.4 mg/kg/dose IV q 4-6 hr up to 20 mg) and sedation Upper GI endoscopy may show erosions or mucosal breaks
with lorazepam (0.05-0.1 mg/kg/ dose IV every 6 hr). in the distal esophageal mucosa, the most reliable evidence
Agents recommended for prophylaxis against future of reflux esophagitis. Mucosal erythema and pallor are
attacks are cyproheptadine (0.25-0.5 mg/kg/day in two highly subjective and nonspecific findings. Complications
or three divided doses) in children below 5 years and, in like stricture esophagus (Fig. 12.4) and Barrett's esophagus
older children, amitriptyline (initiate at 0.25-0.5 mg/kg/day can be picked up at endoscopy. Histological features like
at bedtime; may increase up to maximum of 1.0-1.5 mg/ elongated rete pegs, basal cell layer hyperplasia and
kg/ day) or propranolol (0.25-1 mg/kg/ day; up to 10 mg dilated intercellular spaces, alone or in combination, are
q 8-12 hr). suggestive of reflux esophagitis.
Gastroesophageal Reflux Disease (GERD) Endoscopic biopsy is important to evaluate other causes
of esophagitis and to diagnose Barrett's esophagus. While
Gastroesophageal reflux (GER) is passage of gastric not useful for the diagnosis of GERO, barium contrast
contents into the esophagus with or without regurgitation radiography helps rule out anatomic abnormalities of the
and vomiting. GER is a normal physiologic process that upper gastrointestinal tract that may cause symptoms
occurs several times a day in healthy infants, children and similar to those of GERO. This investigation should be
adults. When this reflux of gastric contents causes done in all infants with vomiting.
troublesome symptoms and/or complications, it is known
as GERD. About 50% of healthy 3-4-month-old infants Nuclear scintigraphy has a role in the diagnosis of
regurgitate at least once per day and most of them outgrow pulmonary aspiration in patients with chronic and
this by 1 year of age. Follow-up studies suggest that infants refractory respiratory symptoms due to GERO.
with persistent spitting beyond 3 months of age are at an Empiric trial of acid suppression: Using proton pump
increased risk of developing GERD in childhood. Children inhibitors for up to 4 weeks is justified in older children
with obesity, repaired esophageal atresia, cystic fibrosis, or adolescents with typical symptoms suggesting GERD.
hiatal hernia, preterm babies and a family history of GERD
are at risk of developing severe chronic GERO. Management: Treatment of GERD depends on patient's
Neurologically impaired children like those with cerebral age and nature and severity of symptoms and includes
palsy have increased risk of severe GERO due to multiple lifestyle changes, pharmacologic therapy and surgery.
factors like low pressure of the lower esophageal sphincter Lifestyle changes: Infants should be placed in left lateral
and predominant supine position. position with the head end elevated by 30 ° in the
Clinical features: The common symptoms associated postprandial period to reduce the frequency of reflux. Cow
with GERD in children are: (i) recurrent regurgitation; milk protein allergy is sometimes a cause of unexplained
(ii) weight loss or poor weight gain; (iii) irritability (in crying and vomiting in infants. Therefore, formula-fed
infants); (iv) heartburn or chest pain (older children); infants with recurrent vomiting may benefit from a 2-4
(v) hematemesis, dysphagia and odynophagia (if weeks trial of an extensively hydrolyzed protein formula.
complicated by esophagitis or stricture esophagus); Infants with inadequate weight gain because of losses by
(vi) wheezing, stridor, cough and hoarseness; and regurgitation may benefit from increasing the energy
(vii) Sandifer syndrome, an uncommon manifestation, density of formula. Careful follow-up with charting of
characterized by spasmodic torsional dystonia with caloric intake and weight gain is essential.
arching of the back and opisthotonic posturing. For children and adolescents with GERD, measures that
are useful include: Dietary modification (to avoid caffeine,
Evaluation: A detailed history and physical examination chocolate and spicy foods), weight loss if obese, sleeping
are generally sufficient to establish the diagnosis of GERD. in the left lateral position with elevation of the head-end
Useful investigations are as follows: of the bed, avoidance of alcohol and cessation of smoking.
21s I Essential Pediatrics
Erect
supine
9.0
8.0
7.0
6.0
5.0
pH 4.0
3.0
2.0
1.0
0.0
4:00:00 PM 8:00:00 PM 12:00:00 AM 4:00:00 AM 8:00:00 AM 12:00:00 PM
Erect
9.0
8.0 . . .'. .. .... t ..... l u... ... 11�.
7.0
pH
6.0
5.0 : : : m1:: : :
4.0
3.0
2.0
1.0
0.0 I I I I I I
12:00:00 PM 4:00:00 PM 8:00:00 PM 12:00:00 AM 4:00:00 AM 8:00:00 AM
Fig. 12.3: 24 hours esophageal pH study. Upper panel shows a normal study and lower panel shows frequent episodes of acidic
reflux with drop in pH to <4 suggestive of GERD
pressure, decreasing the number of episodes of transient The main causes are cerebral palsy, bulbar poliomyelitis,
lower esophageal sphincter relaxation and increasing the muscular dystrophy, brainstem tumors and neuropathy.
nadir pressure during swallow-induced relaxation,
increasing the length of intra-abdominal esophagus, Esophageal dysphagia: This occurs due to conditions
accentuating the angle of His and reducing a hiatal hernia, involving esophageal phase of swallowing, i.e. coordinated
if present. Antireflux surgery may be of benefit in selected peristalsis of esophageal body with simultaneous
children with chronic-relapsing GERD with intractable relaxation of LES. Etiology of esophageal dysphagia can
symptoms or risk of life-threatening complications. be broadly divided into two groups: Motor causes (e.g.
achalasia cardia and diffuse esophageal spasm) and
Suggested Reading structural causes (e.g. strictures, foreign body, Schatzki's
• Li BU, Lefevre F, Chelimsky GG, et al; North American Society for ring, esophageal web, eosinophilic esophagitis and extrinsic
Pediatric Gastroenterology, Hepatology and Nutrition. Consensus compression by aberrant vessel or mediastinal mass).
statement on the diagnosis and management of cyclic vomiting
syndrome. J Pediatr Gastroenterol Nutr 2008; 47:79-93. Differential Diagnosis and Evaluation
• Gastroesophageal reflux: management guidelines for the
Pediatrician. Pediatrics 2013; 13l;e1684-1695. The important causes of dysphagia and their evaluation
are shown in Table 12.2 as well as discussed below.
Dysphagia
Dysphagia refers to a sensation of food being hindered in Congenital esophageal stenosis: This may be of three
its passage from the mouth to the stomach, i.e. difficulty types: Web or diaphragm, fibromuscular stenosis and
in swallowing. Odynophagia is painful swallowing and stenosis due to cartilaginous tracheobronchial remnants.
globus is the sensation of a lump in the throat. Dysphagia Symptoms of vomiting or chest infection due to aspiration
can be divided into two distinct groups: typically develop around 6 months of age when weaning
is started.
Oropharyngeal or transfer dysphagia: Presence of drooling,
choking, coughing and nasal regurgitation suggests Foreign bodies in esophagus: Sharp foreign bodies and
oropharyngeal dysphagia. Disorders involving chewing, batteries can cause damage by perforation secondary to
oral transfer or pharyngeal phase of swallowing cause this. pressure or chemical necrosis and can present with
Table 12.2: Evaluation and management of esophageal lesions that cause dysphagia
Etiology Investigation Finding Treatment
Corrosive (acid or alkali) Barium swallow and meal; Narrowing in one or multiple, Endoscopic dilatation (Balloon
stricture upper GI endoscopy short or long, segments of or Savary-Gilliard dilators)
esophagus; may show
contracted stomach or
pyloric stenosis
Stricture after repair of Barium swallow (Fig. 12.5) Narrowing of a short Endoscopic dilatation
tracheoesophageal fistula segment of esophagus
Congenital stricture Barium swallow; CT chest Stricture in middle or Endoscopic dilatation or surgery
lower esophagus; carti
laginous tissue in
stricture
Postsclerotherapy stricture Barium swallow; upper Narrowing in lower end Endoscopic dilatation
GI endoscopy of esophagus
Peptic stricture Barium swallow; Narrowing in lower Endoscopic dilatation; proton
endoscopy; 24 hours pH esophagus; may pump inhibitor after dilatations
study show hiatus hernia or
erosions
Foreign body Plain X-ray; upper GI Type of foreign body Endoscopic retrieval
endoscopy (Fig. 12.6) and site of impaction
Achalasia cardia Barium swallow; endoscopy Beak-like narrowing in Pneumatic dilatation; Heller's
esophageal manometry lower esophagus cardiomyotomy
Infectious esophagitis (in Upper GI endoscopy; White curd-like deposits Fluconazole (Candida); ganciclovir
immunocompromised children) endoscopic biopsy (Candida); ulcers (cyto (cytomegalovirus) or acyclovir
megalovirus, herpes) (herpes)
GI: Gastrointestinal
21a I Essential Pediatrics
Fig. 12.5: Post-TEF stricture. Black arrow shows the short stricture Fig. 12.7: Barium swallow showing achalasia cardia
and white arrow shows the dilated proximal esophagus
feeding aversion with failure to thrive. The onset is gradual
and the average age at diagnosis in children is around
8--9 years. The barium swallow shows esophageal dilatation
with beak-like narrowing at the LES (Fig. 12.7). Manometry
is the most sensitive and specific tool and shows absent
peristalsis in esophagus; incomplete/absent LES relaxa
tion and raised intraesophageal pressure. Endoscopy is
useful to exclude other etiologies of dysphagia.
Endoscopic pneumatic balloon dilatation and Heller's
cardiomyotomy with antireflux procedure are two main
therapeutic modalities. The experience with per oral
endoscopic myotomy (POEM) is limited.
Suggested Reading
• Gariepy CE, Mousa H. Clinical management of motility disorders
in children. Semin Pediatr Surg 2009; 18:224-28.
• Pandolfino JE, Gawron AJ. Achalasia a systematic review. JAMA
2015; 313:1841-52.
Constipation
Constipation is defined as a delay or difficulty in
Fig. 12.6: Upper GI endoscopy showing foreign body (coin) in defecation, present for 2 or more weeks and sufficient to
esophagus cause significant distress to the patient. It is increasingly
being recognized as a very common problem in children
dysphagia, mediastinitis and/or upper gastrointestinal and is associated with both physical and psychological
bleeding. The vast majority of foreign bodies pass morbidity and a poor quality of life. The normal stool
unimpeded through the GI tract. The most frequent sites frequency decreases from 4 or more per day during
of impaction are at the cricopharynx, mid esophagus at infancy to once per day at 4 years of age. A stool frequency
tracheal bifurcation and just above the LES. of ::;;2/week is considered abnormal for all ages. The
Guidelines recommend that no foreign body should be majority of patients have functional constipation; organic
left in esophagus for more than 24 hours. Endoscopic removal cause is found in -15% (Table 12.3).
under sedation or anesthesia is the standard of therapy.
Achalasia cardia: Children present with dysphagia, Approach
vomiting, weight loss, respiratory symptoms and slow Details about pattern of stooling, time of first passage of
eating whereas toddlers present with coughing and meconium, presence of blood in stools, diet, stressful life
Diseases of Gastrointestinal System and Liver 1219-
Table 12.3: Causes of constipation Management: No investigations are required for diagnosis
Intestinal nerve/muscle disorders: Hirschsprung disease,
in the majority of children with functional constipation.
intestinal neuronal dysplasia, pseudo-obstruction, spinal cord However, an X-ray abdomen may be done to document
abnormalities (tethered cord, myelomeningocele) impaction in select situations, e.g. an obese child who is
Anorectal: Anteriorly placed anus, anal stenosis, rectal stricture, not willing for a per rectal examination. Two main steps
pelvic mass (sacral teratoma) in the management are disimpaction and maintenance
Systemic disease: Hypothyroidism, celiac disease, diabetes
therapy.
insipidus, diabetes mellitus, hypercalcemia, cystic fibrosis, Disimpaction is required in patients who have a rectal
myotonic dystrophy impaction, i.e. presence of a large hard mass of feces on
Developmental: Mental retardation, autism per rectal examination or abdominal fecoliths or retentive
Drugs: Opiates, anticholinergic agents, phenobarbitone, encopresis. Rectal impaction is responsible for progressive
vincristine, lead dilatation of the rectum over time and increased threshold
volume for rectal sensation and defecation. This 'clean out'
events, drug intake and previous surgeries should be known. is essential, if maintenance therapy is to be effective. The
A predominantly liquid and low fiber diet (milk based) is oral route is preferred over rectal as it is less invasive.
common and contributes to constipation. A complete Total bowel wash is done to clean the entire colon using
physical and neurological examination is essential. polyethylene glycol (PEG) in a dose of 1.5 g/kg/day for
Examination for features of spina bifida (pigmentation or 3-4 days at home. Alternatively, PEG electrolyte solution
tuft of hair on lower back), power in lower limbs, perianal can be given in the dose of 15-40 mL/kg/hr till the rectal
sensation, voluntary contraction and tone of anal sphincter output is clear and devoid of solid fecal material. In young
and amount and consistency of stool in rectum on per
children, this should be done using a nasogastric tube and
rectal examination are extremely useful for diagnosis.
in hospital under supervision. Intravenous fluids may be
'Red flags' like failure to thrive, blood in stools, required in small children to maintain adequate hydration.
recurrent fever with loose stools (enterocolitis), recurrent An alternative to oral administration of PEG is the use of
vomiting, lump in abdomen, recurrent chest infections and phosphate enema (contraindicated in <1-year-old) or
features of hyp othyroidism should alert the physician to sodium dioctyl sulfosuccinate enema, 30-60 mL/10 kg
suspect organic etiology. body weight to a maximum of 120 mL, once or twice
daily for 1-2 days. Repeated rectal enemas should be
Functional Constipation avoided.
The increase in intake of low residue diet and sedentary The aim of maintenance therapy is to promote regular
lifestyle is responsible for the increase in functional stooling and prevent reimpaction. Success of this therapy
constipation in children. Functional constipation is defined is defined as passage of 1-2 soft stools per day and no
by the presence of at least 2 or more of the following soiling. It includes the following components:
criteria: (i) two or fewer defecations in the toilet per week; i. Behavioral training involves establishing a positive
(ii) at least 1 episode of fecal incontinence per week; routine of sitting on toilet for passing stools after meals
(iii) history of retentive posturing or excessive volitional regularly (2-3 times per day for 5-10 min) and
stool retention; (iv) history of painful or hard bowel
documenting all stool passage. Embarrassment or
movements; (v) presence of a large fecal mass in the
punishment should be avoided.
rectum; and (vi) history of passage of large diameter stools
that may obstruct the toilet. ii. Dietary changes: A nutritious diet with fruit/vegetables
Children with functional constipation pass large or hard and adequate fluids is given. A short trial of milk and
stools and display stool withholding behavior, milk product free diet may be done in refractory cases
characterized by stiffening of whole body and screaming suspected to have bovine milk allergy.
in infants, to walking on tiptoes or tightening of buttocks iii. Medication: Regular and tailor-made (as per response)
in older children. This is often misunderstood by parents laxative use is the key to success and this should be
as if the child is trying to defecate. Often an acute illness, explained to the family. Osmotic laxatives, like
change in diet, coercive toilet training or non-availability lactulose (1-3 mL/kg/day), and PEG (0.8-1.0 g/kg/
of clean toilet leads to non-passage of stools. The stools day), are the first-line agents. Stimulant laxatives like
become hard and cause pain on passage which leads to senna or bisacodyl are to be used only intermittently
association of defecation with pain and withholding. This as a rescue therapy to avoid impaction. Prokinetics like
further increases stool size and hardness with more pain cisapride are not recommended. In infants, mineral oil
on defecation. Children with functional constipation have and stimulant laxatives should not be used. Glycerin
abdominal pain (10-70%), anorexia (10-25%), enuresis or suppository is preferred over enema for impaction in
urinary tract infections (30%) and psychological problems infants. Premature withdrawal of medications is a very
(20%). common cause of relapse.
2so I Essential Pediatrics
Fig. 12.8: Colonic transit study showing retained radiopaque Fig. 12.9: Barium enema showing Hirschsprung disease. Black
markers in the left colon suggestive of outlet obstruction in a arrow shows the dilated proximal segment and white arrow
child with constipation shows the transition zone
Diseases of Gastrointestinal System and Liver 12a1-
Suprapubic
Acute appendicitis Colitis
Pelvic inflammatory disease Constipation
Tuberculosis abdomen Pelvic inflammatory
disease
Proctitis
Cystitis
Fig. 12. l 0: Causes of abdominal pain as per site of pain. RH right hypochondrium; LH left hypochondrium
Table 12.5: Common causes of abdominal pain distention and infection in the appendix causes
progressive inflammation and, subsequently, perforation.
Infants and young children (<2 years of age): Colic, acute
The patient presents with fever and anorexia followed
gastroenteritis, intussusception, malrotation of gut with
by pain in the periumbilical area. Vomiting follows the
volvulus, incarcerated hernia, trauma, necrotizing enterocolitis
periumbilical pain, unlike in gastroenteritis. As the
Preschool children (2-5 years of age): Acute gastroenteritis, inflammatory fluid spreads, the pain is then felt in the
urinary tract infections, constipation, intussusception, acute right iliac fossa (McBurney point) towards which the child
appendicitis, malrotation of gut with volvulus, intestinal characteristically points with a finger. A retrocecal
perforation with peritonitis, choledochal cyst, lower lobe inflamed appendix may be difficult to diagnose and may
pneumonia, incarcerated hernia, torsion testis, acute manifest as spasm at the hip. The diagnosis is most often
pancreatitis, diabetic ketoacidosis, Henoch-Schonlein purpura, based on clinical suspicion after history and examination.
Meckel diverticulum, trauma
Palpation reveals localized tenderness and is best elicited,
Older children and adolescents: Acute gastroenteritis, gastritis, if there is rebound tenderness.
acute appendicitis, Crohn disease, constipation, urinary tract Hemogram shows polymorphonuclear leukocytosis.
infections, dysmenorrhea, pelvic inflammatory disease, ectopic Urine microscopy should be done to rule out urinary tract
pregnancy, Mittelschmerz, renal calculi, acute pancreatitis, infection. Abdominal ultrasound detects a dilated (>6 mm)
cholecystitis, pneumonia, trauma, early phase of acute viral tubular, aperistaltic structure which is not compressible
hepatitis, testicular or ovarian torsion, intestinal obstruction, and is surrounded by fluid. Ultrasound has a sensitivity
perforation or peritonitis of 85-90% and specificity of 95-100% for diagnosing
appendicitis. Computed tomography may be done
Acute Appendicitis occasionally, if the diagnosis is in doubt. In up to one
Acute appendicitis is the commonest pediatric surgical third of patients, the appendix ruptures before surgery.
emergency and is more common in older children. The Intravenous fluids and antibiotics for gram-negative and
condition is considered as occurring due to obstruction anaerobic coverage should be given in all cases. Early
of the appendiceal lumen by either fecolith or lymphoid surgery is necessary to prevent complications like
tissue, e.g. following viral infection. The obstruction, perforation, appendiceal abscess and sepsis.
Diseases of Gastrointestinal System and Liver l2aa-
lntussusception investigation of choice for diagnosis of gallstones. MRCP
This is a common cause of intestinal obstruction in children and ERCP have a better accuracy than ultrasonography
between 3 months and 6 years. Intussusception refers to in diagnosing common bile duct stones. These children
the telescoping of a proximal segment of intestine should be investigated with hemoglobin, reticulocyte
(intussusceptum) into a distal segment (intussuscipiens). count, peripheral blood picture and other investigations
This may be ileocolic, colocolic or ileoileal. Most cases to look for hemolytic disease.
occur in infants during the weaning period following Management: Symptomatic cholelithiasis is treated by
introduction of a new food, vaccination or upper open or laparoscopic cholecystectomy. Common bile duct
respiratory tract infection. An area of enlarged submucosal calculi can be removed by ERCP or at surgery by common
Peyer's patch probably acts as a lead point. Beyond two bile duct exploration. Children with asymptomatic gall
years of age, the possibility of a submucosal lead point stones without underlying predisposing factors can be
like lipoma and polyp that needs surgical resection should safely followed up. Patients with sickle cell disease should
be considered as failure to resect them will lead to be subjected to prophylactic cholecystectomy, even if gall
recurrence. Inflammatory conditions, like Henoch stones are asymptomatic. Children with other hemolytic
Schonlein purpura, also result in intussusception. As a anemias should be screened by ultrasonography, if they
result, there is venous congestion, bowel edema leading are being considered for splenectomy and cholecystec
to arterial obstruction, bowel ischemia, necrosis, tomy should be done along with splenectomy in those
perforation and shock. The classic triad of abdominal pain, having gallstones.
red currant jelly stools (blood and mucus) and palpable
mass is seen only in a small percentage of children. X-ray Choledochal Cyst
abdomen shows paucity of air in right lower quadrant.
Choledochal cyst refers to abnormal cystic dilatation of
Ultrasound is the investigation of choice that confirms the
biliary tree either as a single or multiple dilatations. This
diagnosis ('doughnut'sign) and provides information
may or may not have associated intrahepatic cystic
about presence of a mass as lead point. Vascularity of
dilatations. It can present in the neonatal period as
bowel is best assessed on color Doppler. Barium enema
cholestasis, mimicking biliary atresia (5% of all neonatal
shows a characteristic 'claw' sign, if the intussusception
cholestasis), or in the older child with recurrent episodes
involves colon. Early reduction either with saline (under
of pain, obstructive jaundice or mass in right upper
ultrasound guidance), barium contrast (both diagnostic
quadrant. Acute or recurrent pancreatitis may be the
and therapeutic) or with air insufflation is advisable.
presentation of choledochal cyst, either due to stone
Reduction with air is safer with lower recurrence rates.
impaction at lower end of common bile duct, or due to
Failure of radiological reduction or suspected intestinal
anomalous pancreatobiliary junction known to be
gangrene may necessitate surgery and resection.
associated with choledochal cyst. Biliary peritonitis
Gallstones {Cholelithiasis) secondary to bile duct perforation can complicate a
choledochal cyst. Untreated cases may go on to develop
Gallstones are of three main types: Cholesterol stones with secondary biliary cirrhosis.
>50% cholesterol, pigment (black or brown) stones and
Ultrasonography is the investigation of choice to
mixed types. Pigment stones are common in children with
diagnose choledochal cyst. MRCP is done to define the
hemolytic anemia. High-risk groups for gallstones include
anatomy of the pancreaticobiliary ductal system before
children with hemolytic anemia, obesity, ileal resection
surgical excision (Fig. 12.11). Definitive treatment is with
or disease, intake of drugs like ceftriaxone, progressive
cyst resection and hepaticojejunostomy in the majority as
familial intrahepatic cholestasis type III and total
there is a risk of malignancy (cholangiocarcinoma) in the
parenteral nutrition. Overall, hemolytic anemia and other
epithelium of the cyst, if left in situ. Antibiotics and
predisposing conditions account for 20-30% and 30-40%
supportive therapy are required before surgery for a child
of gallstones, respectively, while 30-40% cases remain
presenting with obstructive jaundice and cholangitis.
idiopathic.
Clinical presentation: Typical presentation is with acute Ma/rotation
or recurrent episodes of right upper quadrant or epigastric Rotational abnormalities developing during the matura
pain which may radiate to the right shoulder. Icterus and tion of the gut cause recurrent obstruction, occurring as
pain radiating to the back is suggestive of a stone in either the Ladd's band or volvulus of the gut over the
common bile duct or ampulla causing pancreatitis. Fever narrow mesenteric pedicle. About 80-90% cases of
is uncommon; however, if present, it suggests presence volvulus occur within the first year of life. Abdominal pain
of cholecystitis or cholangitis. with bilious vomiting suggests small bowel obstruction;
Diagnosis: Serum bilirubin and alkaline phosphatase are abdominal distension may not be a prominent finding.
elevated, if the stone is in the common bile duct. Raised Findings of malrotation are confirmed on barium meal
amylase suggests pancreatitis. Ultrasonography is the follow through (BMFT), which shows duodenojejunal
2a4 I Essential Pediatrics
Fig. 12.11: Magnetic resonance cholangiopancreatography Fig. 12.12: Barium meal follow through showing malrotation of
(MRCP) showing choledochal cyst intestine
junction on the right of the spine (rather than to the left of antral nodularity as compared to ulcers without such
midline at the level of pylorus), an abnormally positioned infection. Mechanical ventilation and coagulopathy
caecum and small bowel loops on the right side of increase risk of bleeding in stress ulcers.
abdomen (Fig. 12.12). If volvulus is also present, the Diagnosis is established by upper GI endoscopy by
contrast abruptly tapers into a corkscrew appearance at direct visualization of location (gastric or duodenal),
the level of the second portion of duodenum. number and size of ulcer (Fig. 12.13). Endoscopic
After resuscitation, emergency laparotomy is required management can be done at the same time in ulcers with
for correction of the defect, usually by the Ladd's active bleeding or ooze or those with a visible vessel. One
procedure, which includes derotation of the volvulus, can also obtain gastric biopsies for Helicobacter pylori
division of the Ladd's band, widening of the base of the testing.
mesentery, placement of bowel in a state of nonrotation Proton pump inhibitors are the mainstay of therapy.
and appendicectomy. Actively bleeding ulcers require endoscopic therapy, with
sclerosant or adrenaline injection, application of heater
Peptic Ulcer probe or bipolar electrocoagulation, or placement of
Both gastric and duodenal ulcers occur infrequently in hemoclip over bleeding vessel. Evaluation for Helicobacter
children. Ulcers may be primary, i.e. related to Helicobacter
pylori or secondary, e.g. due to drugs (NSAIDs, steroids),
stress (shock, sepsis and ischemia), corrosives, Menetrier's
disease, Crohn's disease and Zollinger-Ellison syndrome.
Clinical presentation depends on the age. Neonates
typically present with bleeding and perforation from a
gastric ulcer, usually occurring in the setting of another
underlying problem, such as sepsis or respiratory distress.
Older infants and toddlers frequently vomit, eat poorly
and have upper GI bleeding. Older children may have
the classical epigastric pain which is relieved by eating.
However, this is noted only in a minority; most patients
have pain that is ill-localized and similar to that seen in
functional dyspepsia. Overt or occult bleeding is seen in
approximately half of school-age children with ulcer
disease. Gastrointestinal bleeding, vomiting with
obstruction and severe pain due to perforation suggest
complicated ulcers. Ulcers associated with Helicobacter
pylori infection affect older children, family history of ulcer Fig. 12.13: Upper gastrointestinal endoscopy showing
disease is usually noted and upper GI endoscopy shows duodenal ulcer in the first part of duodenum
Diseases of Gastrointestinal System and Liver l2as-
pylori is essential in all cases with peptic ulcer and merits an important cause is nonorganic abdominal pain which
specific therapy with two of three antibiotics (amoxicillin, is responsible for nearly 75% of all cases. As per the Rome
metronidazole, clarithromycin) and proton pump III criteria, such pain is termed 'abdominal pain related to
inhibitor. Predisposing factors, including NSAIDs, should functional gastrointestinal disorders.'
be avoided. Surgery is indicated in children presenting
with gastric outlet obstruction or uncontrolled bleeding Chronic Pancreatitis
despite drug and endoscopic treatment. This condition is characterized by recurrent episodes of
abdominal pain and exocrine and/ or endocrine pancreatic
Acute Pancreatitis insufficiency. On imaging, diagnosis is based on demonstra
Acute pancreatitis is less common in children than adults tion of pancreatic calcification and/ or dilated pancreatic
and occurs chiefly due to trauma, drugs (valproate, L duct. Chronic pancreatitis in children may be idiopathic
asparaginase), viral infections (mumps), hemolytic uremic or hereditary, autoimmune, tropical, metabolic (hyper
syndrome, congenital biliary anomalies, Henoch calcemia) or secondary to recurrent acute pancreatitis.
Schonlein purpura and occasionally, gallstones, Children present initially with repeated episodes of
hypercalcemia or hypertriglyceridemia. Diagnosis is based pancreatic pain. Chronic diarrhea with fat malabsorption
on presence of upper abdominal pain (with or without (exocrine insufficiency) and symptoms of diabetes mellitus
radiation to the back), elevated serum amylase or lipase develop later along with failure to thrive. Local
and radiological imaging (ultrasonography, CT scan) complications include pseudocyst, pancreatic ascites,
showing bulky, edematous pancreas. Acute severe pancreatic duct stricture, biliary strictures and portal
pancreatitis may result in acute respiratory distress hypertension due to splenic vein thrombosis. These
syndrome, acute renal failure, shock, GI bleed, patients are also at an increased risk of pancreatic
disseminated intravascular coagulation, hypoglycemia, carcinoma, particularly those with hereditary pancreatitis.
hypocalcemia or infected pancreatic necrosis. Late X-ray abdomen may show pancreatic calcification.
complications include pancreatic abscess and pseudocyst Ultrasound and CT scan demonstrates ductal dilatation
formation (Fig. 12.14). Early supportive care in intensive (Fig. 12.15), strictures, calcification and altered size or
care is critical in severe acute pancreatitis. Radiological, echotexture of pancreas. ERCP and MRCP help define the
endoscopic or surgical interventions may be required for pancreatic ductal anatomy (e.g. prominent stricture,
patients with pseudocyst, pancreatic abscess or infected intraductal calculi) and planning of endoscopic or surgical
necrosis. therapy. Exocrine pancreatic insufficiency is confirmed by
demonstrating excess fat and reduced pancreatic elastase
Chronic Abdominal Pain or chymotrypsin in stool. Fasting and postprandial blood
Chronic abdominal pain refers to the pain that is either sugar help evaluate for endocrine insufficiency. Evalua
episodic or continuous and lasts for a period of at least tion for etiology should include looking for hypercalcemia
2 months. The prevalence of chronic abdominal pain in or hyp erlipidemia and testing for mutations in cationic
children varies from 0.5 to 19% and depends on the age trypsinogen gene to confirm hereditary pancreatitis.
group evaluated. The principles of diagnosis with regard Treatment includes supportive therapy during acute
to clinical evaluation are similar to that in acute abdominal attacks, administration of antioxidants and oral pancreatic
pain but the etiologies differ. In addition to organic causes, enzyme supplements for exocrine pancreatic insufficiency
Fig. 12.14: Contrast-enhanced CT scan showing pseudocyst Fig. 12.15: CT scan showing dilated main pancreatic duct in
in a patient with acute pancreatitis chronic pancreatitis
2ss I Essential Pediatrics
and endoscopic, radiological or surgical treatment for Table 12.6: 'Red flag' signs or features that indicate serious
pseudocyst, ductal stricture and other complications. illnesss in a child with abdominal pain
Surgical procedures like partial pancreatectomy or lateral Pain localized away from umbilicus in right/left upper or lower
pancreatojejunostomy are required in patients not quadrant
responding to medical therapy. Celiac ganglion block is Nocturnal pain
another alternative for pain control. Management of Failure to thrive; weight loss
diabetes mellitus, if present, is essential. Significant vomiting; bilious vomiting
Gastrointestinal blood loss
Abdominal Pain Related to Functional
Chronic diarrhea
Gastrointestinal Disorders
Persistent fever
Abdominal pain related to functional GI disorders is Jaundice
diagnosed in the presence of pain that is present at least Arthritis; rash
once a week in the preceding 2 months and the absence of Family history of inflammatory bowel disease
an organic cause such as an inflammatory, anatomic, Localized tenderness or mass in abdomen; organomegaly
metabolic and neoplastic process. The pain is typically Perianal fistulae
periumbilical and is clearly localized by the child.
After extensive studies, the most accepted under Among the various types mentioned above, functional
standing of childhood functional abdominal pain is of abdominal pain is the most common. The diagnosis of
childhood functional abdominal pain hinges on
'visceral hyperalgesia', referring to an altered excessive
confidently ruling out organic etiology using a careful
perception of normal gut motility that is interpreted by
history and examination; extensive investigations are
the child as pain. This perception is influenced by the unnecessary. The history should include not only details
psychosocial stressors in school and home. The focus on of pain but also family details, child's emotional
the pain is further heightened by the growing concern in environment in home and school, personality, coping
the family and the frequent visits to the doctors. Children skills, school performance and stress factors. The presence
of parents with increased anxiety and functional GI of alarming symptoms (Table 12.6) increases the
problems have an increased risk of developing functional probability of organic disorder and justifies further
pain in abdomen. The different types of functional gastro diagnostic testing. In the absence of red flags, the
intestinal disorders associated with abdominal pain are diagnostic yield of investigations is poor. Hemogram, ESR,
as follows: stool routine and occult blood, and urine microscopy
Functional dyspepsia: Persistent or recurrent pain or should be carried out in all cases to rule out organic
discomfort is centered in the upper abdomen, located disease. Abdominal ultrasonography is not helpful; the
above the umbilicus and not relieved by defecation nor presence of lymph nodes of <10 mm is not a significant
associated with a change in stool frequency or form (i.e. finding. Further investigation is required only in those
no irritable bowel syndrome). with alarm symptoms and based on the likely diagnosis.
The aim of management of children with functional
Irritable bowel syndrome: Abdominal discomfort or pain abdominal pain is to make a positive diagnosis, normalize
is associated with two or more of the following: the lifestyle to not allow pain to curtail daily activities or
improvement with defecation, onset associated with a school performance, and to rectify psychological factors.
change in frequency of stool and onset associated with a The crux of management is counseling the parents and
change in consistency of stool. the child, both jointly and separately. Parents need to be
Abdominal migraine: Paroxysmal episodes of intense, reassured about the benign nature of the ailment and
acute periumbilical pain are noted, lasting for an hour or emphasis is laid upon avoiding too much attention to the
more with intervening periods of normal health lasting child. The concept of visceral hyperalgesia should be
weeks to months. The episodes of pain interfere with explained to parents. Provision of a nutritious diet with
normal activities and are associated with two or more of adequate fiber and avoiding intake of carbonated
beverages and refined food helps in reducing bloating.
the following: Anorexia, nausea, vomiting, headache,
The role of amitriptyline and hypnotherapy is restricted
photophobia and pallor.
to a few refractory cases.
Childhoodfunctional abdominal pain: This refers to episodic
or continuous periumbilical abdominal pain that meets Suggested Reading
insufficient criteria for other types of FGIDs (functional • Chiou E, Nurko S. Management of functional abdominal pain and
gastrointestinal disorders). The criteria for childhood irritable bowel syndrome in children and adolescents. Expert Rev
functional abdominal pain syndrome are satisfied, if the child Gastroenterol Hepatol 2010; 4:293--304.
has functional abdominal pain for at least 25% of the time • Korterink J, Devanarayana NM, Rajindrajith S, Vlieger A, Benninga
MA. Childhood functional abdominal pain: mechanisms and
plus one or more of the following: Some loss of daily management. Nat Rev Gastroenterol Hepatol. 2015; 12(3):159-71.
functioning and additional somatic symptoms such as • Marin JR, Alpern ER. Abdominal pain in children. Emerg Med Clin
headache, limb pain, or difficulty in sleeping. North Am 2011; 29:401-28.
Diseases of Gastrointestinal System and Liver 1287-
cases of diarrhea, especially if the child has been given complications; (iii) assess for malnutrition; (iv) rule out
fluids with extra salt, serum sodium levels may be elevated nondiarrheal illness especially systemic infection; and
to > 150 mEq/L and ECF osmolalilty is increased. (v) assess feeding, both preillness and during illness.
Normally, skin turgor or elasticity is maintained by History: This should include information on: (i) onset of
tissue water and fat. Shrinkage of extracellular water in diarrhea; duration and number of stools per day; (ii) blood
both hypo- and isonatremic dehydration impairs skin in stools; (iii) number of episodes of vomiting; (iv) presence
elasticity. On pinching, it takes a few seconds for the skin of fever, cough, or other significant symptoms (e.g.
fold to return to normal. In patients with hypematremic convulsions, recent measles); (v) type and amount of fluids
dehydration, water moves from inside the cells to the ECF (including breast milk) and food taken during the illness
compartment due to the increased osmolality of ECF, and and pre-illness feeding practices; (vi) drugs or other local
therefore, partially masks the loss of skin turgor. The skin remedies taken (including opioids or antimotility drugs
appears soggy, doughy or leathery. In this situation, a like loperamide that may cause abdominal distension);
severe case of hypematremic dehydration is likely to be and (vii) immunization history.
erroneously underestimated as mild dehydration, unless
severe sequelae of dehydration such as circulatory or renal Examination: The most important assessment is for
impairment are noted. dehydration. The degree of dehydration is assessed as per
Table 12.8. One should look at the child's general
As the ECF compartment is depleted, the blood volume condition, whether he/she is alert, restless or irritable or
is reduced. This results in a weak, thready pulse, low blood lethargic or unconscious. Other important assessments are
pressure and cold extremities. Because of low hydrostatic for the appearance of eyes (normal or sunken) and the
pressure in the renal glomeruli, the filtration of urine is ability to drink water or ORS solution, whether taken
reduced. This is ominous because poorly functioning normally or refused, taken eagerly, or an inability to drink
kidneys cannot regulate metabolic derangements. Urine due to lethargy or coma. Dehydration is also assessed by
flow is a good indicator of the severity of illness. Severe feeling for skin turgor; following pinching, the abdominal
cases are associated with renal failure. skin may flatten immediately, go back slowly or return
Diarrheal stools contain large amounts of potassium. very slowly (more than 2 seconds). Based on the degree
Therefore, serum level of potassium invariably falls, if of dehydration after history and examinasion, the
diarrhea persists for more than a few days. This is more estimated fluid loss is calculated as follows:
pronounced in children with severe malnutrition with
already depleted potassium stores. Affected children Degree of dehydration Assessment offluid loss
present with abdominal distension, paralytic ileus and No dehydration <50 mL/kg
muscle hypotonia. Electrocardiogram may show ST Some dehydration 50-100 mL/kg
depression and flat T waves. Since intestinal secretions Severe dehydration >100 mL/kg
are alkaline, considerable bicarbonate is lost in diarrheal
stools and acidosis usually accompanies dehydration. In addition, one should examine for features of
Patients remain asymptomatic till the base excess falls to malnutrition (anthropometry for weight and height;
12 mmol/L. Below this level, breathing becomes deep and examination for wasting, edema and signs of vitamin
rapid (Kussmaul breathing). deficiency), systemic infection (presence of cough, high
Clinical features can be summed up as follows. The grade fever, fast breathing and/ or chest indrawing
child is thirsty and slightly irritable in early and mild cases suggests pneumonia; high grade fever with splenomegaly
of diarrhea. As the diarrhea continues and dehydration suggests malaria) and fungal infections (oral thrush or
worsens, the child becomes more irritable and develops a perianal satellite lesions).
pinched look. The fontanelle, if open, is depressed, the
Laboratory investigations: The large majority of acute
eyes appear sunken and the tongue and the inner side of
diarrheal episodes can be managed effectively even in
cheeks appear dry. Abdomen may become distended in
absence of laboratory investigations. Stool microscopy is
hypokalemia. The child passes urine at longer intervals.
not helpful in management except in selected situations,
As acidosis worsens, the breathing becomes deep and
such as cholera (darting motion suggests Vibrio cholerae)
rapid. In extreme cases, the child appears moribund, with
and giardiasis (trophozoites). Stool culture is of little value
weak and thready pulses, low blood pressure and reduced
in routine management of acute diarrhea. It is useful to
urine output. Children with severe dehydration may
decide on antibiotic therapy in patients with Shigella
succumb rapidly, if not treated promptly.
dysentery who do not respond to the initial empiric
antibiotics. Tests for stool pH and reducing substances
Assessment of Child with Acute Diarrhea are not indicated in acute diarrhea. Hemogram, blood gas
Goals of assessment: These are to: (i) determine the type estimation, serum electrolytes, renal function tests are not
of diarrhea, i.e. acute watery diarrhea, dysentery or indicated routinely and are performed, only if the child
persistent diarrhea; (ii) look for dehydration and other has associated findings like pallor, labored breathing,
Diseases of Gastrointestinal System and Liver 1289-
altered sensorium, seizures, paralytic ileus or oliguria concentration gradient, which also results in electrolyte
which suggests acid-base imbalance, dyselectrolytemia or absorption (by solvent drag). Since the concentration of
renal failure. glucose increases osmolarity, it is suggested that glucose
concentration should not exceed 111 mmol/L. Meta
Principles of Management analyses have shown that use of low osmolarity ORS
Management of acute diarrhea has four major causes reduction of stool output, decrease in vomiting and
components: (i) rehydration and maintaining hydration; decrease in the use of unscheduled intravenous fluids
(ii) ensuring adequate feeding; (iii) oral supplementation without increasing the risk of hyponatremia. For this
of zinc; and (iv) early recognition of danger signs and reason, the recommendation for use of standard WHO
treatment of complications. ORS (having osmolarity of 311 mmol/L) was changed to
The cornerstone of acute diarrhea management is low osmolarity WHO ORS (having osmolarity of
rehydration by using oral rehydration solutions. After the 245 mmol/L). Since 2004, based on the WHO/UNICEF
history and examination, the child's dehydration status and IAP recommendations, the Government of India has
is classified as no dehydration, some dehydration or severe adopted the low osmolarity ORS as the single universal ORS
dehydration and appropriate treatment is started. to be used for all ages and all types of diarrhea. The com
position of the low osmolarity ORS is given in Table 12.9.
Physiological basis for oral rehydration therapy: In most
In the absence of WHO ORS, one may administer
cases of acute diarrhea, sodium and chloride are actively
culturally acceptable appropriate homemade fluids as
secreted from the gut mucosa due to pathogen-induced
shown in Table 12.10. Oral solutions should be given by a
dysfunction of several actively functioning absorption
spoon or katori and in sips or small volumes rather than a
pumps. However, glucose dependent sodium pump
large volume at one time as this increases the retention of
remains intact and functional transporting one molecule
oral fluids.
of glucose and dragging along a molecule of sodium and
one of water across intestinal mucosa resulting in repletion Table 12.9: Composition of WHO recommended ORS
of sodium and water losses. The glucose dependent
Constituent g!L Osmole or ion mmol/L
sodium and water absorption is the principle behind
replacing glucose and sodium in 1:1 molar ratio in the Sodium chloride 2.6 Sodium 75
WHO oral rehydration solution (ORS). An important Glucose, anhydrous 13.5 Chloride 65
consideration in making ORT is that the osmolarity of Potassium chloride 1.5 Glucose, anhydrous 75
the replacement fluid should not exceed that of blood Trisodium citrate, 2.9 Potassium 20
(290 mmol/L). Keeping the intestinal lumen at lower dihydrate Citrate 10
osmolarity as compared to blood allows for greater Total osmolarity 245
absorption of fluids into the bloodstream across
290 I Essential Pediatrics
Table 12.10: Home available fluids for acute diarrhea Table 12.11: Oral rehydration therapy to prevent dehydration
Acceptable home available fluids (Plan A)
Fluids that contain salt Oral rehydration solution, Age ORS or other culturally ORS to provide for
(preferable) salted drinks (e.g. salted rice appropriate ORT fluids use at home
water or salted yoghurt drink), after each loose stool
vegetable or chicken soup <24 mo 50-100 ml 500 mUday
with salt 2-10 yr 100-200 ml 1000 mUday
Fluids that do not contain Plain water, water in which a >10 yr Ad lib 2000 mUday
salt (acceptable) cereal has been cooked (e.g.
Explain use of ORS, i.e. the amount to be given, how to mix
unsalted rice water), unsalted Give a teaspoonful every 1-2 min for a child under 2 years
soup, yoghurt drinks without Give frequent sips from a cup for an older child
salt, green coconut water, If the child vomits, wait for 10 min. Then give the solution more slowly
weak unsweetened tea, (for example, a spoonful every 2-3 min)
unsweetened fresh fruit juice If diarrhea continues after the ORS packets are used up, tell the mother
to give other fluids as described above or return for more ORS
Unsuitable home available Commercial carbonated
fluids beverages, commercial fruit
juices, sweetened tea ii. Deficit replacement or rehydration therapy is calculated
as 75 mL/kg of ORS, to be given over 4 hours. If ORS
Treatment Plan A: Treatment of "No Dehydration" cannot be taken orally, then nasogastric tube can be
Such children may be treated at home after explanation used. If child's weight cannot be taken, then only age
of feeding and the danger signs to the mother/caregiver. may be used to calculate fluid requirement as shown
in Table 12.12.
The mother may be given WHO ORS for use at home as
per Table 12.11. Danger signs requiring medical attention If, after 4 hours, the child still has some dehydration,
are those of continuing diarrhea beyond 3 days, increased then another treatment with ORS (as in rehydration
volume/ frequency of stools, repeated vomiting, therapy) is to be given. This therapy is effective in 95%
increasing thirst, refusal to feed, fever or blood in stools. cases. Oral rehydration therapy may be ineffective
in children with a high stool purge rate of >5 mL/kg
Treatment Plan B: Treatment of "Some Dehydration" body weight/hr, persistent vomiting >3/hr, paralytic
All cases with obvious signs of dehydration need to be ileus and incorrect preparation of ORS (very dilute
treated in a health center or hospital. However, oral fluid solution).
therapy must be commenced promptly and continued iii. Maintenance fluid therapy to replace losses. This phase
during transport. Fluid requirement is calculated under should begin when signs of dehydration disappear,
the following three headings: (i) provision of normal daily usually within 4 hours. ORS should be administered
fluid requirements; (ii) rehydration to correct the existing in volumes equal to diarrheal losses, usually to a
water or electrolyte deficits; and (iii) maintenance to replace maximum of 10 mL/kg per stool. Breastfeeding and
ongoing losses to prevent recurrence of dehydration. semisolid food are continued after replacement of
i. The daily fluid requirements in children are calculated deficit. Plain water can be offered in between.
as follows: Treatment Plan C: Children with "Severe Dehydration"
Up to 10 kg = 100 mL/kg
10-20 kg= 50 mL/kg Intravenous fluids should be started immediately using
Ringer lactate with 5% dextrose. Normal saline or plain
>20 kg= 20 mL/kg
Ringer solution may be used as an alternative, but 5%
As an example, the daily fluid requirement in a child dextrose alone is not effective. A total of 100 mL/kg of
weighing 15 kg will be 1250 mL (first 10 kg, 10 x 100 fluid is given, over 6 hours in children <12 months and
= 1000 mL; another 5 kg, 5 x 50 = 250 mL, total 1000 + over 3 hours in children >12 months as shown below.
250 = 1250 mL).
Table 12.12: Guidelines for treating patients with some dehydration (Plan B)
Age <4 mo 4-11 mo 12-23 mo 2-4 yr 5-14 yr �15yr
Weight <5 kg 5-8 kg 8-11 kg 11-16 kg 16-20 kg >30 kg
ORS, ml 200-400 400-600 600-800 800-1200 1200-2200 >2200
Number of glasses 1-2 2-3 3-4 4-6 6-11 12-20
!he approximate amoun� of ORS required (in ml) c�n also.be �alcula_ted by multiplyi�g the patient's weight (in kg) times 75. When body weight
1s n�t known, the approximate amount of ORS solution to give in the first 4 hours 1s given according to age
For infants under-6 months who are not breastfed, also give 100-200 ml clean water during this period
Encourage breastfeeding
Diseases of Gastrointestinal System and Liver 1291-
agents, necrotizing enterocolitis or septicemia. In these Lactobacillus GG), L. plantarum, several strains of bifido
cases, oral intake should be withheld. Hypokalemia along bacteria, Enterococcus faecium SF68 and the yeast
with paralytic ileus necessitates intravenous fluids and Saccharomyces boulardii have been shown to have some
nasogastric aspiration. Potassium chloride (30-40 mEq/L) efficacy in reducing the duration of acute diarrhea, if
should be administered intravenously with parenteral started in very early phase of illness. The efficacy of
fluids provided the child is passing urine. probiotic preparations is strain and concentration (dose)
Convulsions associated with diarrhea may be due specific. However, the routine use of probiotics in patients
to (i) hypo- or hypernatremia; (ii) hypoglycemia; with acute diarrhea is not recommended.
(iii) hypokalemia following bicarbonate therapy for
acidosis; (iv) encephalitis; (v) meningitis; (vi) febrile Prevention of Diarrhea and Malnutrition
seizures; or (vii) cerebral venous or sagittal sinus Prevention of diarrhea and its nutritional consequences
thrombosis. The management depends on the etiology. should receive major emphasis in health education. The
three main measures to achieve this are:
Drug Therapy
i. Proper nutrition: Since breast milk offers distinct
Most episodes of diarrhea are self-limiting and do not advantages in promoting growth and development of
require any drug therapy except in a few situations. the infant and protection from diarrheal illness, its
Antibiotics are not recommended for routine treatment continuation should be encouraged. Exclusive breast
of acute diarrhea in children. In acute diarrhea, feeding may not be adequate to sustain growth beyond
antimicrobials are indicated in bacillary dysentery, cholera, the first 6 months of life. Therefore, supplementary
amebiasis and giardiasis. Escherichia coli are normal gut feeding with energy-rich food mixtures containing
flora and their growth on stool culture is not an indication adequate amounts of nutrients should be introduced
for antibiotics. Acute diarrhea may be the manifestation by 6 months of age without stopping breastfeeding.
of systemic infection and malnourished, prematurely born ii. Adequate sanitation: Improvement of environment
and young infants are at a high risk. Thus such babies sanitation, clean water supply, adequate sewage
should be screened and given adequate days of age disposal system and protection of food from exposure
appropriate systemic antibiotics for sepsis. Presence of to bacterial contamination are effective long-term
(i) poor sucking; (ii) abdominal distension; (iii) fever or strategies for control of all infectious illnesses including
hypothermia; (iv) fast breathing; and (v) significant diarrhea. Three 'Cs; clean hands, clean container and
lethargy or inactivity in well-nourished, well-hydrated clean environment are the key messages. Mother
infants points towards sepsis. should be properly educated about this. Complemen
There is little scientific evidence that binding agents tary foods should be protected from contamination
based on pectin, kaolin or bismuth salts are useful. Their during preparation, storage, and at the time of
use is not recommended in acute diarrhea. Antimotility administration.
agents such as synthetic analogues of opiates (diphenoxylate
iii. Vaccination: Evidence suggests that with improvement
hydrochloride or lomotil and loperamide or imodium)
in sanitation and hygiene in developing countries, the
reduce peristalsis or gut motility and should not be used
burden of bacterial and parasitic infection has
in children with acute diarrhea. Reduction of gut motility
decreased and viral agents have assumed an
allows more time for the harmful bacteria to multiply.
increasingly important etiologic role. Effective vaccines
These drugs may cause distension of abdomen, paralytic
are now available against the commonest agent, i.e.
ileus, bacterial overgrowth and sepsis and can be
rotavirus and their use might be an effective strategy
dangerous, even fatal, in infants.
for preventing acute diarrhea.
Antisecretory agents have been used in acute diarrhea.
Racecadotril is an antisecretory drug that exerts its Suggested Reading
antidiarrheal effects by inhibiting intestinal enkephalinase. • Bhatnagar S, Lodha R, Choudhury P, Sachdev HPS, Shah N,
Recent studies reported some evidence in favour of Narayan S, et al. IAP Guidelines 2006 on management of acute
racecadotril over placebo or no intervention in reducing diarrhea. Indian Pediatr 2007; 44:380.
• Piececik-Lech M, Shamir R, Guarino A, Szajewska H. Review article:
the stool output and duration of diarrhea in children with
the management of acute gastroenteritis in children. Aliment
acute diarrhea. However, more data on efficacy is needed Pharmacol Tuer. 2013; 37(3):289-303.
before it can be recommended for routine use in all
children with acute diarrhea. Dysentery
Probiotics, defined as microorganisms that exert beneficial Dysentery refers to the presence of grossly visible blood
effects on human health when they colonize the bowel, in the stools and is a consequence of infection of the colon
have been proposed as adjunctive therapy in the treatment by either bacteria or ameba. Bacillary dysentery is much
of acute diarrhea. Several microorganisms like Lactobacillus more common in children than amebic dysentery. The
rhamnosus (formerly Lactobacillus casei strain GG or bacteria causing bloody diarrhea are Shigella species
Diseases of Gastrointestinal System and Liver 1293-
(S. dysenteriae, S. flexneri, S. boydii and S. sonnei.), entero the gut. This worsens nutrient absorption and initiates
invasive and enterohemorrhagic E. coli, Salmonella and a vicious cycle that can only be broken by proper
Campylobacter jejuni. S.flexneri is the commonest organism nutrition. Persistent diarrhea is more common in
reported in developing countries and S. dysenteriae is malnourished children. Apart from malabsorption,
associated with epidemics of dysentery. malnutrition also results from inadequate calorie
A child with bacillary dysentery presents with fever intake due to anorexia, faulty feeding and improper
and diarrhea. Diarrhea may be watery to start with, but counseling regarding feeding by doctors. One of the
then shows mucus and blood mixed with stools. There is major obstacles to nutritional recovery is secondary
tenesmus, which refers to ineffectual defecation along with lactose intolerance, and in some cases, impaired
straining and suprapubic discomfort. The illness may be digestion of other complex carbohydrates due to
complicated by dehydration, dyselectrolytemia, hemolytic decrease in brush border disaccharidases.
uremic syndrome, convulsions, toxic megacolon, intestinal ii. Pathogenic E. coli, especially the enteroaggregative and
perforation, rectal prolapse and, very rarely, Shigella enteroadherent types, result in malabsorption by
encephalopathy. causing persistent infection.
Administration of ORS, continuation of oral diet, zinc iii. Associated infections of the urinary tract or another
supplementation and antibiotics are the components of focus of infection (more commonly in malnourished
treatment. Stool culture and sensitivity should be sent children) contribute to failure to thrive and mortality.
before starting empirical antibiotics. Antimicrobial agents iv. Prolongation of an acute diarrhea may rarely be a
are the mainstay of therapy of all cases of shigellosis. Based manifestation of cow milk protein allergy. The
on safety, low cost and efficacy, ciprofloxacin (15 mg/kg/ increased gut permeability in diarrhea predisposes to
day in two divided doses for 3 days) has been sensitization to oral food antigens.
recommended by World Health Organization (WHO) as
v. The use of antibiotics in acute diarrhea suppresses
the first line antibiotic for shigellosis. However,
normal gut flora. This may result in bacterial over
antimicrobial resistance to fluoroquinolones had increased
growth with pathogenic bacteria and/or overgrowth
significantly from 2002 to 2011 and only ceftriaxone has
of fungi, resulting in persistent diarrhea and
been shown to be uniformly effective. Keeping this in mind,
malabsorption.
intravenous ceftriaxone (50-100 mg/kg/ day for
3-5 days) should be the first line of treatment in a sick child. vi. Cryptosporidium infection is frequently implicated in
In a stable child, either ciprofloxacin or oral cefixime may persistent diarrhea, even in immunocompetent
be given, but the patient should be monitored for clinical children.
improvement within 48 hours (decrease in fever, stool
frequency and blood in stools). If no improvement is seen Clinical Features
at 48 hours, antibiotics should be changed appropriately. Majority of patients with persistent diarrhea pass several
Oral azithromycin (10 mg/kg/day for 3 days) can be used loose stools daily but remain well hydrated. Dehydration
for shigellosis but the experience is limited. develops only in some patients due to high stool output
Amebic dysentery is less common among children. The or when oral intake is reduced due to associated systemic
onset is insidious. Tinidazole or metronidazole is the drug infections. The major consequences of persistent diarrhea
of choice. Any young child presenting with blood in stools are growth faltering, worsening malnutrition and death
and persistent abdominal pain should be suspected to due to diarrheal or nondiarrheal illness. The presence of
have intussusception and evaluated accordingly. secondary lactose intolerance should be considered when
the stools are explosive (i.e. mixed with gas and passed
PERSISTENT DIARRHEA with noise) and in presence of perianal excoriation. The
stool pH is low and stool test for reducing substances is
Persistent diarrhea is an episode of diarrhea, of presumed positive. Unabsorbed dietary lactose once delivered to
infectious etiology, which starts acutely but lasts for more colon is converted to hydrogen and lactic acid by colonic
than 14 days. It should not be confused with chronic bacteria. Lactic acid results in decreased stool pH, explosive
diarrhea which has a prolonged duration but an insidious stools are due to hydrogen and unabsorbed lactose gives
onset and includes conditions causing malabsorption. positive reducing substances. There is no need for
laboratory testing for stool pH and reducing substances
Etiopathogenesis when the history is classical and excoriation is marked.
Although persistent diarrhea starts as acute infectious
diarrhea, the prolongation of diarrhea is not entirely Management
due to infection. Various factors that are implicated in The principles of management are: (i) correction of de
pathogenesis include: hydration, electrolytes and hypoglycemia; (ii) evaluation
i. The predominant problem is the worsening nutritional for infections using appropriate investigations (hemogram,
status that, in turn, impairs the reparative process in blood culture and urine culture) and their management;
294 I Essential Pediatrics
and (iii) nutritional therapy. Two-thirds of patients with cereal mixtures, e.g. milk or curd mixed rice gruel, milk
persistent diarrhea can be treated on outpatient basis. sooji gruel, or dalia are palatable, provide good quality
Patients in need of hospital admission are those with proteins and some micronutrients and result in faster
(i) age less than 4 months and not breastfed; (ii) presence weight gain than milk-free diets.
of dehydration; (iii) severe malnutrition (weight for height Second diet B (lactose-free diet with reduced starch): About
<3 SD, mid-upper arm circumference <11.5 cm for children 65-70% of children improve on the initial diet A. The
at 6-60 months of age, or bilateral pedal edema); or remainder have impaired digestion of starch and
(iv) presence or suspicion of systemic infection. disaccharides other than lactose. These children, if free of
systemic infection, are advised diet B which is free of milk
Nutrition
(lactose) and provides carbohydrates as a mixture of
Feeding should be started at the earliest. Initially 6-7 feeds cereals and glucose. Milk protein is replaced by chicken,
are given everyday and a total daily caloric intake of egg or protein hydrolysate. The starch content is reduced
100 kcal/kg/day is ensured. Caloric intake should be and partially substituted by glucose. Substituting only part
increased gradually over 1-2 weeks to 150 kcal/kg/day of the cereal with glucose increases the digestibility but at
in order to achieve weight gain. Tube (nasogastric) feeding the same time does not cause a very high osmolarity.
may be done initially in children with poor appetite due
to presence of serious infection. To ensure absorption and Third diet C (monosaccharide-based diet): Overall,
decrease stool output, one may attempt to overcome 80-85% of patients with severe persistent diarrhea will
varying degrees of carbohydrate maldigestion by using recover with sustained weight gain on the initial diet A or
diets with different degrees of carbohydrate exclusion in the second diet B. A small percentage may not tolerate a
the form of diet A (lactose reduced), diet B (lactose free) moderate intake of the cereal in diet B. These children are
and diet C (complex carbohydrate free) diets (Table 12.13). given diet C which contains only glucose and a protein
source as egg white or chicken or commercially available
Initial diet A (reduced lactose diet; milk rice gruel, milk protein hydrolysates. Energy density is increased by
sooji gruel, rice with curds, dalia): This is based on the adding oil to the diet.
fact that secondary lactose intolerance exists in children The strategy of serial carbohydrate exclusion to varying
with persistent diarrhea and malnutrition. Clinical trials degrees in plan A, B and C diets are meant to circumvent
have shown that reduced lactose diet is tolerated equally the problem of carbohydrate malabsorption. In addition
well as totally lactose-free diet, without significantly green (unripe) banana diet is gaining acceptance for
increasing stool output or risk of dehydration. If the treatment of persistent diarrhea. Fermentation of
patient is fed entirely on animal milk, the quantity should nondigestible soluble fibers in cooked green (unripe)
be reduced to 50-60 mL/kg providing not more than 2 g banana by colonic bacteria generates short chain fatty acids
of lactose/kg/ day. To reduce lactose concentration in which are absorbed along with sodium in the colon,
animal milk, it should be mixed with cereals, but not thereby facilitating water absorption by solvent drag and
diluted with water as that reduces the caloric content. Milk also conserving dietary nutrients.
Constituents
Milk (1/3 katori/50 ml) Egg white (3 tsp/half egg white) Chicken puree (5 tsp/15 g) or
Puffed rice powder/cooked rice or Puffed rice powder/cooked rice egg white (3 tsp/half egg white)
sooji (2 tsp/6 g) (3 tsp/9 g)
Sugar (1 Y2 tsp/7 g) Glucose (1 Y2 tsp/7 g) Glucose (1 Y2 tsp/7 g)
Oil (1 tsp/4.5 g) Oil (1 Y2 tsp/7 g) Oil (1 Y2 tsp/7 g)
Water (2/3 katori/100 ml) Water (3/4 katori/120 ml) Water (1 katori/150 ml)
Preparation
Mix milk, sugar and rice, add After whipping the egg white, Boil chicken and make puree after removing bones.
boiled water and mix well, add add rice, glucose and oil and mix Mix it with glucose and oil. Add boiled water to
oil. well. Add boiled water and mix make a smooth flowing feed
rapidly to avoid clumping
Nutrient content
85 kcal and 2.0 g protein 90 kcal and 2.4 g protein 67 kcal and 3.0 g protein per 100 g
per 100 g per 100 g
Diseases of Gastrointestinal System and Liver 1295-
Indications for change from the initial diet (diet A) to the stools/day for 2 consecutive days) and weight gain. Most
next diet (diet B or diet C): The diet should be changed to children will lose weight in the initial 1-2 days and then
the next level, if the child shows (i) marked increase in show steady weight gain as associated infections are
stool frequency (usually more than 10 watery stools/day) treated and diarrhea subsides. All children should be
at any time after at least 48 hours of initiating the diet; followed regularly even after discharge to ensure conti
(ii) features of dehydration any time after initiating nued weight gain and compliance with feeding advice.
treatment; or (iii) failure to gain weight gain by day 7 in
the absence of initial or hospital acquired systemic Prognosis
infection. Unless signs of treatment failure occur earlier, Most patients with persistent diarrhea recover with an
each diet should be given for a minimum period of 7 days. approach of stepped up dietary management as discussed
Resumption of regular diet after discharge: Children above. A small subgroup (<5%) may be refractory and
discharged on totally milk-free diet should be given small require parenteral nutrition and extensive workup. These
quantities of milk as part of a mixed diet after 10 days. If patients generally have high purge rate, continue to lose
they tolerate this and have no signs of lactose intolerance weight, do not tolerate oral feeds and require referral to
(abdominal pain, abdominal distension and excessive specialized pediatric gastroenterology centers.
CHRONIC DIARRHEA
flatulence) then milk can be gradually increased over the
next few days. Age appropriate normal diet can then be
resumed over the next few weeks. Chronic diarrhea is a common problem in children. It is
Supplement vitamins and minerals: Supplemental defined as an insidious onset diarrhea of >2 weeks
multivitamins and minerals, at about twice the RDA, duration in children and >4 weeks in adults. The term
should be given daily to all children for at least 2-4 weeks. chronic diarrhea is not synonymous with persistent
Iron supplements should be introduced only after the diarrhea. The approach, etiology and management of
diarrhea has ceased. Vitamin A (as a single dose) and zinc chronic diarrhea along with a brief outline of some
are supplemented as both of them enhance the recovery common causes is discussed.
from persistent diarrhea. A single oral dose of vitamin A
Approach
should be given routinely, at 2,00,000 IU for children
>12 months or 100,000 IU for children 6-12 months. Approach to chronic diarrhea must be considered with
Children weighing less than 8 kg, irrespective of their age, the following points in mind:
should be given 1,00,000 IU of vitamin A. One should Age of onset: A list of common causes of chronic diarrhea
administer 10-20 mg per day of elemental zinc for at least according to age of onset is shown in Table 12.14.
2 weeks to children between 6 months and 3 years of age. Small or large bowel type of diarrhea: Features in history
Additional supplements for severely malnourished infants and examination that help in differentiating small bowel
and children: Magnesium and potassium supplementation from large bowel diarrhea is shown in Table 12.15.
is provided to these children. Magnesium is given by Typically, large volume diarrhea without blood and
intramuscular route at 0.2 mL/kg/dose of 50% magnesium mucus suggests small bowel type of diarrhea and small
sulfate twice a day for 2-3 days. Potassium is volume stools with blood and mucus suggest large bowel
supplemented at 5-6 mEq/kg/day orally or as part of type of diarrhea.
intravenous infusion during the initial stabilization period. Gastrointestinal versus systemic causes: Diarrhea is most
Role of antibiotics: The indiscriminate use of antibiotics commonly of intestinal origin and sometimes pancreatic,
in the treatment of acute diarrhea is among the reasons or rarely, hepatobiliary in etiology. Cholestasis due to
for persistent diarrhea. Hence, the use of empirical biliary obstruction or intrahepatic cause can cause diarrhea
antibiotics at admission is to be individualized and due to fat malabsorption. Pruritus and malabsorption of
reserved for children with either of the following features: fat-soluble vitamins (A, D, E and K) and calcium are
(i) severe malnutrition (majority of these children have commonly associated. Maldigestion due to deficiency of
associated systemic infections and clinical signs of pancreatic enzymes leads to pancreatic diarrhea in cystic
infection may not be obvious); and (ii) evidence of systemic fibrosis, Shwachman-Diamond syndrome (cyclic neutro
infection. A combination of cephalosporin and amino penia and bone abnormalities) or chronic pancreatitis.
glycoside can be started empirically and thereafter Other causes include Zollinger-Ellison syndrome, and
changed according to reports of culture/ sensitivity. secretory tumors like VIPoma, carcinoid or mastocytosis.
Urinary tract infection is common (seen in 10-15%) and Diarrhea may also be a systemic manifestation of other
should be treated appropriately. conditions like sepsis or collagen vascular disorders.
Specific questions in history should include:
Monitoring Response to Treatment i. Duration of symptoms; nature, frequency and
Successful treatment is characterized by adequate food consistency of stools; and presence of blood, mucus or
intake, reduced frequency of diarrheal stools (<2 liquid visible oil in stools
296 Essential Pediatrics
Table 12.14: Causes of chronic diarrhea according to age of onset (in order of importance)
Age <6 months Age >6 months to 5 years Age >5 years
Cow milk protein allergy Cow milk protein allergy Celiac disease
Lymphangiectasia Celiac disease Giardiasis
Urinary tract infection* Giardiasis Gastrointestinal tuberculosis
Short bowel syndrome** Toddler diarrhea Inflammatory bowel disease
Immunodeficiency states Lymphangiectasia Immunodeficiency
Cystic fibrosis Short bowel syndrome** Bacterial overgrowth
Anatomical defects Tuberculosis Lymphangiectasia
Intractable diarrheas of infancy*** Inflammatory bowel disease Tropical sprue
Microvillous inclusion disease Immunodeficiency lmmunoproliferative small
Tufting enteropathy Bacterial overgrowth intestinal disease
Autoimmune enteropathy Pancreatic insufficiency Pancreatic insufficiency
Glucose galactose malabsorption
Congenital sodium/chloride diarrhea
Should be considered in young infants with chronic diarrhea, particularly if fever is noted
Consider if there is antecedent history of small bowel surgery
These rare conditions should only be considered if the diarrhea is very early in its onset (neonate to 3 months) and common conditions have
been ruled out
ii. Age of onset; relationship of dietary changes, e.g. iii. Signs of vitamin or mineral deficiencies (e.g.
introduction of milk or milk products and wheat or conjunctiva! xerosis, Bitot's spots, angular stomatitis,
wheat products, with onset of diarrhea; and any glossitis, cheilitis, rickets, phrynoderma)
specific dietary preferences, like avoidance of juices iv. Edema, whether symmetric or asymmetric; pitting or
iii. Family history of atopy (food allergy, asthma or allergic non-pitting (lymphedema)
rhinitis), celiac disease, Crohn's disease or cystic fibrosis v. Fever and signs of systemic sepsis
iv. History of abdominal surgery, drug intake, systemic vi. Extragastrointestinal manifestations in eye, skin, joints,
disease, features of intestinal obstruction, pedal edema, oral cavity (suggest inflammatory bowel disease, IBD)
anasarca, recurrent infections at multiple sites, vii.Inspection of perianal area for fissures, anal tags and
previous blood transfusion and coexisting medical fistulae (seen in IBD)
problems which predispose the child to diarrhea (e.g. viii. Oral thrush and scars of recurrent skin infections
congenital immunodeficiency, diabetes mellitus, (suggest immunodeficiency)
hyperthyroidism, cystic fibrosis) ix. Abdominal distention, localized or generalized
tenderness, masses, hepatosplenomegaly and ascites.
Important components of physical examination Approach based on age of onset: In infants <6 months,
include: cow milk protein allergy and intestinal lymphangiectasia
i. Anthropometry should be considered first. The important clues to each
ii. Signs of dehydration etiology are given in Table 12.16.
Diseases of Gastrointestinal System and Liver 1297-
Table 12.16: Diagnostic clues to important causes of chronic common cause of chronic diarrhea in children over 2 years
diarrhea of age in North India. High-risk groups include subjects
Cow milk Onset of diarrhea after introduction of with Type 1 diabetes mellitus, Down syndrome, selective
protein allergy cow or buffalo milk or formula IgA deficiency, autoimmune thyroid disease, Turner
Rectal bleeding (due to colitis) syndrome, Williams syndrome, autoimmune liver disease
Anemia; failure to thrive and first-degree relatives of celiac disease patients. These
Family history of allergy or atopy subjects are at an increased risk of developing celiac
Response to milk withdrawal disease and thus should be screened.
Lymphangiectasia Nonpitting pedal edema suggesting Presentation: The classical presentation is with small
lymphedema bowel diarrhea, growth failure and anemia. A temporal
Recurrent anasarca association of diarrhea and introduction of wheat products
Hypoalbuminemia and hypoproteinemia at weaning may be present. Onset of diarrhea before
Lymphopenia
introduction of wheat products in diet negates a diagnosis
Hypocalcemia
of celiac disease. It may also present without chronic
Cystic fibrosis History of meconium ileus diarrhea as refractory iron deficiency or dimorphic anemia
Predominant or associated lower not responding to oral supplements, short stature, delayed
respiratory tract infections puberty, rickets and osteopenia. Examination reveals
Severe failure to thrive
failure to thrive, loss of subcutaneous fat, clubbing,
Clubbing
anemia, rickets and signs of other vitamin deficiencies.
History of sibling deaths
High sweat chloride (>60 mEq/L)
A high index of suspicion for celiac disease is the key
to diagnosis.
Immuno Predominant fever
deficiencies Recurrent infections involving other sites Diagnosis: The main investigations required for making
History of sibling deaths a diagnosis include:
Organomegaly i. Serology: IgA antibody against tissue transglutaminase
Opportunistic infections on stool (tTG) is an ELISA based test, recommended for initial
examination testing of celiac disease. It has a high sensitivity (92-
100%) and specificity (91-100%) in both children and
In young children, celiac disease is the most common adults. IgA antiendomysial antibody is an equally
cause of chronic diarrhea in North India. Cow milk protein accurate test (sensitivity 88-100%; specificity 91-100%)
allergy usually resolves by 3-5 years; hence, this diagnosis but is more difficult to perform. The diagnosis of celiac
should not be considered in children with onset of diarrhea disease should not be based only on celiac serology as
beyond 5 years. Toddler diarrhea is a diagnosis of exclusion serology may be false positive, false negative and
after common causes have been ruled out. The onset of interlaboratory variations are also present.
diarrhea is between 6 months and 3 years of age. The child ii. Upper GI endoscopy: It may be normal or show absence
passes 3-6 loose stools, mostly during waking hour. of folds or scalloped folds (Fig. 12.16a). Multiple (4-6
Diarrhea worsens with low residue, low fat or high in number) endoscopic biopsies from the bulb and
carbohydrate diet. The child is well thriving, there is no second/third part of duodenum should be taken in
anemia or vitamin deficiencies and the diarrhea resolves all cases.
spontaneously by about 4 years of age. Treatment is with iii. Histology: The characteristic histological changes in
dietary modification; a high (>40%) fat, low carbohydrate celiac disease are increased intraepithelial lymphocytes
diet (especially with decreased intake of juices) and (>30/100 enterocytes), increased crypt length, partial
increase in dietary fiber is recommended. IBD is less to total villous atrophy, decreased villous to crypt ratio
common in this age group as compared to older children. and infiltration of plasma cells and lymphocytes in
Giardiasis can be diagnosed, if multiple fresh stool samples lamina propria (Fig. 12.16b).
(at least 3 in number) are tested for trophozoites. The Diagnosis of celiac disease (based on the modified
laboratory may be asked to use concentration methods. criteria of the European Society of Pediatric Gastro
Presence of cysts of giardia in immunocompetent patients enterology, Hepatology and Nutrition, ESPGHAN)
does not merit a therapy of giardiasis. require the following:
Limited etiologies cause chronic diarrhea in older i. Clinical features compatible with diagnosis.
children (Table 12.16). A brief description of common ii. Positive intestinal biopsy as described above with or
causes of chronic diarrhea is given below. without serology.
iii. Unequivocal response to gluten-free diet (GFD) within
Celiac Disease 12 weeks of initiation of GFD.
This is an enteropathy caused by permanent sensitivity A positive serology makes the diagnosis more definite
to gluten in genetically susceptible subjects. It is the most especially in developing countries where other causes of
29a I Essential Pediatrics
Fig. 12.16: Celiac disease: (a) Upper gastrointestinal endoscopy showing scalloping of duodenal folds (arrow); and (b) Duodenal
histology showing total villous atrophy
villous atrophy are common due to intercurrent infections of milk intake and is characterized by vomiting, pallor,
or undernutrition. shock-like state, urticaria and swelling of lips. (ii) Delayed,
The recent ESPGHAN guidelines suggest that in i.e. T cell mediated: It has an indolent course and presents
symptomatic patients with tTG > lOULN, the diagnosis of mainly with GI symptoms.
celiac disease may be made without a duodenal biopsy Symptoms: The most common presentation is with
provided that the antiendomysial antibody and HLA diarrhea with blood and mucus. Depending upon the site
DQ2/DQ8 are positive and there is a definite response to and extent of involvement, the child may have small
gluten-free diet. However, in view of non-availability and bowel, large bowel or mixed type diarrhea. In an Indian
cost of antiendomysial antibody and HLA testing and study, 40% children presented with bloody diarrhea, 33%
multiple labs reporting tTG as positive/negative only watery and 7% with a mixed type of diarrhea.
without actual titres this approach is not recommended Uncommonly reflux symptoms and hematemesis may be
in our country at present. This is especially important as present indicating upper GI involvement. Respiratory
it is very difficult to confirm or refute the diagnosis of CD symptoms (allergic rhinitis and asthma) and atopic
after initiation of GFD. Thus all efforts should be made to manifestations (eczema, angioedema) may be seen in
make a correct diagnosis with full work-up at onset prior 20-30% and 50-60% cases, respectively. Iron deficiency
to initiation of GFD. anemia, hypoproteinemia and eosinophilia are commonly
Treatment: The treatment involves lifelong GFD and present.
correction of iron, folate and other vitamin/mineral Diagnosis: In India, non-IgE-mediated CMPA is more
deficiencies by supplementation. The patient should be common. Sigmoidoscopy (aphthous ulcers and nodular
assessed at 3 months for response to GFD. After initiation lymphoid hyperplasia as seen in Fig. 12.17a) and rectal
of GFD, all symptoms should subside and weight and biopsy (plenty of eosinophils as seen in Fig. 12.17b) give
height gain should be present. Repeated explanation to clue to the diagnosis in >95% cases irrespective of the
patient and parents by doctors is very helpful in sustaining clinical presentation and should be the first line of
compliance after the child has become asymptomatic. investigation in suspected cases. The gold standard for
diagnosis of any food allergy is the elimination and
Cow Milk Protein Allergy challenge test. Typically, the symptoms subside after milk
Cow milk protein allergy (CMPA) affects 2 to 5% of all withdrawal and recur within 48 hours of re-exposure to
children in the West, with the highest prevalence during milk.
the first year of life. In India, CMPA accounts for -13% of Treatment: All animal milk/milk products have to be
all malabsorption cases in children <2 years of age. A removed from the diet. Soy or extensively hydrolyzed
family history of atopy is common in children with CMPA. formula, both of which are equally effective in terms of
Nearly 50% children outgrow the allergy by 1 year and growth and nutrient intake can be used as alternatives.
-95% by 5 years of age. It is the most common food allergy Although soy is more palatable and cheap but it is not
in small children who are top-fed but can also occur recommended in infants <6 months of age. Also 10-15%
occasionally in breastfed babies due to passage of cow of CMPA have concomitant soy allergy, thus necessitating
milk antigen in breast milk. use of extensively hydrolyzed formulae. A minority of
There are two kinds of reactions to cow milk: children may not tolerate the extensively hydrolyzed
(i) Immediate, i.e. IgE mediated: It occurs within minutes formulae and need elemental amino acid formulas.
Diseases of Gastrointestinal System and Liver 1299-
Fig. 12.17: Cow milk protein allergy: (a) Sigmoidoscopy showing aphthous ulcers; and (b) Rectal biopsy showing eosinophilic
infiltration with crypt abscess
Parental education regarding diet and calcium supplemen mucosa. On UGI endoscopy after fat loading with 2 g/kg of
tation is essential. butter at bedtime, scattered white plaques or chyle-like
substance covering the mucosa may be seen (Fig. 12.18a).
Intestinal Lymphangiectasia Duodenal biopsy reveals dilated lacteals in villi and lamina
It is characterized by ectasia of the bowel lymphatic propria (Fig. 12.18b). The treatment consists of a low fat,
system, which on rupture causes leakage of lymph in the high protein diet with MCT oil, calcium and fat-soluble
bowel. The disease is often associated with abnormal vitamin supplementation. Intravenous albumin is
lymphatics in extremities. Signs and symptoms include required for symptomatic management and total
peripheral edema which could be bilateral and pitting due parenteral nutrition (TPN) is reserved for management
to hypoalbuminemia or asymmetrical and non-pitting due of chylous effusions. Resection may be considered, if the
to lymphedematous limb. Diarrhea, abdominal distension lesion is localized to a small segment of intestine.
and abdominal pain are commonly present. Abdominal
and/ or thoracic chylous effusions may be associated. Immunodeficiency
Presence of hypoalbuminemia, low immunoglobulins, Both congenital and acquired immunodeficiency can cause
hypocalcemia and lymphopenia is characteristic of chronic diarrhea. It should be suspected, if there is history
lymphangiectasia. Barium meal follow-through shows of recurrent infections at multiple sites (chest/GI/skin)
thickening of jejuna! folds with nodular lucencies in and wasting. The common immunodeficiency conditions
Fig. 12.18: Intestinal lymphangiectasia. (a) Upper gastrointestinal endoscopy showing white deposits; and (bl Duodenal histology
shows dilated lacteals
aoo I Essential Pediatrics
presenting with diarrhea include IgA deficiency, severe iv. Protozoa. Microsporidium, Isospora belli, Cryptosporidium,
combined immunodeficiency (SCID), common variable Entamoeba histolytica, Giardia lamblia, Cyclospora,
immunodeficiency (CVID) and chronic granulomatous Blastocystis hominis
disease (CGD). There is increased risk of celiac disease Multiple stool examinations are required to identify the
(10-20-fold increase) and Crohn's disease in patients with causative etiology by using special stains and PCR
IgA deficiency. Diarrhea is either due to enteric infections techniques. Colonic/terminal ileum biopsy and duodenal
like giardia, cryptosporidium, CMV, etc. or due to bacterial fluid examination are the other ways of diagnosing
overgrowth. Diagnosis is made by measuring serum opportunistic infections. Treatment is with specific
immunoglobulins, T cell counts and functions, phagocytic antimicrobials (Table 12.17) along with HAART (highly
function (nitroblue tetrazolium reduction test) depending active antiretroviral therapy).
upon the suspected etiology. Treatment involves
administration of antimicrobials for bacterial overgrowth Drug-Induced Diarrhea
and opportunistic infections and therapy for underlying Diarrhea can be a side effect of many pharmacologic
cause (IV immunoglobulins, y interferon or bone marrow agents. Altered GI motility, mucosal injury and/or change
transplantation). in intestinal microflora are the main etiologic factors. Anti
Acquired immunodeficiency syndrome (AIDS): Chronic biotics can cause loose watery stools by altered bacterial
diarrhea is a common feature in children with AIDS. The flora or bloody stools secondary to Clostridium difficile
impaired mucosal immunity results in recurrent overgrowth and pseudomembranous colitis (PMC).
opportunistic infections and the altered maturation and Stopping the offending agent is often enough. If suspicion
function of enterocytes results in increased permeability of PMC is present then stool for toxin assay and sigmoido
and decreased functional absorptive surface with or scopy is required for confirmation. Metronidazole or oral
without bacterial overgrowth. AIDS enteropathy is vancomycin is the drug of choice for PMC.
characterized by chronic diarrhea and marked weight loss
in absence of enteric pathogens. The children are often Inflammatory Bowel Disease (IBD)
sick with other clinical manifestations but sometimes IBD is a chronic inflammatory disease of the GI tract and
diarrhea may be the only symptom. Presence of oral is of two main types, Crohn's disease and ulcerative colitis.
thrush, lymphadenopathy, hepatosplenomegaly and In -10% cases, the findings are non-specific and subjects
parotiditis (10-20% cases) gives clue to the diagnosis. The cannot be classified into one of the above two groups.
common infections include: These cases are labelled as indeterminate colitis. Nearly
i. Viral. Cytomegalovirus, herpes simplex, adenovirus, 25% of all IBD presents in the pediatric age group.
norovirus Worldwide the incidence of IBD is increasing in children
ii. Bacterial. Salmonella, Shigella, Mycobacterium avium with increase in recent reports of both ulcerative colitis
complex (MAC), Campylobacter jejuni, Clostridium difficile and Crohn's disease from India. The average age of
iii. Fungi. Candidiasis, histoplasmosis, cryptococcosis presentation in children is -10-11 years. Genetics is a very
Fig. 12.19: Inflammatory bowel disease: (a) Deep, linear, serpigenous ulcers on colonoscopy in Crohn's disease; and (bl Confluent
superficial ulcerations with friability on colonoscopy in ulcerative colitis
Abdominal Tuberculosis
The gastrointestinal tract, peritoneum, lymph nodes and/
or solid viscera can be involved in abdominal tuberculosis.
The peritoneal involvement is of two types: Wet (or ascitic)
and dry (or plastic) type. On the other hand, the intestinal
involvement may be ulcerative, hypertrophic or ulcero
hypertrophic type.
The clinical presentation is varied and depends upon
the site of disease and type of pathology. Clinical features
may include chronic diarrhea, features of subacute
intestinal obstruction (abdominal pain, distension, Fig. 12.20: CT scan showing multiple enlarged lymph nodes
vomiting, obstipation), ascites, lump in abdomen (ileocecal with central necrosis in para-aortic and mesenteric regions in
mass, loculated ascites, lymph nodes) and/or systemic abdominal tuberculosis
manifestations (fever, malaise, anorexia and weight loss).
A high index of suspicion followed by documenting
presence of acid-fast bacilli (fine needle aspiration cytology
from lymph nodes, ascitic fluid, endoscopic biopsies) on
Ziehl-Neelsen staining, PCR or culture leads to a definitive
diagnosis. Presence of tubercular granuloma with
caseation in the biopsies (endoscopic, peritoneal or liver)
also helps make the diagnosis. CT abdomen shows
enlarged lymph nodes with central necrosis (Fig. 12.20).
An exudative ascites (low serum ascites albumin gradient,
SAAG <1.1) with lymphocyte predominance and high
adenosine deaminase is typical of tubercular ascites.
Colonoscopy classically shows transverse ulcers in
ascending colon/caecum, deformed/ ulcerated ileocaecal
valve and ulceration/stricture in terminal ileum
(Fig. 12.21). In absence of above features, a probable
diagnosis of abdominal tuberculosis is made when
suggestive clinical features and response to antitubercular
therapy is present. It is important to differentiate intestinal
TB from Crohn' s disease as they mimic each other in Fig. 12.21: Colonoscopy shows ulceration with gaping
clinical presentation but have different treatments. ileocecal valve in a patient with ileocecal tuberculosis
Diseases of Gastrointestinal System and Liver 1303-
Antitubercular drugs are the mainstay of treatment. Hemobilia refers to bleeding from the biliary tree while
Surgery is indicated, if there is bowel perforation, pseudohematobilia is bleeding from the pancreas. Obscure
obstruction or massive hemorrhage. One should suspect GI bleed is defined as bleeding from gastrointestinal tract
multidrug resistant tuberculosis in patients with a definite that persists or recurs without any obvious etiology after
diagnosis of abdominal tuberculosis but a poor response a diagnostic esophagogastroduodenoscopy and colono
to standard antitubercular therapy. scopy. It accounts for -5% of all GI bleeds.
Suggested Reading Upper GI Bleeding
• Braamskamp MJ, Dolman KM, Tabbers MM. Clinical practice.
Protein-losing enteropathy in children. Eur J Pediatr 2010; 169: The causes of hemorrhage from upper GI tract vary in
1179-85. different age groups as shown in Table 12.19. Varices,
• du Toit G, Meyer R, Shah N, et al. Identifying and managing cow esophagitis and gastritis are the commonest causes of
milk protein allergy. Arch Dis Child Educ Pract Ed 2010; 95:134-44. upper GI bleeding in Indian children.
• Feasey NA, Healey P, Gordon MA. Review article: the etiology, Painless passage of large amount of blood in vomitus
investigation and management of diarrhea in the HIV-positive
patient. Aliment Pharmacol Ther 2011; 34:587-603. points towards variceal bleeding. One should always look
• Husby S, Koletzko S, Korponay-Szab6 IR, European Society for for features of liver disease like splenomegaly, jaundice
Pediatric Gastroenterology, Hepatology and Nutrition Guidelines and ascites. In portal hyp ertension, the spleen may reduce
for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr in size just after a bout of massive hematemesis and is
2012; 54:136--oO. thus missed on examination. In a child with portal
• Poddar U, Yachha SK, Krishnani N, Srivastava A. Cow milk protein hypertension, esophageal varices are the commonest cause
allergy: An entity for recognition in developing countries.
Gastroenterol Hepatol 2010; 25:178-82. of upper GI bleeding (Fig. 12.22a). Gastric varices
• Sandhu BK, Fell JM, Beattie RM, et al. on Behalf of the IBD Working (Fig. 12.22b), congestive gastropathy and gastric antral
Group of the British Society of Paediatric Gastroenterology, vascular ectasia can also present with hematemesis.
Hepatology and Nutrition. Guidelines for the Management of
Inflammatory Bowel Disease in Children in the United Kingdom. Management
J Pediatr Gastroenterol Nutr. 2010 Feb; 50:Sl-S13.
General supportive measures, including establishing a
GASTROINTESTINAL BLEEDING good venous access, intake output monitoring, oxygen
supplementation (if required) and charting of vital signs
Gastrointestinal bleeding is a commonly encountered are mandatory. Blood transfusion should be given to
problem in children. Upper gastrointestinal bleeding is achieve hemoglobin of 7 g/ dL. Short-term antibiotic
defined as bleeding from a site proximal to the ligament prophylaxis (third generation cephalosporin for 7 days)
of Treitz (at the level of duodenojejunal flexure). Lower may reduce bacterial infection, and variceal rebleeding,
gastrointestinal bleeding is defined as bleeding from a site and should be administered in children with cirrhosis and
distal to ligament of Treitz. variceal bleeding. Specific treatment depends upon the
Hematemesis is passage of blood in vomiting and suggests patient's condition and expertise of the available
an upper GI site of bleeding. The vomitus may be bright personnel. A combination of pharmacologic and
red or coffee-ground in color depending upon the severity endoscopic therapy is preferred. Early administration of
of hemorrhage and the duration it stayed in contact with vasoactive drugs should be followed by endoscopic
gastric secretions. Melena is passage of black tarry stools therapy within 12 hours of bleed. Following an episode
and suggests an upper GI or small bowel source of bleed. of acute variceal bleeding, all patients should receive
Hematochezia is passage of bright red blood in stools. secondary prophylaxis to prevent rebleeding.
Fig. 12.22: Upper gastrointestinal endoscopy showing (a) Esophageal varices; and (b) Large gastric varices
Administration of somatostatin or octreotide decreases parenchyma. The passage is dilated by a balloon and an
the splanchnic and azygous blood flow, thus reducing expansile metallic mesh prosthesis is placed to maintain
portal pressures. Both agents are equally effective; limited the communication directly between the portal vein and
studies in children have shown control of bleeding in hepatic vein. This procedure results in bypassing liver
64-71% children. Infusion should be given for at least resistance and consequently decreases the portal pressure.
24-48 hours after the bleeding has stopped to prevent Experience of this procedure in children is limited.
recurrence and should not be discontinued abruptly.
Endoscopic sclerotherapy (EST) or variceal ligation Surgical management is required when above measures
(EVL) are the two main methods used to manage have failed or when bleeding is from ectopic varices that
esophageal varices. Using a fiberoptic endoscope, the cannot be effectively controlled by endoscopic procedures.
varices are inspected and their location, size and extent Surgery can be done either in the form of portocaval shunt
are documented. In EST, 2-3 mL of sclerosant (1 % (selective or nonselective) or devascularization with
ethoxysclerol) is injected into each variceal column. EVL esophageal staple transection.
is done with a device called multiple band ligator. The
variceal column is sucked into a cylinder attached at the Lower Gastrointestinal Bleeding
tip of the endoscope and the band is deployed by pulling The causes of lower gastrointestinal bleeding in children
the trip wire around the varix. Both EST and EVL have are shown in Table 12.20. History and physical examina
90-100% efficacy in controlling acute bleeding. tion helps narrow down the differential diagnosis.
Gastric varices are managed with endoscopic injection of Increased frequency of stools with blood and mucus with
tissue adhesive glue, i.e. N-butyl-2-cyanoacrylate or crampy abdominal pain points towards a colitic illness
isobutyl-2-cyanoacrylate. These agents harden within and infectious colitis is by far the commonest cause in
20 seconds of contact with blood and result in rapid control children across all ages. A sick preterm with abdominal
of active bleeding. distension, blood in stools, feed intolerance and systemic
instability is likely to have necrotizing enterocolitis.
Tamponade of varices is required only when the Delayed passage of meconium followed by constipation,
endoscopic and pharmacologic measures have failed. abdominal pain and distension is seen in Hirschsprung's
Sengstaken-Blakemore tube is a triple lumen tube with disease. Allergic colitis is mostly seen in infants who are
connection to an esophageal balloon, a gastric balloon and top fed with cow milk and present with loose stools mixed
one perforated distal end which helps in aspiration of the with blood and anemia. Onset of bloody diarrhea after
stomach contents. The tube is relatively cheap, requires antibiotic use points towards pseudomembranous colitis.
little skill compared to EST and has efficacy of above 75% Presence of extraintestinal manifestations, like aphthous
in controlling acute variceal bleeding. ulcers, joint pains and iritis, gives clue to the diagnosis of
Transjugular intrahepatic portosystemic shunt (TIPS) inflammatory bowel disease (IBO). History of painful
involves insertion of a multipurpose catheter through the defecation and passage of hard stools with blood streaking
jugular vein and superior vena cava with the aid of the of stools is seen in anal fissure. In a patient with history of
puncture device. The catheter is passed via hepatic vein constipation, straining at stools and digital evacuation, the
into a branch of portal vein through the hepatic most likely cause of bleeding is solitary rectal ulcer
Diseases of Gastrointestinal System and Liver laos-
Table 12.20: Causes of lower gastrointestinal bleeding
Neonate or infant Children >2 years
Colitis
Infectious colitis Infectious colitis
Cow milk protein allergy Inflammatory bowel disease
Necrotizing enterocolitis Tuberculosis
Hirschsprung Pseudomembranous colitis
enterocolitis Cow milk protein allergy
Systemic vasculitis Amebiasis, cytomegalovirus,
neutropenic colitis
Others
Anal fissure Anal fissure
lntussusception Polyp or polyposis syndrome
Duplication cyst Solitary rectal ulcer syndrome
Arteriovenous malformation Meckel's diverticulum
Rectal prolapse NSAID-induced ulcer
Meckel's diverticulum Hemorrhoids, rectal prolapse
Hemorrhagic disease Henoch-Schonlein purpura
of newborn Arteriovenous malformation
Coagulopathy Coagulopathy
Fig . 12.23: Colonosc opy showing multiple sessile and
Tumors: Leiomyoma, lymphoma
pedunculated polyps in a child with polyposis coli
syndrome (SRUS). Intussusception is characterized by cutaneous lesions as seen in blue rubber bleb nevus
episodes of abdominal pain, vomiting and red currant syndrome often suggests the diagnosis. Children with HIV
jelly stools, i.e. mixture of blood, mucoid exudates and infection or immunosuppression secondary to chemo
stool. Painless bleeding is seen commonly in polyps therapy can develop CMV enterocolitis or polymicrobial
(Fig. 12.23), Meckel's diverticulum (Fig. 12.24), varices inflammation of cecum (typhlitis), both of which can lead
(Fig. 12.25), ulcer or vascular anomaly. Presence of typical to significant rectal bleeding.
Fig. 12.24: Technetium-99m pertechnetate scan showing Fig. 12.25: Colonoscopy showing rectal varix in a patient with
Meckel's diverticulum EHPVO and lower GI bleeding
306 Essential Pediatrics
Lower GI bleeding
Prothrombin time (PT) and international normalized Table 12.22: Causes of hepatomegaly
ra tio (INR): Deficiency of factors V and vitamin K
Chronic liver disease (cirrhosis or chronic hepatitis): Wilson
dependent factors (II, VII, IX and X) occurs in liver disease.
disease, chronic hepatitis B and C, autoimmune liver disease,
PT is a marker of synthetic function of liver. INR is a Budd-Chiari syndrome, cryptogenic
standardized way of reporting the prothrombin time. It is
Metabolic or storage disorders: Glycogen storage disease,
the ratio of a patient prothrombin time to a normal sample,
Gaucher disease, Niemann-Pick disease, progressive familial
raised to the power of the international sensitivity index
intrahepatic cholestasis, nonalcoholic fatty liver disease
(ISi) value for the analytical system used. ISi ranges
between 1.0 and 2.0 and shows how a batch of tissue factor Infective: Viral hepatitis, liver abscess (pyogenic or amebic),
tuberculosis, salmonella, malaria, kala-azar, hydatid disease
compares to an internationally standardized sample.
Tumors: Lymphoma, leukemia, histiocytosis, neuroblastoma,
INR = (PT test/PT normal)rsr benign hemangioendothelioma, mesenchymal hamartoma,
hepatoblastoma, hepatocellular carcinoma
The reference range for prothrombin time is usually
Biliary. Caroli disease, choledochal cyst, congenital hepatic
around 11-16 seconds; the normal range for the INR is
fibrosis, cystic disease of liver; extrahepatic biliary obstruction
0.8-1.2. A prolongation of PT by >3 seconds is abnormal.
Miscellaneous: Congestive heart failure, constrictive peri
Serum proteins: The half-life of albumin is 20 days; carditis, sarcoidosis
albumin is a marker of liver synthetic functions and is low
in chronic liver disease. Gamma globulins are increased
Table 12.23: Common causes of splenomegaly
in autoimmune hepatitis; the ratio of albumin to globulin
is reversed in cirrhosis, particularly in autoimmune liver Portal hypertension: Cirrhosis, extrahepatic portal venous
disease. Low serum albumin and prolonged PT (un obstruction; congenital hepatic fibrosis, noncirrhotic portal
fibrosis, Budd-Chiari syndrome
responsive to vitamin K) indicate poor synthetic liver
functions, raised ALT and AST indicate inflammation and Storage disorders: Niemann-Pick disease, Gaucher disease,
raised ALP and GGT suggest cholestasis. mucopolysaccharidosis
Hematological malignancies: Leukemia, lymphoma,
Serum ammonia levels: Levels are raised in hepatic histiocytosis
encephalopathy.
Increased splenic function: Collagen vascular disorders,
Cholesterol: Levels are increased in cholestasis. autoimmune hemolytic anemia, inherited hemolytic anemias
Infections: Malaria, enteric fever, viral hepatitis, infectious
Liver Biopsy mononucleosis, kala-azar; congenital infections
Biopsy is a useful investigation for making a histologic Extramedullary hematopoiesis: Osteopetrosis
diagnosis especially in neonatal cholestasis, congenital
hepatic fibrosis, storage disorders like glycogen storage Liver Abscess
diseases and histiocytosis. It is useful for enzymatic
Pyogenic liver abscess is more common than amebic liver
estimation in metabolic diseases and for copper in Wilson
abscess in children. The infection reaches the liver by one
disease. It is helpful in diagnosis of infectious diseases by
of the following routes: (i) portal vein, e.g. in intra-abdominal
immunohistochemistry and monitoring response to
sepsis, umbilical vein infection; (ii) biliary tree obstruction
therapy. Liver biopsy also helps in understanding the
and cholangitis, e.g. choledochal cyst; (iii) systemic sepsis,
stage of liver disease, e.g. chronic hepatitis or cirrhosis,
e.g. endocarditis, osteomyelitis; and (iv) direct inoculation,
degree of fibrosis and inflammation (see Chapter 29).
e.g. in trauma. In children on immunosuppressive
medications or with defects of neutrophil function (e.g.
Hepatomegaly chronic granulomatous disease), there is an increased risk
A palpable liver does not always indicate enlargement. It of developing abscesses, especially due to S. aureus. In
only reflects the relation of the liver to adjacent structures. children with liver abscess without cholangitis or
In normal children, the liver is palpable one cm and in pyelophlebitis, gram-positive infections are the commonest.
infants up to 2 cm below the costal margin. It is important Invasive intestinal amebiasis can lead to amebic liver
to measure the liver span to determine the presence of abscess although a history of amebic colitis in the preceding
hepatomegaly (Table 12.22). The liver span varies with age: period is not common. Amebic liver abscess is usually
Infants 5-6.5 cm; 1-5 years: 6-7 cm; 5-10 years: 7-9 cm; solitary and in the right lobe of liver whereas pyogenic
and 10-15 years: 8-10 cm. The liver is also examined for abscesses may be multiple (secondary to cholangitis) or
tenderness, consistency and character of the surface. single. Nearly three quarters of pyogenic liver abscesses
are in the right lobe of liver.
Splenomegaly Clinical features: The child presents with fever and right
Common causes of splenomegaly are listed in Table 12.23. upper quadrant abdominal pain. Jaundice is uncommon.
-308 Essential Pediatrics
Examination reveals tender hepatomegaly. Empyema, rupture (narrow rim <1 cm). Surgery is required for
pneumonia, subphrenic abscess and cholecystitis can have abscesses complicated by frank intraperitoneal rupture or
a similar clinical presentation and should be differentiated. multiseptate abscesses not responding to percutaneous
Complications include spontaneous rupture into catheter drainage and antibiotics.
peritoneum, pericardium, pleura or bronchial tree and Prognosis: The abscess cavity takes 3-6 months to resolve
metastatic spread to lungs or brain. completely. Cure rate following management with anti
Diagnosis: Leukocytosis and elevated ESR are usually biotics and percutaneous drainage is excellent.
present. Transaminases and alkaline phosphatase are
mildly elevated. X-ray abdomen shows an elevated right Liver Tumors
dome of diaphragm with or without pleural effusion. Liver tumors account for -0.5-2% of all neoplasms in
Diagnosis is confirmed by imaging; ultrasound provides children. Hepatoblastoma, hemangioendothelioma and
good details about abscess size, number, rim and mesenchymal hamartoma are seen primarily in young
liquefaction. Contrast-enhanced CT scan may be required children whereas hepatocellular carcinoma, undifferen
in patients with complications (Fig. 12.27). Amebic tiated embryonal sarcoma and focal nodular hyperplasia
serology (indirect hemagglutination test) is positive in present in the older child. The most common tumors are
>95% children with amebic liver abscess and helps to hepatoblastoma, hepatocellular carcinoma and infantile
differentiate it from pyogenic abscess. However, in the hemangioendothelioma.
developing world, amebic serology may be positive due Infantile hepatic hemangioendothelioma is a benign
to prior intestinal amebiasis and thus a negative amebic tumor and presents mostly in first 6 months of life with
serology helps exclude amebic liver abscess. an abdominal mass. Jaundice, skin hemangiomas and
Management: Patients with pyogenic liver abscesses are congestive heart failure may be associated. The lesion may
treated with broad-spectrum antibiotics (against gram be single or multiple and is made of thin vascular channels.
positive-to cover for Staphylococcus aureus, gram-negative Observation is recommended for focal lesions. Treatment
aerobic and anaerobic bacteria) for 4-6 weeks. options for multifocal and diffuse lesions include
Metronidazole is used for 10-14 days in patients with corticosteroids, propranolol, hepatic artery ligation with
amebic liver abscess. Ultrasound-guided percutaneous or without corticosteroids, hepatic artery embolization,
needle aspiration and/or catheter drainage is required for surgical resection or liver transplantation.
abscesses that fail to improve after 3-4 days of antibiotic Hepatoblastoma is the most common malignant liver
therapy, large abscess in left lobe and those with impending tumor in children. It is of two types: Epithelial (fetal or
embryonal malignant cells) and mixed (epithelial and
mesenchymal elements) and presents with an abdominal
mass and anorexia. Weight loss and pain in abdomen
usually appear late; metastasis occurs to lungs and lymph
nodes and alpha-fetoprotein is raised in the majority of
cases. Ultrasound helps to differentiate between malignant
and vascular lesions. CT and MRI are used to define tumor
extent and resectability (Fig. 12.28). The survival of
patients with a hepatoblastoma has markedly improved
in recent years by combining surgery with pre- and
postoperative chemotherapeutic agents such as cisplatin
and doxorubicin. Liver transplantation is an option for
unresectable hepatoblastoma following chemotherapy in
absence of visible extrahepatic disease.
Hepatocellular carcinoma is usually multicentric. The risk
is increased in patients with chronic hepatitis B or C
infection, tyrosinemia, glycogen storage disease or prior
androgen therapy. The tumor presents as a liver mass with
abdominal distension, anorexia and weight loss. Liver
functions are usually normal and anemia may be present;
alpha-fetoprotein is raised. Imaging with CT/MRI helps
in defining tumor extent, resectability and metastasis. Bone
Fig. 12.27: Computed tomography scan shows a multi scan and CT chest should be done to screen for distant
loculated liver abscess in the right lobe (black arrow) with metastasis. Treatment options include surgical resection
elevated right dome of diaphragm and ascites. Percutaneous along with chemotherapy; chemoembolization and liver
drainage catheter is seen in situ (white arrow) transplantation.
Diseases of Gastrointestinal System and Liver 1309-
(2-6 mg/ dL). The transaminases and synthetic liver leptospirosis and viral hemorrhagic fever. Other
functions are normal. Most patients are asymptomatic conditions that need to be differentiated include drug
apart from jaundice. Pregnancy and oral contraceptives induced hepatitis, acute presentation of autoimmune liver
may worsen jaundice. Liver biopsy is often done for disease or Wilson disease.
exclusion of other causes and shows brown-black
pigmentation. Investigations
Rotor syndrome is a rare, autosomal recessive disorder Direct hyperbilirubinemia with markedly elevated ALT/
manifesting as mild conjugated hyperbilirubinemia. The AST and normal albumin and prothrombin time are usual.
primary defect appears to be a deficiency in the Mild leukopenia with relative lymphocytosis is seen.
intracellular storage capacity of the liver for binding Ultrasound is not routinely required, but shows mildly
anions. The liver histology is normal. enlarged liver with increased echogenicity and edema of
gallbladder wall. Viral serologies help determine the
ACUTE VIRAL HEPATITIS etiology of acute viral hepatitis, as shown in Table 12.25.
Viruses can affect the liver, either primarily, e.g. hepatitis Complications
A, B, C, E or as part of a systemic involvement, e.g.
These include:
cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes
simplex virus (HSV). In Indian children, hepatitis A is the i. Acute liverfailure. The appearance of irritability, altered
commonest cause (40-60%) of acute viral hepatitis, sleep pattern, persistent anorexia and uncorrectable
followed by hepatitis E (10-20%) and hepatitis B (7-17%). coagulopathy (despite administration of vitamin K)
Nearly 8-20% patients have coinfection with more than suggests the development of acute liver failure.
one virus, HAV and HEV being the commonest. Hepatitis ii. Aplastic anemia
A and E are transmitted by feco-oral route whereas HBV iii. Pancreatitis
and HCV are transmitted by parenteral or vertical (mother iv. Serum sickness, vasculitis-like reaction may be seen
to baby) route (Table 12.25) (see also Chapter 11). in hepatitis B infection
v. Hemolysis (cola-colored urine) with renal failure in
Clinical Features subjects with glucose-6-phosphate dehydrogenase
Following exposure, patients show a prodrome charac deficiency
terized by low grade fever, malaise, anorexia and vi. Chronic liver disease: In patients with acute viral
vomiting, followed by appearance of jaundice. Examina hepatitis due to HBV, repeat testing for hepatitis B
tion shows icterus, hepatomegaly and splenomegaly surface antigen should be done after 6 months to
(small, soft in 15-20%). Mild ascites may be present in 10- document clearance or persistence of infection. A
15% cases, which resolves completely on follow-up. Over majority (95%) clear hepatitis B infection after acute
the next few weeks, the appetite improves, jaundice icteric infection.
resolves and the child gets better. In young children,
asymptomatic and anicteric presentation of hepatitis A Management
infection can occur. Maintaining adequate oral intake is essential and
intravenous fluids are given, if persistent vomiting and
Differential Diagnosis dehydration are present. There is no advantage of enforced
The conditions, which mimic the clinical features of viral bed rest, but vigorous activity should be avoided. No
hepatitis include enteric fever, falciparum malaria, specific dietary modification is recommended. The child
should be monitored for appearance of complications like Patients with chronic liver disease may manifest with
encephalopathy. features of hepatocellular failure due to progressive
worsening of liver function as part of the natural course
Prevention of the disease or as a sudden dysfunction due to a super
Public health measures like sanitation, safe drinking water imposed hepatic insult resulting in acute on chronic liver
supply, handwashing and proper food hygiene are of failure (ACLF). Superimposed insult can be due to hepato
utmost importance, especially in epidemics of hepatitis A tropic virus (hepatitis A, E, B) infection, hepatotoxic drug
or E. Proper screening of blood and blood products and intake or sepsis and varies with the geographical area.
safe injection practices are essential. Universal immuniza ALF in children is a condition associated with high
tion for hepatitis B is the most effective way of preventing mortality and the etiology varies among different age
hepatitis B related disease. groups (Table 12.26). Autoimmune liver disease and
Wilson disease are two important causes of chronic liver
Suggested Reading disease in children which may have an acute presentation
• Strassburg CP. Hyperbilirubinemia syndromes. Best Pract Res Clin mimicking ALF. Drugs, especially antitubercular agents
Gastroenterol 2010; 24:555-71. (isoniazid, rifampicin, pyrazinamide) and anticonvulsants
• Yeung LT, Roberts EA. Current issues in the management of are a major cause of ALF. In the West, paracetamol
pediatric viral hepatitis. Liver Int 2010; 30:5-18.
poisoning is a common cause of ALF. Herbal medicines
and mushroom poisoning are also known to cause ALF.
LIVER FAILURE In the neonatal period, liver failure may be a result of
Liver failure refers to a clinical state resulting from metabolic conditions (neonatal hemochromatosis,
hepatocyte dysfunction or necrosis and not a specific galactosemia, hereditary fructose intolerance, tyrosinemia
disease etiology. It may occur de novo in normal children type 1, Niemann-Pick disease), infections and hematological
without any evidence of pre-existing liver disease where conditions like hemophagocytic lymphohistiocytosis. A
it is known as acute liver failure (ALF). careful history and rapid investigations are necessary to
identify the etiology, which has prognostic and therapeutic
Acute liverfailure: An international normalized ratio 2:::1.5 implications. However, 30-40% cases are idiopathic.
with hepatic encephalopathy or an international
normalized ratio� without hepatic encephalopathy along Clinical Features
with biochemical evidence of liver injury in the absence The early clinical manifestations of ALF are nonspecific
of underlying chronic liver disease is considered as acute and characterized by lethargy, anorexia, malaise, nausea
liver failure. The presence of hepatic encephalopathy is and vomiting. Central nervous system manifestations
not essential for diagnosis of ALF in children. All include hepatic encephalopathy and cerebral edema with
international normalized prothrombin values refer to that raised intracranial tension. Hepatic encephalopathy is a
measured after 8 hours of parenteral vitamin K result of inability of the liver to process and excrete
administration. This definition has evolved with the endogenous toxins. Raised levels of ammonia, GABA,
understanding that detection of mild grades of hepatic false neurotransmitters and proinflammatory cytokines
encephalopathy in small children is difficult and any are implicated in its pathogenesis. Hepatic encephalo
behavioral change or irritability in this age group may pathy is classified into four stages (Table 12.27).
not be necessarily due to hepatic encephalopathy. Identification of hepatic encephalopathy in children can
Table 12.30: Specific treatment of conditions causing pediatric CHRONIC LIVER DISEASE
acute liver failure Chronic liver disease (CLO) refers to a spectrum of
Neonatal Antioxidants; chelation; prenatal intra- disorders characterized by ongoing chronic liver damage
hemochromatosis venous immunoglobulin in combination and a potential to progress to cirrhosis or end stage liver
with postnatal exchange transfusion disease. Although a 6-month duration cut off is used for
Tyrosinemia Nitisinone (NTBC); restriction of phenyl- defining chronicity related to hepatitis B and C, it does
alanine and tyrosine in diet not apply to the other causes as irreversible liver damage
Galactosemia Galactose and lactose free diet may have already taken place before symptoms of liver
disease are recognized.
Hereditary fructose Fructose free diet
intolerance
Cirrhosis is a diffuse liver process characterized by cell
injury (necrosis) in response to inflammation/injury and
Mitochondrial Coenzyme Q10, vitamin E, carnitine fibrosis and regeneration (nodule formation). When the
cytopathies disease is silent, the patient may have hepatosplenomegaly
Amanita poisoning Penicillin G, silibinin and N-acetyl and abnormal liver function tests and it is termed as
cysteine compensated cirrhosis. When the patient develops
Herpes simplex High dose acyclovir (60 mg/kg/day) jaundice, gastrointestinal bleed, ascites and/or hepatic
for 21 days encephalopathy, it is known as decompensated cirrhosis.
Acetaminophen N-acetyl-cysteine (see Chapter 27)
poisoning Etiology
The main causes of CLO in children are listed in
Table 12.31. In India, -25% of CLO is due to metabolic
patients listed for transplantation. Antimicrobials with causes (Wilson disease being the commonest), 8-15% are
coverage against gram-positive and gram-negative due to hepatitis B and 2-4% due to autoimmune causes.
organisms (cefotaxime with cloxacillin) along with Nearly 40% patients do not have a known etiology, and
antifungals are used. Aminoglycosides are avoided to are labeled cryptogenic.
prevent renal dysfunction. Close monitoring and early
detection of infection is essential. Coagulopathy does not Clinical Features
necessarily warrant transfusion of fresh frozen plasma The presentation depends on the etiology and pace of
unless bleeding manifestations are clinically evident or disease progression. Patients may present with insidious
an invasive intervention is planned or INR is >7. Proton onset disease with failure to thrive, anorexia, muscle
pump inhibitions are used for stress ulcer prophylaxis. weakness and/or jaundice or abruptly with massive
In spite of adequate supportive care, the mortality in gastrointestinal bleed, acute onset jaundice, along with
ALF is as high as 60-70%. Early identification of children
who would benefit only from liver transplantation is Table 12.31: Causes of chronic liver disease
essential. The King's College criteria are one of the Viral hepatitis Hepatitis B (common), hepatitis C
commonly used criteria to identify adult patients (uncommon)
requiring liver transplantation. Application of these Autoimmune liver Autoimmune hepatitis (common),
criteria in developing countries seems to be limited due disease autoimmune sclerosing cholangitis
to variation in etiology other than paracetamol induced Metabolic Wilson disease, glycogen storage
liver failure. Young age (�3.5 years), bilirubin �16.7 mg/dL, disease (IV)*, progressive familial
prolonged prothrombin time (>40 seconds) and signs of intrahepatic cholestasis*, galactosemia*,
cerebral edema predicted mortality in an Indian study. NASH related, tyrosinemia*, Indian
Table 12.30 lists the specific therapy for common childhood cirrhosis* (rare), cystic
etiologies of ALF. fibrosis, hereditary fructose
intolerance*, alpha-1-antitrypsin
Suggested Reading deficiency, bile acid synthetic defects
• Bernal W, Auzinger G, Dhawan A, Wendon J. Acute liver failure. Venous obstruction Budd-Chiari syndrome, veno-occlusive
Lancet 2010; 376:190-201. disease, constrictive pericarditis,
• Bhatia V, Bavdekar A, Yachha SK et al. Management of acute liver congestive heart failure
failure in infants and children: consensus statement of the pediatric Biliary Biliary atresia*, choledochal cyst*,
gastroenterology chapter, Indian Academy of Pediatrics. Ind Ped primary sclerosing cholangitis, Caroli
2013; 50:477-82. disease, Alagille syndrome
• Shanmugam NP, Bansal S, Greenough A, et al. Neonatal liver Rare causes Niemann-Pick disease, Gaucher disease;
failure: etiologies and management. Eur J Pediatr 2011; 170:573-81. drug induced (valproate, carbamazepine)
• Srivastava A, Yachha SK, Poddar U. Predictors of outcome in
children with acute viral hepatitis and coagulopathy. J Viral Hepat NASH: Nonalcoholic steatohepatitis
2012; 19:e194-201. *Causes in infants and young children <5 yr of age
a14 I Essential Pediatrics
altered sensorium and ascites. Sometimes the patient may Table 12.32: Investigations for chronic liver disease
be asymptomatic and child is noticed to have hepato Common investigations
splenomegaly or elevated transaminases on investigations
for some unrelated illness. Clinical features on Liver function tests Low albumin, reversal of albumin
globulin ratio and prolonged
examination that suggest presence of CLD are:
prothrombin time
Characteristics of liver: The liver may be firm to hard, High conjugated bilirubin suggests
nodular or have irregular margins in cirrhosis. Differential liver dysfunction or obstruction
left lobe enlargement is a feature of CLD. A small, non Raised transaminases suggest
palpable shrunken liver is a feature of post-necrotic hepatocellular injury; raised alkaline
cirrhosis. phosphatase and gamma glutamyl
Stigmata of CLD: These include spider angiomata, palmar transpeptidase suggest biliary disease
erythema, clubbing, leukonychia, muscle wasting, delayed Ultrasonography Nodular liver, mass lesion, dilated
puberty and gynecomastia. Testicular atrophy and parotid portal vein and collaterals, ascites,
enlargement are present in adults with alcoholic liver splenomegaly
disease, but not in children. Upper GI endoscopy Portal hypertension: Esophageal or
Portal hypertension: Splenomegaly, ascites, tortuous veins gastric varices
over abdominal wall with flow away from umbilicus, i.e. Liver biopsy Breaking of lamina limitans and
caput medusae; esophageal varices with/without gastric lobular inflammation; nodule
varices on endoscopy. formation and loss of architecture in
cirrhosis; may also aid in diagnosis of
Features of hepatic encephalopathy: Asterixis, constructional specific diseases
apraxia or altered sensorium (Table 12.27) may be seen.
Specific to etiology
Evaluation Viral markers HBsAg, HBeAg, anti-HBe, anti-HGV,
Evaluation of patients with suspected CLD is two HBV DNA, HGV RNA
pronged: (i) determine etiology of CLD and (ii) assess Autoimmune Anti-smooth muscle, anti-liver kidney
degree of liver dysfunction and presence of complications hepatitis microsomal, antinuclear antibodies
(Table 12.32). Based on clinical and laboratory features, Wilson disease Ceruloplasmin, Kayser-Fleischer ring;
liver damage is graded using scores like the CHILD score 24 hours urine copper; liver copper
and pediatric end stage liver disease (PELD) score. Alpha-1-antitrypsin Serum alpha-1-antitrypsin levels; Pl
Complications of CLD are: (i) hepatic encephalopathy; deficiency type
(ii) portal hypertension with variceal bleeding, Galactosemia Positive nonglucose reducing
portopulmonary hypertension and hepatopulmonary substances in urine; galactose-1-
syndrome; (iii) ascites and spontaneous bacterial phosphate uridyltransferase assay
peritonitis; (iv) hepatorenal syndrome; (v) coagulopathy; Cystic fibrosis Sweat chloride test; genetic analysis
(vi) nutrition failure; (vii) increased risk of infections; and Tyrosinemia Urinary succinylacetone level
(viii) hepatocellular carcinoma.
Budd-Chiari Doppler ultrasonography for hepatic
syndrome vein, inferior vena cava
Hepatic Encephalopathy Sclerosing Magnetic resonance cholangiopancreato
Hepatic encephalopathy refers to neuropsychiatric cholangitis graphy; liver biopsy
abnormalities that result from liver dysfunction. It is a Storage disorders Bone marrow, fundus examination;
principal manifestations of CLD and can be graded liver biopsy
(Table 12.27). Various factors like gastrointestinal bleed,
infection, use of sedatives, dehydration due to aggressive disaccharides like lactulose and lactitol reach the colon
diuresis, constipation and electrolyte imbalance can intact and then are metabolized by bacteria into variety
precipitate encephalopathy. Identification and reversal of of small molecular weight organic acids. It acts by
the precipitating event is of importance. As ammonia is acidifying fecal contents and trapping the diffusible
an important putative metabolite, efforts are targeted ammonia as ammonium ion in the fecal stream along with
towards reducing its production and absorption and alteration in colonic flora (loss of ammonia producing
facilitating its excretion. Oral antibiotics and synthetic bacteria). In infants and children, protein intake should
disaccharides have been shown to be effective in not be restricted to the point of causing growth failure or
minimizing ammonia production in these patients. compromising overall nutritional status and a target range
Neomycin was used in the past but it has serious side of 1-2 g/kg/day is often recommended. Vegetable
effects of deafness and renal toxicity. Rifaxirnin is a new proteins, which are rich in branched chain amino acids
drug with a better safety profile. Nonabsorbable are preferred over animal proteins.
Diseases of Gastrointestinal System and Liver 1315-
High gradient ascites (SAAG :2::1.l g/dL) suggests portal facilitates maintenance of normokalemia. If weight loss
hypertension and is seen in cirrhosis, fulminant hepatic and decrease in abdominal girth are inadequate, the doses
failure, Budd-Chiari syndrome and portal vein thrombosis. of both spironolactone and furosemide should be
Low gradient ascites (SAAG <1.1 g/dL) occurs in absence increased simultaneously. Along with diuretic therapy,
of portal hypertension in conditions such as peritoneal patients should be on a sodium restricted diet. One gram
carcinomatosis, tuberculous peritonitis, pancreatic ascites, of table salt contains 17 mEq of sodium and one gram of
biliary leak ascites, nephrotic syndrome and serositis. sodium approximates 44 mEq of sodium. Restriction of
Elevated ascitic fluid level of amylase indicates sodium in diet is limited to 1-2 mEq/kg/day for infants
pancreatitis or intestinal perforation. Polymicrobial and children and 1 to 2 g/day (44 to 88 mEq of sodium/
infection is consistent with intestinal perforation, whereas day) in adolescents.
monomicrobial infection suggests spontaneous bacterial If the ascites is massive or the patient is having
peritonitis. Uroascites is present when the concentration respiratory discomfort, large volume paracentesis should
of urea and creatinine are higher in the ascitic fluid than be done preferably under cover of albumin infusion.
in serum. In biliary ascites, the ascitic fluid bilirubin is Patients who are resistant to above therapy can be treated
>6 mg/dL and in chylous ascites the ascitic fluid is milky with transjugular intrahepatic portosystemic shunting
in appearance and has a triglyceride concentration of (TIPS) as a temporary measure till orthotopic liver
>200 mg/dL. transplantation is done.
Suggested Reading end stage liver stage who are either refractory or intolerant
• Plessier A, Valla DC. Budd-Chiari syndrome. Semin Liver Dis 2008; to immunosuppressive therapy. Patients presenting with
28:259-69. acute liver failure need liver transplantation, as they are
• Kathuria A, Srivastava A, Yachha SK et al. Budd Chiari syndrome less likely to respond to medical treatment. A high index
in children: clinical features, percutaneous radiological intervention of suspicion and timely diagnosis of autoimmune liver
and outcome. Eur J Gastroenterol Hepatol 2014; 26:1030-8.
disease is crucial.
AUTOIMMUNE LIVER DISEASE
Suggested Reading
Autoimmune liver disease is characterized by hyper • Mieli-Vergani Gl, Vergani D. Paediatric autoimmune liver disease.
gammaglobulinemia, presence of circulating auto Arch Dis Child. 2013; 98(12):1012-7.
antibodies, necroinflammatory histology (interface • Zachou K, Muratori P, Koukoulis GK et al. Review article:
hepatitis, portal lymphoplasmacytic cell infiltration) on autoimmune hepatitis-current management and challenges.
biopsy and response to immunosuppressive agents. The Aliment Pharmacol Tuer 2013; 38:887-913.
condition is common in girls. In children, autoimmune
liver disease consists of autoimmune hepatitis, auto CHRONIC HEPATITIS B INFECTION
immune sclerosing cholangitis and de novo autoimmune Hepatitis B virus (HBV) infection is a worldwide heath
hepatitis after liver transplantation. The following two problem and may result in AVH, ALF, chronic hepatitis,
types of autoimmune hepatitis are recognized: cirrhosis and hepatocellular carcinoma (HCC). The
Type 1: Presence of antinuclear antibody and/or anti epidemiology, natural history and evaluation for the
smooth muscle antibody; constitutes 60-70% cases. infection are discussed in Chapter 11. The age at time of
HBV infection affects the outcome, with >90% of infected
Type 2: Presence of anti-liver kidney microsomal antibody
neonates becoming chronic carriers as compared to 20-
(LKM); accounts for 20-30% cases.
25% children infected in preschool age and only 5%
Clinical Presentation adults.
clinical and biochemical findings. The diagnosis of Chronic right heart failure may lead to hepatomegaly,
NAFLD is suspected when there is raised serum ALT or splenomegaly and over long periods result in cardiac
evidence of fatty liver on radiological studies. Liver cirrhosis. Alagille syndrome, caused by syndromic paucity
histology is required for diagnosis of NASH. of intralobular bile ducts results in infantile cholestasis;
patients also show peripheral pulmonary stenosis,
Treatment: The first step in treating NAFLD is to identify tetralogy of Fallot and atrial or ventricular septal defects.
it. Besides height and weight, waist circumference In biliary atresia, splenic malformation syndrome
provides highly informative data and is a surrogate for anomaly, there may be vascular malformations and
visceral obesity. The treatment has two goals-to reverse congenital heart disease.
liver disease and to promote healthy growth. Lifestyle
changes aimed at weight reduction are essential. Dietary Sepsis and Systemic Infections
changes and increased physical activity lead to diminished
insulin resistance and are the main stay of therapy. Gram-positive and gram-negative bacterial infections may
Vitamin E has been shown to be safe and effective in result in jaundice. Up to one-third of neonatal jaundice
improving NASH histology in children and its use is has been attributed to sepsis. The mechanism may vary
recommended. Other medications like orlistat, metformin, from impaired canalicular bile transport due to defective
UDCA and thiozolidinodiones require more data to prove transporter polarization in hepatocytes without hepatic
efficacy. The role of bariatric surgery has not been necrosis to elevated bilirubin load due to hemolysis in
established for childhood obesity. Prevention of over clostridium infections and hepatocellular necrosis in
weight and obesity in children is the best strategy to pneumococcal infections. Typhoid might result in elevated
overcome the problem of NAFLD. alkaline phosphatase, transaminases and lactate
dehydrogenase. Transaminase elevation and liver dys
Suggested Reading function is also present in dengue hemorrhagic fever and
• Barshop NJ, Sirlin CB, Schwimmer JB, Lavine JE. Review article: malaria.
epidemiology, pathogenesis and potential treatments of pediatric
non alcoholic fatty liver disease. Aliment Pharmacol Ther 2008; Immunological Disorders
28:13-24.
• Mann JP, Goonetilleke R, McKieman P. Pediatric non-alcoholic fatty
Juvenile idiopathic arthritis may be associated with
liver disease: a practical overview for non specialist. Arch Dis Child hepatomegaly and elevated transaminases. Systemic
2015; 100:673-7. lupus erythematosus may be associated with hepato
• Mitchel EB, Lavine JE. Review article: the management of pediatric megaly or autoimmune hepatitis. Transplacental transfer
non-alcoholic liver disease. Aliment Pharmacol Ther 2014; 40: of autoantibodies might lead to neonatal SLE with
1155-70.
transient cholestasis, congenital heart block, dermatitis
and hematological abnormalities.
Hepatic Manifestations of Systemic Diseases
Apart from disorders that directly involve the liver, a Hemolytic Anemias
number of disorders affecting other organ systems also In thalassemia, the repeated transfusions and the increased
have hepatic manifestations. While, in some disorders, iron absorption due to ineffective erythropoiesis leads to
these manifestations may be benign, in others the hepatic chronic iron overload, fibrosis and cirrhosis. Recurrent
manifestations might significantly affect the outcome. transfusions increase the risk of acquiring hepatitis B and
hepatitis C infections. Sickle cell anemia has a similar risk
lschemic Hepatitis of transfusion related hepatitis but more specific problems
Severe shock may lead to hypoperfusion of the liver. This are acute hepatic crisis which is a result of ischemic
shock may be the result of sepsis, acute cardiogenic shock insult. These individuals are also at higher risk of pigment
or severe intraoperative hypoperfusion as in cardiac stones resulting in acute and chronic cholecystitis. These
surgery. It usually manifests as an elevation of trans episodes may be difficult to differentiate from acute
aminases to high levels. The degree of hepatic injury hepatic crisis.
depends on the duration and severity of shock. Thus,
coagulopathy as evidenced by prolonged prothrombin Malignancies
time and encephalopathy may result. Jaundice is a late Leukemias and lymphomas might be associated with
manifestation. hepatic infiltration, presenting as jaundice. Hemophago
cytic lymphohistiocytosis, either familial or infection
Cardiac Disorders induced, presents with fever, jaundice, hepatospleno
Apart from an acute cardiogenic shock or intraoperative megaly, liver dysfunction and cytopenia. It is an important
hypoperfusion in cardiac surgery, liver involvement may differential diagnosis for liver failure in the first few
be seen as a result of congestion in right heart failure or as months of life. Sclerosing cholangitis may be a complica
part of syndromes that involve both the liver and the heart. tion of Langerhans cell histiocytosis.
Diseases of Gastrointestinal System and Liver 1325-
I I
Jaundice >2 weeks of life
High colored urine
+
Injection vitamin K I
I Sick (lethargic, ascites, encephalopathy, coagulopathy, hypoglycemia, I
seizures, edema), failure to thrive
Yes
I ! No
Possibilities
Galactosemia, tyrosinemia,
I Pale stools, to be seen by physician I
neonatal hemochromatosis
Sepsis, urinary tract infection
I
Congenital intrauterine infections No !ves
Herpes infection, congenital malaria
Hemophagocytic lymphohistiocytosis Possibilities Possibilities
Progressive familial intrahepatic cholestasis Biliary atresia
Hypopituitarism
Paucity of intrahepatic bile ducts Choledochal cyst
Cystic fibrosis lnspissated bile duct syndrome
Bile acid synthetic defects Caroli disease
Alpha-1-antitrypsin deficiency Sclerosing cholangitis
I
I
l
Workup as per likely cause Wolman's disease, Niemann-Pick type C
Idiopathic neonatal hepatitis
Ultrasound abdomen
Choledochal cyst
Biliary atresia
lntrahepatic biliary radical dilatation
l
Liver biopsy
Further workup as per likely cause
i ,,
Surgery for:
•I Supportive therapy for cholestasis Choledochal cyst
I Specific therapy as per cause
I
Biliary atresia
out biliary atresia. However, a non-excretory pattern, i.e. tension, ascites and hepatic encephalopathy. The
no activity in intestine at 24 hours in HIDA scan can be management is begun as soon as the child is seen, parallel
seen in both biliary atresia and severe intrahepatic chole to investigations.
stasis. Thus, the absence of excretion does not necessarily General management: This includes the following:
mean biliary atresia. Laparotomy and peroperative
cholangiography (POC) may be required in an infant with i. Nutritional. Adequate caloric intake (125-150% of RDA
equivocal biopsy, findings and no excretion on HIDA scan, based on ideal body weight) with medium chain
to evaluate for biliary atresia. In experienced centres, with triglyceride supplementation is necessary. Breast
fast reporting of liver biopsy the histology report is feeding should be continued and supplementation
available much before HIDA reports and helps in avoiding with high MCT formulae should be done; 2-3% calories
a negative laporatomy (patent biliary pathway on POC). should come from long chain triglycerides to prevent
Ultrasound of abdomen is more relevant in determining deficiency of essential fatty acids. Nasogastric feed
the presence of dilated CBD/ intrahepatic biliary radicle is offered to anorexic infants. Supplementation of
dilatation (seen in choledochal cyst), cysts at the porta fat-soluble and water-soluble vitamins is done
(seen in cystic variants of biliary atresia and choledochal (Table 12.37). In addition, these infants require
cyst), muliple intrahepatic cysts communicating with supplements of calcium, phosphorus and magnesium
biliary tree (Caroli's disease), hemangioma (relevant for and correction of anemia.
liver biopsy) and looking for situs inversus (seen in some ii. For infants with pruritus, urodeoxycholic acid (UDCA,
cases of biliary atresia-relevant for liver biopsy). Even 10-20 mg/kg/day), rifampicin (5-10 mg/kg/day) and
though an absent gallbladder, poorly contractile gall cholestyramine (250 mg/kg/ day, max 8 g/day) are
bladder, small gallbladder and triangular cord sign used. UDCA is the first agent and others are used in
(echogenic density of :?:3 mm located immediately cranial patients with persistent symptoms.
to the portal vein bifurcation) are finding associated with iii. Management of other complications like ascites,
biliary atresia, the condition should not be ruled out or gastrointestinal bleeding and hepatic encephalopathy
diagnosed on the basis of an ultrasound alone. Dilatation is discussed in respective sections in the chapter.
of intrahepatic biliary radical is not seen in biliary atresia Specific management: This is available only for some
as it is a pan ductular disease. etiologies as follows:
In an infant with frankly pigmented stools, intrahepatic i. Biliary atresia is managed by Kasai procedure (hepato
portoenterostomy). The best results are obtained, if it
causes need to be considered. There is no utility of HIDA
is done early (<60 days of age) and at centers with
in this situation as it will definitely be excretory.
expertise. Liver transplantation is indicated in children
Liver biopsy (light microscopy and immunohisto who fail to drain bile after Kasai procedure or have
chemistry) is useful in making a specific diagnosis but is progressed to end stage cirrhosis either despite surgical
not of much use in most situations where a metabolic cause treatment or due to late diagnosis.
is suspected. A detailed metabolic workup is required for ii. Clwledochal cyst: Excision of cyst and hepaticojejunostomy.
infants with conditions like progressive familial intra iii. Herpes simplex: Intravenous acyclovir
hepatic cholestasis types I and II, tyrosinemia, mito iv. Bacterial sepsis: Intravenous antibiotics
chondrial cytopathies and bile acid synthesis defects, etc. v. Toxoplasmosis: Pyrimethamine and sulfadiazine with
folinic acid
Management
vi. Galactosemia: Lactose free diet
Delayed diagnosis leads to problems of undemutrition, vii.Hemochromatosis: IV immunoglobulins (IVIG) with
coagulopathy, pruritus (older infants), portal hyper- exchange transfusion may be useful
There is considerable delay in referral of patients with a split graft (left lateral graft or left lobe) from a living
neonatal cholestasis to higher centers in India. This results donor. Auxiliary liver transplantation is another method
in delayed etiologic diagnosis, missed opportunity for where native liver is not removed and a liver graft from
corrective biliary atresia surgery in first 60 days and liver the donor is surgically placed in addition to the native
decompensation in patients with metabolic etiology. Thus liver. This is usually done for Crigler-Najjar type I or acute
all efforts should be targeted towards early identification liver failure.
of neonates with conjugated hyperbilirubinemia and their The main indications for liver transplantation are biliary
referral to centres with expertise. atresia, fulminant hepatic failure and chronic liver disease
secondary to multiple causes and hepatic tumors. Careful
Suggested Reading selection of a blood group compatible donor is necessary,
• Guideline for the evaluation of cholestatic jaundice in infants: including detailed evaluation of liver functions and viral
Recommendations of the North American Society for Pediatric serologies. The recipient's diseased liver is removed and
Gastroenterology, Hepatology and Nutrition. J Pediatr the new liver is transplanted, ensuring vascular and biliary
Gastroenterol Nutr 2004; 39:115-28. anastomosis. Patients require lifelong immuno
• Roberts EA. Neonatal hepatitis syndrome. Semin Neonatol 2003;
8:357-74
suppression using corticosteroids, tacrolimus and
• Bhatia V, Bavdekar A, Matthai J, Waikar Y, Sibal A. Management mycophenolate mofetil initially and later maintenance
of neonatal cholestasis: consensus statement of the Pediatric therapy with tacrolimus. Rejection and infection are major
Gastroenterology chapter of Indian Academy of Pediatrics. Ind complications following transplantation. Five-year patient
Pediatr 2014; 51: 203-10. survival rate exceeds 80%.
Liver Transplantation Suggested Reading
Liver transplantation is possible for a number of disorders. • Karnath BM, Olthoff KM. Liver transplantation in children: Update
The graft is obtained either from the cadaver or can be 2010. Pediatr Clin N Am 2010; 57:401-14.
- -
:�
Chapter
13
Hematological Disorders
Tulika Seth
Hematopoiesis ANEMIA
The hemangioblast is the stem cell from which endothelial Anemia is a sign, it is important to investigate the cause
and hematopoietic cells develop. Stem cells that give rise of anemia to ensure that it is not due to a serious
to only blood cells are called hematopoietic stem cells. underlying ailment and to define the correct management
They give rise to two colony-forming units (CFU), one is approach.
the common myeloid precursor: Granulocytes, erythro
cytes, monocytes and megakaryocytes, also termed CFU Definition
GEMM. The second is the common lymphoid precursor,
Anemia is present when the hemoglobin level in the blood
dedicated to the production of lymphocytes and called
is two standard deviations below the mean for the
CFU-L. The CFU-GEMM gives rise to two progenitors,
particular age and sex (Tables 13.1, 13.2). The physiologic
specific for both the erythrocyte and the megakaryocyte
definition of anemia is a condition in which tissue hypoxia
(CFU-EMk), and another for granulocytes and monocytes
occurs due to inadequate oxygen carrying capacity of
(CFU-GMo). Each of these develops into specific lineages,
blood. According to the National Family Health Survey
the CFU-GMo gives rise to four lineage-specific CFUs,
(NFHS-4) data, the incidence of anemia in urban children
three dedicated to each of the granulocyte lineages (CFU
is 55.9%, rural is 59.4% and overall is 58.4%.
Eo for eosinophils, CFU-N for neutrophils and CFU-Baso
for basophils) and CFU-Mo that is specific for monocytes.
The CFU-L gives rise directly to three lymphoid cells: B
Physiological Adaptations
lymphocytes, T lymphocytes and natural killer cells. This Anemia leads to decreased oxygen-carrying capacity of
complex and sequential development of hematopoietic the blood and compensatory physiological adjustments.
cells is driven and regulated by local growth factors and Tissue hypoxia develops when the enhanced release of
cytokines. oxygen from hemoglobin and increase of blood flow to
Table 13.2: Cutoffs for hemoglobin and hematocrit proposed Approach to Diagnosis
by the World Health Organization to define anemia The history may give clues for the etiology of anemia. There
Age group Hemoglobin (gldL) Hematocrit % may be obstetric history of maternal infections, anemia or
Children, 6 mo to 5 years <11.0 <33 collagen vascular diseases, or presence of prematurity,
Children, 5-11 years <11.5 <34 blood loss, jaundice [secondary to ABO or Rh incompatibility,
glucose-6-phosphate dehydrogenase (G6PD) deficiency
Children, 12-13 years <12.0 <36
and sepsis], hemangioma or cephalhematoma. History is
Non-pregnant women <12.0 <36 taken regarding the diet, type and quantity of milk, time of
Men <13.0 <39 weaning and intake of vitamins and hematinics. Nutritional
Source: WHO 1997 iron deficiency anemia often occurs between 6 months and
2 years due to inadequate weaning, chronic diarrhea or cow
the tissues is insufficient to meet requirements. The milk allergy. Adolescent growth spurt, menstruating and
maintenance of blood volume occurs by an increase in the pregnant teens are at risk for iron deficiency. A vegetarian
volume of plasma and redistribution of blood flow. diet and use of goat milk may result in megaloblastic
Cardiac output increases in anemia as a consequence of anemia. History of pica, drug intake, chronic diarrhea, prior
increased stroke volume, this high output state increases surgery, acute and prolonged infections, liver and renal
oxygen delivery to tissues by increasing the flow of blood. disease, transfusions and age of onset of symptoms should
Diversion of blood flow occurs from tissues with lesser be taken. Thalassemia major usually presents at 4-6 months
oxygen requirements to those with greater needs. Thus of age, and 70% present with symptoms by one-year.
skin blood flow is reduced, while cerebral and muscle Diamond-Blackfan (pure red cell) anemia, usually presents
blood flow are increased. at 3-month or earlier and shows a consistently low
reticulocyte count and absence of erythroid precursors in
Clinical Features the marrow. Fanconi anemia has a variable and later onset,
The hemoglobin level at which symptoms of anemia with children presenting at 3-4 years of age or even in
develop depends on two factors, the rate of development adulthood. A family history of anemia, gallstones and
of anemia and state of the cardiovascular system. In requirement for blood transfusions may suggest the
general, symptoms occur at a higher hemoglobin level diagnosis of chronic hemolytic anemia, including hereditary
with rapidly developing anemia, e.g. due to acute spherocytosis or G6PD deficiency.
hemorrhage. Examination is done for clues to the cause of anemia,
e.g. radial limb anomalies (bone marrow failure),
Tiredness, lassitude, easy fatigability and generalized
splenomegaly (hemolytic anemia, infection, storage
muscular weakness are most frequent and the earliest
diseases), and lymphadenopathy and hepatosplenomegaly
symptoms of anemia. This presents as poor feeding,
(malignancies, malaria, tuberculosis). Petechia, purpura,
irritability and inadequate school performance; pallor is
icterus and bossing also help to diagnose the cause.
the most prominent and characteristic sign. Pallor of nail
beds, oral mucous membranes and conjunctivae are Laboratory Investigation
reliable indicators of anemia. Dyspnea on exertion,
It is important to know the age and detailed history of the
tachycardia and palpitation are common symptoms.
child, this information will provide direction to the
Hemic murmurs become prominent with severity of
laboratory investigation. The complete hemogram will
anemia. These are midsystolic flow murmurs, reflecting reveal, if there is isolated anemia, or if other cell lines are
increased velocity of blood passing through the valves. affected. The red cell indices will demonstrate the type of
They are heard in the pulmonary area, but can be heard anemia; while the mean corpuscular volume (MCV)
in areas corresponding to any of the heart valves. Systolic denotes the size of the red cells, the mean corpuscular
bruits, postural hyp otension and congestive heart failure hemoglobin (MCH) and mean corpuscular hemoglobin
may be seen in patients with moderate to severe anemia. content (MCHC) provide information on red cell
Nervous system symptoms include dizziness, headache, hemoglobinization (Table 13.3). Using the MCV, anemias
humming in ears, fainting, tinnitus, lack of concentration can be classified into microcytic/normocytic/macrocytic
and drowsiness; with severe anemia, clouding of anemia (Figs 13.1-13.3). Abnormal red cell indices can exist
consciousness may occur. in subjects even when the underlying disorder is not
Severe anemia is characterized by a high output state sufficiently severe to cause anemia. In thalassemia minor
with elevated pulse pressure and a 'collapsing' character. or iron deficiency, the MCV, MCH and MCHC are low
Electrocardiographic changes may be found in approxi and in megaloblastosis, the MCV is elevated. The red cell
mately 30% of patients with hemoglobin of less than distribution width (RDW) gives the size difference in the
6 g/ dL. Findings on ECG are normal QRS waves, red blood cells, low RDW means all the red blood cells
depression of the ST segments, and flattening or inversion are small and uniform in size, while a large RDW shows
of T waves. that the cells vary in size greatly. Examination of the
Hematological Disorders 331
Table 13.3: Red cell indices and serum iron studies in normal children
Red cell indices Birth 0.5-2 yr 6-12 yr Girls, 12-18 yr Boys, 12-18 yr
Mean corpuscular volume (fl) 108 78 86 90 88
Mean corpuscular hemoglobin (pg) 34 27 29 30 30
Mean corpuscular hemoglobin concentration (g/dl) 33 33 34 34 34
Red cell distribution width (RDW)* 12.8 ±1.2%
Serum iron 60-170 µg/dl (10-30 µmol/L)
Serum ferritin, median (range) 100 (15-300) ng/ml (boys); 40 (15-200) ng/ml (girls)
Total iron binding capacity 250-400 µg/dl (47-70 µmol/L)
Transferrin saturation** 20-50%
*RDW = standard deviation (SD) of red blood cell volume x 100/mean corpuscular volume.
**Transferrin saturation = Serum iron x 100/total iron binding capacity
Hemoglobin Hemoglobinopathy
electrophoresis or HPLC hemoglobin SS,
S-C, S-p thalassemia
Iron deficiency
Abnormal Normal
I I
,1.
Low serum iron Hemoglobinopathies, Sideroblastic anemia
Normal or high ferritin e.g. thalassemia
Normal or low TIBC p major, p minor, a.
Elevated Normal
Inflammatory Anemia of
disease chronic disease
Fig. 13. l: Approach to microcytic anemia. HPLC high performance liquid chromatography
peripheral smear will reveal the red cell morphology, Table 13.4: Reticulocyte count in evaluation of anemia
presence of schistocytes, polychromasia, specific red cell Low reticulocyte count
morphology or parasites may help in making the Congenital or acquired, aplastic or hypoplastic anemia
diagnosis. The reticulocyte count helps to determine if Transient eythroblastopenia of childhood
anemia is caused by red cell destruction or decreased Pure red cell aplasia
production, the corrected or absolute reticulocyte count Parvovirus 819 infection
is more useful (Table 13.4). When nutritional anemias are Bone marrow infiltration by malignancy, storage disorder
suspected, iron status, vitamin B 12 and folic acid levels High reticulocyte count
are determined. The reticulocyte count is decreased in Hemolysis: Autoimmune hemolytic anemia, hereditary
bone marrow failure syndromes, transient erythro spherocytosis
blastopenia of infancy and infections, e.g. parvovirus. In Hemorrhage
cases of anemia with increased reticulocyte count, a Splenic sequestration
Coombs test will help to identify, if this is due to immune Recovery from vitamin 8 12, folic acid or iron deficiency
Sepsis
or hereditary hemolytic anemia.
332 Essential Pediatrics
Reticulocyte count
+ +
Normal or reduced Increased
Serum iron Screen for renal, hepatic, Positive tests for hemolysis
+ • endocrine disease
l
Low Normal or high Yes No
! !
l
Hemolytic anemia Hemorrhage
t
Negative Positive
Recovery from nutritional
deficiency or sepsis
Anemia of chronic disease Bone marrow biopsy Anemia of renal, hepatic,
Early iron deficiency Autoimmune
endocrine disease
hemolytic anemia,
thalassemia
Infiltrative disease (leukemia, metastasis, myelofibrosis)
Aplastic anemia, pure red cell aplasia
Myelodysplastic syndrome
Congenital dyserythropoietic anemia
Macrocytosis
Yes No
+
I Megaloblastic anemia likely I
+
Levels of vitamin B 12 and folic acid Reticulocyte count
(or response to therapy)
Bone marrow examination
+ +
Low levels or anemia No megaloblastic changes in Decreased Increased
improves with therapy; marrow or no improvement
megaloblastic changes with therapy
l
in bone marrow Liver function tests,
thyroid hormone
Abnormal Normal
+
Megalobastic anemia Look for other causes Hypothyroidism
Liver disease
I Bone marrow aspiration I
Therapy with vitamin B12 Hypothyroidism '
and folate Drugs (phenytoin, 6-mercaptopurine) Aplastic anemia
Treat underlying cause Congenital deficiency of Red cell aplasia
transcobalamin II or intrinsic factor Congenital dyserythropoietic anemia
Cyanotic congenital heart disease Myelodysplastic syndrome
Down syndrome Sideroblastic anemia
Suggested Reading
• National Family Health Survey-4 (2017) Government of India,
available at http://rchiips.org
• Orkin SH, Nathan DG, Ginsburg D, Look AT, Fisher DE, Lux SE
(Eds.) (2009) Nathan and Oski Hematology of Infancy and
Childhood, 7th edn. Philadelphia: Saunders Elsevier.
Pathophysiology
Diminished dietary iron absorption in the proximal small
intestine or excessive loss of body iron can result in iron
deficiency. Iron is essential for multiple metabolic
processes, including oxygen transport, DNA synthesis, Fig. 13.4: Peripheral smear from a child with iron deficiency
and electron transport. In severe iron deficiency, iron anemia, shows microcytosis (the red blood cells are smaller
than the small lymphocyte in the field), hypochromia (central
containing enzymes are low and can affect immune and
pallor > l /3rd of cell diameter), thrombocytosis, and a few
tissue function. Iron deficiency anemia can result in ovalocytes and tear drop cells (moderate anisopoikilocytosis).
diminished growth and learning and have serious Jenner-Giemsa xl 000
consequences in children. Dietary constituents, e.g.
phytates, phosphates and tannates, make non-heme iron increased. Serum iron is reduced, total iron binding
unabsorbable. capacity (TIBC) is increased and transferrin is reduced to
Healthy newborn infants have a total body iron of less than 16% (normal 25-50%). The reduction in serum
250 mg (-80 parts per million, ppm) that decreases to -60 ferritin occurs early, and correlates with total body iron
ppm in the first 6 months of life. Body iron is regulated stores. Ferritin, an acute phase reactant, is elevated in
carefully by absorptive cells in the proximal small inflammatory conditions, and may thus be falsely high in
intestine, which alter iron absorption to match body losses a sick child. High free erythroprotoporphyrin (FEP) is seen
of iron. Breast milk iron content is more bioavailable than before anemia develops.
cow milk. Besides this fact, infants who consume cow milk
have more iron deficiency because bovine milk has a Treatment
higher concentration of calcium, which competes with iron The cause of anemia should be identified and corrected.
for absorption and they may have gastrointestinal blood Hookworm infestation is the commonest cause of occult
loss due to milk allergy. Intercurrent infections and gastrointestinal blood loss in rural India at all ages. Dietary
infestations compound the problem. counseling and treatment of any other causative factors
are required to prevent recurrence or failure of therapy.
Clinical Evaluation
Close follow-up is required to assess for adequate response
Dietary history is important, including intake of milk, and correction of anemia, this will help to identify iron
weaning foods and supplements. Pica increases the risk therapy failure (Table 13.5).
of infestations and lead poisoning. Common features of Oral iron preparations should be taken on an empty
anemia are present in proportion to the severity and rate stomach or in between meals for best absorption. About
of development. Behavioral symptoms, such as irritability
and anorexia, precede weakness, fatigue, leg cramps, Table 13.5: Reasons for non-response to hematinic therapy
breathlessness and tachycardia. Congestive heart failure for iron deficiency anemia
and splenomegaly may occur with severe, persistent, Poor compliance with therapy
untreated iron deficiency. Angular stomatitis, glossitis,
Poorly absorbed iron preparation, e.g. enteric coated
koilonychia and platynychia are seen in severe iron
Use of H2 blockers or proton pump inhibitors that cause
deficiency. achlorhydria
Laboratory Diagnosis Interaction with food and medications
Associated vitamin 8 12 or folic acid deficiency
The peripheral smear (Fig. 13.4) shows that red cells are Underlying hemolytic anemia, inflammation or infection
microcytic and hypochromic, with anisocytosis,
Malabsorption, e.g. celiac disease, giardiasis, H. pylori infection
poikilocytosis and increased red cell distribution width
High rate of ongoing blood loss
(RDW). The MCV and MCHC are reduced. Red cell
Alternative etiology, e.g. sideroblastic anemia, thalassemias, etc.
number is reduced, unlike in thalassemia where it is
334 Essential Pediatrics
10-20% patients develop gastrointestinal side effects such DNA synthesis is impaired because of lack of methyl
as nausea, epigastric discomfort, vomiting, constipation tetrahydrofolate (a folic acid derivative). Vitamin B 12 plays
and diarrhea. Enteric-coated preparations have fewer side an important role as a cofactor in this reaction, which is
effects, but are also less efficacious and more expensive. necessary for DNA base synthesis.
The most cost-effective oral preparation is ferrous sulfate
(20% elemental iron). The dose for treatment of anemia is Etiology
3-6 mg/kg/day elemental iron. The reticulocyte count The two most common causes of megaloblastic anemia
increases within 72-96 hours after initiating therapy. After are vitamin B 12 deficiency (cobalamin) and folic acid
correction of anemia, oral iron should be continued for deficiency. Folate deficiency can be caused by decreased
4-6 months to replenish iron stores. ingestion, impaired absorption (e.g. celiac disease,
Indications of parenteral iron therapy are limited to malabsorption states), impaired utilization (e.g.
conditions such as: (i) intolerance to oral iron, (ii) methotrexate, 6-mercaptopurine, trimethoprim,
malabsorptive states, and (iii) ongoing blood loss at a rate azathioprine, phenytoin) (Table 13.6) and increased
where oral replacement cannot match iron loss. Intra requirement (e.g. infancy, hyperthyroidism, chronic
venous preparations are preferred over intramuscular; hemolytic disease). Vitamin B 12 deficiency can be caused
iron sucrose IV preparations are safe and effective. They by decreased ingestion, impaired absorption (e.g.
have been used in children with end stage renal disease intestinal parasites, intrinsic intestinal disease, failure to
on dialysis and inflammatory bowel disease. release vitamin B 12 from protein, intrinsic factor
deficiency), or impaired utilization (e.g. congenital
Dose Calculation for Parenteral Iron enzyme deficiencies: orotic aciduria). Folate deficiency can
Total dose (mg)= [Target Hb-Acutal Hb] x Weight (kg) occur during prolonged parenteral nutrition and
x 2.4 + [15 x weight (kg)] hemodialysis, as folic acid is lost in dialysis fluid. History
As iron deficiency anemia is readily corrected with of autoimmune disorders may be found in patients of
medication, blood transfusions should be avoided in pernicious anemia.
young, stable patients. Red cell transfusions are needed Nutritional deficiency is more common in vegan
in emergency situations, as in patients where the rate of families (vegetarian with little or no dairy products) and
blood loss exceeds the expected rise of hemoglobin, for those consuming only goat milk (folate deficient). In
urgent surgery, hemorrhage or severe anemia with infants, it is related to maternal deficiency with inadequate
congestive cardiac failure. In very severe anemia with body stores and prolonged exclusive breastfeeding (breast
congestive cardiac failure, transfusions must be given very milk is a poor source of vitamin B 12 and associated with
slowly (2-3 mL/kg) with monitoring and diuretic therapy reduced access to other foods). Giardia infection is shown
if necessary. to cause folate malabsorption. H. pylori infections are
implicated in vitamin B 12 malabsorption in adults. Rarely
Suggested Reading inherited metabolic disorders may cause megaloblastic
• Sachdeva HPS, Gera T, Nestel P. Effect of iron supplementation anemia (Table 13.7).
on mental and motor development in children: systemic review of
randomized controlled trials. Public Health Nutr 2005; 8: 117-32 Clinical Manifestations
• Shelley E Crary, Katherine Hall, George R Buchanan. Intravenous
iron sucrose for children with iron deficiency failing to respond to
A careful dietary history is essential to the diagnosis of
oral iron therapy. PBC 2011;56(4):615-619. megaloblastic anemia. The type and quantity of foods
• Kotecha PV. Nutritional anemia in young children with focus on should be documented. Medication intake and history of
Asia and India. Indian J Community Med 2011; 36: 8-16. any other contributing medical disorders and infestation
needs to be taken. Anemia, anorexia, irritability and easy
MEGALOBLASTIC ANEMIA fatigability are clinical features common to other causes
Megaloblastic anemia is a distinct type of anemia
characterized by macrocytic red blood cells and erythroid Table 13.6: Drugs that cause megaloblastic anemia
precursors, which show nuclear dysmaturity. Common Impaired folic acid absorption: Phenytoin, phenobarbital
causes are deficiency of vitamin B 12 (cobalarnin) and folic Impaired cobalamin absorption: Proton pump inhibitors
acid. The incidence varies with dietary practices and Interference with to/ate metabolis m: Methotrexate,
socioeconomic patterns. A study has estimated the trimethoprim, pyrimethamine
incidence of folate deficiency as 6.8%, vitamin B 12 32% and Interference with cobalamin metabolism: Metformin, neomycin
combined deficiency as 20% in north Indian children.
Purine analogs: 6-Mercaptopurine, 6-thioguanine, azathioprine
Pathophysiology Ribonucleotide reductase inhibitors: Hydroxyurea, cytarabine
arabinoside
Megaloblastic changes affect all hematopoietic cell lines
Pyrimidine analogs: Zidovudine, 5-fluorouracil
with resultant anemia, thrombocytopenia and leukopenia.
Hematological Disorders I 33s
2 weeks, then weekly until the hematocrit value is normal Clinical Features
and then monthly for life. Patients with neurological In acute hemolysis, symptoms are related to the rate of
complications should receive 1000 µg IM every day for fall of hemoglobin. In rapidly occurring hemolysis, the
2 weeks, then every 2 weeks for 6 months and monthly symptoms are more numerous and pronounced. Evidence
for life. Oral supplements can be administered; however, of anemia as seen by weakness, pallor, fatigue may be seen.
absorption is variable and may be insufficient in some In some hemolytic anemias, jaundice is a prominent
patients. In dietary insufficiency, no standard duration of finding and red urine occurs in intravascular hemolysis.
therapy has been defined. Dietary counseling is advised, Splenomegaly is seen in autoimmune and many
along with vitamin B 12 supplements (oral daily or congenital forms of hemolytic anemias. The presence of
parenteral dose every 3-12 months). gallstones and icterus (hereditary spherocytosis),
hemolytic/thalassemic facies (thalassemia major,
Suggested Reading
intermedia) (Fig. 13.6), leg ulcers (sickle cell disease) can
• Devalia V, Hamilton MS, Molley AM. Guidelines for the diagnosis help lead investigations; confirmatory tests are still
and treatment of cobalamin and folate disorders. Br J Haematology
2014; 166:496-513.
required.
Laboratory Manifestations
HEMOLYTIC ANEMIAS
Laboratory findings in hemolytic anemia are: (i) increased
The term 'hemolytic anemia' is limited to conditions in erythrocyte destruction (Table 13.9), (ii) compensatory
which rate of red cell destruction is accelerated and ability increase in erythropoiesis (Table 13.10), and (iii) features
of the bone marrow to respond to the anemia is specific to particular hemolytic anemia. An elevated
unimpaired. Table 13.8 lists important causes. Under corrected reticulocyte count may be the only feature of
maximal stimulation, the normal marrow is capable of mild hemolytic anemia. The Coombs test is the most
increasing its production about 6--8 times its basal level.
The reticulocyte count is useful in determining the rate of
red cell destruction. The normal reticulocyte count value
in the newborn is 3.2+1.4% and in children l.2+0.7%.
Table 13.10: Laboratory signs of accelerated erythropoiesis Hemolytic disorders may be divided into inherited and
Peripheral blood acquired varieties. This classification has a pathogenetic
significance because the nature of hereditary lesions differs
Polychromasia or reticulocytosis
from those acquired. Most intrinsic defects are inherited
Macrocytosis
and the extrinsic are acquired. There are a few exceptions
Increase in nucleated red cells
to this generalization; these include paroxysmal nocturnal
Bone marrow hemoglobinuria, an acquired disorder characterized by
Erythroid hyperplasia an intrinsic red cell defect.
Iron kinetic studies
Increased plasma iron turnover Management
Increased erythrocyte iron turnover
In an acute attack of hemolysis, it is important to maintain
fluid balance and renal output. Shock is managed by
important initially test to perform to define the etiology standard measures. Blood transfusions, so useful in acute
of hemolysis. A direct antiglobin (direct Coombs) test is anemia of other types, must be used with caution in
positive in most cases of immune hemolytic anemia and patients with acquired anemias. Even with careful blood
implies that the erythrocyte is coated with IgG or C3 matching, destruction of transfused blood with increased
component of complement. However, the test may be
burden on excretory organs and risk of thromboses may
negative in 2-5% of patients with immune hemolysis.
occur. Acute autoimmune hemolytic anemia is treated
Haptoglobin and hemopexin are proteins which bind with steroids (prednisone 1-2 mg/kg/day), gradually
to hemoglobin and heme released from red cells following tapered over several months, once the patient shows
their destruction. The protein complexes formed after resolution of hemolysis. In chronic hemolysis, the etiology
intravascular hemolysis are removed by circulation.
needs to be investigated and treated accordingly.
Haptoglobin and hemopexin levels are, therefore, low in
patients with hemolytic anemia. When haptoglobin is Hereditary Spherocytosis
saturated, free plasma hemoglobin can be detected. While
the level of indirect bilirubin provides evidence for Several membrane protein defects are identified in
hemolysis, it is relatively insensitive and is elevated only hereditary spherocytosis. Many of these result in
if the liver function is impaired or when hemolysis is instability of spectrin and ankyrin, the major skeletal
extensive. membrane proteins. The degree of skeletal membrane
protein deficiency correlates with the degree of hemolysis.
lntravascular and Extravascular Hemolysis Structural changes lead to membrane instability, loss of
Intravascular hemolysis occurs when the released surface area, abnormal membrane permeability and
hemoglobin is released into the plasma (hemoglobinemia). reduced red cell deformability. These defects are
A part of the circulating free hemoglobin is converted to accentuated by metabolic depletion, demonstrated by
methemoglobin, which binds with albumin to form increase in osmotic fragility after 24 hours incubation of
methemalbumin, this confers a brown colour to plasma blood at 37°C. The spleen is the site of destruction of these
for several days following hemolysis. When the amount non-deformable erythrocytes.
of hemoglobin exceeds the haptoglobin binding capacity Patients have a mild to moderate chronic hemolytic
it is excreted in the urine (hemoglobinuria), and to some anemia. The MCV is decreased; the MCHC is increased
extent is reabsorbed in the proximal renal tubules. The due to cellular dehydration. The red cell distribution width
loss of heme-laden tubular cells is seen as hemosiderinuria. (ROW) is increased due to the presence of spherocytes
In extravascular hemolysis, hyperbilirubinemia is seen, and increased reticulocytes. Patients often present with
but no free hemoglobin is seen in the plasma. Hence no jaundice; splenomegaly is seen in -75% patients and
hemoglobinemia, hemoglobinuria or hemosiderinuria is pigment gallstones are frequent.
found in the latter. Patients require lifelong folic acid supplementation
A peripheral smear is useful in evaluation of hemolytic (1-5 mg/day) due to high turnover rate of erythropoiesis.
anemia. The smear may show malarial parasites, Splenectomy does not cure the underlying disorder but
spherocytes (hereditary spherocytosis, following reduces the degree of hemolysis, and is considered in
transfusion), bite cells (G6PO deficiency), microcytosis patients with severe hemolysis and high transfusion
with fragmented red cells (thalassemia) and thrombo requirement. In children with excessively large spleens,
cytopenia with schistocytes (disseminated intravascular splenectomy may diminish the risk of its traumatic
coagulopathy, thrombotic microangiopathy). Specific rupture. Splenectomy is performed after 6 years of age,
tests, e.g. hemoglobin electrophoresis, osmotic fragility, following immunization for H. influenzae type b,
enzyme assays (G6PO, pyruvate kinase deficiency), and S. pneumoniae and N. meningitidis. Prolonged prophylactic
assay for COSS/59 (paroxysmal nocturnal hemoglobinuria) therapy with penicillin may be required following
are required. splenectomy to reduce the risk of sepsis.
33a I Essential Pediatrics
Spectrum of p Thalassemias
fJ thalassemia trait: Patients have mild anemia and
abnormal red cell indices; high performance liquid
chromatography (HPLC) or hemoglobin electrophoresis
shows elevated levels of HbA2 or HbF, or both. Peripheral
blood film examination shows marked hypochromia,
microcytosis (without anisocytosis, which is found with
iron deficiency) and target cells.
Laboratory Studies
Complete blood count and peripheral blood film results
are sufficient to suspect the diagnosis. In thalassemia major
and intermedia, the hemoglobin level ranges from 2-8 g/dL;
MCV and MCH are significantly low. Reticulocyte count
is elevated to 5-8% and leukocytosis is usually present. A
shift to the left is also encountered, reflecting the hemo-
1ytic process. The platelet count is usually normal, unless
the spleen is markedly enlarged and causing hyper
splenism.
Peripheral blood film reveals hypochromasia and
microcytosis, polychromatophilia, nucleated red blood
cells, basophilic stippling and occasional immature
leukocytes (Figs 13.7 and 13.8). An HPLC sample must be
sent prior to the first blood transfusion to confirm the
diagnosis of thalassemia that shows absence of HbA and Fig. 13.8: Peripheral smear from an asymptomatic patient with
high levels of HbF. Elevated HbA2 is characteristic of hemoglobin E disease, showing microcytosis, hypochromia,
thalassemia trait. target cells and nucleated red blood cells. Jenner-Giemsa xl 000
Hematological Disorders I 341
nerves. Compression fractures and paravertebral sickle cell gene have sickle cell disease; those who are
expansion of extramedullary masses, which behave like heterozygous have the sickle trait.
tumors, are seen during the second decade of life.
Clinical Evaluation
Psychosocial: As these children survive into adulthood,
problems related to employment, marriage and having History is taken for the site, character, frequency, duration
families, as well as the stress of chronic illness will need and severity of pain, and precipitating or relieving factors.
to be addressed. Pain is the most common presentation of a vaso-occlusive
crisis. Shortness of breath or dyspnea is suggestive of acute
Cure of Thalassemia Major chest syndrome. Neurological symptoms, such as
unilateral weakness, aphasia, paresthesias, and visual
Hematopoietic stem cell transplantation (HSCT) is the only
symptoms (retinal hemorrhage) may suggest stroke or
known curative treatment for thalassemia. Poor outcome
infarct. Sudden increase in pallor, syncope or sudden pain
of HSCT occurs in patients with hepatomegaly, portal
or increase in left-sided abdomen mass may indicate a
fibrosis and inadequate chelation prior to transplant. The
splenic sequestration crisis.
event-free survival rate for patients who have all three
Icterus (unconjugated bilirubin), pallor and mild
features is 59%, compared to 90% for those who do not.
splenomegaly in a young child are the usual presentations.
Management of Other Thalassemia States The disease may manifest as a febrile episode as patients
are prone to pneumococcal, Salmonella and other bacterial
Thalassemia intermedia patients require monitoring to infections. Each episode of fever should be screened for a
assess the need for transfusion as persistently low focus of infection and treated promptly. Tachypnea
hemoglobin may retard growth. Hydroxyurea at a dose suggests pneumonia, congestive heart failure or acute
of 15-20 mg/kg/day may be used in an attempt to increase chest syndrome. Hypoxia is commonly seen in patients
HbF production and reduce the need for transfusions. This with acute chest syndrome. Severe anemia may occur with
therapy is most effective in those children with XLMl aplastic crisis; patients may have signs of congestive heart
mutation. failure. Hypotension and tachycardia are signs of septic
Patients with thalassemia trait do not require medical shock or sequestration crisis. Growth retardation and
follow-up after the initial diagnosis; iron therapy should gallstones are common and need medical attention. The
not be used unless definite deficiency is confirmed. spleen undergoes autoinfarction and is usually not
Genetic counseling is indicated to create awareness and palpable beyond 6 years of age.
prevent thalassemia major in subsequent offspring.
Types of Crisis
Suggested Reading
i. Vasa-occlusive crisis: This crisis occurs when the
• Nadkarni A, Gorakshakar AC, Krishnamoorthy R, et al. Molecular
pathogenesis and clinical variability of beta thalassemia syndromes
microcirculation is obstructed by sickled red cells,
among Indians. Am J Hematol 2001; 68: 75-80. resulting in ischemic injury. Pain is the chief complaint;
• Prevention and control of hemoglobinopathies in India: bones (e.g. femur, tibia and lower vertebrae) are
Thalassemias, sickle cell disease and other variant hemoglobins. frequently involved. Vaso-occlusion may present as
National Health Mission, Governemtn of lndia.nhm.gov.in/nrhm dactylitis or as hand and foot syndrome (painful
components
swollen hands and/or feet in children). Vaso-occlusion
may mimic an acute abdomen. The spleen develops
SICKLE CELL ANEMIA
autoinfarcts and becomes fibrotic. In the kidney, it
Sickle cell anemia, which occurs in India with a gene results in papillary necrosis, which results in
frequency of 4.3%, is relatively common in multiple states isosthenuria (inability to concentrate urine). Vaso
including Odisha, Maharashtra, Madhya Pradesh, occlusive crises can involve the lungs and cause acute
Jharkhand and Gujarat. chest syndrome; retinal hemorrhages in the eye and
involvement of corpus cavernosum, leading to
Pathophysiology priapism. Involvement of the femoral head results in
Sickle cell anemia, an autosomal recessive disease, results avascular necrosis. Cerebrovascular accidents may
from the substitution of valine for glutamic acid at position occur in children, and tend to be recurrent.
6 of the beta-globin gene. Sickle red cells are less ii. Acute chest syndrome: This is a vaso-occlusive crisis,
deformable, and obstruct the microcirculation, resulting with chest pain, cough, tachypnea, dyspnea, hypoxemia
in tissue hyp oxia that perpetuates sickling. Deoxygenation and fever. The condition requires hospitalization with
of the heme moiety of sickle hemoglobin (HbSS) leads to need for IV fluids, oxygen, bronchodilators and
hydrophobic interactions between adjacent molecules that antibiotics (including for Mycoplasma and Chlamydia).
aggregate into larger polymers. The affected cells are iii. Sequestration crisis: Sickle cells block splenic outflow
rapidly hemolyzed and have a lifespan of -10-20 days and pooling of blood in the engorged spleen, resulting
(normal 120 days). Patients who are homozygous for the in splenic sequestration.
Hematological Disorders I 343
Pancytopenia Prognosis
Severe anemia can result in high-output cardiac failure,
Peripheral blood smear, reticulocyte count, neutropenia can lead to bacterial and fungal infections;
red cell indices, indirect bilirubin
severe bleeding can occur due to thrombocytopenia. The
severity and extent of cytopenia determine prognosis.
Reduced reticulocyte Hemolysis or Blasts on
With current HSCT regimens, most patients with severe
count, normal indirect reticulocytosis peripheral aplastic anemia show 60-70% long-term survival; better
1
bT
11rub'1n, no ev1'dence smear survival is reported in favorable subgroups.
of hemolysis
i Suggested Reading
Deficiency of vitamin B120 folate Sepsis
Bone marrow failure, fibrosis
Bone marrow infiltration
Storage disorders (Gaucher)
Paroxysmal
nocturnal
I
Leukemia
Hypersplenism Lymphoma
I • Mahapatra M, Singh PK, Agarwal M, et al. Epidemiology, clinical
and hematological profile and management of aplastic anemia:
AIIMS experience. JAPI 2015; 63: 30-35.
hemoglobinuria
HEMATOPOIETIC STEM CELL TRANSPLANTATION
Fig. 13.11 : Algorithm for evaluation of pancytopenia Bone marrow transplantation (BMT) is more correctly
called hematopoietic stem cell transplantation (HSCT).
congenital dyserythropoietic anemia (red cells lysed by This is an established life-saving procedure for a number
other acidified sera but not patient sera). A recent of malignant and non-malignant diseases. The
transfusion with packed red cells may induce a false hematopoietic stem cell transplants are of the following
negative test result. A specific test for paroxysmal types: (1) Autologous transplant-when the source of stem
nocturnal hemoglobinuria is assay for two complement cells is harvested from the patient and (2) Allogeneic
regulatory proteins normally present on red cells, COSS transplant-when stem cells are collected from a human
(decay accelerating factor, OAF) and CDS9 (membrane leukocyte antigen (HLA) matched sibling or unrelated
inhibitor of reactive lysis, MIRL). Deficiency of CDSS/S9 donor. The commonly used sources of hematopoietic stem
on red cells is the hallmark of the disease. Peripheral blood cells are cytokine mobilized peripheral blood, bone
cells in Fanconi anemia show characteristic hyper marrow and umbilical cord blood.
sensitivity and chromosomal breakage with cross-linking Indications
agents (mitomycin C and diepoxybutane). The chromosomal
fragility is seen even in patients who lack physical stigmata The indications for hematopoietic stem cell transplantation
of the disease. can be conveniently divided into two groups (Table 13.13):
(a) Malignant disorders-here the cure is by the high doses
Treatment of chemotherapy or radiation therapy, while the transplant
serves to rescue the patient from the myelotoxic effects of
Supportive care such as packed red cells for anemia, the anti-cancer therapy. In allogeneic type of transplants,
platelets for thrombocytopenia and antibiotics for infection there is an additional benefit of the immunological
is needed. Hematopoietic stem cell transplant (HSCT) is response of 'graft versus cancer effect', which contributes
the only curative therapy. Criteria for referral for HSCT to controlling the disease. (b) Non-malignant diseases
is: (i) patients who are young, (ii) severe aplastic anemia, in these conditions the abnormal marrow is destroyed and
and (iii) a matched related sibling donor. Patients with replaced by the healthy unaffected donor marrow. This
severe acquired aplastic anemia who cannot undergo
HSCT may benefit from therapy with antithymocyte Table 13.13: Indications for stem cell transplantation
globulin (ATG) or anti-lymphocyte globulin (ALG) and Malignant disorders Non-malignant disorders
cyclosporine. Granulocyte colony-stimulating factor (G Acute myeloid leukemia Thalassemia
CSF) is indicated in patients with neutropenia with Chronic myeloid leukemia Aplastic anemia
infection. If the neutrophil count does not increase, this Acute lymphoblastic leukemia Fanconi anemia
therapy should be discontinued after 7 days, because of (high risk) Immunodeficiency syndromes
the risk of malignancy. Hodgkin disease Inborn errors of metabolism
Therapy with ATG or cyclosporine is contraindicated Non-Hodgkin lymphoma Autoimmune diseases (rare)
in patients with Fanconi anemia. The only curative (relapsed or refractory)
treatment for them is HSCT. However, this will neither Neuroblastoma
cure the physical and renal manifestations of the disease, Ewing sarcoma
nor prevent the risk of cancer. Palliative therapy with oral Myelodysplastic syndromes
androgens has been used in patients of Fanconi anemia Gliomas
Other solid tumors
who cannot undergo HSCT.
a4s I Essential Pediatrics
corrects genetic or acquired disease of blood and bone Venous access: A long-term, silastic, multi-lumen catheter
marrow. is needed for IV medications, infusion of stem cells, blood
sampling, and administration of blood components and
Allogeneic Hematopoietic Bone Marrow Transplant nutrition.
Donor Requirement
Infections: Bacterial and fungal infections are a major
For an allogeneic transplant, a human leukocyte antigen complication in early and late post-transplant period.
(HLA) identical sibling is the ideal donor. In spite of HLA Prompt institution of appropriate antibiotics is needed.
identity, there is always variation in minor histocompati Later, viral infections assume increasing importance, the
bility loci, which may lead to graft rejection or graft versus chief being cytomegalovirus, herpes simplex virus and
host disease. It is possible to have a successful transplant varicella zoster. Bacterial infections with encapsulated
using a partially matched sibling as a donor, or an organisms can occur after 3-6 months.
unrelated HLA identical donor, but complications of graft
versus host disease and graft rejection are severe. Most Blood components: Patients require multiple red cell and
centers in India do not conduct unrelated transplants. platelet transfusions during the period of pancytopenia,
Unlike other organ transplants, ABO blood group until engraftment occurs. Patients are immunosuppressed
compatibility is not essential. After successful hematopoietic and at risk of developing transfusion associated-graft
transplantation, the blood group of the recipient will versus host disease. To prevent this, all cellular blood
change to that of the donor. products should be irradiated prior to transfusion, to
inactivate donor lymphocytes.
Conditioning Procedure
Growth factors: Hematopoietic growth factors, such as
Myeloablative conditioning: The standard preparatory granulocyte colony-stimulating factor, are administered
regimens given prior to hematopoietic transplantation are to reduce the duration of neutropenia.
myeloablative (suppression of bone marrow). Patients
receive extremely high doses of chemotherapy. The aim Failure of Engraftment
is threefold: (a) eradication of malignant cells or abnormal Failure to engraft after HSCT (graft dysfunction) or
clone of cells, (b) suppression of the immune system of inability to sustain graft (graft rejection) is an uncommon
the host so that the allograft is not rejected, and (c) clearing but serious complication. Causes include insufficient stem
a "physical space" to allow adequate growth of donor stem cell dose, infections, graft-versus-host disease and other
cells. immunological processes. The incidence is higher in
Non-myeloablative conditioning: This aims to suppress unrelated donor and HLA mismatched transplant.
the immunity of the recipient sufficiently to allow
allogeneic engraftment, without destroying the recipient Graft Versus Host Disease
marrow. These regimens have less toxicity, but higher risk Graft versus host disease (GVHD) may be acute or chronic.
of relapse. Acute GVHD occurs within the first 3 months after
transplant and affects 3 tissues: Skin, gut and liver and
Technical Aspects may be accompanied by fever. The severity is graded
The donor marrow is harvested by repeated aspiration based on the extent of skin involvement, degree of jaundice
from the posterior iliac crests, under general anesthesia and severity of diarrhea. Chronic GVHD develops later
(though now chiefly collected as peripheral blood stem than 100 days after transplant and often follows acute
cells by apheresis after G-CSF mobilization). The GVHD, but may also develop de novo. Clinically, it
hematopoietic stem cells (HSC) are collected in a bag with resembles autoimmune disorders like scleroderma with
anticoagulant. The number of stem cells (CD34+) required skin rash, sicca complex, sclerosing bronchiolitis and
for successful engraftment is estimated to be about 3 x hepatic dysfunction. The mortality varies from 20-40%.
10 6 per kg of recipient body weight. Transfused through Management is with immunosuppressive agents.
the veins, the stem cells home into the recipient marrow
space and start engrafting. Engraftment is considered Autologous Stem Cell Transplantation
established when the peripheral neutrophil count reaches Autologous bone marrow or peripheral blood stem cell
500 I mm3 on 3 successive days. transplantation is a procedure similar to allogeneic bone
marrow transplant, the major difference being that the
Supportive Care patient's own stem cells are used for engraftment. The
Protective isolation: After transplantation, it takes about concept of performing autologous stem cell transplant is
2-3 weeks before engraftment occurs, that is the time when to permit administration of very high doses of chemo
the stem cells start producing adequate number of radiotherapy which would otherwise be fatal, due to
neutrophils, platelets and erythrocytes. During this period, severe myelosuppression. First the patient's marrow or
very intensive support is required. stem cells are collected prior to chemotherapy, they are
Hematological Disorders I 341
then used to 'rescue' the patient from the myelotoxicity disorder and magnitude of blood loss. Administration of
after the chemotherapy. The procedure is only indicated replacement fluids/blood is necessary. Following this, the
for malignancies which are chemo- or radiosensitive, e.g. child should be evaluated for the etiology of bleeding,
leukemia, lymphoma, neuroblastoma and other solid which may be due to platelets (Tables 13.14 and 13.15),
tumors. coagulation defects (Table 13.16) or dysfunctional
Peripheral blood stem cell transplantations (PBSCT) fibrinolysis. Clinical assessment (including type of
have virtually replaced bone marrow for autologous stem bleeding and antecedent events) and results of initial
cell transplantation. Engraftment takes place more rapidly screening help to rapidly identify the cause, and enable
when peripheral stem cells are used instead of bone specific management.
marrow cells. The advantage of autologous transplant over
allogeneic transplant is that there is no graft versus host Table 13.14: Causes of thrombocytopenia
disease, and once engraftment occurs then graft rejection Idiopathic thrombocytopenic purpura
is unlikely. Infections: Disseminated intravascular coagulation, malaria,
kala-azar, dengue hemorrhagic fever, hepatitis B and C, HIV,
Peripheral Blood Stem Cell Transplantion (PBSCT) congenital (TORCH) infections, infection associated
The procedure is similar to bone marrow transplant except hemophagocytosis syndrome
for differences in the method of collection of stem cells Medications: Valproate, penicillins, heparin, quinine, digoxin
and slight changes in the engraftment potential. Peripheral Thrombotic microangiopathy: Thrombotic thrombocytopenic
blood contains 0.1 % stem cells; this number is increased purpura; hemolytic uremic syndrome
by administration of colony-stimulating factors. For Malignancies: Leukemia, lymphoma, neuroblastoma
allogenic PBSCT, administration of G-CSF for 4-5 days Autoimmune or related disorders: Systemic lupus
results in higher number of circulating stem cells, which erythematosus, Evans syndrome, antiphospholipid syndrome,
can be collected by apheresis. The donor is spared the pain neonatal immune thrombocytopenia
of marrow aspiration. For autologous PBSCT, stem cells Immunodeficiency. Wiskott-Aldrich syndrome, HIV/Al DS
are collected similarly, but chemotherapy is given prior
Bone marrow failure: Thrombocytopenia with absent radii,
to the harvest to reduce tumor contamination and yield Fanconi anemia, Shwachman-Diamond syndrome
higher proportion of stem cells.
Marrow replacement Osteopetrosis, Gaucher disease
Cord Blood Stem Cell Transplantation Others: Hypersplenism, Kasabach-Merritt syndrome
Placental blood, which is routinely discarded in clinical
practice, is a rich source for allogeneic hematopoietic stem Table 13.15: Qualitative disorders of platelet function
cells. The main limitation of cord blood transplants is the Inherited disorders
limited number of nucleated cells available in a single unit. Glanzmann thrombasthenia (GP lb deficiency)
As compared to bone marrow transplantation, the time Bernard-Soulier syndrome (GP llb - llla deficiency)
for engraftment in cord blood transplantation is much Gray platelet syndrome
longer, taking a month for neutrophil engraftment and Dense body deficiency
>50 days for platelet engraftment. There is also a higher
incidence of non-engraftment, leading to high morbidity Acquired disorders
and mortality. The main advantage is a lower incidence Medications
and severity of GVHD. Chronic renal failure
Cardiopulmonary bypass
Suggested Reading
• Seth S, Kanga U, Sood P, et al. Audit of peripheral stem cell
Table 13.16: Common coagulation disorders
transplant for aplastic anemia in multi-transfused and infected
patients. Transplant Proc 2012; 44: 922-24. Inherited disorders
• Kumar R, Prem S, Mahapatra M, et al. Fludarabine, Hemophilia A and B
cyclophosphamide and horse antithymocyte globulin conditioning
von Willebrand disease
regimen for allogeneic peripheral blood stem cell transplantation
performed in non-HEPA filter rooms for multiply transfused Specific factor deficiencies
patients with severe aplastic anemia. Bone Marrow Transplant Factor VII, X, XIII deficiency
2006; 37: 745-9. Afibrinogenemia
Acquired disorders
DISORDERS OF HEMOSTASIS AND THROMBOSIS
Liver disease
Approach to a Bleeding Child Vitamin K deficiency
Warfarin overdose
An important initial step is to stabilize the bleeding patient. Disseminated intravascular coagulation
Assessment of vitals provides a clue to the severity of the
a4a I Essential Pediatrics
!
The process of hemostasis is divided into cellular and fluid Contact activation
phases. The former involves platelets and the vascular Xll--+Xlla VII
wall, while the latter involves plasma proteins. The
physiology of hemostasis is complex, involving a fine
+
Xl-+Xla Calcium+
balance between flow of blood and local responses to tissue factor
IX-+IXa
vascular injury. The fluid phase is divided into three
X ----VIia
VIiia
!
processes: (i) multiple-step zymogen pathway that leads
l
+ Calcium Iii
to thrombin generation, (ii) thrombin-induced formation
of fibrin clot, and (iii) complex fibrinolytic mechanisms + Platelet factor Xa
that limit clot propagation.
6!1�ium +
The physiology of hemostasis includes the generation
of insoluble fibrin and activation of platelets to form a Platelet factor
hemostatic plug. Pro- and anticoagulant pathways, Factor XIII
platelet number and their function, and vascular factors I Prothrombin (factor ll)j-. Thrombin (Ila) 1---1
control this process. The coagulation cascade is often
depicted as involving two pathways: Intrinsic and
extrinsic. The extrinsic pathway, the primary initiating
pathway for coagulation, is measured by prothrombin
time (PT). The intrinsic system that works as a regulatory I Fibrinogen (factor I) 1-I ------11o I I Fibrin
Table 13.17: Differences in bleeding patterns between platelet disorders and coagulation disorders
Platelet disorders Coagulation disorder
Site of bleeding Skin, mucous membranes (mucosal bleeds: Soft tissues, joints, muscles (deep bleeds)
epistaxis, oral, gastrointestinal tract)
Petechiae Yes No
Ecchymoses Small, superficial Large, deep
Hemarthrosis, muscle bleeding Extremely rare Common
Bleeding after minor trauma Yes No
Bleeding after surgery Immediate; usually mild Delayed (1-2 days); often severe
Example von Willebrand disease, idiopathic Hemophilia
thrombocytopenic purpura
Hematological Disorders 349
Suggested Reading
• Clinical and laboratory approach to the patient with bleeding. In:
Nathan and Oski's Hematology of Infancy and Childhood, 6th edn.
Nathan DG, Orkin SH, Ginsburg D, Look AT. Lusher JM, eds. WB
Saunders: Philadelphia; pp 1515-1526.
Fig. 13.13: Large ecchymotic patch on the upper limb of a Idiopathic Thrombocytopenic Purpura (ITP)
young girl with von Willebrand disease ITP continues to carry its acronym, although the condition
is no longer idiopathic, and is considered to have an
Laboratory Investigations immune basis. This is the commonest bleeding disorder
A hemogram is done for platelet count, morphology of presenting in children between 1 and 7 years of age. It is
platelets and red cells, and screen for microangiopathic important to correctly diagnose this entity and differentiate
hemolysis. The peripheral smear is made from a fresh it from other ominous conditions. Thrombocytopenia
finger stick, avoiding artefactual errors due to EDTA lasting less than 6 months is termed acute, and greater
anticoagulation. Initial screening tests are PT and aPTT than 6 months is termed chronic. The majority of children
(Fig. 13.14). Specific factor assays are done to identify and (60-75%) are likely to have acute ITP that resolves within
grade factor deficiencies. The aPTT is used for monitoring 2---4 months of diagnosis, regardless of therapy.
heparin therapy; PT and ratio of PT to an international
normalized standard (INR) are used to assess therapeutic Pathogenesis
warfarin affect. Normal platelet counts vary between 150 and 400 x 1()3/mm3
Bleeding time is rarely used due to the problems of in children above one week of age. ITP is believed to have
reproducibility and reliability. This test is abnormal if the an immune pathogenesis, against the platelet glycoprotein
platelet count is below 100,000/µL (Table 13.14). In systemic lib/Illa complex. Platelets with surface antibodies are
vasculitic disorders (Henoch-Schonlein purpura) and trapped in the spleen, and removed by macrophages. The
• • •
Abnormal Abnormal aPTT Abnormal PT
PT and aPTT Normal PT Normal aPTT
,
Infection Oral anticoagulants Hemophilia A and B Anticoagulant therapy
Hypersplenism Liver dysfunction von Willebrand Factor VII deficiency
Immune thrombocytopenia Vitamin K deficiency disease
Thrombotic microangiopathy Disseminated intravascular
Malignancy coagulation
Fanconi anemia
Thrombocytopenia with
absent radii
Platelet dysfunction
Table 13.18: Vascular causes of bleeding production of megakaryocytes and help exclude marrow
Henoch-Schonlein purpura infiltration or bone marrow failure.
Table 13.21: Types of blood component therapy, their constituents and guidelines for use
Component Constituents Indication Dose Precautions
Fresh frozen All coagulation factors as Coagulation factor 15 mUkg or 1 bag per Infuse soon after thawing; need
plasma (FFP) in normal plasma; contains deficiencies with pro- 10 kg (constitutes ABO compatible units; may
0.7-1.0 U/mL of longed prothrombin 25-30% replacement cause fluid overload
factors II, V, VII, VIII, IX, time; thrombotic therapy for coagulation
X, XI, XII, XIII and thrombocytopenic factors)
2.5 mg/ml fibrinogen purpura
Cryoprecipitate Fibrinogen 150 mg/bag, Fibrinogen deficiency 1 bag per 5 kg will raise
factor VIII 80-120 units/ or consumption; factor fibrinogen levels by
bag, factor XIII and vWD VIII deficiency (hemo- 70 mg/dL
(does not contain factor philia A), vWD disease;
IX) factor XIII deficiency
Random donor Platelets; �5.5 x 10 10 Thrombocytopenia One unit raises platelet Infuse rapidly; do NOT
platelets (RDP) platelets per bag counts by 500CH 0,000/ refrigerate prior to transfusion
mm3; 1 unit every
1O kg raises counts
by 30,000-50,000/mm3
Single donor Platelets; contains at least Thrombocytopenia One collection is equi- Precautions as above
platelets (SOP) 3 x 10 1 1 platelets valent to approxi-
mately 6 units of
random platelets
Fresh blood All components of blood To replace acute and Only to be used in Not a good source for platelets
massive blood loss severe trauma or coagulation factors
as4 I Essential Pediatrics
Novel therapies: Supplementation with activated protein Symptoms due to deep vein thrombosis include pain
C has shown promise in critically ill patients. High-dose and swelling of the limb; erythema and tenderness on foot
therapy with antithrombin III has shown benefit in some dorsiflexion (Homan sign) may be seen. Pulmonary
neonatal studies. embolism may present with anxiety, breathlessness,
pleuritic chest pain, fever and cough. Symptoms of central
Suggested Reading nervous system thrombosis include headache, vomiting,
• BCSH Secretary, British Society for Hematology. Guidel ines for lethargy, seizures, focal weakness or hemiplegia. Strokes
diagnosis and management of dissem inated intravascular may occur in utero; the newborn may then present with
coagulation. Br J Haematol 2009; 145: 24-33. seizures and lethargy. Precipitating factors like infection,
dehydration and trauma are common. Patients with renal
THROMBOTIC DISORDERS vein thrombosis show flank pain and hematuria. Signs of
The incidence of thrombosis is lower in children than arterial thrombosis include diminished or absent
adults; thrombosis related morbidity is, however, peripheral pulses and cool extremities.
significant. Children till 6-month-old have lower levels of
the vitamin K dependent coagulation factors II, IX, and X, Laboratory Evaluation
compared to adults. Levels of thrombin inhibitors, such Since clotting factors are consumed in an acute thrombosis,
as antithrombin and heparin cofactor II, plasminogen, their low level may be the result of the pre-existing
protein C and S are low at birth. Protein S levels approach thrombosis. The child should be evaluated to rule out DIC
adult values by the age of 3-6 months, but protein C levels with complete blood count, peripheral smear, D-dimer,
are low even into childhood. Thrombin generation is prothrombin time (PT), activated partial thromboplastin
decreased (low prothrombin levels) and delayed in time (aPTT) and fibrinogen level.
newborns compared to adults. The incidence of Imaging studies include: (i) Color Doppler imaging.
thrombosis is highest in infants and in adolescence. Signals are absent in thrombosed vessels and the lumen
cannot be compressed with direct pressure. However,
Clinical Evaluation this may not be sufficiently sensitive to detect thrombosis
Conditions associated with arterial thrombosis include in vessels such as subclavian veins, superior vena cava
congenital heart disease, recent cardiac catheterization, or brachiocephalic veins; (ii) Echocardiography. This is
fever, recent surgery, trauma, central venous catheter use, useful for vena cava and proximal subclavian vein
and underlying nephrotic syndrome, collagen vascular thrombosis; (iii) Computerized tomography. Useful for
disease and dehydration (Table 13.22). The age at which detecting venous sinus thrombosis; however, both MRI
thrombosis occurred and type of thrombosis (deep vein, and MRA are better at detecting early arterial ischemic
arterial or stroke) should be documented. strokes; (iv) Chest radiography. Reveal findings of
pulmonary embolism which include small pleural
Table 13.22: Factors which increase risk of effusions with wedge-shaped pleural-based opacity of
thrombosis in children pulmonary infarction; (v) Ventilation-perfusion (V /Q)
Acquired conditions scan. Sensitive procedure for detecting pulmonary
Infections: Viral, bacterial sepsis embolism.
Disseminated intravascular coagulation
Dehydration Management
Central venous catheter Urgent stabilization is required. If respiratory distress or
Surgery, trauma neurological problems exist, management in an intensive
Cyanotic congenital heart disease care unit is required. If possible, screening tests for
Antiphospholipid antibody syndrome hypercoagulable state should be sent prior to initiating
Acute lymphoblastic leukemia; therapy (L-asparaginase and anticoagulation therapy. Children with lower extremity
steroids) deep vein thrombosis can be fitted for compression
Nephrotic syndrome stockings. Initial therapy requires heparin (unfractionated,
Inherited prothrombotic disorders low molecular weight) followed by oral warfarin therapy.
While underdosing hampers resolution of the thrombus,
Resistance to activated protein C
close monitoring is required to prevent overdose and risk
Factor V Leiden
of bleeding. The international normalized ratio (INR),
Protein C deficiency
which is PT of patient compared to an international
Protein S deficiency
standard, is kept in the therapeutic range -2-3. The
Antithrombin deficiency
duration of therapy depends on the risk of recurrence;
Prothrombin gene G20210A mutation
this can be assessed by testing for thrombophilia status,
Elevated lipoprotein (a) level
best done 3 months after the event and after stopping
Hyperhomocysteinemia
anticoagulants.
Hematological Disorders 355
Table 13.24: Common causes of eosinophilia Table 13.26: Common causes of neutropenia
Acute Acute
Allergic disorders: Asthma, atopic dermatitis, urticaria, drug Infections: Severe sepsis; tuberculosis, Shigella, brucellosis;
hypersensitivity, pemphigoid dengue, varicella, Epstein-Barr virus, cytomegalovirus, HIV;
Parasitic infestations: Toxocara, ascaris, amebiasis, strongy kala-azar, malaria; rickettsia
loidiasis, filaria, toxoplasmosis, trichinosis, schistosomiasis, Drugs: Sulfonamides, phenytoin, phenobarbital, penicillin,
malaria, scabies phenothiazines
Fungal infections: Bronchopulmonary aspergillosis, coccidio Bone marrow infiltration: Leukemia, lymphoma, neuroblastoma
mycosis Hypersplenism
Malignancy: Hodgkin lymphoma, T cell lymphoma, acute Chemotherapy: Busulphan, cyclophosphamide, radiation
myelogenous leukemia, myeloproliferative syndrome
Chronic
Hypereosinophilic syndrome
Aplastic anemia: Acquired; inherited (Fanconi anemia)
Chronic Autoimmune diseases: Systemic lupus erythematosus, Crohn
Allergic disorders: Pemphigus, dermatitis herpetiformis disease, rheumatoid arthritis
Autoimmune disorders: Inflammatory bowel disease, Vitamin 8 12 or folate deficiency
rheumatoid arthritis Bone marrow infiltration: Myelodysplasia, chronic myelogenous
Myeloproliferative syndrome, hypereosinophilic syndrome leukemia, chronic idiopathic neutropenia
Loeffler syndrome Paroxysmal nocturnal hemoglobinuria
Immunodeficiency syndromes: Hyper-lgE, Wiskott-Aldrich Inherited disorders: Cyclic neutropenia; severe congenital
syndrome; Omenn syndrome; graft versus host reaction neutropenia; chronic benign neutropenia; Kostmann syndrome;
Miscellaneous: Thrombocytopenia with absent radii; renal Shwachman-Diamond syndrome; dyskeratosis congenita;
allograft rejection; Addison disease Chediak-Higashi syndrome; glycogen storage disease type 1 B
Associated with immunodeficiency: Hyper-lgM syndrome; HIV
Table 13.25: Common causes of lymphocytosis
Infections: Infectious mononucleosis, infectious hepatitis, chemotaxis leading to increased bacterial infections. In the
cytomegalovirus, tuberculosis, pertussis accelerated phase, there is lymphohistiocytic infiltration
Endocrine: Thyrotoxicosis, Addison disease of organs.
Malignancy. Acute lymphoblastic leukemia, lymphoma Leukocyte adhesion defect has deficiency of CD11 and CD18
on the neutrophils, resulting in defects in adhesion,
marrow failure, malignancy or its treatment. It can also chemotaxis and C3bi-mediated phagocytosis. This causes
be due to rare metabolic disorders like glycogen storage delayed umbilical cord separation in the newborn and leads
disease type lb, Shwachman-Diamond syndrome and to repeated, severe infections and periodontitis later in life.
Kostmann syndrome (Table 13.26). Chronic granulomatous disease is an X-linked or rarely
Lymphopenia: The condition is frequent in inherited autosomal recessive defect of the respiratory burst oxidase
immunodeficiency syndromes due to decreased production in the granulocytic cells. It results in infections in the lungs,
of B or T lymphocytes, and in Wiskott-Aldrich syndrome. skin and gastrointestinal tract due to S. aureus, Aspergillus
Lymphopenia is also found in acquired immunodeficiency spp., and Serratia marcescens, which lead to deep-seated
syndrome, systemic lupus erythematosus, protein losing granulomatous lesions. Other immunodeficiencies have
enteropathy and following treatment with anti-thymocyte quantitative defects in T, B or both lymphocyte subsets
globulin and corticosteroids. with maturation or functional defects, which may lead to
life-threatening infections.
Qualitative Defects
Suggested Reading
Chediak-Higashi syndrome is identified by characteristic
giant lysosomes in granulocytes and oculocutaneous • The phagocytic system and disorders of granulopoiesis and
granulocyte function. In: Nathan and Oski's, Hematology of Infancy
albinism. The condition is due to defect in CHS1 gene that and Childhood, 7th edn. Eds. Orkin SH, Nathan DG, Ginsburg D,
encodes for lysosomal trafficking, resulting in ineffective Look AT, Fisher DE, Lux SE. WB Saunders, Philadelphia, 2009; pp
granulopoiesis, delayed degranulation and defects in 1109-1220.
Chapter
14
Otorhinolaryngology
Prem Sagar • Alok Thakar • Sandeep Samant
DISEASES OF THE EAR and irritability. Older children may report impaired
hearing. History of recent upper respiratory tract infection
Acute Otitis Media
is common. Otoscopy reveals a red and bulging tympanic
Otitis media is a common early childhood morbidity that membrane or perforation of the tympanic membrane with
refers to viral or bacterial infection of the 'middle ear cleft'. otorrhea (opaque, yellow-green or reddish-brown fluid).
The middle ear cleft is a term that includes the pneumatic Cleaning of the fluid reveals an intact drum, as the rupture
spaces of the middle ear cavity medial to the tympanic is small and closes promptly after spontaneous
membrane, the attic superiorly, the mastoid antrum
perforation. The diagnosis of otitis media is considered in
posterior to the attic, and pneumatized air cells in temporal
the presence of the following criteria: Rapid onset of
bone that surround the mastoid antrum and extend to the
symptoms, signs of middle ear effusion and signs and
petrous apex. Anatomic features that predispose a young
child to ear infections include a shorter, more horizontal symptoms of middle ear inflammation.
and compliant eustachian tube, and bacterial carriage in Treatment: Antimicrobial therapy is recommended in all
the adenoids. Risk factors include exposure to cigarette patients except a few who may qualify for a trial of
smoke, overcrowding, bottle feeding, use of pacifier, day observation (Table 14.1). Amoxicillin is the first choice of
care center attendance, cleft palate, Down syndrome, therapy. Higher doses (80-90 mg/kg/day) are considered
allergy, immune dysfunction and gastroesophageal reflux. where streptococcal resistance is endemic. Coamoxiclav,
Incidence: The peak incidence of acute otitis media in cefaclor, cefuroxime and newer generation cephalosporins
childhood is in infancy and decreases with advancing age. are useful second-line drugs. Macrolides are considered
Acute otitis media is uncommon beyond the age of 7 years. in patients allergic to penicillin and/or cephalosporins.
Etiology: The most common causative organisms are Antibiotic therapy is continued for at least 7 days.
Streptococcus pneumoniae, Haemophilus influenzae and Otoscopy should be repeated after 3-4 days and at
Moraxella catarrhalis in -75% cases; less common pathogens 3 weeks. Adjuvant treatment with oral and topical
include S. pyogenes, S. aureus and Pseudomonas aeruginosa; decongestant agents is not necessary. Antihistaminic
viruses may be the sole pathogen in 15% of cases. agents, which contribute little to resolution of otitis media
Diagnosis: The condition is characterized by rapid onset and may precipitate sinus infections by drying mucosal
of symptoms such as otalgia or ear tugging, fever, crying secretions, are not recommended.
Table 14.1: Recommendations for initial management for uncomplicated acute otitis media
Age, months Severe symptoms*, otorrhea or uncertain access to No severe symptoms* or otorrhea;
follow-up follow-up assured
Unilateral Bilateral Unilateral Bilateral
6-23 Antibiotic therapy Antibiotic therapy Treat or observe** Antibiotic therapy
�24 Antibiotic therapy Antibiotic therapy Treat or observe** Treat or observe**
Clinical practice guideline: Diagnosis and management of acute otitis media. Pediatrics 2013; 131:e964-99
*Include toxic-appearance; otalgia persisting for >48 hours; temperature >39 ° C (102.2 ° F) in last 48 hours
**If observation is offered, follow up must be ensured and antibiotics are begun if the child worsens or fails to improve within 48 to 72 hours of onset
of symptoms
357
ass I Essential Pediatrics
Recurrent Acute Otitis Media within 3 months. Older children who are not at risk for
Recurrent acute otitis media refers to three or more speech and learning disabilities may be kept under
episodes in any 6 months or four or more episodes in a observation without medical or surgical intervention.
year. Children experiencing recurrent otitis media are Children who can cooperate should be advised auto
considered for tympanostomy tube insertion as it reduces inflation during the period of observation. Age appropriate
the frequency of these episodes. Adenoidectomy may be hearing tests should be performed, if effusion persists
considered, if there is associated airway obstruction. beyond 3 months or if hearing loss, speech delay or
Patients with recurrent acute otitis media do not benefit learning difficulty is suspected. Use of antihistamines,
from concurrent tonsillectomy. decongestants, corticosteroids and antibiotics is not
routinely required.
Otitis Media with Effusion Surgery is indicated in patients with: (i) otitis media
Otitis media with effusion refers to serous or mucoid fluid with effusion lasting 3 months or longer along with
occupying the normally air-filled spaces of the middle ear persistent hearing loss, poor scholastic performance,
cleft. Inflammatory signs are absent and the prime behavioral problems, ear discomfort or difficulty in
symptom is hearing loss due to poor conduction of sound balance; (ii) recurrent or persistent otitis media with
pressure from the external to inner ear. effusion in a child at increased risk of speech and learning
disabilities (permanent hearing loss, speech and language
Etiology: Otitis media with effusion occurs due to disorder, autism spectrum disorder, Down syndrome,
eustachian tube obstruction and may follow an episode uncorrectable visual impairment or developmental delay);
of acute otitis media. Effusions are found in -40% patients and (iii) otitis media with effusion associated with
at 1 month after acute otitis media and in 10% after structural damage to the tympanic membrane or middle
3 months. Otitis media with effusion may occur de novo ear.
(without history of acute otitis media), particularly in
patients with adenoid hypertrophy or nasal allergies. The initial surgical procedure consists of myringotomy
and tympanostomy tube placement. The tympanic
Diagnosis: Most children are asymptomatic or complain membrane is penetrated by a small radial myringotomy
of hearing loss and ear fullness; there is no otalgia. (approximately 1 mm) placed in the anteroinferior
Otoscopy reveals dull gray, yellow or blue tympanic quadrant, the middle ear effusion is aspirated and a
membrane with middle ear effusion (Fig. 14.1). Air fluid tympanostomy tube (grommet) is placed through the
level or bubbles may be observed medial to the tympanic myringotomy incision (Fig. 14.2). Tympanostomy tube
membrane. Diagnosis is confirmed by demonstrating placement drains the effusion and improves middle ear
reduced tympanic membrane mobility on pneumatic ventilation. This leads to resolution of mucosal edema and
otoscopy (Seigel speculum examination) or type B pattern restoration of the patency of eustachian tube and
on tympanometry. ultimately improvement in ear discomfort and hearing
Therapy and outcome: About two-thirds of serous middle ear loss. After a few months, tympanostomy tubes extrude
effusions in children 2-7 years old resolve spontaneously spontaneously and the myringotomy closes soon after.
Fig. 14.1: Otitis media with effusion. Note the dull lustreless Fig. 14.2: Tympanostomy tube in situ in the anteroinferior quadrant
tympanic membrane (Courtesy: Textbook of ENT, Hazarika) of the tympanic membrane (Courtesy: Textbook of ENT, Hazarika)
Otorhinolaryngology lasg-
Mean time for spontaneous extrusion of short-term
tympanostomy tubes (e.g. Goode, Shepard) is 6---9 months.
Tubes designed for long-term retention (e.g. T-tube,
Armstrong tube) last 12-18 months. Children with
tympanostomy tubes should wear earplugs to avoid entry
of water into the middle ear space. Complications after
tympanostomy insertion, noted in 5-10% cases, include
recurrent otorrhea, early extrusion, tube blockage and
persistent perforation. Long-term tubes are associated
with higher rates of complication.
Patients with obvious adenoid hypertrophy should
simultaneously undergo adenoidectomy to avoid
obstructing the eustachian tube opening, particularly in
cases with recurrence after tympanostomy tube extrusion.
Isolated tonsillectomy or myringotomy should not be
performed to treat otitis media with effusion. Patients with
persistent otitis media with effusion and hearing loss
should be offered hearing amplification with hearing aids,
if surgery cannot be performed.
Fig. 14.3: Otoscopy in a child with chronic suppurative otitis
Prevention: The incidence of acute otitis media and otitis media showing subtotal central perforation [Courtesy: Textbook
media with effusion is reduced with exclusive breast of ENT, Hazarika)
feeding for the first 6 months of life, avoiding bottle
feeding in supine position and use of pacifiers, eliminating media; tubotympanic disease is considered safe. However,
passive smoking, and vaccination against pneumococci complications are possible with both types of disease.
and Haemophilus spp. Perforations in the tympanic membrane are described
based on their size and location. Those involving the pars
Chronic Otitis Media tensa and not affecting the bony margin are central
Chronic otitis media is defined as chronic inflammation perforations (Fig. 14.3). Perforations affecting the postero
of the middle ear space and mastoid air cells. It may result superior tympanic membrane and marginal perforations
in perforation of the tympanic membrane, tympano (i.e. those reaching the margin of the membrane) are
sclerosis, retraction pocket in the tympanic membrane, associated with retraction pockets and cholesteatoma
ossicular damage or cholesteatoma leading to ear formation.
discharge and/ or hearing loss. Chronic suppurative otitis Management: Medical therapy chiefly consists of topical
media (CSOM) is diagnosed in the presence of an ear antibiotics and aural toilet. Parents are instructed to avoid
discharge persisting for longer than 6 weeks. water exposure. Topical quinolones are effective and safe.
Risk factors: Perforations in the tympanic membrane Complicated infections and/ or signs of systemic involve
following otitis media or tympanostomy tube placement ment merit the use of systemic antibiotics. Secondary
may not heal due to persistent infection, leading to chronic fungal otitis externa may develop as a complication of
otitis media. Factors preventing resolution of otitis media topical antibiotic therapy. Otolaryngology referral is
include recurrent infections through a perforated tympanic necessary to rule out cholesteatoma. Surgery is indicated
membrane, ascending infection from nasopharynx in cases that do not respond to conservative treatment,
through the eustachian tube and colonization of middle and involves repair of the tympanic membrane perforation
ears by bacteria. Commonly isolated organisms include (tympanoplasty) with or without mastoidectomy.
P. aeruginosa, S. aureus, Proteus, E. coli and anaerobes.
Cholesteatoma
Presentation and classification: Patients usually present
with mucoid or mucopurulent ear discharge and/ or This term refers to a sac of squamous epithelium extending
hearing loss that is chiefly mild to moderate and of from the tympanic membrane into the middle ear. It is
conductive type. Chronic otitis is broadly categorized into usually acquired and related to eustachian tube dys
two varieties. Simple central perforations of the pars tensa function. It is unclear whether a cholesteatoma arises from
are classified as tubotympanic. Disease affecting the attic extension of a tympanic membrane retraction pocket, or
and posterosuperior region, especially if associated with from aberrant inward migration of normal epithelium.
cholesteatoma, retraction pockets or persistent Cholesteatoma may cause serious complications by its
granulation, is classified as atticoantral. Atticoantral slow expansion and destruction of surrounding bone.
disease, associated with high risk of intracranial and Diagnosis: Patients with cholesteatoma present with a
intratemporal complications, is termed unsafe chronic otitis chronically draining ear and hearing loss. Diagnosis is
aso I Essential Pediatrics
headache, malaise and high spiking fever. Treatment is Sensorineural Hearing Loss
with parenteral antibiotics and drainage of the mastoid. Sensorineural hearing loss is caused by pathology in the
cochlea, auditory nerve or central auditory pathway.
Otitis Externa
Congenital and acquired hearing loss is equally prevalent.
Acute otitis externa (swimmer's ear) presents with itching, The most common cause of acquired sensorineural hearing
pain and fullness of the ear, with or without otorrhea. loss is meningitis; other causes are prematurity, hyper
Erythema and edema of the ear canal and tenderness on bilirubinemia, perinatal hypoxia, acquired immuno
moving the pinnae or tragus are diagnostic. Risk factors deficiency syndrome, head trauma and medications (e.g.
include swimming, impacted cerumen, use of hearing aid, aminoglycosides, loop diuretics). The chief etiology of
eczema and trauma from foreign objects. Chief pathogens congenital hearing loss is intrauterine infections (e.g.
include P. aeruginosa, Staphylococcus, Proteus, E. coli and TORCH, syphilis). Almost 30% of congenital hearing loss
Aspergillus or Candida sp. Management with aural toileting is associated with one of 300 inherited disorders, including
and topical antibiotic drops is associated with clinical cure Pendred syndrome (euthyroid goiter), Jervell and Lange
rates of up to 80%. If edema is significant, a ribbon gauze Nielsen syndrome (prolonged QT waves, syncope), Usher
or wick may be placed in the external auditory canal to syndrome (retinitis pigmentosa and blindness), Alport
keep it patent and allow delivery of topical ear drops. Oral syndrome (microscopic hematuria and renal failure),
antibiotics are reserved for cases who fail to improve and branchio-oto-renal syndrome, neurofibromatosis and
complicated cases. Waardenburg syndrome. Over 65 genes are associated with
Otomycosis or fungal otitis externa is common in humid inherited hearing defects. Mutations in GJB2, encoding for
weather or following treatment of a bacterial infection. connexin 26 (expressed in the inner ear and involved in
Patients present with ear pain and pruritus; Aspergillus cochlear homeostasis) account for one-half of patients with
and Candida spp. are common pathogens. Otoscopy autosomal recessive non-syndromic hearing loss.
reveals thick cream-colored discharge associated with
fungal spores and filaments. The condition is managed Screening tor Hearing Loss
with aural toilet and topical antifungal (e.g. clotrimazole) Significant hearing loss is present in 1-3 per 1000
drops. newborns, particularly in babies requiring neonatal
Otic furunculosis is a very painful, superficial abscess in intensive care. Hearing loss has significant implications
the outer portion of the ear canal, typically due to S. aureus. for development of speech, language and cognitive skills.
Oral antibiotics and analgesics ensure relief; incision and Effective hearing aids and cochlear implants are now
drainage is rarely required. available that, if applied early in life and supplemented
Eczematous or psoriatic otitis externa refers to with auditory training, can lead to near-normal hearing,
inflammatory conditions characterized by ear discharge, good acquisition of speech and language, and integration
pruritis and/ or scaling of skin of the ear canal. Contact, into normal schooling. Hence, most countries as well as
atopic or seborrheic dermatitis is usually present. the Indian Academy of Pediatrics recommend universal
screening for hearing loss in newborn period. An
Hearing Loss important initiative in infant hearing screening and
Hearing loss in children may be congenital or acquired. intervention program is the '1-3-6' guideline. This
Based on pathology, hearing loss is categorized as recommends screening all newborns for hearing loss by
conductive, sensorineural or mixed. Early detection of 1 month of age, completing secondary diagnostic testing
hearing loss in children is important as untreated hearing for infants who fail the first screening by 3 months, and
loss interferes with development of speech, language and ensuring early intervention for diagnosed hearing loss by
cognitive skills. 6 months, enabling language and social development in
line with physical development. However, some forms of
Conductive Hearing Loss early-onset hearing loss are not apparent at birth. The
Any pathology that interferes with the conduction of sound American Academy of Pediatrics Joint Committee on
through the ear canal, tympanic membrane or middle ear Infant Hearing lists risk factors that should prompt
ossicles may cause conductive hearing loss. Hearing loss is continued monitoring of hearing status, even if the initial
usually acquired and mild to moderate in severity. screening is normal (Table 14.3).
Common causes include otitis media with effusion,
tympanic membrane perforation, tympanosclerosis and Screening in Older Children
cholesteatoma. Less commonly, conductive hearing loss is Indications for hearing screening in older children are
congenital, associated with congenital ossicular fixation or parental concern for hearing or speech, poor language
discontinuity and atresia of the ear canal. Hearing loss may development or decline in language skills, ear infections,
be associated with middle ear abnormalities, e.g. Apert, difficulty in understanding conversation or inappropriate
Crouzon and Treacher Collins syndromes. response to commands. Examination includes otoscopy
362 Essential Pediatrics
T able 14.3: Indications for continued hearing monitoring hearing aid are considered for cochlear implantation.
despite normal hearing on neonatal screening Patients in whom cochlear implants are not feasible are
Caregiver concern regarding hearing, speech, or develop
taught sign language and enrolment in deaf education
mental delay programs.
Family history of childhood hearing loss
Pediatric Cochlear Implantation
Neonatal intensive care for >5 days or any of the following:
Extracorporeal membrane oxygenation; assisted ventilation; A cochlear implant directly stimulates the residual
exposure to ototoxic antibiotics or loop diuretics; hyper cochlear nerve cells in the spiral ganglion (cochlea). The
bilirubinemia requiring exchange transfusion US FDA approves cochlear implantation in adults with
In utero infections (CMV, rubella, syphilis, herpes, toxo
bilateral severe to profound (>70 dB hearing loss)
plasmosis) sensorineural hearing loss who have poor speech
discrimination and fail hearing aids. Decisions are tougher
Findings of a syndrome associated with hearing loss
in children as audiological testing is less reliable. Similar
Postnatal infection known to cause hearing loss (e.g. meningitis) to adults, cochlear implantation is advised for children
Syndromes associated with progressive hearing loss (e.g. with severe to profound sensorineural hearing loss with
neurofibromatosis) unsatisfactory benefit from a trial of hearing aid use for
Neurodegenerative disorders (e.g. Hunter syndrome, Friedreich 3-6 months. As early introduction of sound is crucial to
ataxia) develop processes for sound awareness and speech
Head trauma
development in the auditory cortex, hearing should be
aided as early as possible. Evaluation before surgery
Recurrent or persistent (�3 months) otitis media with effusion includes computed tomography and magnetic resonance
Chemotherapy or radiation to head and neck imaging to assess anatomic anomalies and confirm the
presence of cochlear nerve. Multielectrode implants that
with attention to middle ear pathology. Doubtful cases provide information across various frequencies are
require referral for audiologic evaluation. Techniques that positioned sequentially along the cochlea to allow sound
assess hearing sensitivity are selected based on child's age to be coded and transmitted for the entire sound spectrum
and ability to cooperate with testing (Table 14.4). (Fig. 14.5).
Fig. 14.5a: X-ray (modified Stenver view) of the mastoid showing Fig. 14.5b: Cochlear implantee in a rehabilitation session. Note
cochlear implant with multichannel stimulating electrodes along the external component. including a microphone behind the
the cochlear turn (arrow). Note the receiver stimulator pinna and a transmitter superiorly over the mastoid that transmits
component placed posterosuperiorly and the ball/ground amplified sound to the internal receiver stimulator complex
electrode located superiorly transcutaneously
smear, skin tests for common allergens and increased
DISEASES OF NOSE AND SINUSES serum total or allergen-specific IgE are not essential.
Further, skin tests may be negative in children during the
Rhinitis first 1-2 years of illness while the sensitization is confined
Inflammation of mucosa lining the nose may occur alone to nose and sinuses. Differential diagnosis includes food
(rhinitis) or with paranasal sinuses (rhinosinusitis). allergy (egg protein, cow milk, sea food). Management
comprises of allergen avoidance. Topical corticosteroid
Viral Rhinitis sprays provide symptomatic relief. Topical decongestants
Viral rhinitis (common cold) is the most frequent cause of are discouraged due to the risk of rebound congestion and
nasal obstruction and rhinorrhea in children, occurring rhinitis medicamentosa.
up to 6-8 times a year, usually due to infection with
Bacterial Rhinosinusitis
rhinovirus, influenza or adenovirus. Symptoms include
malaise, low to moderate grade fever, nasal congestion Four pairs of paranasal sinuses surround the nose and
and rhinorrhea, with or without sore throat. Antipyretics, help humidify inspired air. The maxillary and ethmoid
saline nasal drops, oral decongestants and antihistamines sinuses are present at birth and get easily infected in
provide symptomatic relief. Annual influenza vaccination childhood. Sphenoid and frontal sinuses develop at
reduces the incidence of severe cases. Less than 5% approximately 9-10 months and 7-8 years of age,
affected children develop superimposed bacterial respectively, and rarely get infected alone.
rhinosinusitis and suppurative otitis media. Acute bacterial rhinosinusitis: Rhinosinusitis is termed
acute, if symptoms are for less than 12 weeks. It usually
Allergic Rhinitis
follows viral rhinitis, but may develop de nova and re
The condition is due to an IgE-mediated reaction to specific currently in the presence of predisposing factors such as
allergens, commonly inhaled house dust mite, pollen and allergic rhinitis, adenoid inflammation and hypertrophy,
spores. Coexisting atopic dermatitis and asthma are cystic fibrosis, immunodeficiency, ciliary dyskinesia,
common. Presentation is with sneezing, itching, nasal daycare attendance, exposure to tobacco smoke and
obstruction and clear rhinorrhea that are seasonal (hay gastroesophageal reflux. Viral infections cause mucosa!
fever) or perennial with intermittent exacerbations. edema and ciliary hypoactivity causing obstruction of
Examination shows pale nasal mucosa, hypertrophied sinus ostia (openings of sinuses into the nasal cavity) and
nasal turbinates and thin mucoid rhinorrhea with or stasis of secretions. Obstructed sinuses are likely to get
without conjunctiva! itching and redness. Diagnosis is infected by bacteria from the nasopharynx, usually S.
clinical; supportive tests such as eosinophilia on nasal pneumoniae, H. influenzae and M. catarrhalis.
as4 I Essential Pediatrics
Persistent fever, facial pain or heaviness, nasal obstruc ostia. Nasal steroid sprays are safe and do not impact facial
tion or purulent discharge, cough, dental pain and earache or body growth. Saline irrigation decreases mucosal
or fullness beyond 7-10 days of upper respiratory tract edema and improves mucociliary clearance of the nose
infection suggest the diagnosis of infective rhinosinusitis. and paranasal sinuses. Managing underlying gastro
Periorbital edema, proptosis, diplopia, severe headache, esophageal reflux with proton pump inhibitors may defer
vomiting, seizures or focal neurological deficits suggest the need for surgery. Computed tomography and referral
ocular or central neurological system involvement, to a specialist is recommended in patients refractory to
meriting computed tomography. 3-6 weeks of medical management and those with
Orbital extension, contributing to 90% of complications, complications.
follows direct extension of infection from the ethmoid
sinuses, and is classified as inflammatory edema, orbital Allergic Fungal Rhinosinusitis
or preseptal cellulitis, subperiosteal abscess, orbital Allergic fungal rhinosinusitis is increasingly recognized
abscess and cavernous sinus thrombosis (Fig. 14.6). in atopic immunocompetent children, chiefly adolescents,
Ophthalmoplegia, vision loss and toxemia indicate but is less common than in adults. It is caused by
infection of cavernous sinuses. Intracranial complications, hypersensitivity to fungal antigens. Patients present with
including meningitis and brain abscesses, are common nasal obstruction, discharge and headache. Evaluation
with frontal and sphenoid sinusitis. shows unilateral or bilateral nasal polypi. Proptosis and
While a proportion of cases resolve spontaneously, telecanthus suggest extensive disease with expansion of
therapy with oral antibiotics (amoxicillin, coamoxiclav for the ethmoid (lateral displacement of orbit) or frontal
10--14 days) is preferred. Longer courses and/or second sinuses (inferolateral displacement of orbit). CT imaging
line antibiotics may be indicated based on organism shows characteristic non-erosive expansion of sinuses
sensitivity and nature of illness. Measures, such as oral or with opacification and intermittent hyperdensities.
topical decongestants, mucolytics and nasal saline provide Management consists of endoscopic removal of polypi and
early symptomatic relief. Patients with complications may widening of sinus ostia. Topical steroid sprays reduce
require parenteral antibiotics with or without endoscopic mucosal edema and prevent as well as delay recurrences.
sinus surgery and abscess drainage.
Chronic bacterial rhinosinusitis: When symptoms of Nasal Obstruction
rhinosinusitis persist for >12 weeks, infection with Apart from chronic rhinosinusitis, common and important
S. aureus, anaerobes and even fungi should be considered causes of chronic nasal obstruction are adenoid hyper
apart from usual bacterial pathogens. Nasal obstruction, trophy, deviated nasal septum and choanal atresia.
purulent discharge, chronic cough, facial heaviness, dental
pain, malaise and headache are common features. Young Adenoid Hypertrophy
children may be just irritable. Prolonged inflammation
causes formation of polyps in paranasal sinuses, ethmoid Adenoids are the lymphoid tissue located in the roof and
sinuses being most commonly affected. posterior wall of nasopharynx that protects the upper
Chronic bacterial rhinosinusitis is treated with a broad aerodigestive tract against inhaled antigens. Adenoids
spectrum antibiotic (coamoxiclav, broad-spectrum usually grow until the age of 5-years due to heightened
cephalosporin or fluoroquinolone) for 3-6 weeks. Oral immunologic activity, often causing some airway
decongestants and topical corticosteroid sprays (e.g. obstruction following which it gradually shrinks. Chronic
mometasone or fluticasone) hasten symptomatic relief by bacterial infection, gastroesophageal reflux and passive
reducing mucosal edema, improving patency of sinus smoking may cause persistent adenoidal hypertrophy,
leading to nasopharyngeal obstruction. An obstructed
nasopharyngeal airway leads to chronic mouth breathing
and dental malocclusion, while dysfunction of eustachian
tube causes otitis media with effusion and conductive
hearing loss. When associated with tonsillar hypertrophy,
patients may show features of obstructive sleep apnea.
Diagnosis is based on examination and endoscopic
evaluation. Lateral radiograph of the neck reveals enlarged
soft tissue in nasopharynx, occluding the airway (Fig. 14.7).
Pubertal growth of the midface and regression of
adenoids provide symptomatic relief of adenoid-related
nasal obstruction beyond the age of 9 years. Medical
management of symptomatic adenoid hypertrophy
Fig. 14.6: Acute bacterial rhinosinusitis with orbital cellulitis. Note includes courses of antibiotics, prolonged use of aqueous
the marked lid edema, congestion and proptosis nasal steroid spray and treatment of gastroesophageal
Otorhinolaryngology 1365-
Choanal Atresia
This term refers to congenital failure of the nasal cavities
to open into the nasopharynx. Unilateral or bilateral
choanal atresia or stenosis is hypothesized to be caused
by complete or partial persistence of buccopharyngeal Fig. 14.8: Axial computed tomography of paranasal sinuses
membrane (separating oral cavity from pharynx) or showing right (R)-sided bony and membranous choanal atresia
nasobuccal membrane (separating nose from oral cavity) and left (L)-sided complete bony atresia
a66 I Essential Pediatrics
cauterization. Coagulopathy should be ruled out in Cleft lip and cleft palate occur due to incomplete fusion
children with family history, bleeding from other sites or of the developing maxillary and nasal processes. Cleft lip
refractory or severe epistaxis. Uncommon causes of may be unilateral or bilateral, and incomplete (when only
recurrent epistaxis include juvenile nasopharyngeal the lip is bifid) or complete (associated with cleft in the
angiofibroma and hereditary hemorrhagic telangiectasia alveolar ridge). Likewise, cleft palate may be unilateral or
(Osler-Weber-Rendu syndrome), the latter presenting bilateral, and incomplete (cleft in palate posterior to
with severe recurrent epistaxis, gastrointestinal bleeding incisive foramen) or complete (cleft involving entire length
and pulmonary hemorrhage. of palate). 40% cases of cleft lip or palate are associated
with other congenital anomalies; syndromic associations
Suggested Reading include Goldenhar and Treacher Collins syndromes. Cleft
• Beswick DM, Messner AH, Hwang PH. Pediatric chronic palate leads to feeding difficulty, abnormal nasal
rhinosinusitis management in rhinologists and pediatric breathing, abnormal speech, hearing impairment and
otolaryngologists. Ann Oto! Rhino! Laryngol 2017; 126:634-639. impaired dentofacial growth. Staged surgical reconstruc
• Klosterman T. The management of vascular malformations of the tion of the lip and palatal defects is performed.
airway: Natural history, investigations, medical, surgical and
radiological management. Otolaryngol Clin North Am 2018; Micrognathia refers to a disproportionately small
51:213-23.
mandible. Congenital micrognathia may be isolated or
DISEASES OF ORAL CAVITY AND PHARYNX associated with Pierre Robin sequence (with cleft palate
and glossoptosis). Unilateral mandibular hypoplasia may
Inflammatory Disorders present with other features of hemifacial macrosomia.
Micrognathia may cause difficulty in feeding, dental
Recurrent aphthous stomatitis presents as variably-sized
overcrowding and in severe cases where the tongue is
painful white ulcers with surrounding erythema, located
displaced posteriorly, breathing difficulty. Milder cases
on the oral mucosa and/ or tongue. The precise etiology
resolve spontaneously. Neonates with breathing difficulty
is unknown. Minor ( <1 cm) ulcers resolve spontaneously
require prone nursing and/ or oropharyngeal airway.
over several days. Major ulcers (> 1 cm) are less common,
Severely symptomatic patients require surgical
may affect the soft palate or tonsils, and heal slowly (4-6
procedures like tongue advancement, mandibular
weeks) sometimes with scarring. Though most cases are
distraction osteogenesis or tracheotomy.
idiopathic, recurrent ulcers are seen in Behcet disease and
cyclic neutropenia. Symptomatic management includes Macroglossia refers to disproportionately large tongue
local application of protective and analgesic pastes or compared to other structures of the oral cavity. Cases may
anesthetic gels, failing which topical or, rarely, systemic be idiopathic or syndromic, associated with Down or
steroids may be tried. Beckwith-Wiedemann syndromes, neurofibromatosis or
Herpetic stomatitis caused by herpes simplex virus type congenital hypothyroidism. Macroglossia may be
1 is highly contagious. Erythematous gingiva and mucosal acquired, due to infections, trauma, tumor or vascular
hemorrhage are associated with clusters of painful malformation. The condition may lead to drooling, speech
vesicles, evolving to gray pseudomembranous mucosal impairment, feeding difficulty, abnormal growth of
ulcers. Symptomatic treatment includes analgesics and alveolus and dentition, or airway obstruction. Speech
oral or intravenous hydration. While oral acyclovir hastens rehabilitation and/ or surgical reduction may be needed.
recovery, lesions usually heal spontaneously in 10-14 days.
Oral candidiasis (thrush) caused by Candida appears as Stuttering, Stammering
small white curd-like lesions on tongue and oral mucosa. Stuttering is dysfluency of speech characterized by
While common in infants <6 months of age, the condition abnormal repetition of syllables and prolonged
is often seen in patients receiving prolonged antibiotics interruptions. The most common pattern is developmental
or corticosteroids. Other risk factors include poor oral stuttering, appearing usually at 3-4 years, when there is
hygiene, xerostomia, diabetes, leukemia or immuno inappropriate stuttering for the level of language
deficiency. Topical nystatin or oral fluconazole are effective. development. Acquired stuttering is uncommon and may
follow emotional trauma or neurological illness. Stuttering
Congenital Disorders is usually not associated with structural orofacial
Ankyloglossia (tongue tie) refers to limitation of anterior anomalies like tongue tie or adenotonsillar hypertrophy.
tongue mobility due to congenitally short lingual Surgical intervention for these abnormalities is not useful.
frenulum. Mild forms are common, do not affect speech Mild forms of dysfluency improve spontaneously;
and improve as the patients grow. A very short and tight persistent stammering requires speech and language
frenulum might restrict tongue protrusion beyond the lips, therapy starting in preschool years. Delayed intervention
may be associated with clefting of the tongue tip, and is associated with persistent stammering into adulthood
interfere with feeding and speech. and significant psychosocial morbidity.
Otorhinolaryngology 1367-
Sore Throat
Viral pharyngitis is common and caused by rhinovirus,
influenza or parainfluenza virus, adenovirus or coxsackie
virus. Patients present with fever, sore throat, dysphagia,
rhinorrhea, nasal obstruction, cough and bodyache.
Examination shows non-exudative erythema of pharynx
and tonsils and tender cervical lymphadenopathy.
Supportive treatment with analgesics, saline gargles and
saline nasal drops is sufficient. Antibiotics are required in
cases of secondary bacterial infection.
Infectious mononucleosis, caused by Epstein-Barr virus,
affects teenagers and is transmitted via body fluids,
commonly saliva. Patients present with fatigue, high fever,
malaise, sore throat, dysphagia and odynophagia.
Examination shows enlarged tonsils, edema of soft palate,
palatal petechiae, significant cervical lymphadenopathy,
hepatosplenomegaly, and a fine rash over arms or trunk.
Differential leukocyte count indicates that over 50% are Fig. 14. 9: Acute staphylococcal pseudomembranous tonsillitis
lymphocytes and more than 10% lymphocytes have an with unilateral hypertrophy of the right tonsil. This condition has
atypical appearance. Monospot or Paul-Bunnell tests are to be differentiated from other causes of white patch on the
useful for screening; presence of anti-VCA IgM antibody tonsil (Courtesy: Textbook of ENT, Hazarika)
confirms the diagnosis. Management is supportive,
comprising of hydration, bed rest, analgesics and strongly suspected, therapy against Streptococcus should
antipyretics. Patients with respiratory difficulty or extreme begin without awaiting microbiological confirmation.
dysphagia due to severely enlarged tonsils may require Initial therapy is with penicillin or a first generation
corticosteroids. Ampicillin may cause generalized itchy cephalosporin for 10 days. Coamoxiclav, clindamycin or
maculopapular rash and should be avoided. Severe airway erythromycin and metronidazole are considered in
obstruction may necessitate tonsillectomy or tracheotomy. refractory cases. Complications include peritonsillar,
Diph theria: Though its incidence has declined parapharyngeal or retropharyngeal abscesses; non
significantly following immunization, early diagnosis of suppurative complications are scarlet fever, acute
this potentially lethal condition is critical. The patient rheumatic fever and poststreptococcal glomerulonephritis.
appears ill and toxic. Examination shows exudative
tonsillopharyngitis with a thick gray membrane over the Tonsillectomy
tonsils extending to the palate, pharynx and occasionally Indications for tonsilloadenoid resection include
larynx that bleeds when removal is attempted. Cervical adenotonsillar hypertrophy causing obstructive sleep
lymphadenopathy is common. Gram staining and culture apnea, speech defects, craniofacial growth abnormality,
confirms infection with the causative Gram-positive dysphagia, failure to thrive or cor pulmonale. Other
bacillus Corynebacterium diphtheriae. Clinical suspicion is indications for tonsillectomy are recurrent acute tonsillitis,
enough to warrant immediate treatment with diphtheria recurrent tonsillitis associated with valvar heart disease
antitoxin without awaiting microbiological confirmation. or recurrent febrile seizures, recurrent peritonsillar
Therapy is with high dose penicillin or erythromycin. abscess, infectious mononucleosis with severely
Airway obstruction is managed with tracheotomy. obstructing tonsils refractory to medical management, and
Acute bacterial pharyngotonsillitis is usually caused by suspected tonsillar neoplasia.
group A �-hemolytic streptococci. Less common
pathogens include non-group A streptococci, S. aureus,
Obstructive Sleep Apnea
H. influenzae, M. catarrhalis, diphtheria, gonococci, Obstructive sleep apnea is characterized by partial or
Chlamydia and Mycoplasma spp. Pharyngitis presents with complete upper airway obstruction during sleep. The chief
fever, throat pain, odynophagia and occasionally, etiology is adenotonsillar hyp ertrophy. Disease associa
headache, abdominal pain, nausea and vomiting. Enlarged tions include obesity, allergic rhinitis, laryngomalacia,
erythematous bilateral tonsils with yellow follicles are mucopolysaccharidoses, Down syndrome, craniofacial
typical (Fig. 14.9). Severe cases show purulent exudation syndromes, cerebral palsy, hypothyroidism and nasal
with or without membrane formation on tonsils, and masses. Sequelae of obstructive sleep apnea are
cervical lymphadenopathy. A rapid strep test helps hypoxemia, hypercapnia and acidosis that contribute to
distinguish viral from streptococcal pharyngotonsillitis; behavioral and neurocognitive impairment with poor
negative results should be confirmed by throat culture. If learning, attention deficit and hyperactivity, cardio-
ass I Essential Pediatrics
Bacterial tracheitis typically caused by S. aureus, affects endotracheal intubation. A snugly fitting endotracheal
younger children and follows a viral upper respiratory tract tube may cause mucosal trauma and inflammation in the
infection. The child appears toxic and has brassy cough with subglottis, the narrowest part of the larynx leading to
biphasic or expiratory stridor. X-ray neck shows an irregular scarring. Patients present with progressive biphasic stridor
tracheal wall. Bronchoscopy is diagnostic and allows a few days after extubation. Minor stenosis requires careful
culture and removal of purulent tracheal secretions. observation; severe stenosis requires release of stenosis
Retropharyngeal abscess is a suppurative complication with CO2 laser and dilatation, widening with cartilage
of bacterial pharyngitis or dental infection, with abscess grafts or excision of stenotic segment, with tracheotomy.
formation in lymph nodes between the pharynx and Special T-shaped silicone tracheostomy tubes are used for
prevertebral fascia. Patients appear toxic with high fever, temporary stenting until complete healing. If prolonged
stridor, drooling and reduced neck mobility. Spread of inubation is expected, early tracheotomy prevents the
infection into the mediastinum can be fatal. The diagnosis complication of post-intubation subglottic stenosis. The
is confirmed by lateral neck radiograph and contrast CT. use of cuffed tracheostomy tubes should be avoided in
Management comprises parenteral antibiotics and surgical children; if a cuffed tube is essential, intermittent deflation
drainage of abscess by transoral or transcervical approach. is advised.
Tracheotomy may be necessary to secure the airway. Another complication of prolonged intubation is
laryngeal granuloma, typically located in the posterior part
Congenital Causes of the vocal cord. Small granulomas cause hoarseness
Laryngomalacia is the most frequent congenital laryngeal while large lesions present with breathing difficulty. They
anomaly and the chief cause of chronic stridor in infancy. are diagnosed by endoscopy and amenable to endoscopic
The condition is characterized by inspiratory stridor that removal.
increases when the child is supine or crying, and decreases Foreign Body Aspiration
in a prone position. Flexible endoscopy reveals omega
shaped epiglottis, short aryepiglottic folds and partial Foreign body aspiration should always be considered in
collapse of a flaccid supraglottic airway with inspiration. children presenting with acute onset stridor and airway
Laryngomalacia is generally benign and self-limited, with obstruction (Fig. 14.11). If a foreign body is not expelled
most cases resolving by 18 months of age. Concomitant by coughing, it migrates into the lower airway lodging
gastroesophageal reflux should be managed medically. most commonly in the subglottis, the narrowest lumen in
Surgical intervention, in form of supraglottoplasty or the airway leading to breathing difficulty. Objects such
temporary tracheostomy, is advised, if respiratory distress as balloons pose the greatest risk of choking to death,
is significant. followed by round objects such as balls or marbles. Rigid
bronchoscopy and removal of foreign body by an
Voc al cord paralysis is the second most common experienced surgeon is urgently required. Small foreign
congenital laryngeal anomaly. Bilateral vocal cord
paralysis presents with high-pitched inspiratory stridor
and cyanosis. It is usually caused by palsy of the recurrent
laryngeal nerve due to excessive stretching of the neck
during vaginal delivery. The condition may be idiopathic
or associated with Arnold-Chiari malformation,
hydrocephalus or hypoxia. Unilateral vocal cord paralysis,
in contrast, presents with mild stridor or weak cry.
Aspiration may occur, if cord immobility is due to vagus
nerve paralysis, as the superior laryngeal nerve (that
carries laryngeal mucosal sensation) is also affected.
Iatrogenic injury to the left recurrent laryngeal nerve
during ligation of patent ductus arteriosus may be a cause.
Diagnosis is made on fiberoptic laryngoscopy, which
reveals bilateral or unilateral vocal cord immobility.
Unilateral cord palsy without aspiration does not need
active treatment in most cases as hoarseness improves
with time. Tracheotomy might be required to secure the
airway in bilateral cord paralysis.
Iatrogenic Causes
Acquired subglottic stenosis is the most common cause Fig. 14.11 : Foreign body, broken part of tracheostomy tube. in
of acquired stridor, and usually follows long-term the lower trachea and left main bronchus
370 Essential Pediatrics
bodies may lodge in secondary bronchioles and present repair, either by endoscopy or using transcervical
later with pneumonia. Management comprises of approach.
bronchoscopy for foreign body removal, lavage and
physiotherapy to clear up secretions and antibiotics. Suggested Reading
Occasionally, thoracotomy may be required for foreign • Bagwell T, Hollingsworth A, Thompson T, et al. Management of
bodies that cannot be retrieved endoscopically. croup in the emergency department: the role of multidose
nebulized epinephrine. Pediatr Emerg Care 2017; doi: 10.1097 /
Tracheostomy PEC.0000000000001276.
• Marchese A, Langhan ML. Management of airway obstruction and
The requirement of prolonged ventilatory support, stridor in pediatric patients. Pediatr Emerg Med Pract 2017; 14:1-24.
neurologic dysfunction causing aspiration, and need for • McCaffer C, Blackmore K, Flood LM. Laryngomalacia: Is there an
pulmonary toileting are indications for tracheostomy. evidence base for management? J Laryngol Otol 2017; 131:946-54.
Caretakers should be explained about the implications of
tracheostomy, including the inability of patients to DISEASES OF THE SALIVARY GLANDS
vocalize and the care required. Tracheostomy is performed Infections
under general anesthesia with mechanical ventilation
Bacterial parotid sialoadenitis is frequent in young
provided through an endotracheal tube or laryngeal mask.
children and presents with painful unilateral parotid
The trachea is opened at the level of the third or fourth
swelling. Purulent material can be expressed intraorally
ring by a vertical incision that is kept patent using two
from the parotid duct upon parotid massage. Management
non-absorbable sutures placed on either side of the
involves oral antibiotics, hydration, sialogogues, parotid
incision. Usually, an uncuffed tracheostomy tube is placed
gland massage and warm compresses.
in children unless there is concern of aspiration, in which
case a cuffed tube may be used. Care after tracheotomy Mumps: Patients usually present with bilateral painful
includes repeated suctioning to maintain patency, change parotid enlargement and mild fever, and rarely, with acute
of tube every 5-7 days, chest physiotherapy and peri unilateral hearing loss or vestibular weakness. Therapy
stomal skin care. When tracheostomy is performed in comprises adequate hydration and analgesics.
infancy and kept for long, speech and language Tuberculosis may affect the parotid or other salivary
development may be delayed or impaired. glands with or without lung involvement. Sarcoidosis may
present with unilateral or bilateral parotid swelling, along
Hoarseness systemic symptoms and peripheral lymphadenopathy.
Vocal nodules are the chief cause of hoarseness in children. HIV infection commonly involves the parotid glands,
Caused by vocal abuse, these are seen most often in presenting as bilateral intraglandular cysts that recur after
children who scream habitually. The severity of needle aspiration.
hoarseness fluctuates, worsening with vocal abuse and
improving with rest. Endoscopy reveals small, bilateral, Drooling
opposing nodules at the junction of anterior and middle Drooling (sialorrhea) is common in infancy but persists
thirds of the vocal cord. Speech therapy is advised; surgery beyond 2-3 years in children with neuromuscular
is rarely indicated. disorders and in mouth breathers. Common causes of
Reflux is implicated in occurrence of laryngitis, subglottic drooling are dental malocclusion, adenoid hypertrophy,
stenosis, chronic sinusitis and otitis media with effusion. cerebral palsy and lip incompetency. Chronic drooling
Diagnosis is established with 24-hour pH monitoring. may lead to skin excoriation, dyselectrolytemia, social
Patients respond to lifestyle changes and use of proton isolation, learning difficulties and, in severe cases,
pump inhibitors; fundoplication is required in severe cases. aspiration pneumonia. Initial treatment is conservative
and includes correcting the posture, orodental rehabilita
Hypothyroid myxedema may occasionally cause vocal fold tion, oromotor training and anticholinergic agents like
edema, presenting as hoarseness or stridor. glycopyrrolate. Injection of Botox into the salivary glands
Laryngotracheal cleft is a rare congenital defect in the provides relief for 3-6 months. Refractory patients,
posterior part of cricoid cartilage of the larynx. The >5 years old, are considered for surgery, including
condition may be associated with Opitz-Frias or Pallister bilateral submandibular gland excision, ductal ligation or
Hall syndromes. Symptomatic clefts require multilayer rerouting, or resection of parasympathetic fibers.
Chapter
15
Disorders of Respiratory System
Sushil K Kabra
age. Arterial pa02 is -75 mm Hg in the newborn period • Suppurative lung disease: Bronchiectasis, cystic fibrosis
and around 5-year reaches adult levels of 95 mm Hg. • Foreign body retained in bronchi
• Congenital malformations, sequestrated lobe,
Suggested Reading bronchomalacia
• Warburton D. Overview of lung development in the newborn • Immune deficiency, primary ciliary dyskinesia
human. Neonatology 2017; 111:398-401.
• Anatomic lesions: Tumors, tracheal stenosis, H-type
tracheoesophageal fistula
COMMON RESPIRATORY SYMPTOMS
• Psychogenic, habit cough
Cough • Post-nasal discharge, sinusitis
After maximal inspiration, air is suddenly released • Gastroesophageal reflux disease
through the partially closed glottis, because of forceful • Interstitial lung disease
contraction of the expiratory muscles. This produces a
bout of cough. The cough reflex is controlled by a center Expectoration
in the medulla. Irritation of the pharynx, larynx, trachea, Children have difficulty in expectorating, and hence
bronchi and pleura is transmitted by afferent impulses swallow respiratory secretions. Older children with
through the vagus or glossopharyngeal nerves. Efferent chronic respiratory problems may bring out expectoration.
pathways relay to the larynx and respiratory muscles. Common causes of significant expectoration include
Cough is an important defense mechanism that helps bronchiectasis, lung abscess, bronchitis, asthma, and
remove infected secretions from the trachea and bronchi. tuberculosis. The amount and nature of expectoration may
Cough should not be suppressed in young children as give clue about the etiology. Investigations such as cell
retention of secretions may cause atelectasis and count, Gram stain and culture or stain for AFB and culture
pulmonary complications. On the other hand, persistent help in diagnosis and guiding treatment.
cough interferes with sleep and feeding. It fatigues the
child and may result in vomiting. Hemoptysis
Hemoptysis is defined as blood-stained expectoration.
Causes of Acute Cough Causes of hemoptysis may be necrotizing pneumonia,
• Upper respiratory tract infection. Common cold, foreign body aspiration, bleeding diathesis, cavitatory
postnasal discharge due to sinusitis, hypertrophied tuberculosis, idiopathic pulmonary hemosiderosis, mitral
tonsils and adenoids, pharyngitis, laryngitis and stenosis, dilated cardiomyopathy, Goodpasture syndrome
tracheobronchitis and small vessel vasculitis.
• Nasobronchial allergy and asthma
• Bronchiolitis, pneumonia, and pulmonary abscess; Respiratory Sounds
empyema Sounds originating from the respiratory system may be
• Measles heard with or without a stethoscope (Table 15.1). The
• Whooping cough intensity and pitch of these sounds vary based on their site
of origin within the respiratory tract, the dictum being that
• Foreign body in air passages the pitch increases and the intensity decreases as one goes
lower into the respiratory tract. Snoring is a loud but low
Causes of Chronic and Recurrent Cough
pitched sound because it results from the oropharynx, while
• Inflammatory disorders of airway: Asthma and Loeffler wheeze is high pitched and less intense since it originates
syndrome from the lower tract. Generally, extrathoracic airway
• Infection: Viral, bacterial, chlamydia, mycoplasma, obstruction produces inspiratory sounds, intrathoracic
tuberculosis, parasitic major airway produces inspiratory as well as expiratory
• Inhalation of environmental irritants such as tobacco sounds and distal airway obstruction produces
smoke, dust predominantly expiratory sounds.
Rattling Stridor
Rattling is due to excessive secretions in the pharynx or Stridor indicates upper respiratory obstruction and is
tracheobronchial tree, as in asthma, bronchitis, trachea accompanied by hoarseness, brassy cough, dyspnea,
bronchial stenosis and aspiration of gastrointestinal contents retractions of the chest during inspiration and restlessness.
into the tracheobronchial tree may also result in rattling. Accessory muscles of respiration are usually being used.
Stridor is common in infants and attributed to the (i) small
Wheezing size of the larynx, (ii) loose submucous connective tissue
Wheezing refers to high-pitched whistling sounds audible around the glottis, and (iii) rigid cricoid cartilage encircling
without auscultation. Wheezing causes considerable the subglottic zone.
anxiety to the parents. Partial obstruction of the bronchi Acute stridor: Acute upper airway obstruction in the
and bronchioles leading to narrowing produces wheezing. region of glottis may be produced by inflammation and
However, sufficient air must flow through the narrowed edema, and may be life-threatening. The obstruction may
airway to produce the wheezing sound. Wheezing may either be supraglottic (epiglottitis) or subglottic (infectious
be due to causes within the lumen or in walls of the bronchi. croup) (Table 15.2).
• Wheeze associated lower respiratory tract infection; viral
infection with wheeze: Wheezing is often due to Chronic stridor: Congenital laryngeal stridor is caused by
heightened sensitivity of the respiratory tract, following flaccidity (laryngomalacia) or easy collapsibility of the
infections that cause bronchospasm. Attacks of aryepiglottic folds or epiglottis. This condition manifests
wheezing are preceded by a cold or acute respiratory by the end of the first week or during the second week
disease. These are most frequent between 3 and 8 years after birth. The stridor is characteristically intermittent,
of age and become less frequent thereafter. These and is aggravated by crying or feeding. It is modified in
episodes may be relieved by use of bronchodilators. sleep or by change of posture. While the loud inspiratory
• Bronchiolitis sound frightens the parents, the infant is relatively
comfortable. Respiratory distress and chest retractions are
• Bronchial asthma
absent or minimal, and feeding behavior and activity are
• Tropical eosinophilia is more frequent in adults than in generally normal. Breathing difficulty may be significant,
children. It is an unusual from of infection with if micrognathia and cleft palate are associated. Congenital
filariasis, e.g. Dirofilaria imitis, W. bancrofti and B. malayi. laryngeal stridor disappears spontaneously by
Clinical features simulate chronic recurrent asthma. 6-12 months of age. Infants may develop aspiration of
X-ray films show fine infiltrates with snowflake like feeds and frequent lung infections.
appearance, which should be distinguished from
Congenital laryngeal tracheal stenosis or web is characterized
miliary tuberculosis. Leukocyte count shows
by weak cry, hoarse labored breathing and reduced air entry
eosinophilia. The patients are treated with diethyl
in infants. In subglottic tracheal stenosis, the cry is un
carbamazine (10 mg/kg) in 3 divided doses orally for
affected and the stridor is both inspiratory and expiratory.
2 to 3 weeks. Two or three courses may be given.
Laryngeal cysts or neoplasm including angioma,
• Loeffler syndrome occurs due to migration of Ascaris
papilloma, lymphangioma and retention cysts may cause
larvae through the lungs, resulting in transient episodes
stridor. Stridor is common in infants with hydrocephalus
of wheezing, respiratory distress and eosinophilia.
and Down syndrome.
• Hypersensitivity pneumonitis.
Bilateral vocal cord paralysis may result from brainstem
• Inhaled foreign bodies cause sudden onset unilateral injury. Unilateral paralysis is due to the involvement of
localized wheeze. the recurrent laryngeal nerve that is more common on the
• Enlarged mediastinal nodes (tuberculosis or neoplasm), left side, due to the longer course of the nerve that hooks
anomalous left pulmonary artery compressing the right around the aorta from the front to back.
main bronchus, cystic fibrosis, pulmonary hemo
siderosis and mediastinal cysts constitute rare causes Extrinsic obstruction: Vascular rings show intermittent
of wheezing. stridor that becomes worse when the neck is flexed. Infants
Table 15.2: Distinguishing between stridor due to supraglottic and tracheal obstruction
Clinical features Supraglottic obstruction Tracheal obstruction
Stridor lnspiratory Usually expiratory
Severity Usually less serious More serious
Cry Muffled Normal
Dyspnea Less severe More marked
Cough Less marked Deep barking, brassy
a14 I Essential Pediatrics
• Miller A, Enright PL. PFT interpretive strategies: American Cough syrups suppress cough and retention of mucoid
Thoracic Society/European Respiratory Society 2005 guideline secretions that predispose to spasmodic cough, wheezing,
gaps. Respir Care 2012; 57:127-33.
• Nicolai T. The role of rigid and flexible bronchoscopy in children.
atelectasis and suppuration. These agents should be
Pediatr Respir Rev 2011; 12:190-5. avoided in infants and young children.
Antibiotics are of little value in viral infections. These are
UPPER RESPIRATORY TRACT INFECTIONS used, if the secretions become purulent, the fever continues
Nasopharyngitis (Common Cold) to rise and if the child develops bronchopneumonia.
Common cold is the most frequent illness in childhood, Nursing care includes protecting from sudden exposure
caused by adenoviruses, influenza, rhinovirus, para to chills. Feeding should be continued to maintain hydration.
influenza or respiratory syncytial viruses. These are spread
Acute Tonsillopharyngitis (Sore Throat)
by droplet infection. Predisposing factors include chilling,
sudden exposure to cold air, and overcrowding. Rhinitis Acute inflammation of the pharynx and tonsils is usually
could also be due to allergy. caused by viral infections such as adenovirus, influenza,
parainfluenza, enterovirus and Ebstein-Barr virus. It may
Clinical Features also be caused by measles, rubella, Streptococcus pyogenes
especially group A 13-hemolytic streptococci, Mycoplasma
These include fever, thin nasal discharge and irritability. pneumoniae and Candida albicans.
Cervical lymph nodes may enlarge. Nasopharyngeal
congestion causes nasal obstruction and respiratory Clinical Features
distress. Eustachian tube opening may be blocked leading
to serous otitis media and congestion of tympanic Fever, malaise, headache, nausea and sore throat are
membrane. In allergic rhinitis, there is a clear mucoid characteristic. It is difficult to distinguish clinical
discharge with sneezing. There is no contact with an syndromes due to viral or streptococcal infections.
infected patient and history of allergy is usually present. Hoarseness, cough and rhinitis are common in viral
Wheezing may occur in a significant proportion of cases. infection. In these, the onset is gradual and there is less
toxemia. In streptococcal infections, cervical lymph nodes
Narrowing of the airway and pharyngeal irritation
are enlarged and illness is more acute with high fever,
causes dry hacking cough. Excessive lacrimation is due
exudates over tonsillar surface and absence of nasal
to the blocked lacrimal ducts in the nose. Nasal discharge
discharge or conjunctivitis. Young children may not
may become purulent, if secondarily infected. The illness
complain of sore throat, but refuse to feed normally.
usually lasts for 2-3 days but cold may persist up to two
weeks. Complications
Complications The illness may be complicated in the acute stage by otitis
media, sinusitis, and peritonsillar and retropharyngeal
Otitis media, laryngitis, sinusitis, bronchiolitis,
abscesses. The infection may spread down the
bronchopneumonia and exacerbation of asthma.
tracheobronchial tree and cause tracheobronchitis and
pneumonia. Streptococcal sore throat may be followed a
Differential Diagnosis
few days later by immune-mediated conditions, presenting
Nasal foreign b ody may present with unilateral with acute rheumatic fever and acute glomerulonephritis.
serosanguineous or purulent discharge from nose.
Diagnosis
Snuffles is clear mucoid discharge from the nose in the
first few weeks of life. Snuffles of congenital syphilis is The possibility of pharyngitis due to group A beta
rare and causes bilateral serosanguineous discharge hemolytic streptococci should be considered in patient
commonly excoriating the upper lip and leaving fine scars. presenting with fever, exudates in throat, tender enlarged
Nasal strictures may ulcerate leaving a flat nasal bridge. cervical nodes and absent nasal or conjunctiva! congestion.
Throat culture for group A 13-hemolytic streptococci helps
Treatment in definitive diagnosis. Neutrophil count is often elevated.
Rapid diagnostic tests for 13-hemolytic streptococci are not
Relieve nasal congestion: Nose drops of saline may give
frequently available.
symptomatic relief. Nasal decongestants (ephedrine,
xylomatozoline) may cause rebound congestion and Differential Diagnosis
should be avoided. Antihistaminics dry up thin secretions
and relieve sneezing but should be avoided in the first Herpangina is an acute febrile illness caused by group A
6 months of life. Newer non-sedating agents (loratidine, Coxsackievirus. Patients have dysphagia, sore throat and
cetirizine) are useful in allergic rhinitis. papulovesicular lesions surrounded by erythema over the
tongue, pharynx, anterior tonsillar pillars and soft palate.
Fever is controlled by antipyretics such as paracetamol. Pharynx appears congested.
376 Essential Pediatrics
Diphtheria is characterized by moderate grade fever, • Casey JR, Pichichero ME. Meta analysis of short course antibiotic
severe toxemia, sore throat and membrane formation over treatment for group A streptococcal tonsillopharyngitis. Pediatr
Infect Dis J 2005; 24:909-17.
the fauces or palate. The diagnosis is confirmed by urgent • De Sutter AI, Saraswat A, van Driel ML.Antihistamines for the
smear examination from throat swab. common cold. Cochrane Database Syst Rev 2015; 11:CD009345.
Agranulocytosis may present with similar symptoms;
blood count shows neutropenia. LOWER RESPIRATORY TRACT INFECTIONS
Patients with pharyngoconjunctival fever present with Acute lower respiratory tract infections are the leading
fever, conjunctivitis, pharyngitis and cervical cause of death in children below 5 years of age. Diseases
lymphadenitis due to infection with adenovirus type III. under this heading include the croup syndromes,
Infectious mononucleosis is characterized by lympha bronchitis, bronchiolitis and pneumonia.
denopathy, morbilliform rash, hepatosplenomegaly and
Croup
sometimes aseptic meningitis.
The term croup is used for conditions with a peculiar
Treatment: Paracetamol is administered for fever. Soft
brassy cough with or without inspiratory stridor,
food is given because swallowing is painful. Warm saline
hoarseness or respiratory distress. Conditions associated
gargles are prescribed for older children. Younger children
with this syndrome include acute epiglottitis, laryngitis,
are encouraged to sip warm tea.
laryngotracheobronchitis and spasmodic laryngitis.
Antibiotics are not used for viral infections. Infections
with 13-hemolytic streptococci are treated with penicillin Epiglottitis
V orally, injections of procaine penicillin or oral
erythromycin for 10 days. Parents must be counseled Supraglottitis including epiglottitis and inflammatory
regarding the need to complete 10 days therapy with edema of the hypopharynx, is caused chiefly by
antibiotics. If compliance is a problem, a single dose of Haemophilus influenzae type b. The illness starts with a minor
intramuscular benzathine penicillin is advised. upper respiratory tract illness, which progresses rapidly
Cotrimoxazole and fluoroquinolones, which are otherwise within a few hours. The child has high fever and difficulty
used for a variety of indications, should not be used in in swallowing. The child is not able to phonate and often
these patients. sits up leaning forwards with his neck extended and saliva
dribbling from his chin which appears to be thrust
Recurrent Attacks of Sore Throat forwards. Accessory muscles of respiration are active and
Parents often seek advice for the treatment of recurrent there is marked suprastemal and subcostal retractions. As
sore throat in their children. A detailed history and the child becomes fatigued, the stridor diminishes. The
physical examination is done. Paranasal sinuses and ears diagnosis of epiglottitis is made by a cautious direct laryngo
should be examined for infection that if present, should scopy; the epiglottis is angry red and swollen. Injudicious
be appropriately treated. Smoky and dusty atmosphere attempt to examine the throat may, at times cause death
should be avoided. Damp environment and overcrowding by sudden reflex spasm of the larynx. In case these
predispose children to recurrent upper respiratory tract procedures are considered essential, the equipment and
infections. personnel for respiratory resuscitation should be readily
available.
Every episode of bacterial pharyngitis should be treated
with adequate doses of antibiotics for at least 10 days. A Laryngitis and Laryngotracheobronchitis {Infectious Croup)
single intramuscular dose of benzathine penicillin is also
adequate. Patients with 13-lactamase producing bacteria These conditions are almost always caused by viral infec
in the pharynx should receive coamoxiclav. Clindamycin tions, chiefly parainfluenza type 1. Other viruses include
is an effective agent to eradicate the carrier state. In respiratory syncytial, parainfluenza types 2 and 3, influenza,
patients with recurrent streptococcal sore throat, penicillin adeno and rhinovirus. The onset of illness is gradual with
prophylaxis for 3-6 months is recommended. cold for a few days before the child develops brassy cough
Tonsillectomy does not prevent recurrence of strepto and an inspiratory stridor. As obstruction increases, the
coccal infections. The procedure may be recommended in stridor is marked; suprasternal and sternal recessions
children with multiple episodes of tonsillitis or in case of become manifest. The child becomes restless and anxious
tonsillar or peritonsillar abscess. It may reduce the incidence with tachypnea due to increasing hypoxemia. Eventually
of group A beta-hemolytic streptococcal infection. cyanosis appears. As obstruction worsens, breath sounds
are inaudible and stridor may apparently decrease.
Suggested Reading Spasmodic Croup
• Alves Galva.a MG, Rocha Crispino Santos MA, Alves da Cunha
AJ. Antibiotics for preventing suppurative complications from
It occurs in children between the age of 1 and 3 years.
undifferentiated acute respiratory infections in children under five There is at times no preceding coryza. The child wakes
years of age. Cochrane Database Syst Rev 2016; 2:CD007880. up suddenly in the early hours of the morning with
Disorders of Respiratory System 1377-
Pneumococcal Pneumonia
Respiratory infections due to S. pneumoniae are transmitted
by droplets and are common in winter months. Over
crowding and reduced host resistance predisposes the
children to infection with pneumococci. Bacteria multiply
in the alveoli, resulting in an inflammatory exudate.
Scattered areas of consolidation occur that coalesce around
bronchi and later become lobular or lobar in distribution.
The incubation period is 1 to 3 days. The onset is abrupt
with headache, chills, cough and high fever. Cough is
initially dry but may be associated with thick rusty sputum.
Child may develop chest pain that is occasionally referred
to the shoulder or abdomen. Respiration is rapid. In severe
cases, there may be grunting, chest indrawing, difficulty in
feeding and cyanosis. Percussion note is impaired, air entry Fig. 15.2: X-ray chest showing staphylococcal pneumonia. Note
is diminished, and crepitations and bronchial breathing is consolidation in both lung fields with pneumatocoeles (arrow)
heard over areas of consolidation. Bronchophony and
whispering pectoriloquy may be observed. Meningismus fibrosis or follow staphylococcal pyoderma. Debilitating
may be present in apical pneumonia. conditions including malnutrition, diabetes mellitus and
The diagnosis is made on history, examination, X-ray macrophage dysfunction also predispose to infection with
findings of lobar consolidation (Fig. 15.1) and leukocytosis. staphylococci.
Bacteriological confirmation is difficult but sputum may In infants, the pneumonic process is diffuse initially,
be examined by Gram staining and culture. Blood culture but soon the lesions suppurate resulting in broncho
may be positive in 5-10% cases. Demonstration of alveolar destruction. Multiple microabscesses are formed,
polysaccharide antigen in urine and blood is not specific which erode the bronchial wall and discharge their
for pneumonia, since it may be positive in patients with contents in the bronchi. Air enters the abscess cavity
colonization in throat. during inspiration; progressive inflation results in
Penicillin G 50000 IU/kg/day is given IV or IM in formation of pneumatoceles that are pathognomonic of
divided doses for 7 days. Therapy with IV cefotaxime, staphylococcal pneumonia (Fig. 15.2). Staphylococcal lung
ceftriaxone or coamoxiclav is equally effective. abscesses may erode into the pericardium causing
purulent pericarditis. Empyema below 2 years of age is nearly
Staphylococcal Pneumonia always staphylococcal in etiology.
Staphylococcal pneumonia occurs in infancy and Pulmonary infection may be associated with
childhood. Pneumonia may be primary infection of the disseminated disease, with abscesses in joints, bone,
parenchyma or secondary to staphylococcal septicemia. muscles, pericardium, liver, mastoid or brain. The
It may be a complication of measles, influenza and cystic diagnosis of staphylococcal pneumonia is suspected in
infants with pneumonia with features of systemic
staphylococcal infection. Complications of pyo
pneumothorax and pericarditis are highly suggestive of
the diagnosis.
The child is hospitalized. Fever is controlled with
antipyretics and hydration is maintained by IV fluids.
Oxygen is administered to relieve the dyspnea and
cyanosis. Antibiotic therapy should be prompt and carried
out with penicillin G, coamoxiclav, cloxacillin or
ceftriaxone. If the patient does not respond, vancomycin,
teicoplanin or linezolid may be used. Prolonged therapy
(2-6 weeks) is desirable.
Streptococcal Pneumonia
Pneumonia due to Gram-negative Organisms
Streptococcal infection by group A beta-hemolytic strepto
cocci may follow measles, varicella, influenza or pertussis. E. coli, Klebsiella and Pseudomonas affect small children
Though uncommon in India, group B streptococcal ( <2 months old), children with malnutrition and poor
pneumonia is an important cause of respiratory distress immunity. Pseudomonas may colonize airways of patients
in newborns. Streptococci cause interstitial pneumonia, with cystic fibrosis and causes recurrent pulmonary
which may at times be hemorrhagic. exacerbations. The onset of illness is gradual and assumes
The onset is abrupt with fever, chills, cough, dyspnea, serious proportions. Signs of consolidation are minimal.
rapid respiration and blood-streaked sputum. Signs of Constitutional symptoms are more prominent than
bronchopneumonia are generally less pronounced, as the respiratory distress. Radiograph shows multiple areas of
pathology is usually interstitial. Thin serosanguineous or consolidation; those with E. coli or Klebsiella pneumoniae
purulent empyema is a complication. may have pneumatoceles. Administration of IV cefotaxime
Radiograph shows interstitial pneumonia with or ceftriaxone (75-100 mg/kg/day) with or without an
segmental involvement, diffuse peribronchial densities or aminoglycoside is recommended for 10 to 14 days. In case
an effusion, which needs to be distinguished from primary of suspected Pseudomonas infection, ceftazadime is the
atypical pneumonia. Blood counts show neutrophilic drug of choice.
leukocytosis. Penicillin G is recommended at doses of
50,000 to 100,000 IU/kg body weight, daily in divided
Viral Pneumonia
doses for 7-10 days. Alternative antibiotics include second
or third generation cephalosporins (cefaclor, cefuroxime, Respiratory syncytial virus is the chief cause under
ceftriaxone, cefotaxime). 6 months of age. At other ages, parainfluenza, influenza
and adenoviruses are common, presenting with extensive
Primary Atypical Pneumonia interstitial pneumonia. Clinical signs of consolidation are
The etiological agent of primary atypical pneumonia is absent. Radiological signs consist of perihilar and
Mycoplasma pneumoniae, a small free living organism. peribronchial infiltrates.
Other pathogens include Chlamydia and Legionella spp. The
disease is transmitted by droplet infection, occurring in Aliphatic Hydrocarbon Associated Pneumonia
epidemics chiefly in winter among children in
Kerosene exerts its toxic effects on the lungs and central
overcrowded living. Disease due to Mycoplasma spp. is
nervous system. Milk and alcohol promote absorption
uncommon below 4 years of age, although subclinical and
through the gastrointestinal tract. Since kerosene has low
mild infections are reported.
viscosity and low surface tension, it diffuses quickly from
The incubation period is 12 to 14 days; onset of the
the pharynx into the lungs. Features of hydrocarbon
illness may be insidious or abrupt. Initial symptoms are
pneumonia include cough, dyspnea, high fever, vomiting,
malaise, headache, fever, sore throat, myalgia and cough.
drowsiness and coma. Physical signs are minimal. X-ray
Cough is dry at first but later associated with mucoid
expectoration, which may be blood streaked. Dyspnea is film of the chest shows ill-defined homogeneous or patchy
unusual. There are very few physical signs, except mild opacities, and may resemble miliary mottling.
pharyngeal congestion, cervical lymphadenopathy and a Vomiting is not induced. Gastric lavage is avoided to
few crepitations. Cold agglutinins are elevated in 30-60% prevent inadvertent aspiration. The patient is kept on
patients; hemolytic anemia is uncommon. oxygen. Routine antibiotics are not indicated.
380 Essential Pediatrics
Table 15.4: Children (2 months to 5 years) with cough or difficult breathing: Facilitate treatment decisions
Category Essential features Treatment category
Cough or cold No fast breathing; no indicators of severe pneumonia Home care; home remedy for cough;
paracetamol for fever
Pneumonia with or without Fast breathing: 2-12 months �50/minute; Home care; oral amoxicillin
lower chest indrawing 1-5 years �40/minute
Lower chest indrawing, normal saturation
Severe pneumonia Lower chest indrawing; unable to drink or Inpatient care IM, IV benzylpenicillin or
breastfeed, convulsions, lethargy, unconsciousness, ampicillin and gentamicin
severe respiratory distress, central cyanosis
Disorders of Respiratory System 1381-
Bronchodilators, inhaled or systemic steroids and (ii) release of airborne allergens in atmosphere that
epinephrine have not been found useful in infants with exacerbate asthma.
acute bronchiolitis. If a patient shows improvement with
bronchodilator or epinephrine, further doses may be given Emotions: Stress, through the vagus nerve, may initiate
every� hours. Inhaled hypertonic saline has been shown bronchial smooth muscle constriction.
to be effective in a subgroup of patients. Its routine use is Food : Allergy to food proteins or additives has an
not recommended. Continuous positive airway pressure insignificant role in pathogenesis of asthma.
(CPAP) or assisted ventilation is required to manage
respiratory failure. Extracorporeal membrane oxygenation Endocrine: Children may get increase in symptoms during
is effective in severe cases. puberty.
Diagnosis
Triggers of Asthma
The diagnosis of asthma is clinical in most cases. Recurrent
Infections: Viral infections in young children are
attacks of wheezing or spasmodic cough are highly
important triggers of airway narrowing. Viral infections
suggestive of bronchial asthma. Cough, which is asso
might interfere with the integrity of mucosal surface by
ciated with asthma generally, worsens after exercise.
opening up tight intraepithelial cell junctions, inducing
Sputum is clear and mucoid, but might be yellow due to
epithelial shedding. They also result in mucosal edema
large number of eosinophils.
and mucus secretion.
Pulmonary function tests (PFT) are important for
Exercise: Exercise-induced asthma occurs in genetically
diagnosis of doubtful cases and monitoring response to
susceptible individuals with hyperreactive airways
therapy. Important parameters on spirometry include
because of evaporative water losses from the respiratory
PEFR, FEVl, FVC and FEV25-75, all being decreased in
tract. Water loss induces mucosal hyperosmolarity, which
asthma. FEVl is commonly used for documenting the
stimulates mediator release from mast cells.
severity of asthma. FEV25-75 is effort independent and
Weather: Sudden change of weather may result in: more sensitive indicator of airway obstruction. PEFR is
(i) evaporative water losses from lower airways; and measured with flow meter, while spirometry is required
Disorders of Respiratory System 1383-
for others. Abnormalities in PEFR suggestive of asthma Cystic fibrosis presents with recurrent wheezing; patients
include: Diurnal variation of more than 20%, �80% of show clubbing and malabsorption. X-ray chest shows
predicted, and improvement of 2".20% after bronchodilator hyperinflation, peribronchial cuffing and pneumonia. The
therapy. diagnosis is made on sweat testing.
Absolute eosinophil counts might help distinguish allergic
Management of Asthma
from infectious nature of chronic respiratory disease.
When eosinophilia is present, the symptoms generally Bronchial asthma cannot be cured but can be controlled.
respond to antispasmodic therapy. Goals of therapy are: (i) maintain near normal pulmonary
function; (ii) maintain near normal physical activity;
Chest X-ray film shows bilateral and symmetric air (iii) prevent nighttime cough or wheezing with minimal
trapping in case of asthma. Patches of atelectasis due to
chronic symptoms; (iv) prevent recurrences; (v) avoid
mucus plugs are not unusual. Main pulmonary artery may
adverse effects of therapy. Effective long-term manage
be prominent in severe cases due to pulmonary
ment of asthma involves three major areas:
hypertension. Bronchial cuffing may occur due to the
presence of edema fluid in perivascular and peribronchial i. Identification and elimination of exacerbating factors
interstitial space. Extensive areas of collapse or ii. Pharmacological therapy
consolidation should suggest an alternative diagnosis. iii. Education of patient and parents about nature of
Occasionally, the chest radiograph may be normal. disease and steps to avoid acute exacerbation
Allergy tests (e.g. skin test, RAST radioallergosorbent Identity and Eliminate Exacerbating Factors
allergen specific IgE) have limited usefulness. Blood IgE
may be raised in children with atopic asthma, but cannot Factors associated with development and precipitation of
be used as diagnostic test. The role of skin tests to identify asthma are passive smoking, associated allergic disorders,
sensitivity to different antigens, and desensitization is inadequate ventilation at home with dampness, cold air,
limited. cold food, smoke, dust and pets in the family. Acute viral
respiratory infections are one of the chief causes of
Differential Diagnosis exacerbation.
Following measures may help in reducing risk of
Bronchiolitis occurs within the first 2 years, usually within
recurrences:
the first 6 months of life, usually in winter or spring.
i. The bedroom should be clean and free from dust. Wet
Generally, there is a single attack. Repeated attacks
mopping of the floor is encouraged.
indicate viral infection associated wheeze or multi-trigger
ii. Since heavy tapestry attracts dust, light plain cloth
wheeze or asthma. Hyperinflation of chest with scattered
sheets should be used as curtains in the child's
areas of infiltration may be seen in chest X-ray. Asthma
bedroom.
may start at any age; more than 3 episodes are usual and
iii. Periodic cleaning of carpets, stuffed furniture, loose
wheezing is prominent. Infants with bronchiolitis and
clothing and hangings, calendars and books.
atopic dermatitis, high IgE levels or family history of
iv. The child's bed should be made of light material and
allergy need follow up for later development of asthma.
aired regularly.
Congenital malformations with obstruction (vascular v. Caressing of animal pets is discouraged, as the child
rings due to aberrant right subclavian artery or double may be sensitive to their fur.
aortic arch, bronchogenic cysts, tracheomalacia) should vi. It is usually not necessary to restrict the diet, since
be excluded in differential diagnosis. food allergy is not the cause in most cases.
Aspiration of foreign body may result in localized area of vii. Adolescent patients should refrain from smoking.
wheeze, hyperresonance and reduced air entry. A history viii. Exposure to strong odors such as wet paint,
of foreign body aspiration may be forgotten. Most children disinfectants and smoke should be minimized.
have frequent infections in the lung. ix. The child should avoid attics or basements, especially
Hypersensitivity pneumonitis may follow inhalation of
if unoccupied and closed.
organic dust (molds, wood, cotton or fur dust, bird Pharmacotherapy
droppings, grain) or exposure to specific agents (epoxy
resins, PAS, sulfonamide, nitrofurantoin). Patients have Pharmacological therapy of bronchial asthma involves
fever, chills, dyspnea, malaise, aches and pain, rales agents that relax smooth muscle and dilate airways, and
(crackles) and weight loss. X-ray chest shows interstitial those that decrease inflammation. Medications for long
pneumonia with prominent bronchial markings. Levels term treatment of asthma include bronchodilators,
of IgG antibodies to specific antigen are increased. Skin steroids, mast cell stabilizers, leukotriene modifiers and
test shows Arthus phenomenon with local hemorrhage, theophylline (Table 15.5).
edema and pain within 8 hours. The diagnosis is Bronchodilators: Commonly used short-acting broncho
established on lung biopsy. dilators are adrenaline, terbutaline and salbutamol, all
as4 I Essential Pediatrics
having a quick onset of action. Adrenaline stimulates a reduces the risk for systemic adverse effects. Commonly
and both 13 receptors, with ensuing cardiac side effects. used inhaled steroids include beclomethasone, budesonide
Terbutaline and salbutamol are specific 132 agonist and and fluticasone; budesonide (BDS) and fluticasone are
hence, have less cardiac effects. While adrenaline is given considered superior to beclomethasone (BDP). The chief
subcutaneously, the others can be given by oral, inhalation concern with long-term use of inhaled steroids is their
or parenteral route. Inhalation route is preferred because adverse effect on growth with 20% reduction in growth
of rapid onset of action and a few side effects. velocity reported in the first year. The growth velocity
Long-acting 132 agonists are salmeterol and formoterol. later recovers and ultimately children attain predicted
The onset of action is delayed by 30-60 minutes but lasts adult height.
12-24 hours. Their safety and efficacy has been shown in Mast cell stabilizers: Cromolyn sodium reduces bronchial
children above 4 years of age. reactivity and symptoms induced by irritants, antigens
Corticosteroids: Corticosteroids, being potent anti and exercise. Indications for use of cromolyn include mild
inflammatory agents, are the cornerstone of long-term to moderate persistent asthma and exercise-induced
treatment of asthma. Systemic glucocorticoids, when used asthma. The medication should be given for 6-8 weeks
early for therapy of exacerbation, reduce emergency visits before declaring it ineffective. Nedocromil is another agent
and hospitalization. Therapy with inhaled corticosteroids used for control of mild to moderate asthma. Ketotifen is
Disorders of Respiratory System lass-
Table 15.6: Assessment of symptom control
Feature Controlled: All of the following Partially controlled: Any Uncontrolled
measure present in any week
Daytime symptoms None (twice a week or less) More than twice per week Three or more features of
Limitation of activity None Any partially controlled asthma
Nocturnal symptoms, None Any present in any week
awakening
Need for reliever or None (less than twice a week) More than twice per week
rescue drugs
administered orally; significant clinical improvement is Table 15.7: Assessment of risk of exacerbation in near future
seen after 14 weeks of therapy.
Uncontrolled asthma symptoms
Leukotriene modifiers: Leukotriene inhibitors are useful One or more severe exacerbation requiring hospitalization in
for treatment of mild to moderate persistent asthma and previous year
exercise-induced asthma. These agents act either by Ever intubated or PICU admissions
decreasing the synthesis of leukotrienes (zileuton) or by Start of the usual 'flare-up' season
antagonizing the receptors (montelukast and zafirlukast). Exposure: Tobacco smoke; indoor or outdoor air pollution;
Montelukast and zafirlukast are approved for use in indoor allergens
children with asthma; montelukast can be used in children Major psychological or socioeconomic problems for child or
> 1 year of age while zafirlukast > 12 years. family
Theophylline: Theophylline has concentration-dependent Poor adherence with controller medication, or incorrect inhaler
technique
effects. While the bronchodilator effect is by inhibition of
phosphodiesterase, the agent also has anti-inflammatory Co-morbidities: Obesity, rhino-sinusitis, confirmed food allergy
and immunomodulatory effects at therapeutic serum
Assessment of risk of exacerbations: Based on history,
concentration. Recent guidelines recommend theophylline
children are assessed for risk of exacerbations (Table 15.7).
as an alternative second-line therapy (combined with
Appropriate treatment to children who are at risk of
glucocorticoids) in moderate persistent asthma in children
exacerbation may help in prevention of exacerbation.
�5 years, as second-line therapy for mild persistent asthma
in older children and adults, and adjunctive therapy (for Selection of medication: After assessment of control of
nocturnal symptoms) in moderate or severe persistent asthma and risk for exacerbation, antiasthma drugs are
asthma. selected. Treatment of asthma according to the assessment
is shown in Table 15.8.
Immunotherapy: This consists of administering gradually Infrequent episodes with no risk for exacerbation are
increasing quantities of an allergen extract to a sensitive treated with salbutamol or terbutaline as and when
subject, so as to ameliorate symptoms associated with required. The oral route is used, if inhalation is not possible
subsequent exposure to the causative allergen. This form for any reason. Children with infrequent episodes but
of therapy is considered occasionally in highly selected having risk factor(s) for exacerbation, or children with day
children who are sensitive to specific allergens, e.g. grass time symptoms >2 per week or nighttime symptoms once
pollen, mites. Immunotherapy is carried out only under a month should be treated with low dose inhaled steroids
specialist supervision. with salbutamol inhalation, as and when required. An
alternate strategy is montelukast or sustained release
Pharmacological management includes the following key theophylline.
steps: (i) assessment of symptom control; (ii) assessment
Children with troublesome symptoms on most days or
of risk of exacerbation; (iii) selection of medication; waking once a week or more, need low dose inhalation
(iv) selection of appropriate inhalation device; and steroids in 2 divided doses and long-acting 13-agonist
(v) monitoring.
(formoterol, salmeterol) above 12 years of age, and medium
Assessment of symptom control: Control of disease is dose steroids below 12 years. Children with severe
graded based on frequency and severity of symptoms, and uncontrolled symptoms need high dose inhalation steroids
functional impairment. This is assessed by asking for in divided doses and long-acting 13-agonists. Montelukast
frequency of symptoms including daytime symptoms, can be used as add on treatment for better control of
limitation of activity, nocturnal symptoms and need for symptoms. Persistent symptoms might require the use of
rescue medications, in past 4 weeks (Table 15.6), and low dose prednisolone, preferably on alternate days.
classifying as controlled, partially controlled and Selection of appropriate inhalation device: Drugs for
uncontrolled. maintenance treatment can be administered by inhalation
386 Essential Pediatrics
require additional agents like short- and long-acting tration, use of spacer and potential harmful effects of
13-agonists or leukotriene modifiers. Short-acting drugs. Parents concerned about the use of steroids needs
13-agonists should be taken before going for exercise. Long to be reassured that in conventional inhalation dosage,
acting 13-agonists administered in the morning show action the risk of serious illness outweighs the side effects of
throughout the day. Leukotriene modifiers are satisfactory medication. Peak flow monitoring done properly by
alternative to long-acting 13-agonists. informed parents can help by:
Seasonal Asthma i. Detecting early deterioration in lung function
ii. Managing patients who have difficulty in sensing the
A proportion of children get symptoms of asthma for a brief
change in severity of airway obstruction
period in particular season. They remain asymptomatic for
the rest of the year. These children can receive maintenance iii. Managing patients whose asthma severity changes
treatment 2 weeks in advance. Medications are selected very rapidly
according to severity of asthma. After the season is over,
Home Treatment of Acute Exacerbation
patients are reexamined after discontinuing the medications.
The parent/patient is instructed regarding recognition
Newer Therapies and management of acute exacerbation of asthma at home.
A number of novel therapies have been examined for A written action plan is given. Acute exacerbation is
clinical use. Monoclonal antibodies against IgE identified by increase in cough, wheeze and breathless
(omalizumab), IL4, ILS and IL13 may have promise as ness. PEFR, if measured, may be 15% lower from the
therapy for patients with refractory illness. baseline. For acute exacerbation, parents should administer
short-acting 13-agonists by MDI ± spacer ± facemask one
Education of Parents puff at a time repeated every 30-60 seconds up to a
Education of patients and their parents is an important maximum of 10 puffs with monitoring of symptoms. If
aspect of management. A description of the etiopatho symptoms are relieved and PEFR is increased at end of
genesis of asthma in plain language should be made. The inhalation, the child can continue the 13-agonists
spectrum of severity of the illness, likely course and (salbutamol or terbutaline) every 4-6 hours and plan a
satisfactory outcome is explained. Parents need to be visit to the physician. If there is no improvement or partial
involved in the steps required to minimize exposure to improvement or symptoms of life threatening attack at
potential environmental triggers. Avoidance of all kinds any time, the child should be transferred to a hospital.
of smoke at home, including tobacco smoke, wood Patients with life-threatening asthma or those failing
burning and kerosene stove is emphasized. Parents should to show satisfactory response to inhalation therapy at
be advised regarding minimizing the use of carpets, home should receive a single dose of oral prednisolone
curtains and other dust attracting articles. (1-2 mg/kg) before going to the hospital.
Parents should be asked to maintain a record of daily
symptoms such as cough, coryza, wheeze and breathless Managing Acute Exacerbation
ness. A record of sleep disturbances, absence from school An increase in symptoms (cough, wheeze, and/or
due to illness and medication required to keep the child breathlessness) is termed as exacerbation of asthma. The
symptom-free is advised. These records help in stepping severity of exacerbation is variable and can be classified
up or down the pharmacotherapy. as mild, moderate, severe based on physical examination,
The parents, and where possible the patient, should measurement of PEFR/FEVl and oxygen saturation
understand how the medications work, proper adminis- (Table 15.10).
Disorders of Respiratory System 1389-
a self-management plan or instructions should be given bronchiectasis. In children, incidence of right and left
to the parents. bronchial location of foreign body is nearly equal.
Bronchoscopy should be undertaken, if the clinical and
Recurrent Wheezing in Children below 5-Year-Old radiological picture suggests the diagnosis even when a
Wheezing is a common clinical symptom and -50% history of foreign body aspiration is not forthcoming.
children have had one episode of wheezing by 6 years. Some Foreign bodies are removed through a rigid bronchoscope.
patients show episodic wheezing during repeated viral Appropriate antibiotics are given for secondary infection.
infections. These episodes decrease by 5 years of age, with
decline in incidence of viral infections. On the other hand, Suggested Reading
a few children may have wheezing following viral infection • Foltran F, Ballali S, Passali FM, at al. Foreign bodies in the airways:
as well as other triggers. Some patients continue to wheeze Meta-analysis of published papers. Int J Pediatr Otorhinolaryngol
2012; 76 Suppl 1:512-9
even after 5 years of age and are treated as asthma.
Young children respond well to bronchodilators. Each
episode should thus be treated with inhaled salbutamol APPROACH TO CHRONIC COUGH
and in severe cases a short course of systemic steroids. Chronic cough can be distressing and often a cause for
Children getting frequent episodes of wheezing should consultation. The diagnosis is possible by analysis of the
receive low dose inhaled corticosteroids for 8-12 weeks. following: Age of the child; nature of cough and sputum;
If the response is satisfactory, inhaled steroids are stopped relationship to time or posture; any wheezing or stridor;
and child is followed for recurrence of symptoms. In case effect of season; response to previous therapy; nutrition;
of recurrence, such children are treated as older children signs in the chest; clubbing.
with asthma. Staccato paroxysms of cough suggest whooping cough
or Chlamydia infection. Barking or brassy cough with
Suggested Reading change in the voice indicates laryngotracheal disease. In
• Anderson WC 3rd, Gleason MC, Miyazawa N, Szefler SJ. case of postnasal drip, cough is an attempt to clear the
Approaching current and new drug therapies for pediatric asthma.
throat and is described as hawking. Cough of psychogenic
Pediatr Clin North Am 2017; 64:1197-1207.
• Global Strategy for Asthma Management and Prevention (2016 nature is 'honking' (Table 15.11).
update) http://ginasthma.org/wp-content/uploads/2016/04/ Purulent sputum indicates the presence of suppurative
GINA-2016-main-report_tracked.pdf lung disease. Although sputum is mucoid in asthma,
• Pike KC, Levy ML, Moreiras J, Fleming L. Managing problematic yellowish sputum may be present due to eosinophils.
severe asthma: beyond the guidelines. Arch Dis Child 2017; doi:
10.1136/archdischild-2016; 311-368.
Hemoptysis indicates the possibility of bronchiectasis,
tuberculosis, mitral stenosis, cystic fibrosis or foreign body
FOREIGN BODY ASPIRATION in the bronchus. Wheezing is indicative of asthma.
Chronic cough that is more common in certain seasons
Young children between 1 and 4 years of age are prone to during the year should arouse suspicion of asthma. Chronic
aspirate small objects in their air passages. Unless cough occurring only in winters indicates a viral etiology.
recognized and treated, this results in significant Malnutrition associated with chronic cough may be found
respiratory morbidity, such as recurrent wheezing, cough in patients with tuberculosis, bronchiectasis, pertussis,
and pneumonia. Immediate response to foreign body cystic fibrosis, severe chronic asthma or immune deficiency.
aspiration is a choke, gag, cough or localized wheeze. After Chest X-ray film, examination of the sputum, blood
the initial episode, symptoms may improve for some time counts and tuberculin test are necessary for diagnosis.
and the whole episode forgotten. Bronchoscopy may be necessary in some cases. CT scan is
Subsequently, the course of illness depends on the non-invasive important investigation.
nature of foreign body, its size, extent and site of
obstruction. Foreign bodies of organic or vegetable source Table 15.11: Diagnosis of chronic cough in relation to age
swell up and cause more symptoms. A partial obstruction Age Cases
may cause ball valve type effect leading to localized Onset in Laryngeal webs, vascular rings or
hyperinflation. The overlying chest wall may show first month H-type tracheoesophageal fistula,
hyperresonance, diminished vocal resonance and poor air congenital infections
entry. In small children, it may be difficult to elicit Early infancy Gastroesophageal reflux
hyperresonance. Thus a localized area of poor air entry in
Late infancy Bronchitis, asthma, cystic fibrosis, whooping
a child with chronic respiratory illness should arouse cough
suspicion of a foreign body. Complete obstruction and
Preschool age Recurrent bronchitis, asthma, foreign body,
surrounding inflammation cause distal atelectasis and
suppurative lung disease, eosinophilia
suppuration of the surrounding parenchyma of the lungs.
The elastic recoil of the bronchi is lost and the bronchi At all ages Asthma, whooping cough, viral bronchitis,
tuberculosis, foreign body aspiration
show segmental dilatation with eventual development of
Disorders of Respiratory System 1391-
Suggested Reading
• Castellani C, Duff AJA, Bell SC, et al. ECFS best practice guidelines:
the 2018 revision. J Cyst Fibrosis 2018; 17:153-178.
• Manda! A, Kabra SK, Lodha R. Cystic fibrosis in India: Present,
past and future. J Pulm Med Respir Res 2015; 1:002.
16
Disorders of
Cardiovascular System
R Krishna Kumar • Manu Raj
Diseases of the cardiovascular system are an important Table 16.1: Heart failure due to diastolic dysfunction
cause of childhood morbidity and mortality. The majority
Mitral or tricuspid valve stenosis*
of heart diseases presenting in early childhood are
congenital, resulting from structural defects during Constrictive pericarditis
development. Rheumatic heart disease continues to be Restrictive cardiomyopathy
prevalent in India. Systemic hypertension is increasingly Acute ventricular volume overload (acute aortic or mitral
recognized in childhood and predisposes to cardiovascular valve regurgitation)
morbidity. A variety of other cardiovascular conditions Myocardial ischemia#
may present in childhood. The management of these Marked ventricular hypertrophy (hypertrophic cardio-myopathy,
patients requires an integrated approach with inputs from storage disorders, severe hypertension, severe aortic or
various specialties. pulmonary valve stenosis)
Dilated cardiomyopathy#
CONGESTIVE CARDIAC FAILURE
*Elevated atrial pressures with normal ventricular diastolic pressures
Congestive cardiac failure is the inability of the heart to #Qften have combined systolic and diastolic dysfunction
maintain an output, at rest or during stress, necessary for
the metabolic needs of the body (systolic failure) and the
inability to receive blood into the ventricular cavities at
low pressure during diastole (diastolic failure). Thus, due
Table 16.2: Causes of congestive cardiac failure
to systolic failure, it is unable to propel blood into the aorta Infants
and in diastolic failure it receives inadequate amount of Congenital heart disease
blood. Diastolic heart failure is recognized by clinical Myocarditis and primary myocardial disease
features of heart failure and evidence of increased filling Tachyarrhythmias, bradyarrhythmias
pressures with preserved systolic function and in many Kawasaki disease with coronary occlusion
instances, cardiac output. An increase in left-sided Pulmonary hypertension (persistent pulmonary hypertension
pressures results in dyspnea from pulmonary congestion. of the newborn; primary pulmonary hypertension; hypoxia, e.g.
An increase in right-sided pressures results in upper airway obstruction)
hepatomegaly and edema. Besides hypertrophied Miscellaneous causes
ventricles, diastolic failure occurs in restrictive heart Anemia
disease and constrictive pericarditis. Hypoglycemia
Infections
Etiopathogenesis Hypocalcemia
The common causes of diastolic failure are indicated in Neonatal asphyxia (myocardial dysfunction, pulmonary
Table 16.1. While mitral and tricuspid valve stenoses result hypertension)
in elevated atrial pressure, they are not, in the strictest Children
sense diastolic heart failure. The causes of congestive
Rheumatic fever, rheumatic heart disease
failure can be classified according to age (Table 16.2).
Congenital heart disease complicated by anemia, infection or
Rheumatic fever and rheumatic heart disease is typically
endocarditis
encountered beyond 5 years age; its prevalence appears
Systemic hypertension
to be declining in selected urban populations. Heart failure
Myocarditis, primary myocardial disease
from congenital heart disease typically happens within
Pulmonary hypertension (primary, secondary)
the first 1-2 years of life. Patients with left-to-right shunts
394
Disorders of Cardiovascular System 1395
-
tend to develop CCF around 6 to 8 weeks of life. Unlike irritable and crying all the time. Often a mother may state
left to right shunts, congenital leakage of the mitral or the that the baby breathes too fast while feeding or that the
tricuspid valve can result in heart failure at an early age. baby is more comfortable and breathes better when held
Congenital tricuspid regurgitation (TR) manifests early against the shoulder-which is the equivalent of
because the elevated pulmonary artery pressures increases orthopnea in older children. Not infrequently, the baby is
its severity. If the TR is not severe, it may improve with brought with persistent hoarse crying, wheezing,
time as pulmonary vascular resistance declines. excessive perspiration and less commonly, because of
The age of occurrence of heart failure may point facial puffiness (Table 16.4).
towards the underlying cause (Table 16.3). Heart failure
at an unexpectedly early age should prompt the search Signs
for an associated condition such as coarctation. Left-sided failure is indicated by tachypnea and tachy
Arrhythmias are an important cause of congestive cardia. Persistent cough, especially on lying down, hoarse
cardiac failure in infancy. Heart rates above 180/ min tend cry and wheezing are other evidences of left-sided failure;
to precipitate heart failure. If the tachycardia persists for basal rales in the chest are usually not audible. Right-sided
36 hours, about 20% will develop heart failure and almost failure is indicated by hepatomegaly and facial puffiness.
50% will do so in 48 hours. Any long-standing tachy Examination of the neck veins in small babies is not
arrhythmia can be associated with ventricular dysfunction helpful. Firstly, it is difficult to evaluate the short neck
that may mimic cardiomyopathy. Typical examples include with baby fat and secondly, hemodynamic studies show
ectopic atrial tachycardia and permanent junctional re that right atrial mean pressures stays normal in many
entrant tachycardia. Severe bradycardia, typically from infants with congestive failure. Edema on the feet occurs
complete heart block, can also result in heart failure. late. Common to both left- and right-sided failure is the
With a normal heart, hemoglobin levels of 5 g/ dL can presence of cardiac enlargement, third sound gallop and
result in heart failure. In a diseased heart, failure may be poor peripheral pulses with or without cyanosis (Table 16.5).
precipitated even with hemoglobin levels of 7-8 g/ dL.
Treatment
Clinical Features Management of heart failure is a four-pronged approach
The recognition of cardiac failure in older children is based for correction of inadequate cardiac output: (i) reducing
on the same principles as in adults. cardiac work, (ii) augmenting myocardial contractility, (iii)
improving cardiac performance, and (iv) correcting the
Symptoms underlying cause. Identifying the cause is important since
Slow weight gain is related to two factors. The infant takes it has direct bearing on survival.
small feeds because of easy fatigability and there is an
excessive loss of calories from increased work of breathing. Reducing Cardiac Work (Fig. 16. l)
Uncommonly, there may be an unusual gain in weight The work of the heart is reduced by restricting patient
due to collection of water, manifesting as facial puffiness activities, sedatives, treatment of fever, anemia, obesity,
or rarely as edema on the feet. The difficulty in feeding and by vasodilators. Mechanical ventilation helps when
may manifest itself as 'poor feeder', a complaint that the heart failure is severe by eliminating the work of breathing.
baby does not take more than one to two ounces of milk Neonates with heart failure are nursed in an incubator
at a time or that he is hungry within a few minutes after and handled minimally. The baby is kept propped up at
taking a small feed. Since hunger persists, the infant is an incline of about 30° . The pooling of edema fluid in the
Table 16.4: Symptoms of cardiac failure Anemia imposes stress on the heart because of the
Poor weight gain
decreased oxygen carrying capacity of blood. Anemia
results in tachycardia and in a hyperkinetic circulatory
Difficulty in feeding state. Correction of anemia decreases cardiac work.
Breathes too fast; breathes better when held against the Typically, packed cell volumes of 10-20 mL/kg are
shoulder required to correct severe anemia; a single dose of
Persistent cough and wheezing furosemide IV is often given prior to the transfusion. Less
Irritability, excessive perspiration and restlessness common conditions causing stress to the heart are repeated
pulmonary emboli, thyrotoxicosis and obesity.
Pedal edema
Vasodilators counteract the compensatory mechanisms
Table 16.5: Signs of congestive cardiac failure in heart failure and improve cardiac output (Fig. 16.1).
Left-sided Failure of either side Right-sided failure Arteriolar and venous vasoconstriction is mediated
failure through catecholamines. Arteriolar constriction maintains
blood pressure by increasing the systemic vascular
Tachypnea Cardiac enlargement Hepatomegaly
resistance, which increases the work of heart (Fig. 16.2).
Tachycardia Gallop rhythm (S3) Facial edema Venoconstriction results in decreased venous capacitance
Cough Peripheral cyanosis Jugular venous and increased venous return, increasing the filling
engorgement pressures of the ventricles to increase the cardiac output.
Wheezing Small volume pulse Since compensatory mechanisms are inappropriately
Rales in chest Lack of weight gain Pedal edema
excessive, vasodilators, by reducing the arteriolar and
venous vasoconstriction, reduce the work of heart.
Nitrates are used as preferential venodilators.
ACE inhibitors (captopril, enalapril) are effective for
J, Peripheral resistance J, Venous return
treating heart failure in infants and children. These agents
suppress renin-angiotensin-aldosterone system thereby
reducing vasoconstriction and salt and water retention.
By suppressing catecholamines, they prevent arrhythmias
and other adverse effects on the myocardium. The major
side effect of ACE inhibitors is cough, which can be
troublesome. Persistent cough may necessitate the use of
angiotensin receptor blockers, such as losartan. Initially,
it is necessary to monitor the renal function: Urine analysis,
blood levels of creatinine and electrolytes once a week for
6 to 8 weeks. These medications may cause first-dose
Better work capacity
hypotension; the first dose should be one-quarter of the
calculated dose.
Fig. 16. l : By reducing the systemic vascular resistance and Although beta-blockers might precipitate CCF, they
decreasing the venous tone vasodilators provide better work improve symptoms especially in patients with dilated
capacity. LVEDP left ventricular end-diastolic pressure cardiomyopathy, who continue to have tachycardia.
Useful agents include metoprolol and carvedilol. The latter
dependent areas reduces the collection of fluid in lungs,
thus reducing the work of breathing. At a temperature of
Congestive cardiac failure
36-37° C, the overall circulatory and metabolic needs are
minimal, thus reducing work of heart. Humidified oxygen
to maintain a concentration of 40 to 50% improves
impaired oxygenation secondary to pulmonary
congestion. If the infant or the child is restless or dyspneic, I Arteriolar I Venous
sedation may be appropriate. Opiates (e.g. morphine) or
benzodiazepine (midazolam) are useful for sedation in
selected circumstances to reduce anxiety and lower the
catecholamine secretion, thereby reducing physical
activity, respiratory and heart rates. i Venous return
Fever, anemia and infection increase the work of the
heart. In infants and small children, the presence of
Increased work of heart
superadded pulmonary infection is difficult to recognize.
Antibiotics are, therefore, sometimes administered Fig. 16.2: Low cardiac output (CO) results in vasoconstriction,
empirically. In older children, antibiotics are used, only if increasing systemic vascular resistance (SVR) and venous tone
evidence of infection is present. leading to increase in the work of heart
Disorders of Cardiovascular System 1397
-
is preferred since it has properties of beta-blockers with hepatic, renal and pulmonary insufficiency increase the
peripheral vasodilation; treatment is started at low dose sensitivity of the myocardium to digitalis. Digoxin is
and increased depending on tolerability (0.08 to 0.4 mg/ beneficial for symptom relief and is advised in patients
kg/day, maximum 1.0 mg/kg/ day). Calcium channel with mild, moderately severe or severe congestive failure,
adversely affect cardiac contractility blockers and should with or without sinus rhythm. Digoxin can be combined
be avoided unless indicated for systemic hypertension. with ACE inhibitors for synergistic effect.
In the acute care setting, sodium nitroprusside is used
as a vasodilator, since it acts on the venous and arterial Intravenous lnotropic Agents
systems. Phosphodiesterase inhibitors, such as milrinone These agents belong to three groups: (i) catecholamine
and calcium sensitizers (levosimendan), have become inotropes: dopamine, dobutamine and adrenaline, (ii)
popular especially in postoperative period. These agents phosphodiesterase inhibitors: amrinone and milrinone
have powerful vasodilatory and inotropic effects. Specific (combine inotropic effects with peripheral vasodilation,
indications for use of vasodilators include acute mitral or inodilators) and (iii) levosimendan, a calcium sensitizer
aortic regurgitation, ventricular dysfunction resulting that is used in acute care settings as a potent inodilator with
from myocarditis, anomalous coronary artery from systemic and coronary vasodilatation. Unlike milrinone,
pulmonary artery and in the early postoperative setting. it does not increase risk of rhythm disturbances.
If blood pressure is low, dopamine should be used, as an
Augmenting Myocardial Contractility intravenous infusion. At a dose of less than 5 µg/kg/min,
Inotropic agents like digoxin improve cardiac output by dopamine causes peripheral vasodilation and increases
augmenting myocardial contractility. It has a rapid onset myocardial contractility. Renal blood flow improves,
of action and is eliminated quickly. It is available for oral resulting in natriuresis; higher doses result in peripheral
and parenteral administration. Oral digoxin is available vasoconstriction. The dose of dobutamine is 2.5 to 15 µg /
as 0.25 mg tablets and as digoxin elixir (1 mL = 0.05 mg) kg/min; the dose should be increased gradually until the
(Table 16.6). Parenteral digoxin (0.5 mg/2 mL) is available; desired response is achieved. In patients with dilated
its dose is 70% of the oral dose. Infants tolerate digitalis cardiomyopathy, dobutamine is used as 24 hours infusion
well. In a hospitalized patient, full digitalization should once or twice a week and retains its effectiveness for varying
be sought to maximize benefit. Children are digitalized lengths of time. Milrinone is given in infusion 0.3-0.7 µg/
within a 24-hour period; 1h of the calculated digitalizing kg/min following a loading dose of 50 µg/kg. The dose
dose is given initially, followed by 1,4 in 6-8 hours and the of levosimendan is 6 to 12 µg/kg loading dose over
final 1,4 after another 6-8 hours. The maintenance dose is 10 minutes followed by 0.05 to 0.2 µg/kg/min as infusion.
usually one-quarter of the digitalizing dose (Table 16.6).
Improving Cardiac Performance by
Before the third daily dose, an electrocardiogram is done
Reducing Venous Return (Preload)
to rule out digitalis toxicity. Toxicity can be controlled by
omitting the next one or two doses. The PR interval is a Diuretics reduce the blood volume, decrease venous
useful indicator; if it exceeds the initial interval by 50%, return and ventricular filling. This tends to reduce the
digitalis toxicity is present. The upper limit of normal PR heart size. The larger the heart, the more the wall tension
interval in infants is 0.14 second. and the poorer is its performance. With reduction in heart
Digitalis is used with caution in the following situations: size and volume, the myocardial function and the cardiac
(i) premature neonates; (ii) heart failure due to output improve. Diuretics reduce the total body sodium
myocarditis; and (iii) very cyanotic patients. Myocardial thereby, reducing blood pressure and peripheral vascular
damage, gross cardiomegaly, hypoxia, acidosis, and resistance. This helps in increasing the cardiac output and
reducing the work of the heart.
Table 16.6: Dosage of digoxin and diuretics Diuretics are the first line of management in congestive
Digitalizing Maintenance failure. The action of oral furosemide starts within 20 min.
dose, mg/kg dose Furosemide should be used in combination with a
µglkglday potassium sparing diuretic (triamterene, spironolactone,
Digoxin amiloride). The combination prevents potassium and
Premature, neonates 0.04 0.01 magnesium and reduces the risk of arrhythmias.
1 month to one year 0.08 0.02-0.025 Furosemide activates the renin-angiotensin-aldosterone
1 to 3 years 0.06 0.015-0.02 axis, which is responsible for vasoconstriction and sodium
Above 3 years 0.04 0.017 and water retention. When furosemide is combined with
ACE inhibitors, the combination suppresses the axis and
Diuretics
is, therefore, synergistic.
Furosemide 1-3 mg/kg per day orally or Sodium restriction is recommended but difficult to
1 mg/kg per dose IV implement in infants and young children. Low sodium
Spironolactone 1 mg/kg orally every 12 hours diets should be used, only if the heart failure cannot be
aga I Essential Pediatrics
controlled with digitalis, diuretics and ACE inhibitors. CONGENITAL HEART DISEASE
However, it is prudent to advise such patients to avoid
Congenital heart disease (CHD) encompasses a broad
salt-rich foods such as chips and pickles. Since heart failure and diverse range of conditions that manifest from
increases calorie requirements, adequate intake is advised. prenatal period to late adulthood. In common terms, CHD
Correcting the Underlying Cause refers to structural heart defects that are present at birth.
Diagnosis requires a systematic approach including
The focus of management of CHF has shifted towards history, physical examination, chest X-ray, ECG and
identifying and correcting the underlying cause. It is now echocardiography. Palliative or corrective surgery is
possible to rapidly identify the cause of CHF in most feasible for most patients with CHD, if undertaken in a
children with suspected heart disease. Many of these are timely fashion.
managed by curative or palliative operations. A diagnosis
of idiopathic dilated cardiomyopathy requires exclusion Epidemiology and Etiology
of conditions that are known to cause ventricular CHD accounts for nearly one-third of all major congenital
dysfunction. The conditions that might be missed are anomalies. The prevalence of CHD in infancy is estimated
sustained tachyarrhythmias, coarctation of aorta and at 6-8 per 1000 live births; 25% are life-threatening and
obstructive aortitis, anomalous origin of the left coronary require early intervention. A proportion of patients with
artery from pulmonary artery and hypocalcemia. It is CHD have an identifiable genetic basis (Table 16.7).
important to look for subtle evidence of sustained Table 16.8 shows the association of CHD with acquired
tachyarrhythmias. Anomalous origin of the left coronary disorders and teratogens.
artery is treated surgically.The presence of CCF in a child
with rheumatic heart disease does not necessarily mean Physiology of Congenital Heart Disease
presence of active carditis. In any patient of rheumatic
Pressure, Flow and Resistances
heart disease, if active carditis has been excluded and an
adequate trial has been given to medical management, The pressures and resistances in the pulmonary and
operative treatment should be considered. Uncommon systemic circulations are indicated in Table 16.9. The
causes of CCF in infants include upper respiratory obstruc pulmonary and systemic flows are equal, if there are no
tion, hypoglycemia, neonatal asphyxia and hyp ocalcemia. abnormal communications between the two sides.
Table 16.8: Prenatal exposures that increase risk of Increase in pulmonary vascular resistance means
congenital heart disease obstructive disease in the pulmonary circuit. The
pulmonary vessels develop medial hyp ertrophy and later
Gestational diabetes (transposition, atrioventricular septal intimal changes are added, to further obstruct the flow of
defects, hypoplastic left heart, cardiomyopathy, PDA)
blood through the pulmonary circulation. After a certain
Febrile illness in first trimester (increased risk) stage, it is an irreversible process. The increase in
Rubella (PDA, peripheral pulmonary stenosis, VSD) resistance to flow in the pulmonary circuit is associated
with reduction in flow. The increase in pressure in the
Lupus (complete heart block)
pulmonary artery associated with normal resistance is
Phenylketonuria (VSD, TOF, PDA, single ventricle) called hyperkinetic pulmonary arterial hypertension
Vitamin deficiency (increased risk of heart disease) whereas when the pressure is increased due to increase
Teratogens (first trimester), e.g. anticonvulsants, NSAIDs, in pulmonary vascular resistance, it is called obstructive
cotrimoxazole, thalidomide, retinoic acid pulmonary arterial hypertension. Clinically, the two
Exposure to organic solvents, herbicides, pesticides, ionizing conditions can be distinguished on clinical examination.
radiation
Fetal Circulation (Fig. 16.3)
NSAIDs: Nonsteroidal anti-inflammatory drugs; PDA: Patent ductus
The heart assumes its normal four-chambered shape by
arteriosus; TOF: Tetralogy of Fallo!; VSD: Ventricular septal defect
the end of 6 weeks of intrauterine life. From then on only
According to Poiseuille's equation, modified for minor changes occur and consist mainly in the growth of
application to blood flow through vessels, the heart as a whole with increasing age of the fetus. For
the exchange of gases, the fetus is dependent on placental
Pressure = Flow x Resistance
circulation, whereas the neonate is dependent on the
The pressure is measured in mm Hg, flow in liters/ lungs. Immediately following birth, the lungs expand with
min and resistance in dynes/sec/cm5 or units (80 dynes/ air and the gas exchange function is transferred from the
sec/cm5 = 1 unit). Although this equation is not strictly placenta to the lungs; following various circulatory
accurate when applied to flow of blood in pulmonary and adjustments.
systemic circuits, it helps in understanding the hemo
Blood oxygenated in the placenta is returned by way
dynamics.
of umbilical veins, which enter the fetus at the umbilicus
Systemic pressure = Systemic flow x peripheral vascular and join the portal vein (Fig. 16.3). The ductus venosus
resistance provides a low resistance byp ass between the portal vein
Pulmonary arterial pressure = Pulmonary flow x pulmonary and the inferior vena cava. Most of the umbilical venous
vascular resistance blood shunts through the ductus venosus to the inferior
It is thus obvious that the pressure in a vessel is vena cava. Only a small proportion mixes with the portal
dependent on the flow through the vessel and the resistance, venous blood and passes through the liver. Blood from
offered by the vessel to the flow of blood. It is possible to inferior vena cava comprising that from hepatic veins,
increase the pressure in a vessel either by increasing the umbilical veins and that from lower extremities and
flow or by increasing the resistance. Increase in flow kidneys enters the right atrium. On reaching the right
through the pulmonary artery means a left-to-right shunt, atrium, the bloodstream is divided into two by the inferior
as occurs in atrial or ventricular septal defect or patent margin of septum secundum-the crista dividens. About
ductus arteriosus. Generally, this increase in flow is not one-third of the inferior vena cava blood enters the left
associated with significant increase in pressure as the atrium, through the foramen ovale, the rest two-thirds mix
distensibility characteristics of the pulmonary artery are with the venous return from the superior vena cava to
such that it can accommodate almost three times the normal enter the right ventricle.
flow without an increase in pressure. Hence, large left-to The blood reaching the left atrium from the right atrium
right shunts can take place without an increase in pressure. mixes with small amount of blood reaching the left atrium
Table 16.9: Systolic and diastolic pressures and resistance in the pulmonary and systemic circuits
Chamber/vessel Pressure (mm Hg) Chamber/vessel Pressure (mm Hg)
Superior vena cava 0-6 Pulmonary vein 6-1 O
Right atrium 0-6 Left atrium 6-10
Right ventricle 25/0-6 Left ventricle 80-120/5-10
Pulmonary artery 25/10 Aorta 80-120/60-85
Resistance, dynes/sec/cm5
Pulmonary vascular 80-240 Systemic vascular 800-1600
400 I Essential Pediatrics
At birth Adult
SVC PV SVC PV
IVC
i 10 10
L i PV IVC 0-6 6-10
L PV
RA LA RA LA
60/10 60/10
25/0-6 120/0-10
RV LV RV LV
60/40 60/40 PA Ao
PA
I DA
Ao
25/10 120/75
Fig. 16.4: Pressure and resistance in the right- and left-sided chambers and vessels at birth compared to adults. Ao aorta; DA
ductus arteriosus; IVC inferior vena cava; L A left atrium; LV left ventricle; PA pulmonary artery; PV pulmonary vein; PVR peripheral
vascular resistance; RA right atrium; RV right ventricle; SVC superior vena cava
i. Pretricuspid versus post-tricuspid shunts of the prolonged right ventricular ejection time and
ii. VSD-PS physiology prolonged "hang-out" interval resulting from increased
iii. Single ventricle physiology capacitance of the pulmonary circulation. Pulmonary
iv. Duct-dependent lesions arterial hypertension (PAH) is typically absent or, at most,
v. Unfavorable streaming and parallel circulation mild. The presence of moderate or severe PAH in ASD is
worrisome and suggests the onset of irreversible changes
Pretricuspid versus Post-tricuspid Shunts in the pulmonary vasculature.
Acyanotic heart disease with left-to-right shunts is Post-tricuspid shunts are different in that there is direct
traditionally classified as pretricuspid and post-tricuspid transmission of pressure from the systemic to the
shunts. There are important differences in physiology that pulmonary circuit at the ventricular level (VSD) or great
impact clinical manifestations and natural history. Left arteries (PDA and aortopulmonary window). The shunted
to-right shunts at or proximal to the level of the atria are blood passes through the lungs and finally leads to a
known as pretricuspid shunts. They include atrial septal diastolic volume overload of the left ventricle. The
defects and partial anomalous pulmonary venous hemodynamic consequences are dictated by the size of
connection. The left-to-right shunt and the consequent the defect. For patients with large post-tricuspid shunts,
excessive pulmonary blood flow is dictated by relative symptoms begin in early infancy, typically after regression
stiffness of the two ventricles. Since the right ventricle is of elevated pulmonary vascular resistance in the newborn
relatively stiff (non-compliant) at birth and during early period.
infancy, the shunt is small. Over the years, the pulmonary The excessive pulmonary blood flow returns to left
vasculature becomes capacious and right ventricle atrium and flows through the mitral valve resulting in
progressively enlarges to accommodate the excessive apical diastolic flow murmur that is a consistent marker
pulmonary blood flow. This explains why atrial septal of large post-tricuspid shunts. The left atrium and ventricle
defects (ASD) seldom manifest with symptoms of are dilated as a result of this extra volume. Elevated
pulmonary over-circulation during infancy and pulmonary artery pressure is an inevitable consequence
childhood. The clinical signs are also easily explained by of large post-tricuspid shunts, and is labeled hyperkinetic
the physiology of pretricuspid shunts. The diastolic flow PAH. This needs to be distinguished from elevated
murmur of ASD is across the much larger tricuspid valve pulmonary vascular resistance that results from long
and is, therefore, relatively subtle or even inaudible. The standing exposure to increased pulmonary blood flow.
excessive blood in the right ventricle is ejected into the Correction of large post-tricuspid shunts results in rapid
pulmonary artery resulting in an ejection systolic murmur. and dramatic reduction in elevated pulmonary artery
The second heart sound splits widely and is fixed because pressures.
402 Essential Pediatrics
Table 16.10: Broad physiologic categories of The best example of VSD-PS physiology is tetralogy of
congenital heart disease Fallot (TOF). In its least severe form, TOF is often not
Acyanotic heart disease: Left-to-right shunts associated with cyanosis (pink TOF). Here PS is significant
Pretricuspid: Partial anomalous pulmonary venous drainage, enough to result in a large pressure gradient across the
atrial septal defect right ventricular outflow tract (RVOT), but not severe
Ventricular: Ventricular septal defects (VSD)
enough to result in a reduction in pulmonary blood flow.
Pink TOF is typically associated with a loud ejection
Great artery: Aortopulmonary window, patent ductus; ruptured
sinus of Valsalva
systolic murmur because of a reasonable volume of blood
flowing across the RVOT. As the severity of PS increases,
Both pre- and post-tricuspid: Atrioventricular septal defect, left
ventricle to right atrial communications pulmonary blood flow declines and the intensity of
murmur declines progressively. Identical symptoms and
Acyanotic heart disease: Obstructive lesions physical findings are present in (i) complete transposition
Inflow: Cor-triatriatum, obstructive lesions of the mitral valve of great arteries with VSD and pulmonic stenosis,
Right ventricle: lnfundibular stenosis, pulmonary valve stenosis, (ii) double outlet right ventricle with pulmonic stenosis
branch pulmonary artery stenosis and a large subaortic VSD, (iii) tricuspid atresia with
Left ventricle: Subaortic membrane, valvar aortic stenosis, diminished pulmonary blood flow, (iv) single ventricle
supravalvar aortic stenosis, coarctation of aorta with pulmonic stenosis, and (v) corrected transposition
Miscellaneous: Coronary artery abnormalities, congenital mitral of great arteries with VSD and pulmonic stenosis.
and tricuspid valve regurgitation
Cyanotic heart disease Single Ventricle Physiology
Reduced pulmonary blood flow This refers to a group of conditions where there is complete
Intact interventricular septum: Pulmonary atresia with intact mixing of pulmonary and systemic venous returns. In
ventricular septum, critical pulmonic stenosis with right-to-left addition to single ventricle (double inlet ventricle), a
shunt at atrial level, Ebstein anomaly; isolated right ventricular variety of conditions come under the category of single
hypoplasia ventricular physiology. Atresia of one of the AV valves,
Unrestrictive ventricular communication: All conditions listed severe hypoplasia of one of the ventricles, severe
under VSD with pulmonic stenosis straddling of one of the AV valves over a large VSD are
Increased pulmonary blood flow all examples of situations where there is mixing of
Pretricuspid: Total anomalous pulmonary venous pulmonary and systemic venous returns. The clinical
communication, common atrium manifestations are dictated by whether or not there is PS.
Post-tricuspid: All single ventricle physiology lesions without
In absence of PS, there is excessive pulmonary flow
pulmonic stenosis, persistent truncus arteriosus, transposition especially in infants because of the relatively lower
of great vessels pulmonary vascular resistance. The proportion of
oxygenated blood from pulmonary veins that mixes with
Pulmonary hypertension
the systemic venous return is high. Cyanosis is minimal
Pulmonary vascular obstructive disease (Eisenmenger and measured oxygen saturation may be 90% or more.
physiology)
However, preserved oxygenation is at the cost of heart
Miscellaneous failure and permanent elevation of pulmonary vascular
Pulmonary arteriovenous malformation, anomalous drainage resistance (pulmonary vascular obstructive disease). If the
of systemic veins to LA child survives infancy, pulmonary vascular resistance
progressively increases with increasing cyanosis.
VSD-PS Physiology (Fa/lot Physiology] Single ventricle and its variants can be associated with
This situation is characterized by a large communication varying degrees of PS. The features are similar to VSD-PS
at the ventricular level together with varying degrees of physiology except for relatively severe hypoxia because
obstruction to pulmonary blood flow. Typically, this is in of free mixing of systemic and pulmonary venous return.
the form of subvalvar (infundibular), valvar, annular Palliative operations are the only option for most
(small annulus) and occasionally supravalvar stenosis. The conditions. The definitive procedure is the Fontan
free communication between the two ventricles results in operation that allows separation of systemic venous return
equalization of pressures. Severity of PS dictates the from pulmonary venous return thereby, eliminating
volume of blood flowing through pulmonary arteries and, cyanosis.
therefore, amount of oxygenated blood returning via
pulmonary veins. Severe PS results in right-to-left shunt Duct-Dependent Lesions
across the VSD with varying degrees of hypoxia and, An infant or a newborn with CHO that is dependent on
consequently, cyanosis. Cyanosis is directly proportionate the patency of the ductus arteriosus for survival can be
to the severity of PS. Because the right ventricle is readily termed as having a duct-dependent lesion. These are
decompressed by the large VSD, heart failure is unusual. newborns where the systemic blood supply is critically
Disorders of Cardiovascular System 1403-
dependent on an open PDA (duct-dependent systemic Difficult Feeding and Poor Growth
circulation, DDSC) or pulmonary blood flow is duct The parent may report that the child has difficulty feeding.
dependent (duct-dependent pulmonary circulation, This is usually a feature of an infant with congestive heart
DDPC). Closure of the PDA in DDSC results in systemic failure and may include slow feeding, small volumes
hypoperfusion (often mistaken as neonatal sepsis), as in consumed during each feed, tiring easily following feeds
hypoplastic left heart syndrome, where the entire systemic and requirement of periods of rest during feeds. Excessive
circulation is supported by the right ventricle through the sweating involving forehead or occiput is commonly
PDA, and interrupted aortic arch where the descending associated. Not infrequently, no history of feeding difficulty
aortic flow is entirely through the PDA. Severe coarctation may be obtained, but examination of growth charts reveals
and critical aortic stenosis are also examples of DDSC. _
that the growth is not appropriate for age. A recent declm.e
Closure of PDA in DDPC results in severe hypoxia and in growth rate (falling off the growth curve) or weight that
cyanosis in neonates; examples include all forms of is inappropriate for age ( <5th centile) may result from a
pulmonary atresia (irrespective of underlying heart defect) large left-to-right shunt. Characteristically, growth
where the PDA is the predominant source of pulmonary retardation affects weight more than height.
blood flow. Patients with pulmonary atresia, where
pulmonary blood supply is from major aortopulmonary Difficult Breathing
collaterals, may survive even after the PDA closes. Critical
Tachypnea (respiratory rate >60/min in infants <2 months;
PS can present as duct-dependent pulmonary blood flow.
>50/min in older infants; >40/min after 1 year) is a
Newborns with severe Ebstein anomaly can also present
manifestation of heart failure in newborns. For infants,
as DDPC (physiologic pulmonary atresia) even though
subcostal or intercostal retractions together with flaring
the pulmonary valve is anatomically normal, because of
of nostrils are frequently associated with tachyp nea.
inability of the right ventricle to function effectively.
Neonates with duct-dependent physiology require Frequent Respiratory Infections
prostaglandin El (PGEl) for survival. Early recognition
of a duct-dependent situation allows early initiation of The association of respiratory infections that are frequent,
PGEl and stabilization until definitive procedure is severe and difficult to treat with large left-to-right shunts
accomplished. is frequent but not a specific feature.
There are only three lesions that produce a pansystolic Abnormal electrocardiogram: Electrocardiogram is used to
murmur: VSD, mitral regurgitation and tricuspid determine the mean QRS axis, right or left atrial
regurgitation. An ejection systolic murmur may be due to hypertrophy and right or left ventricular hypertrophy.
an organic cause or it may be functional. An ejection Criteria for ventricular hypertrophy, based only on voltage
systolic murmur associated with a thrill is an organic criteria are not diagnostic for the presence of heart disease,
murmur.Grade ill ejection systolic murmur of a functional since these may be affected by changes in blood viscosity,
type may be heard in anemia or high fever especially in electrolyte imbalance, position of electrodes and thickness
small children. of the chest wall.
A number of children around the age of 5 years may have a
Abnormal X-ray: The reason for abnormal X-ray as a minor
soft, short ejection systolic murmur. If it is accompanied with
criterion is twofold. In infants and smaller children, the
a normal second sound, then it is unlikely to be significant.
heart size varies with expiration and inspiration. If there
Before labeling a murmur as innocent, it is necessary to
is cardiomegaly on an inspiratory film, it suggests heart
reassess after an interval. Typically, innocent murmurs
disease. The second reason is that enlarged thymus in
are often detected during a febrile illness and often
children up to 2-year-old might mimic cardiomegaly.
disappear. It may be necessary to obtain an ECG and an
Fluoroscopy is helpful in separating the shadow of the
echocardiogram to rule out heart disease and allay
thymus from the heart.
parental anxiety.
Abnormal blood pressure: It is difficult to obtain accurate
Diastolic murmur: A diastolic murmur almost always
blood pressure in smaller children. It is important to use
indicates the presence of organic heart disease.
appropriate sized cuffs while measuring blood pressure.
Central cyanosis: Central cyanosis suggests that either
unoxygenated blood is entering the systemic circulation Diagnostic Implications of the Second Heart Sound
through a right-to-left shunt or blood passing through the Of the various heart sounds and murmurs, the most
lungs is not getting fully oxygenated. Oxygen saturation important is the assessment of the second heart sound
of the arterial blood is less than normal (normal being (Fig. 16.5). The normal second heart sound can be
around 98%). If blood is not getting oxygenated in the described in three parts:
lungs, it is called pulmonary venous desaturation and i. It has two components: Aortic closure sound (A2) and
indicates severe lung disease. Cyanosis due to a right-to pulmonary closure sound (P2).
left shunt indicates presence of heart disease. Central
cyanosis is present in fingers, toes and mucous membranes
Second Heart Sound
(mouth, tongue). It results in polycythemia and clubbing.
•
Peripheral cyanosis does not imply the presence of heart Splitting Expiration Inspiration
D
disease. Peripheral cyanosis results due to increased oxygen
extraction from the blood by the tissues, and is seen in fingers Normal
•
and toes but not in mucous membranes.The arterial oxygen
saturation is normal. Presence of central cyanosis indicates
CHD if lung disease has been excluded. However, cyanosis
Wide and variable
D
•
that is obvious clinically usually results from significant
desaturation (typically <85%). Poor lighting, anemia and Wide and fixed
dark skin may mask cyanosis. The routine use of pulse
oximeters allows detection of mild hypoxia. Saturations
<95% while breathing room air are abnormal.
Congestive cardiac failure: Presence of congestive cardiac
Paradoxical
D
.{]
failure indicates heart disease except in neonates and
Single second sound
infants, where it might occur due to extracardiac causes, �
including anemia hypocalcemia and hypoglycemia.
I
Minor criteria
Systolic murmur less than grade III: However, soft, less than A2D
grade III, murmurs by themselves do not exclude heart P2.
disease.
Abnormal second sound: Abnormalities of the second sound Fig. 16.5: Second sound (S2): The relationship of aortic (A2)
always indicate presence of heart disease. It has been and pulmonic component (P2) in inspiration and expiration.
included as a minor criterion only because auscultation is Single S2 means that it may be either A2 or P2 or a combination
an individual and subjective finding. of both
Disorders of Cardiovascular System 1405-
ii. During quiet breathing, both the components are is wide in expiration but narrows during inspiration
superimposed on each other during expiration, thus (Fig. 16.5). A single second sound means that it is either
only a single second sound is heard. During inspira A2 or P2 or a combination. The decision whether it is aortic
tion, the aortic component comes early whereas the or pulmonic or a combination, depends not on the location
pulmonary component is delayed, resulting in a split or intensity of the single second sound, but on the clinical
in which the A2 precedes the P2. profile. In tetralogy of Fallot, only a single S2 is heard and
iii. The aortic component is louder than the pulmonary it is the A2 since the pulmonic component is delayed and
component, except in young infants. so soft that it is inaudible. In VSD with pulmonary arterial
When we say that the second sound is normal, it is in hypertension and right-to-left shunt (Eisenmenger
context of the above three aspects. Abnormalities of the complex), single S2 represents a combination of A2 and
second sound might occur in each of these aspects. P2. While based on auscultation alone, it might be difficult
to differentiate between tetralogy of Fallot and
Abnormalities of aortic component: The A2 may be Eisenmenger complex, the history and chest X-ray can
accentuated or diminished in intensity. It can also occur distinguish these conditions.
early or late in timing. The A2 is accentuated in systemic
hypertension from any cause and in AR; diminished or Imaging Studies
may be absent when the aortic valve is immobile because Echocardiography: Echocardiography has revolutionized
of fibrosis or calcification; or if absent, in aortic valve the diagnosis of CHD and its diagnostic yield makes this
atresia. The A2 is delayed when the left ventricular ejection investigation cost-effective (Fig. 16.6). This is particularly
is prolonged as in aortic valvar or subvalvar stenosis, true for infants and newborns where excellent images are
patent ductus arteriosus with a large left to right shunt, readily obtained. Transesophageal echocardiography can
AR, left bundle branch block and left ventricular failure. supplement transthoracic studies in older children.
The A2 occurs early in VSD, mitral regurgitation and
constrictive pericarditis. Cardiac magnetic resonance imaging: Cardiac MRI is
important for evaluation of CHD, especially in older
Abnormalities of pulmonic component: The P2 may be patients and for postoperative evaluation. MRI also
accentuated or diminished in intensity or delayed in defines extracardiac structures such as branch pulmonary
timing. Although it may occur early in tricuspid arteries, pulmonary veins and aortopulmonary collaterals.
regurgitation, it is not recognized since tricuspid Useful physiologic data (blood flow calculations at a
regurgitation as an isolated lesion (without pulmonary number of locations; estimate of ventricular function) is
arterial hypertension) is rare. Accentuated P2 is present obtained. Limitations include lack of expertise for
in pulmonary arterial hypertension from any cause. The interpretation and need for general anesthesia to enable
P2 is diminished in intensity in pulmonic stenosis. It is breath-holding.
absent when the pulmonary valve is absent as in
pulmonary valvar atresia. The P2 is delayed in pulmonic Computed tomography: CT overcomes some of the
stenosis, atrial septal defect, right bundle branch block, limitations of MRI because it has a much lower image
total anomalous pulmonary venous connection and type acquisition time. However, exposure to ionizing radiation
A WPW syndrome. is a concern.
Abnormalities in splitting of the second sound (S2): The Diagnostic cardiac catheterization: The role of diagnostic
normal S2 is single (or closely split, <0.03 sec) in expiration cardiac catheterization for patients with CHD has declined
and split in inspiration with the louder A2 preceding P2. with the availability of high quality echocardiography,
Wide splitting of the second sound is defined as splitting MRI and CT. Since cardiac catheterization is an invasive
during expiration due to an early A2 or late P2 or the A2- procedure, its performance requires planning so that the
P2 interval of 0.03 sec or more during expiration. If the information desired may be obtained with minimum risk
interval increases during inspiration, it is called wide to the patient. Diagnostic cardiac catheterization should
variable splitting, but if it is the same in expiration and be advised, if non-invasive investigations do not provide
inspiration it is defined as widely split and fixed S2. Wide information that is required for surgery.
and variable splitting of S2 is seen in pulmonic stenosis,
mitral regurgitation and VSD. In pulmonic stenosis, it is Definitive and Palliative Treatment
due to a delay in P2 whereas in mitral regurgitation and To ensure the best possible results of management of CHD,
VSD, it is due to an early A2. Wide and fixed splitting of it is necessary to have a team of qualified individuals who
the S2 occurs in atrial septal defect, right bundle branch are part of a comprehensive pediatric heart program.
block and total anomalous pulmonary venous connection
and is due to a delay in P2. Surgery
The delay in A2 results in closely split, single or Surgery is still the best option for definitive treatment or
paradoxically split S2. In paradoxically split S2, the split palliation of most CHD. Surgeries for CHD are broadly
40s I Essential Pediatrics
Apical
Fig. 16.6: Two-dimensional echocardiography. An illustrative example of how the ventricular septum can be sectioned at different
levels to screen for ventricular septa! defects. The lines with arrows represent levels at which cross-sectional images are obtained.
The still frames of the respective echocardiograms are shown in relation to each of the level at which a section is obtained. Ao
aorta; LV left ventricle; PA pulmonary artery; RV right ventricle; RVOT right ventricular outflow tract
classified as open heart (requiring use of cardiopulmonary ventricle continues to support the systemic circulation,
bypass-CPB) and closed heart (not requiring CPB). Most TOF repair where the pulmonary valve is rendered
corrective operations and many palliative operations fall incompetent through a transannular patch and operations
under the former category. These procedures are generally that require the placement of a right ventricle to
a more significant and expensive undertaking because of pulmonary artery conduit. Corrective surgeries associated
the use of the CPB circuit. The morbidity of open heart with excellent long-term survival include the arterial
operations is proportionate to the duration of exposure to switch operation, repair of total anomalous pulmonary
CPB and the cross-clamp time (the period of time when venous connection and coarctation.
heart beating is deliberately brought to a standstill through
the use of cardioplegia). Surgery for single ventricle physiology: This category
includes all anatomic examples of single ventricle. In
Corrective operations: Corrective surgery is possible for addition, this includes situations when one atrio
atrial and ventricular septal defects, with no significant ventricular valve is atretic or one of the ventricles is
long-term concerns. If the repair of TOF does not result in hypoplastic. The surgical management of single ventricle
pulmonary valve incompetence, long-term concerns are physiology is performed in stages. The first stage involves
minimal. Certain operations require careful follow-up early pulmonary arterial band (usually under the age of
because long-term concerns are substantial, especially 3 months) for patients who have increased pulmonary
after 10-20 years follow-up. These include the Senning blood flow and the modified Blalock-Taussig shunt for
operations (atrial switch) for transposition where the right those who have reduced pulmonary blood flow with
Disorders of Cardiovascular System 1407-
cyanosis. The second operation is the bidirectional Glenn few months of life). Large acyanotic post-tricuspid shunts
shunt. The superior vena cava is anastomosed to the right are also prone to early development of PAH and should be
pulmonary artery. This operation allows effective ideally corrected early, preferably within the first year. In
palliation until the age of 4-6 years, sometimes longer. pretricuspid shunts, PAH develops slowly and
The Fontan operation is finally required for elimination unpredictably. While most patients with ASD will have
of cyanosis. All the systemic venous return is routed to mild or no PAH throughout their lives, a small proportion
the pulmonary artery. There are important long-term develops accelerated changes in pulmonary vasculature.
issues in a substantial proportion of survivors. Features associated with early development of PAH are:
Large size of the defect; presence of pulmonary venous
Catheter Interventions hypertension; airway obstruction; syndromic association,
Catheter interventions are possible in many patients. Many (e.g. trisomy 2 1); prolonged duration of increased
defects such as secundum ASD, PDA and selected muscular pulmonary blood flow; and residence at high altitude.
VSD can be closed in the catheterization laboratory. Infective endocarditis or endarteritis (IE): Endocarditis
Additionally, balloon valvotomy is now the first line of can complicate CHD, especially in patients with significant
treatment for stenosis of the pulmonary and aortic valves turbulence created by high-pressure gradients, e.g.
(Table 16.12). These interventions are far less traumatic than restrictive VSD and PDA, tetralogy of Fallot and left
surgery, accomplished with ease and allow rapid recovery. ventricular outflow obstruction. Some surgical operations
Complications of Congenital Heart Disease (Blalock-Taussig shunt) are also associated with increased
risk of IE or endarteritis. Lesions with little or no turbulent
Pulmonary arterial hypertension (PAH): Lesions that have flows, such as ASD, do not show an increased risk. The
the greatest likelihood of developing PAH include cyanotic importance of good dental hygiene cannot be over
heart disease with increased pulmonary blood flow. Here emphasized.
irreversible changes in pulmonary vasculature develop
rapidly, often during infancy. It is important to correct or Impaired growth and nutrition: This is affected in all
appropriately palliate these lesions early (within the first forms of CHD and is striking in large left-to-right shunts.
Patients with CHD show high prevalence of malnutrition, Tachypnea is prominent feature without significant
which improves after correction of the underlying subcostal recession. Cyanosis deepens as the spell
condition. progresses. Later gasping respiration and apnea ensues,
which leads to limpness and ultimately anoxic seizures.
Myocardial dysfunction: Chronic volume overload Spells can last from minutes to hours. Auscultation reveals
results in ventricular enlargement and ventricular softening or disappearance of pulmonary ejection
dysfunction that is reversed after correction. A proportion murmur. The management is summarized in Table 16.13.
of patients with severe hypoxia may develop severe
dysfunction involving both ventricles. Heart failure is Natural History
mostly the result of hemodynamic consequences of
Some CHD have a tendency towards spontaneous closure
increased pulmonary blood flow, mitral or tricuspid valve
and this influences the timing of intervention. Defects
regurgitation and severe myocardial hypertrophy. Systolic
known to close spontaneously are atrial and ventricular
dysfunction is a relatively less common cause.
septal defects, and patent ductus arteriosus. Variables
Neurologic consequences and development delay: Chronic influencing the likelihood of spontaneous closure include:
hypoxia, in utero hypoxia and hypoperfusion and open Age at evaluation (lower likelihood of closure with
heart surgery contribute substantially to morbidity. Brain increasing age), size of the defect (smaller defects more
abscess is uniquely associated with cyanotic heart disease
(typically beyond the age of 2 years). Table 16.13: Management of hypercyanotic spells
Immediate steps
Erythrocytosis: Older children with cyanotic CHD are Check airway; deliver oxygen by face mask or nasal cannula
prone to complications from chronically elevated red cell
Knee chest position
turnover. These include symptoms of hyperviscosity,
Sedate with morphine (0.2 mg/kg SC or ketamine 3-5 mg/kg/
gout, renal failure and gallstones.
dose IM)
Rhythm disorders and sudden death: Chronic enlarge Sodium bicarbonate at 1-2 mUkg (diluted 1:1 or in 10 mUkg
ment of heart chambers predispose to tachyarrhythmia. N/5 in 5% dextrose)
Chronic right atrial enlargement (ASD, Ebstein syndrome, Correct hypovolemia (10 mUkg of dextrose normal saline)
severe tricuspid regurgitation) predisposes to atrial flutter. Transfuse packed red cell, if anemic (hemoglobin <12 g/dl)
Chronic right ventricular enlargement predisposes to Metoprolol at 0.1 mg/kg IV slowly over 5 min; repeat every
ventricular tachycardia and may precipitate sudden 5 min; for maximum 3 doses; may be followed by infusion at
cardiac arrest. This is a significant long-term concern after 1-2 µg/kg/min
TOF repair where the pulmonary valve is rendered Monitor saturation, heart rates and blood pressure; keep heart
incompetent. Left ventricular hypertrophy and rate below 100/minute
dysfunction is also associated with high risk of ventricular
Persistent desaturation and no significant improvement
tachycardia.
Consider vasopressor infusion: Methoxamine 0.1--0.2 mg/kg/
Cyanotic spells: Patients with the VSD-PS physiology are dose IV or 0.1- 0.4 mg/kg/dose IM, or phenylephrine 5 µg/kg
prone to cyanotic spells. Cyanotic spells occur due to acute as IV bolus and 1-4 µg/kg/min as infusion
decrease in pulmonary blood flow, increased right-to-left If spells persist: Paralyze the patient, electively intubate and
shunt and systemic desaturation due to (i) infundibular ventilate; plan for palliative or corrective surgery
spasm secondary to increase in circulating catecholamines, Seizures are managed with diazepam at 0.2 mg/kg IV or
during feeding or crying; or (ii) activation of mechano midazolam at 0.1-0.2 mg/kg/dose IV
receptors in right ventricle (due to decrease in systemic Following a spell
venous return) or in left ventricle (due to reduced
Conduct a careful neurological examination; CNS imaging, if
pulmonary blood flow). These changes result in peripheral focal deficits are present
vasodilatation and fall in systemic vascular resistance,
Initiate therapy with beta-blocker at the maximally tolerated
producing increased right-to-left shunt and systemic dose (propranolol 0.5-1.5 mg/kg q 6-8 hr); helps improve
desaturation. resting saturation and decreases frequency of spells
A cyanotic spell is an emergency, which requires Ensure detailed echocardiography for disease morphology
prompt recognition and intervention to prevent disabling Plan early corrective or palliative surgery
cerebrovascular insults or death. The spell needs to be
Administer iron in therapeutic (if anemic) or prophylactic dose
taken seriously also because it indicates the need for early
operation. It is commonly seen below 2 years (peaks Prevention
between 2 and 6 months). The onset is spontaneous and Counsel parents regarding the possibility of recurrence of spells
unpredictable and occurs more often in early morning, and precipitating factors (dehydration, fever, pain)
although it can occur at anytime in the day. The infant Encourage early surgical repair
cries incessantly, and is irritable and inconsolable.
Disorders of Cardiovascular System 1409-
likely to close) and location of defects (fossa ovalis ASD Detection of serious defects through fetal echocardio
and perimembranous and muscular VSDs often close) graphy enables delivery at a center with a pediatric heart
(Table 16.14). program. While echocardiography is recommended for
Without correction, many children especially those with future pregnancies after diagnosis of serious CHD in a
cyanotic CHD, will not survive beyond early childhood. child, this has low yield because only 2-8% CHD recur,
The outcomes are improved by correction through surgery with the highest risk for obstructive lesions of the left heart.
and, in some situations, through catheter interventions.
Despite curative surgery, some patients have important ACYANOTIC CONGENITAL HEART DEFECTS
long-term sequelae. For example, patients with tetralogy Atrial Septal Defect
of Fallot who have undergone "curative" repair might
show progressive right ventricular dilation with increased Atrial septal defect (ASD) as an isolated anomaly accounts
risk of late heart failure and sudden cardiac death. There for 5-10% of all CHD. Based on anatomy, ASD is classified
are concerns after the arterial switch operation (aortic root as follows (Fig. 16.7):
dilation, silent coronary occlusion), AV canal repair (AV Fossa ovalis ASD: They are located in the central portion
valve regurgitation) and coarctation (residual of atrial septum, in the position of foramen ovale. These
hypertension, aortic aneurysm). Operations that involve defects are amenable to closure in the catheterization
placement of conduits (pulmonary atresia, Rastelli laboratory.
operations) require replacement upon growth of the child.
Conditions associated with satisfactory long-term survival Sinus venosus ASD: These are located at junction of
include small left-to-right shunts and bicuspid aortic superior vena cava and right atrium. These defects do not
valves. Survival is satisfactory for many patients with have a superior margin because the superior vena cava
atrial septal defect, coarctation of aorta, pink TOF, straddles the defect. These defects are associated with
mild Ebstein anomaly and some forms of corrected anomalous drainage of one or more right pulmonary
transposition of great arteries. veins.
Prevention of CHD Ostium primum ASD: These defects are created by failure
of septum primum, and are in lower part of the atrial
Most CHD do not have an identifiable etiology and there
is no effective strategy for their prevention. Education of
public on the risks associated with consanguinity, drugs
and teratogens in the first trimester of pregnancy and
widespread immunization against rubella have limited Fossa ovalis A
role in preventing CHD. Fetal echocardiography is an
important modality for early diagnosis of CHD.
Conditions that involve major chamber discrepancy (such Superior vena
as hypoplastic left heart syndrome), single ventricle and
common AV canal can be identified by routine four
chamber view screening as early as 14-16 weeks gestation.
With some refinement, additional conditions such as
tetralogy of Fallot, large VSD, transposition of great vessels
and persistent truncus arteriosus can be detected. Once a
serious CHD is identified, it is vital to counsel the families
about postnatal manifestations, natural history, surgical Inferior vena cava Coronary sinus orifice
options and their long-term outlook. Before 20 weeks of Fig. 16.7: Right-sided cardiac chambers showing the three
gestation, medical termination of pregnancy is an option. commonest 1ypes of atrial septa! defects (ASD]
410 I Essential Pediatrics
-
I :1
Coronary sinus ASD: An unroofed coronary sinus is a rare :1 �I '-
communication between the coronary sinus and the left I 1"' ;'\ ti
""
atrium, which produces features similar to other types of
ASD.
<
Physiology and Findings
The physiology of ASD is that of a pretricuspid shunt.
The enlarged right ventricle results in a parasternal ,., ,. '
"
r/ V
impulse. The ejection systolic murmur originates from the ·•
pulmonary valve because of the increased blood flow. An
increased flow through the tricuspid valve may result in
a soft delayed diastolic rumble at the lower left sternal
V
border. The overload of the right ventricle due to an
increase in venous return prolongs the time required for
EF
·-
its emptying resulting in delayed P2. This delay also
results from the prolonged 'hang-out' interval because of ,, " - ,-, "\ [ \
'""':::
·�
b
� :1
very low resistance in the pulmonary circulation.
Additionally, since the two atria are linked via the large <
ASD, inspiration does not produce any net pressure
change between them, and respiration-related fluctuations
in systemic venous return to the right side of the heart are Fig. 16.9: Electrocardiogram of atrial septal defect of the
secundum type showing rSR' pattern in lead Vl
abolished; thereby the fixed S2 (Fig. 16.8).
The electrocardiogram of ostium secundum ASD is
characterized by right axis deviation and right ventricular
hypertrophy. The characteristic configuration of the lead
Vl is rsR' seen in almost 90% patients (Fig. 16.9). Presence
of left axis deviation beyond -30 ° suggests ostium primum
ASD (Fig. 16.10). The chest X-ray (Fig. 16.11) shows mild
to moderate cardiomegaly, right atrial and right
••: : • :::: ·::: ::" :::: :... •• :::: :::: ::: :::: :o:+: �- ''.:: ::· ·::: :·: ·::: ::,; ,;;::-*: �
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:1:· : :� :�: 1: : :· :·1: :•. !1! : :
Sounds
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�· t.: "ii"'"� .. :Joi- u::: ' ;r, ... '• · �.... · · .:Al ... " K:: ••• ••• •• · •• ..... .
'"
\l 11� t])J! : �\! :!1 !f ]ii l! hli !:: i\i1 Ii\ '.;i l!i i)t1 i) ji��
.... .... , •11
1
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RV LV ''" ""'
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to.,,,,.,
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1111
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1
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Murmurs
Shunt murmur: Absent PA Ao :::
Phono
I.,_..ESM DOM
ilt
1r 11: ii :�I; rn, rn ('. hi .:., 1( �: l( :ti . �ui ;, �17; fg:� -�g --1-,
ng (1":l -.�: -ff;'.
·. :· .::.:=• :. • .•:·,:: · :.: : :·: : :: �.·: : :: :.·:: : ::7 :: : ;: : : :: ::: ::::: ::.
--f,-tlJI-J-��;t,:-�..:.:.t,:.:..+-.VI
••• "' "' ""I 11 ' , • ., '"
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t•�111
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"' '"''''II Ill I••• II• '" "''" "" •II• I I Ill "" to.,,,"" OIll · UI It
'"" "' +•oo l• """' """' " lltt I Ill ,., ""'" "" •• tll ol"
ECG
ventricular enlargement, prominent main pulmonary Fig. 16.12: Echocardiogram of ASD. Subxiphoid short axis view
artery segment, a relatively small aortic shadow and of the atrial septum shows deficient posterior-inferior rim (arrow).
plethoric lung fields. The left atrium does not enlarge in LA left atrium; RA right atrium; SVC superior vena cava
size in atrial septal defect, unless associated with other
anomalies like mitral regurgitation. Echocardiogram
shows increased size of the right ventricle with paradoxical Ventricular Septal Defect (VSD)
ventricular septal motion. 2D echo in subcostal view often This is the most common congenital cardiac lesion
best identifies the defect. The echocardiogram allows identified at birth accounting for one-quarter of all CHD.
decision regarding suitability of catheter closure, based VSD is a communication between the two ventricles; 90%
on measurements of the defect and the adequacy of are located in the membranous part of the ventricular
margins (Fig. 16.12). septum with variable extension into the muscular septum.
Others are located in the muscular septum and can be
Assessment of the Severity multiple (Fig. 16.13).
The size of the left-to-right shunt is directly proportional Hemodynamics
to the intensity of the murmurs and heart size. The larger
the shunt, the more the cardiomegaly and the louder the VSD results in shunting of oxygenated blood from the left
pulmonary and tricuspid murmurs. to the right ventricle. The left ventricle starts contracting
before the right ventricle. The flow of blood from the left
Natural History and Complications to-right ventricle starts early in systole. When the defect
is restrictive, a high pressure gradient is maintained
Heart failure is exceptional in infancy. A small proportion between the two ventricles throughout the systole. The
of patients might develop pulmonary hypertension by the murmur starts early, masking the first sound and
second or third decade. Closure of ASD is recommended continues throughout the systole with almost the same
to prevent complications of atrial arrhythmias and heart intensity appearing as a pansystolic murmur on
failure in late adulthood. auscultation and palpable as a thrill. Toward the end of
systole, the declining left ventricular pressure becomes
Treatment lower than the aortic pressure. This results in closure of
Most fossa ovalis defects with good margins can be closed the aortic valve and occurrence of A2. At this time,
percutaneously in the catheterization laboratory with however, the left ventricular pressure is still higher than
occlusive devices. Others require surgical closure. Closure the right ventricular pressure and the left-to-right shunt
is recommended before school entry to prevent late continues. The pansystolic murmur, therefore, ends
complications. Small defects ( <8 mm) can be observed. beyond A2 completely masking it (Fig. 16.14).
Spontaneous closure is well recognized in small defects The left-to-right ventricular shunt occurs during systole
that are diagnosed in infancy or early childhood. at a time when the right ventricle is also contracting and
412 Essential Pediatrics
r
VSDs can occur anywhere in the muscular part of septum
varies with respiration in patients with VSD and a large
left-to-right shunt. There is also an increase in the intensity
of the P2.
Ventricular Septal Defect
i '-----��Jl � Clinical Features
Sounds Patients with VSD can become symptomatic around 6 to
S1 : Masked by murmur 10 weeks of age with congestive cardiac failure. Premature
S2 : Masked by murmur at LLSB; --+ RA LA babies with a VSD can become symptomatic even earlier.
J\ tJi
at second LIS widely split
but mobile Palpitation, dyspnea on exertion and frequent chest
S3 : With small L-,R shunts infection are the main symptoms in older children. The
precordium is hyperkinetic with a systolic thrill at the left
RV sternal border. The heart size is moderately enlarged with
Murmurs
Shunt murmur : Pansystolic
Jil;GH
PA Ao
a left ventricular type of apex. The first and the second
sounds are masked by a pansystolic murmur at the left
sternal border. The second sound can, however, be made
Flow murmurs : (a) Pulmonary: Ejection systolic (drowned} out at the second left interspace or higher. It is widely
(b) Mitral delayed diastolic
split and variable with accentuated P2. A third sound may
be audible at the apex. A loud pansystolic murmur is
S1 A2 P2 ESM
PHONO present at the left sternal border. The maximum intensity
11
....,.; ..
2 LIS
,,..,,4,.,11 • 91@';n
�llfllM'' i of the murmur may be in the third, fourth or the fifth left
interspace. It is well heard at the second left interspace
,.
PSM
DOM but not conducted beyond the apex. A delayed diastolic
.. ,lift'� murmur, starting with the third sound is audible at the
LLSB
apex (Fig. 16.16).
The electrocardiogram in VSD is variable. Initially, all
patients with VSD have right ventricular hypertrophy.
Because of the delay in the fall of pulmonary vascular
resistance due to the presence of VSD, the regression of
Fig. 16.14: Summary of auscultatory findings in ventricular septal pulmonary arterial hypertension is delayed and right
defect. 2 LIS second left interspace; LLSB lower left sternal border; ventricular hypertrophy regresses more slowly. In small
PSM pansystolic murmur; DDM delayed diastolic murmur; ESM or medium-sized VSD, the electrocardiogram becomes
ejection systolic murmur.
normal. In patients with VSD and a large left-to-right
shunt, without pulmonary arterial hypertension, the
its volume is decreasing. The left-to-right shunt, therefore, electrocardiogram shows left ventricular hypertrophy by
streams to the pulmonary artery more or less directly. This the time they are 6-12 months old. There are, however,
flow of blood across the normal pulmonary valve results no ST and T changes suggestive of left ventricular strain
in an ejection systolic murmur at the pulmonary valve. pattern. Patients of VSD who have either pulmonic
Disorders of Cardiovascular System 1413-
Assessment of Severity
If the VSD is small, the left-to-right shunt murmur
continues to be pansystolic but since the shunt is small,
the second sound is normally split and the intensity of P2
is normal. There is also absence of the delayed diastolic
mitral murmur. If the VSD is very small, it acts as a stenotic
area resulting in an ejection systolic murmur. This is a
relatively common cause of systolic murmurs in young
infants that disappear because of the spontaneous closure.
If the VSD is large, it results in transmission of left
ventricular systolic pressure to the right ventricle. The
right ventricular pressure increases and the difference in
the systolic pressure between the two ventricles reduces.
Fig. 16.15: Chest X-ray in ventricular septal defect. Note the The systolic left-to-right shunt murmur becomes shorter
cardiac enlargement mainly involving the left ventricle together and softer, and on the bedside is heard as an ejection
with increased lung vasculature as suggested by the size and systolic murmur.
increased number of end-on vessels in the lung fields Patients of VSD may have either hyperkinetic or
obstructive pulmonary arterial hypertension. The P2 is
stenosis or pulmonary arterial hypertension may show accentuated in both. In the former, there is large left-to
right as well as left ventricular hyp ertrophy or pure right right shunt whereas the latter is associated with a small
ventricular hypertrophy. The mean QRS axis in the frontal left-to-right shunt. In hyperkinetic pulmonary arterial
plane generally lies between +30 ° and +90 °. hyp ertension, the cardiac impulse is hyperkinetic with a
The cardiac silhouette on chest X-ray is left ventricular pansystolic murmur and thrill, wide and variably split S2
type with the heart size determined by the size of the left with accentuated P2 and a mitral delayed diastolic
to-right shunt (Fig. 16.15). The pulmonary vasculature is murmur. Obstructive pulmonary arterial hypertension is
increased; aorta appears normal or smaller than normal associated with a forcible parastemal impulse, the thrill
in size. There may be left atrial enlargement in patients is absent or faint, the systolic murmur is ejection type, the
with large left-to-right shunts. Patients of VSD with a small S2 is spilt in inspiration (closely split) with accentuated
shunt either because the ventricular defect is small or P2 and there is no mitral murmur. Thus, on the basis of
because of the associated pulmonic stenosis or pulmonary the assessment of physical findings, it is possible to
arterial hypertension have a normal-sized heart. Echo- separate very small, small, medium-sized and large VSD.
Fig. 16.16: Echocardiogram (right frame) with anatomic correlates (left) in membranous ventricular septal defects. This view is a
parasternal short axis view. Arrow points to the VSD that is partly closed by aneurysm of septal leaflet of the tricuspid valve. Ao aortic
root; LA left atrium; LVOT left ventricular outflow tract; RA right atrium, RV right ventricle; LAA left atrial appendage; STL septal
tricuspid leaflet; PA pulmonary artery
414 I Essential Pediatrics
It is also possible to decide whether there is associated (pulmonary flow more than twice the systemic flow); and
pulmonic stenosis or pulmonary arterial hypertension of (iii) if there is associated pulmonic stenosis, pulmonary
the hyperkinetic or obstructive variety. arterial hypertension or aortic regurgitation. Surgical
Echocardiography allows further refinement of clinical treatment is not indicated in patients with a small VSD
evaluation. Left atrial and left ventricular enlargement is (exception subpulmonic VSD with aortic valve prolapse)
consistent with a large shunt. The size of the defect can be and in those who have severe pulmonary arterial
measured; Doppler echo estimates the gradient between hypertension and significant right-to-left shunt.
the left and right ventricles, helping in the assessment of Operative treatment consists of closure of VSD with the
right ventricular and pulmonary artery pressure. Flow use of a patch. The operation is performed through the
direction across the defect is indicative of the pulmonary right atrium. The operation can be done as early as a few
vascular resistance. A predominantly left to right flow is months after birth, if congestive failure cannot be
often indicative of operable status. controlled with medical management. With evidence of
Course and Complications pulmonary hypertension, the operation should be performed
as early as possible. Modern centers prefer to close VSD
Patients with VSD have a very variable course. A patient surgically in young infants. It is unwise to make the sick
with a small VSD usually remian asymptomatic infants to wait for a certain weight threshold because most
throughout life. They may develop congestive cardiac infants with large VSD do not gain weight satisfactorily.
failure in infancy, which is potentially life-threatening. It Episodes of respiratory infections require hospitalization
is estimated that almost 70% of all ventricular defects and are particularly difficult to manage. For sick infants
become smaller in size. A smaller proportion will with pneumonia who require mechanical ventilation,
disappear entirely. In almost 90% of patients who have surgery is considered after initial control of the infection.
spontaneous closure of the defect, it occurs by the age of Major complications of surgery, including complete heart
three years, though it may occur as late as 25 years or more. block or bifascicular block and residual VSD are rare.
Muscular VSD have the highest likelihood of spontaneous Catheter closure of VSD is best suited for muscular
closure. Perimembranous VSD close with the help of the defects in relatively older children (>8-10 kg). Peri
septal leaflet of the tricuspid valve and subpulmonic VSDs membranous defects can also be closed in the
often become smaller as the aortic valve prolapses through catheterization laboratory. However, the risk of complete
it. However, this is not a desirable consequence and is heart block with the membranous VSD closure is real and
often an indication for surgical closure. can occur late after implantation.
Patients with an uncomplicated VSD may: (i) pulmonic
stenosis due to hypertrophy of the right ventricular Patent Ductus Arteriosus
infundibulum, (ii) pulmonary arterial hypertension or
rarely, (iii) aortic regurgitation due to prolapse of the right Patent ductus arteriosus (PDA) is a communication
coronary or the non-coronary cusp of the aortic valve. between the pulmonary artery and the aorta. The aortic
Development of pulmonary arterial hypertension is a attachment of the ductus arteriosus is just distal to the left
dreaded complication in obstructive type of pulmonary subclavian artery. The ductus arteriosus closes functionally
arterial hypertension, the patient becomes inoperable. and anatomically soon after birth; its persistence is called
PDA.
VSD is the commonest congenital lesion complicated
by infective endocarditis. The incidence of infective Hemodynamics and Clinical Features
endocarditis has been estimated as 2/100 patients in a
follow-up of 10 years, that is 1/500 patient years. The PDA results in a left-to-right shunt from the aorta to the
incidence of infective endocarditis is small enough that it pulmonary artery. The flow occurs both during systole
is not an indication for operation in small defects. and diastole as a pressure gradient is present throughout
However, it is important to emphasize good oral-dental the cardiac cycle between the two great arteries, if the
hygiene in all patients with VSD. pulmonary artery pressure is normal. The flow of blood
results in a murmur that starts in systole, after the first
Treatment sound, and reaches a peak at the second sound. The
Medical management consists of control of congestive murmur then diminishes in intensity and is audible during
cardiac failure, treatment of chest infections and only a part of the diastole. Thus, it is a continuous murmur.
prevention and treatment of anemia and infective PDA results in a systolic as well as diastolic overloading
endocarditis. The patients should be followed carefully of the pulmonary artery. The increased flow after passing
to assess the development of pulmonic stenosis, through the lungs reaches the left atrium. To accommodate
pulmonary arterial hypertension or aortic regurgitation. the flow, the left atrium enlarges in size. The increased
volume of blood reaching the left atrium enters the left
Surgical treatment is indicated if: (i) congestive cardiac ventricle in diastole, across a normal mitral valve. The
failure occurs in infancy; (ii) the left-to-right shunt is large passage of this increased flow across the mitral valve
Disorders of Cardiovascular System 1415-
Hemodynamics
Physiologically, the pulmonic stenosis causes concentric
right ventricular hypertrophy without cardiac enlargement
and an increase in right ventricular pressure (Fig. 16.21).
When the right ventricular pressure is as high as the left
ventricular or the aortic pressure, a right-to-left shunt
appears to decompress the right ventricle. Once the right
and left ventricular pressures have become identical,
increasing severity of pulmonic stenosis reduces the flow
of blood into the pulmonary artery and increases the right
to-left shunt. As the systolic pressures between the two
ventricles are identical, there is little or no left-to-right
shunt and the VSO is silent. The right-to-left shunt is also
Fig. 16.20: Angiograms (aortogram) obtained before and after silent since it occurs at insignificant difference in pressure
coil occlusion of a moderately large patent ductus arteriosus between the right ventricle and the aorta. The flow from
(PDA) showing complete occlusion the right ventricle into the pulmonary artery occurs across
the pulmonic stenosis producing an ejection systolic
CYANOTIC HEART DISEASE murmur. The more severe the pulmonic stenosis, the less
the flow into the pulmonary artery and the bigger the
Tetralogy of Fallot right-to-left shunt. Thus, the severity of cyanosis is directly
Among cyanotic CHO, tetralogy of Fallot (TOF) has a proportional to the severity of pulmonic stenosis, but the
relatively favorable natural history that allows survival intensity of the systolic murmur is inversely related to the
beyond infancy in about 75% of cases. As a result, it is the severity of pulmonic stenosis.
most common cyanotic CHO encountered beyond the age The VSO of TOF is always large enough to allow free
of 1 year, constituting almost 75% of all patients. The exit to the right-to-left shunt. Since the right ventricle is
physiology is that of VSO with pulmonic stenosis, as effectively decompressed by VSO, congestive failure
described above. Anatomically, it is characterized by the seldom occurs. Exceptions to this rule are (i) anemia;
classic tetrad of severe right ventricle outflow obstruction, (ii) infective endocarditis; (iii) systemic hypertension;
large VSO, aorta that overrides the VSO and right (iv) right ventricular dysfunction from long-standing
ventricular hyp ertrophy. Multiple anatomical variations severe hypoxia, and (v) aortic or tricuspid valve
exist, which influence treatment (Table 16.15). regurgitation.
Ao PA Ao PA
Fig. 16.21: Diagrammatic portrayal: (a) Ventricular septal defect, (b) ventricular septal defect with moderate pulmonic stenosis,
and (c) Fallot's tetralogy. (a) In the absence of pulmonic stenosis, the rtght ventricular (RV) and the pulmonary artery (PA) pressures
are normal or slightly elevated. Since the left ventricular (LV) pressure is higher, there is a systolic flow of blood from the LV into the
PA through the RV. (b) If a VSD is associated with moderate pulmonic stenosis, the RV systolic pressure increases and there is RV
hypertrophy. The left-to-right shunt decreases and the VSD murmur becomes softer. The pulmonic stenosis murmur, however, is
loud. (c). In Fallot's tetralogy, the RV and LV pressures are identical. There is no left-to-right shunt and as such the VSD is silent. The
flow from RV to PA decreases, decreasing the intensity of pulmonic stenosis murmur. A right-to-left shunt occurs from RV to aorta
(Ao) at identical pressures. As such the right-to-left shunt is silent
The right ventricular outflow obstruction results in a Physical examination discloses cyanosis, clubbing,
delay in the P2. Since the pulmonary artery pressure is slightly prominent 'a' waves in the jugular venous pulse,
reduced, the P2 is also reduced in intensity. The late and normal-sized heart with a mild parastemal impulse, normal
soft P2 is generally inaudible in TOP. The S2 is, therefore, first sound, single second sound and an ejection systolic
single and the audible sound is A2. Since the aorta is murmur which ends before the audible single second sound
somewhat anteriorly displaced, the audible single A2 is (Fig. 16.22). The electrocardiogram in TOF shows right axis
quite loud. The ascending aorta in TOP is large and may deviation with right ventricular hypertrophy. T waves are
result in an aortic ejection click. On auscultation, the usually inverted in right precordial leads; P pulmonale may
diastolic interval is completely clear in TOP as there is no be present, but is uncommon. Vl may show pure R waves
third or fourth sound or a diastolic murmur. Concentric but transition to R/S complex occurs at V2. Chest X-ray
shows a normal-sized heart with upturned apex suggestive
right ventricular hypertrophy reduces distensibility of the
of right ventricular hypertrophy. The absence of main
right ventricle during diastole. The right atrial contraction
pulmonary artery segment gives it the shape described as
at the end of diastole causes relatively large 'a' waves.
However, these waves not too tall unless right ventricular
Tetralogy of Fallot
dysfunction is present.
�!+!
-
Sounds
S1: Normal j RA LA
Clinical Features
H t
S2: Single-only A2 heard
Patients with TOP may become symptomatic at any time P2 soft and delayed: Inaudible
X: Usually constant; inconstant
��\,
after birth. Neonates as well as infants may develop anoxic if valvar PS
spells (paroxysmal attacks of dyspnea). Cyanosis may be
present from birth or make its appearance some years after Murmurs
birth. The commonest symptoms are dyspnea on exertion Shunt murmur: Absent
and exercise intolerance. The patients assume a sitting Flow murmurs: Pulmonary: Ejection systolic
The smaller the flow the
posture (squatting) as soon as they get dyspneic. Although shorter the murmur
squatting is not specific for TOP, it is the commonest S1 A2 ESM
congenital lesion in which squatting is noted. Anoxic spells
occur predominantly after waking up or following
exertion. The child starts crying, becomes dyspneic, bluer
than before and may lose consciousness. Convulsions may
occur. The frequency varies from once in a few days to Fig. 16.22: Summary of auscultatory findings in tetralogy of
numerous attacks every day. Fallot. X systolic click. PS pulmonic stenosis
Disorders of Cardiovascular System 1419-
Treatment
The medical management of TOF is limited to prevention
and management of complications and correction of
anemia. Oral beta-blockers help prevent cyanotic spells.
Maximally tolerated doses of propranolol ranging from
Fig. 16.23: Chest X-ray in tetralogy of Fallot with right aortic 0.5-1.5 mg/kg/dose should be administered. Iron
arch. The key findings are reduced lung vasculature as supplementation is recommended for all infants and
suggested by the dark lung fields, normal heart size, concavity young children with TOF. The management of anoxic
in the region of the main pulmonary artery (pulmonary bay). spells is indicated in Table 16.13.
This X-ray also shows a right aortic arch. The arrow indicates the Definitive surgery for TOF involves closure of VSD and
indentation of the right arch on the right side of the trachea
relief of the right ventricular outflow tract obstruction.
Coeur en Sabot. The aorta is enlarged and right aortic arch is The relief of the obstruction might involve placement of a
present in 30% cases. The right aortic arch in a postero transannular patch across the pulmonary valve resulting
anterior roentgenogram is recognized by its concave in severe pulmonary regurgitation. There is growing
impression on the right side of trachea. The pulmonary emphasis on retaining the pulmonary valve during initial
fields are oligemic (Fig. 16.23). repair to prevent pulmonary regurgitation and its major
late consequences (RV dilation, arrhythmia, heart failure
The murmur shortens and the cyanosis increases with
increasing severity of the right ventricular outflow tract and sudden death). However, this is not possible, if the
pulmonary annulus is small.
obstruction. Paroxysmal attacks of dyspnea can be present
with mild as well as severe TOF. However, effort Although definitive operation is feasible in young
intolerance is directly related to the severity. infants, some centers opt for palliative options initially.
This is typically done through the Blalock-Taussig shunt,
Diagnosis which consists of subclavian artery-pulmonary artery
The diagnosis of TOF is confirmed by echocardiography; anastomosis using a Goretex graft. Alternatives include
cardiac catheterization is seldom necessary. Additional balloon dilation of the pulmonary valve or stenting of
specific information required for surgical decision is also the patent arterial duct (if present). A number of long
obtained through echocardiography. Cardiac catheteriza term concerns have emerged in survivors of TOF repair
tion or CT/MRI may be required in older children with 2-3 decades after the operation. These include heart
limited echo windows and in selected specific failure and risk of ventricular tachyarrhythmias as a
circumstances (associated aortopulmonary collaterals, result of right ventricular dilation that results from
uncertainties in coronary artery anatomy). chronic pulmonary regurgitation, as well as the scar on
the right ventricle, if ventriculotomy has been done
Course and Complications during operation.
The pulmonic stenosis becomes progressively severe with
age, and dyspnea and increasing exercise intolerance limit Tricuspid Atresia
patient activities. Each attack of anoxic spell is potentially Congenital absence of the tricuspid valve is called
fatal. Anemia, by decreasing the oxygen-carrying capacity tricuspid atresia (Fig. 16.24). The right ventricle is
of blood, reduces the exercise tolerance still further. It can hypoplastic. The inflow portion is absent. The hemo
result in cardiac enlargement and congestive cardiac d ynamics is described above; see single ventricle
failure. Patients are prone to infective endocarditis. physiology.
-420 Essential Pediatrics
Fig. 16.24: Tricuspid atresia: (a) Normally related great arteries. Systemic venous blood reaching the RA through the superior (SVC)
and inferior vena cava (IVC) reaches the LA through an atrial defect (or patent foramen ovale). There is complete mixing of the
systemic and pulmonary venous blood in the LA. The LV is large. Aorta (Ao) arises from the LV. A muscular ventricular septal defect
is the only route through which blood can reach the hypoplastic right ventricle (RV Inf.). The pulmonary trunk (PT) arises from the right
ventricle. (b) Transposed great arteries with tricuspid atresia. The PT is arising from the LV whereas the Ao is arising from RV. LA left
artium; RA right artium; RPA and LPA right and left pulmonary artery; RV Inf. right ventricular infundibulum; RV and LV right and left
ventricle; SVC and IVC superior and inferior vena cava; RPV and LPV right and left pulmonary veins
..
II Ill aVR aVL aVF anomaly. Note the downward displacement of the septa I leaflet
ii f.,;
.. "'
F j:: ",.1,. '
.;. w .. .."'
-j
H•
,
..,
I �··· ::::r:
' i-·
of the tricuspid valve. aRV atrialized right ventricle; LA left atrium;
"' i 11 :; LV left ventricle; RA right atrium; RV right ventricle
fj,l···· '*1' 'l! tt
L µ· .• µ!' f:' . f',' ... c;;.
.. - � ,,
!;!- )ir: ,I+
r .,,,
.
·�: '
,..., "'" +•
: /' .J,11,..
\J n:: ::: VJ ,(" 1::
.. ., this is also referred to as D-TGA. Since the systemic and
/"_
... ,., :::•:: ... :•:: I::• ;',
,:
::: ,: fr ;,:tt;:: ::· :: :' :':
1::,: t:::: :: i::: ;
...
IHI 1::: ,:,. :: .. b
,
pulmonary circulations are separate, survival depends on
the presence of atrial, ventricular or aortopulmonary
.::: •·· ·�t ll communications. TGA is classified into (i) with intact
t:.. '"
jt;. " ·"···· :,,: .. :: :· A:: .. J IV' :::• :: ;: ;:: : ventricular septum, and (ii) with VSD. The latter group is
�s ,..
: 'j "' ii' •+
"'"'t*'tr:"''
·A
._.
Transposition
(T Y) cn
RV ._. LV g'
RA
I
I I
LV
AO ._. PA
:J
-' I
PA AO
\ Br. Coll
)
Complete Corrected
1S11
S3: RV inASD RV '- LV
Echocardiography is necessary to arrive at the specific S4: RA inASD PA Ao
diagnosis. Since the mortality of unoperated patients is
high and patients develop Eisenmenger syndrome early Murmurs 'IPDA'
. . L-oitterentia1
Pulmonary regurg1tat1on (Graham-Steell)
in life, it is necessary that patients presenting with cyanosis
Ejection systolic± cyanosi s
and increased pulmonary blood flow be referred to S1 X S2 ESM
specialized centers as early as possible. PHON0
11...., � 11 ....
Cyanotic Heart Disease with Early OM
Pulmonary Arterial Hypertension
Patients with Eisenmenger syndrome have severe
pulmonary arterial hypertension resulting in right-to-left Fig. 16.33: Summary of auscultatory findings in Eisenmenger
shunt at the atrial, ventricular or pulmonary arterial level. syndrome
Eisenmenger complex consists of pulmonary arterial
hypertension with a VSD providing the right-to-left shunt. pulmonary component of the second sound is accentuated
and louder than the aortic component. The splitting of
Hemodynamics the second sound remains wide and fixed in atrial septal
The pulmonary arterial hyp ertension is due to pulmonary defect. Due to superimposition of A2 and P2, the second
vascular obstructive disease. If a communication is present sound is single in patients who have a VSD. Patients who
at the pulmonary arterial level or the ventricular level, have a PDA continue to have a normally split second
the right ventricular pressure cannot go beyond the sound. A constant pulmonary ejection click, unlike in
systemic pressure. The right-to-left shunt decompresses patients of valvar pulmonic stenosis, is well heard both
the right ventricle. The right ventricle has only concentric during inspiration and expiration at the second left
hyp ertrophy without significant increase in the size. In interspace. A functional pulmonary regurgitation murmur
patients who have a PDA or VSD, there is only a mild can be present along the left sternal border. Patients with
parastemal impulse without significant heave. In patients atrial septal defect, in whom Eisenmenger physiology is
who do not have a VSD or PDA, the right ventricle besides uncommon, can develop tricuspid regurgitation (Fig. 16.33).
hypertrophy also dilates. The right-to-left shunt at the Electrocardiogram reveals right axis deviation and right
atrial level is an indication of right ventricular failure to ventricular hypertrophy, P pulmonale may be present. The
accommodate this volume and push into the pulmonary chest radiograph is characteristic, showing prominent
artery. Patients of Eisenmenger syndrome with pulmonary artery segment, large right and left main
communication at the atrial level only exhibit a parastemal pulmonary arteries and their branches, and oligemic
heave and cardiac enlargement. peripheral lung fields (Fig. 16.34).
A right-to-left shunt at the atrial level or the ventricular
level reaches the ascending aorta and is thus distributed Treatment
to the whole systemic circulation. This results in equal Ideally, pulmonary vascular obstructive disease should
cyanosis of fingers and toes. A right-to-left shunt through be prevented. This means early diagnosis and correction
a PDA is directed downwards into the descending aorta, of all CHD associated with increased pulmonary blood
which results in differential cyanosis affecting lower limbs, flow. Patients with cyanosis and increased pulmonary
with pink upper limbs. blood flow develop Eisenmenger physiology very early
and need to be operated by 2-3 months of age. Medications
Clinical Features are available for the management of pulmonary hyp er
Patients present with history of cyanosis, fatigue, effort tension.
intolerance and dyspnea. There may also be history of
repeated chest infections in childhood. On physical OBSTRUCTIVE LESIONS
examination, they have cyanosis and clubbing. Differential
cyanosis separates patients who have a PDA from those Aortic Stenosis
who have a VSD or atrial septal defect. The features Pathologically, the site of obstruction may be at valve level,
indicative of pulmonary arterial hypertension consist of above the valve (supravalvar) or below the valve
parasternal impulse and palpable second sound. The (subvalvar). At the valve level, aortic stenosis (AS) results
42s I Essential Pediatrics
Clinical Features
Patients with mild to moderate AS are asymptomatic. With
severe stenosis, the initial symptom is generally dyspnea
Fig. 16.34: Chest X-ray in Eisenmenger syndrome following on exertion. The patients may also give history of angina
ventricular septal defect. The proximal right pulmonary artery is on effort and syncope. Presence of any one of these three
enlarged. There is a relative paucity of vasculature in the symptoms suggests severe AS. The blood pressure is
periphery with a sudden tapering of caliber of the right normal with mild disease; the width of pulse pressure
pulmonary artery (pruning) relates inversely with severity of AS resulting in low
amplitude prolonged duration pulse. Cardiac size remains
from either unicuspid or a bicuspid aortic valve. Rarely the normal unless left ventricular failure is present. The apical
aortic valve annulus may itself be small. Supravalvar aortic impulse is forcible or heaving. In severe AS, the fourth
stenosis results from obstruction in root of aorta, above the sound may be palpable. If left ventricular failure is present,
aortic valve, as in Williams syndrome. Subvalvar aortic the S3 may be palpable. A systolic thrill is palpable at the
stenosis may be discrete (membranous), fibromuscular or second right interspace, suprastemal notch and the carotid
muscular (hypertrophic obstructive cardiomyopathy). arteries. Sl is normal and followed by an ejection click in
valvar aortic stenosis. The aortic component of the second
Hemodynamics sound (A2) is delayed but not diminished in intensity in
Valvar obstruction is overcome by raising the systolic AS. The delay results in closely split, single or paradoxically
pressure of the left ventricle. This is brought about by split second sound according to the severity of obstruction.
concentric hypertrophy of the left ventricle. Because of a With severe AS, S4 is audible, while in patients with left
powerful, muscular left ventricle, the emptying of the left ventricular failure, S3 is palpable and audible. The ejection
ventricle is complete but the duration of the systole is systolic murmur starting after the ejection click reaches a
prolonged. The prolongation of left ventricular ejection peak in mid-systole (Fig. 16.35}. With increasing severity,
time causes delayed closure of the aortic valve resulting the peak gets delayed so that the maximum intensity of the
in delayed A2. Flow across the obstruction results in the murmur is closer to the end rather than being midsystolic.
aortic ejection systolic murmur that is typically diamond With immobile valves, due to fibrosis or calcification, the
shaped, starting after the first sound and ending before systolic click as well as A2 diminish in intensity and may
the aortic component of the second sound with a mid become inaudible (Fig. 16.36}.
systolic peak. The systolic murmur is always palpable as Subvalvar AS is distinguished by absence of ejection
a thrill at the second right interspace, suprasternal notch click and post-stenotic dilatation of the ascending aorta
and the carotid vessels. The powerful left ventricle can on X-ray. An aortic regurgitation murmur may be audible.
maintain a normal forward cardiac output. The prolonged The maximum intensity of the systolic murmur and thrill
ejection results in a characteristic pulse that is best is in the 3rd or 4th left interspace. Supravalvar AS
described as slowly rising to a peak that is sustained and (Williams syndrome) is associated with elfin fades, mental
then has a slow down slope. The peak is low so that the retardation, dental abnormalities, strabismus and
pulse is of low amplitude and prolonged duration. peripheral pulmonic stenosis. Since the obstruction is
Concentric hypertrophy of the left ventricle results in above the aortic valve, the pressure in the segment of aorta
decreased distensibility of the left ventricle in diastole before the obstruction is elevated and results in loud A2.
reduced compliance. In severe AS with marked left The jet through the supravalvar narrowing may be
Disorders of Cardiovascular System 1427-
r� J\ LV
Aortic Stenosis
-
Sounds
S1-Normal LA
S2-A2 Delayed
P2 Normal
Normal splitting single �II /!
Paradoxical splitting
S3: With LV failure
S4: Severe stenosis
PA
LV
--- ''
Murmurs
Ejection systolic (Diamond shaped)
.,
(INSP) S1X ESM A2P2
Mild
1, etJ II
111 ... 11
------S+l1-+�--•-..+A-2__ -_-_-_-_-_-_
� ESM
Fig. 16.35: Summary of auscultatory findings In aortic stenosls.
S4 fourth sound; X aortic click Fig. 16.36: Aortic stenosis: Diagrammatic portrayal of the
hemodynamic basis for aortic stenosis murmur. The first sound
directed toward the innominate artery resulting in higher [S l ) occurs as the left ventricular [LV) pressure increases above
systolic pressure in the right arm compared to left. left atrial (LA) pressure. This is followed by the ejection click [X)
The electrocardiogram reveals left ventricular occurring after the aortic valve opens. The shape of the gradient
hyp ertrophy. Presence of ST and T wave changes suggest between LV and aorta [Ao) corresponds to the shape of the
severe disease (Fig. 16.37). However, a normal electro aortic ejection systolic murmur (ESM). The murmur ends before
cardiogram does not exclude severe AS. Chest X-ray the aortic components of the second sound [A2)
n n:,r,t..
t trr?
+f'IL 7c I/ 1 13 ii Wt
·-C
i=
I- �
-
•
l-
:tt m l+t l +! =1
-
•
.... ll HF
, I l"'
�. �
t�
��'
b I-
=1
j
.LL
��-
n-.i
++
f++
.:I,
:!ll- 6 :l3
�
3
=1
i:
L
: +t
::j a j
1 .I·
:
� � �
-
wgg
,-,'l :t l
!j ;:i
H
tl 3. l 3
H +;
Fig. 16.37: Electrocardiogram from a patient with severe aortic stenosis showing prominent left ventricular voltages together with
ST segment depression and T wave inversion in lateral leads (strain pattern)
42a I Essential Pediatrics
shows a normal-sized heart with dilated ascending aorta aorta; the medial wall is spared. It may be distal or
in valvar AS. In supravalvar and subvalvar stenoses, the proximal to the ductus or ligamentum arteriosus and also
thoracic roentgenogram may be normal. Presence of the left subclavian artery. A bicuspid aortic valve is a
cardiac enlargement indicates severe AS. Echocardiogram common association.
can identify the site of stenosis, and assess the gradient
across the obstruction accurately. Hemodynamics
In fetal life, the right ventricular output passes into the
Assessment of Severity descending aorta through the ductus arteriosus. The left
The severity of AS is determined, based on the following ventricular output empties into the innominate, left carotid
i. Symptomatic patients have severe AS; lack of and left subclavian arteries and little output reaches the
symptoms does not exclude severe disease. descending aorta. The portion of the aorta distal to the
ii. Narrower the pulse pressure, the more severe the AS. left subclavian and before the portion where the ductus
iii. Systolic thrill at second right interspace suggests at arteriosus joins is called the isthmus. At birth, the isthmus
least moderately severe AS. is the narrowest part of the aorta. Following closure of
iv. The later the peak of the ejection systolic murmur, the the ductus arteriosus, the descending aorta must receive
more severe the narrowing. its total supply from the left ventricle via the ascending
v. Delay in A2 correlates well with severity. With mild aorta. Neonates with severe coarctation, therefore, become
AS, the S2 is normally split; with moderate AS, it is symptomatic immediately as the duct starts to close.
closely split; with severe or critical AS, it is single or However, a significant proportion present late.
paradoxically split. The exact cause of systemic hypertension is not known;
aortic obstruction is partly responsible. The narrow pulse
vi. Presence of S4 is indirect evidence for severe AS.
pressure in the descending aorta distal to coarctation is
vii. Presence of S3 indicates severe AS and congestive
implicated in the renal mechanism for causation of
cardiac failure.
hypertension. The obstruction stimulates growth of
viii. ST and T changes in the electrocardiogram suggest collateral vessels between the proximal and distal
severe stenosis. segments. The intercostal vessels also participate in
ix. Cardiac enlargement on chest radiograph indicates decompressing the hypertensive upper segment. They
severe AS with left ventricular failure. enlarge and become palpable at the lower borders of the
x. Doppler can quantitate the gradient across the aortic ribs. Palpable collaterals are also felt at the medial and
valve accurately. Two-dimensional echo reveals inferior angle of scapula. Because of the decompression
concentric left ventricular hyp ertrophy; ventricular of upper segment by collaterals, the resting blood pressure
dysfunction is associated with heart failure. in upper extremities may be normal, but rises on exercise.
Treatment Clinical Features
Patients with AS should be followed closely, with 6-12 Coarctation has a continuum of severity and the age at
monthly electrocardiogram. Symptoms should be presentation is linked to severity. Newborns with severe
carefully evaluated. Doppler echo can be used to coarctation present as soon as the duct starts to close.
quantitate the gradient at each visit and ventricular Infants with coarctation present with left ventricular
function is monitored. Severe AS is risk for sudden death. dysfunction and heart failure. It is important to examine
Patients should be discouraged from outdoor games, femoral pulses in newborns and infants with heart failure.
athletics, competitive sports and strenuous exercises, if Later in life, coarctation is often not associated with
AS is significant (gradient of >50 mm Hg). symptoms.
Balloon aortic valvuloplasty is the procedure of choice The only symptoms in uncomplicated coarctation may
for valvar AS. A balloon introduced through the femoral be intermittent claudication, pain and weakness of legs
artery can be placed at the aortic valve and inflated to and dyspnea on running. Examination shows delayed and
tear the valve along the commissure. It is indicated, if the weak femorals and strong brachial arteries. The heart size
gradient is above 75 mm Hg. Supravalvar and subvalvar remains normal with a forcible or heaving left ventricular
AS do not respond to balloon dilation; the procedure apex. A systolic thrill may be palpable in the suprastemal
should also be avoided in patients with significant aortic notch. There are prominent arterial pulsations in the
regurgitation. Surgical options include aortic valve repair suprastemal notch and the carotid vessels. The first sound
and replacement with a prosthetic valve. is accentuated and sometimes followed by a constant
ejection click. The second sound is normally split with a
Coarctation of the Aorta loud aortic component. A variable intensity ejection
Coarctation of the aorta is located at the junction of the systolic murmur is heard with the point of maximum
arch with the descending aorta. It is a sharp indentation intensity over the back in the interscapular area. The
involving the anterior, lateral and posterior wall of the murmur starts late in systole after a considerable gap from
Disorders of Cardiovascular System 1429-
E S M 2 P2
Rheumatic heart disease (RHD) constitutes from 5 to 50%
(lnsa:. ) ___
pt.... 1x
s tt d
.. ••..A+ + _ _____:_M:..:.:i:.:
� 11.11 l __:__ of the cardiac patients in Indian hospitals.
(lnsp and Exp) 2 Age and sex: The incidence of rheumatic fever following
oderate
S
M
..
11 • • I streptococcal throat infection is 0.3% in the general
(Exp) S4 P2A2 evere population and 1 to 3% in presence of epidemics of
111 .... 11
S
streptococcal pharyngitis. The illness commonly affects
those between 5 and 15 years of age; first episodes are
rare before 3 years or after 30 years age. Although the sexes
Fig. 16.39: Summary of auscultatory findings in pulmonic stenosis are nearly equally affected, mitral valve disease and chorea
is more common in girls whereas aortic valve involvement
is often seen in boys.
regurgitation may appear. Since the right atrium offers
less resistance to flow of blood than obstruction at the Predisposing factors: Poor socioeconomic conditions,
pulmonary valve, the flow through the pulmonary valve unhygienic living conditions and overcrowding pre
diminishes reducing the intensity as well as the duration dispose to streptococcal infections.
of ejection systolic murmur.
Etiopathogenesis
The electrocardiogram shows right axis deviation and
right ventricular hypertrophy, suggested by pure R waves The etiology of rheumatic fever is unknown. A strong
or qR complex in V4R and Vl leads. P pulmonale suggests association with beta hemolytic streptococci of group A
is indicated by a number of observations:
severe PS. Chest X-ray shows a normal-sized heart with
normal pulmonary vasculature in mild, moderate as well i. History of preceding sore throat is available in 50%
as severe PS. Pulmonary oligemia occurs, if the patients patients; more than 85% show elevated levels of anti
streptococcal antibody titer.
develop a right-to-left shunt at the atrial level in severe or
critical PS. The main pulmonary artery exhibits post ii. Epidemics of streptococcal infection are followed by
stenotic dilatation. Echocardiography can identify the site higher incidence of rheumatic fever.
and severity of obstruction and helps in planning catheter iii. The seasonal variation of rheumatic fever and
intervention. streptococcal infection is identical.
iv. In patients with established RHD, streptococcal infec
Treatment tion is followed by recurrence of acute rheumatic fever.
v. Penicillin prophylaxis for streptococcal infection
Valvar PS generally does not increase in severity with
prevents recurrences of rheumatic fever in those
time unless it is severe or diagnosed in the newborn
patients who have had it earlier.
period. Patients with mild PS (gradient of 50 mm Hg or
less) need annual review. Balloon pulmonary Streptococci have never been isolated from rheumatic
valvuloplasty is the treatment of choice for isolated lesions in joints, heart or the bloodstream. Rheumatic fever
valvar PS. The procedure is sometimes technically appears to be the result of the host's unusual response at
challenging in newborn with critical PS. Surgical both the cellular and humoral level to Streptococcus
treatment is indicated only if balloon valvotomy is (Fig. 16.40). Following streptococcal sore throat, there is a
unsuccessful, as in patients with dysplastic valves or latent period of 10 days to several weeks before the onset
small pulmonary valve annulus. of rheumatic fever. Streptococcal cell wall proteins as well
as carbohydrates may induce production of antibodies that
Suggested Reading are capable of reacting with human connective tissue,
• Allen HD, Shaddy RE, Driscoll DJ, Feltes TF, Moss Adams' Heart
resulting in rheumatic fever.
disease in infants, children and adolescents, 8th Edition, Kluwer/ Only heart valves are permanently damaged during
Lippincott William and Wilkins, Philadelphia, USA, 2012. an episode of rheumatic fever. All other affected tissues
Disorders of Cardiovascular System 1431-
STAGE 1
� /\ h-
---+
Immune recogniti�nv v �
�;�
STAGE 2
Rheumatogenic
streptococci
A TNF-a, othern
STAGE 3
Antibody
�(;)
attachment
STAGE4
T cell recruitment
CD4 and CDS
infiltration
Fig. 16.40: Pathogenesis of rheumatic fever. It is proposed that the endothelium suffers initial damage due to a humoral immune
response, the damage resulting in vascular cell adhesion molecule l (VCAM-1) being expressed on the endothelium. This is followed by
activation of cellular immune response. As a resutt CD4+, CD8+ T lymphocytes and macrophages get attached to the valvar endothelium
and migrate to the connective tissue core. This sets up an inflammatory response. The inflammation is accompanied by neovascularization
of the valve substance. IFN-y Interferon gamma, TNF-a tumor necrosis factor alpha, Th l T helper cells l
Table 16.16: Revised Jones criteria for acute rheumatic fever (2015)
American Heart Association and World Heart Federation
For all populations
Initial episode of acute rheumatic fever: Two major or one major + two minor criteria
Recurrent episodes of acute rheumatic fever: Two major, one major + two minor, or three minor
Essential criteria: Previous evidence of group A beta hemolytic streptococcal infection
Low-Risk Populations Moderate, High-Risk Populations
Incidence <2/100,000 in school-going children;
rheumatic heart disease prevalence <1/1000
Major criteria Major criteria
Carditis: Clinical or subclinical Carditis: Clinical or subclinical
Arthritis: Polyarthritis only Arthritis: Polyarthritis, monoarthritis
Chorea Polyarthralgia
Erythema marginatum Chorea
Subcutaneous nodules Erythema marginatum
Subcutaneous nodules
Minor criteria Minor criteria
Polyarthralgia Monoarthralgia
Fever (>38.5° C) Fever (>38.0° C)
ESR �60 mm in the first hour; CRP �3.0 mg/dl ESR �30 mm in the first hour; CRP �3.0 mg/dl
Prolonged PR interval, after accounting for age variability Prolonged PR interval, after accounting for age variability
(unless carditis is a major criterion) (unless carditis is a major criterion)
Gewitz MH, et al. Revision of the Jones criteria for the diagnosis of acute rheumatic fever in the era of doppler echocardiography. Circulation
2015;131 :1806-18
This is a soft delayed diastolic mitral murmur heard movement. It is an early manifestation and occurs in
transiently during the course of acute rheumatic fever 70-75% of cases according to western literature. However,
possibly as a result of flow across the inflamed and the figures from India indicate that arthritis is seen in
thickened mitral valve. 30 to 50% of patients. The pain and swelling appear rather
Endocarditis is represented by a pansystolic murmur quickly, last 3 to 7 days and subside spontaneously to
of mitral regurgitation with or without an associated appear in some other joint. There is no residual damage
aortic regurgitation murmur. Pathologically mitral valve to the joint. Arthritis tends to be commoner in older
is involved in all cases of rheumatic fever with carditis. patients.
Clinically, however, 5-8% patients may present as pure
Subcutaneous nodules: Subcutaneous nodules appear on
aortic regurgitation. Thus almost 95% patients will have
bony prominences like elbows, shins, occiput and spine.
mitral regurgitation murmur, a quarter of them also have
They vary in size from pinhead to an almond. They are
an aortic regurgitation murmur and only 5% present as
non-tender. Subcutaneous nodules are a late manifestation
pure aortic regurgitation. Tricuspid valvulitis resulting
and appear around 6 weeks after the onset of rheumatic
in tricuspid regurgitation occurs in 10-30% of cases.
fever though they have been described as early as 3 weeks
Isolated tricuspid valvulitis as a manifestation of
from the onset. They occur in about 3 to 20% of cases of
rheumatic endocarditis does not occur. Clinical evidence
rheumatic fever in India. Patients who have subcutaneous
of pulmonary valve involvement in acute rheumatic fever
nodules almost always have carditis. They last from a few
is never seen. The acute hemodynamic overload resulting
days to weeks but have been known to last for almost a
from acute mitral regurgitation and/ or aortic
year.
regurgitation leads to left ventricular failure and is the
main reason for the morbidity and mortality of rheumatic Chorea: Sydenham's chorea is also a late manifestation
fever and RHO. occurring about three months after the onset of acute
rheumatic fever. Generally, by the time a patient manifests
Subclinical carditis: Carditis may occasionally be clinically
chorea, the signs of inflammation usually subside. Chorea
silent and only identified by echocardiography that shows
consists of semi-purposeful, jerky movements resulting
mitral regurgitation.
in deranged speech, muscular incoordination, awkward
Arthritis: Rheumatic arthritis is a polyarthritis involving gait and weakness. The affected child is emotionally
large joints that include knees, ankles and elbows. disturbed and drops things she or he is carrying. It is three
Uncommonly smaller joints may also be involved. It is a to four times more common in females as compared to
migratory polyarthritis with the affected joints showing males. Untreated, it has a self-limiting course of two to
redness, warmth, swelling, pain and limitation of six weeks.
Disorders of Cardiovascular System 1433-
Erythema marginatum: It is an early manifestation, cannot be equated with diagnosis, since this may happen
predominantly seen over the trunk. It starts as a red spot with asymptomatic carriers.
with a pale center, increasing in size to coalesce with
adjacent spots to form a serpiginous outline; the rash in Echocardiography: The recent revision of Jones criteria
non-itching. Recognition of skin manifestations may be now includes echocardiographic findings for the diagnosis
difficult in dark-skinned patients. of rheumatic carditis. Features suggestive of rheumatic
carditis include annular dilatation, elongation of the
Minor Criteria chordae to the anterior leaflet of the mitral valve causing
a prolapse and lack of coaptation of the two leaflets
Clinical criteria resulting in mitral regurgitation. There is focal nodular
Fever: Rheumatic fever is almost always associated with thickening of the tips of the mitral leaflets; they however
fever. The temperature rarely goes above 39.5° C. do not show the independent chaotic movement seen with
Arthralgia: Arthralgia is a subjective pain whereas arthritis infective endocarditis. Occasionally, the tip of the mitral
means subjective symptoms and objective signs of valve leaflet is flail because of chordal rupture resulting
inflammation. While arthritis is a major manifestation, in severe mitral regurgitation. The left atrial and
arthralgia is a minor manifestation. Figures from India ventricular size is increased. Involvement of aortic valve
indicate that arthritis and arthralgia together occur in is recognized as aortic regurgitation.
about 90% of the patients Echocardiography has improved recognition of carditis,
which at times is not possible on auscultation. This has
Previous rheumatic fever or rheumatic heart disease: This lead to the recognition of subclinical carditis, characterized
criterion applies only for recurrent episodes of rheumatic by no clinical but echocardiographic findings of mitral
fever. regurgitation. While the course of patients with subclinical
carditis is not clear, most patients are advised long-term
Laboratory manifestations
penicillin prophylaxis.
Acute phase reactants: The leukocyte count usually lies
between 10000 to 15000 / cu mm. The sedimentation rate Treatment
is elevated during acute rheumatic fever and remains so
for 4 to 10 weeks in almost 80% patients. In a small Management is symptomatic combined with suppressive
proportion of patients, it may remain elevated even therapy.
beyond 12 weeks. Although congestive cardiac failure Bed rest: Bed rest is generally recommended for acute
tends to bring the sedimentation rate down towards rheumatic fever. Prolonged bed rest (>2-3 weeks) is
normal, it is unlikely that patients of acute rheumatic fever seldom necessary unless there is clinically apparent
with congestive failure will have a normal sedimentation carditis with heart failure.
rate. C-reactive protein is elevated in all patients of acute
rheumatic fever, and subsides rapidly if the patient is Penicillin: After obtaining throat cultures, the patient
treated with corticosteroids. While absence of raised C should receive penicillin. A single injection of benzathine
reactive protein is against the diagnosis of rheumatic fever, penicillin is given when the diagnosis of rheumatic fever
its presence is non-specific. is made. Penicillin V (250 mg four times a day for 10 days)
is an alternative; erythromycin (250 mg four times a day
Prolonged PR interval: Prolonged PR interval can get for 10 days) is given to those with penicillin allergy.
prolonged in many infections, nor is diagnostic of carditis.
Higher grades of block like second degree atrioventricular Suppressive Therapy
block especially Wenckebach type may be seen. Complete
Aspirin or corticosteroids are given as suppressive
atrioventricular block is extremely rare.
therapy. Since untreated rheumatic fever subsides in
12 weeks in 80% of the patients, either of the two
Essential Criteria suppressive agents is given for 12 weeks. Steroids are a
These include evidence of recent streptococcal infection. more potent suppressive agent as compared to aspirin.
Elevated levels of antistreptolysin O (ASO) indicate However, there is no proof that the use of steroids results
previous streptococcal infection and not rheumatic fever. in less cardiac damage as compared to aspirin. A number
Although generally the higher the level the more likely of observations indicate that steroids act faster and are
one can conclude a recent infection, lower levels do not superior at least in the initial phases. Pericardia! friction
exclude a recent streptococcal infection. A basal ASO titer rub tends to disappear within three to five days after
of 50 U / dL that goes up to 250 U / dL is indicative of recent starting the steroids. Subcutaneous nodules also resolve
streptococcal infection. Rising titer of ASO is a strong faster with use of steroids. Patients who have carditis with
evidence for recent infection. congestive cardiac failure have a higher mortality if aspirin
Positive throat culture for streptococci, at diagnosis of is used compared to steroids. In selecting the medication,
rheumatic fever, is uncommon. A positive culture also the following guidelines are followed:
434 I Essential Pediatrics
• Carditis with congestive cardiac failure: Corticosteroids Table 16.17: Secondary prophylaxis following an
• Carditis without congestive cardiac failure: Either episode of rheumatic fever
corticosteroids or aspirin; former preferred Antibiotic Mode of administration, dose
• No evidence of carditis: Aspirin Benzathine Single intramuscular injection every 3 to
The total duration of therapy is 12 weeks. Aspirin is penicillin 4 weeks*, 1200 000 units for patients
given at a dose of 90-120 mg/kg/day (in 4 divided doses) �30 kg; and 600 000 units for <30 kg
for 10 weeks, and then tapered in the next two weeks. Penicillin V 250 mg orally twice daily
Alternatively, prednisolone (2 mg/kg daily; maximum
Erythromycin (for 250 mg orally twice daily
dose 60 mg) is given for three weeks and then tapered
penicillin allergy)
gradually in next 9 weeks. The management of congestive
cardiac failure is based on principles discussed above. *In high prevalence regions, 3 wk injections are recommended for
prophylaxis, in patients >30 kg and every 2 weeks in patients <30 kg
Surgical replacement of the mitral and/or aortic valve
is sometimes indicated, if the patient is deteriorating
despite aggressive decongestive measures. Acute hemo RHEUMATIC HEART DISEASE
dynamic overload due to mitral or aortic regurgitation is The sequelae of rheumatic fever consist of mitral, aortic
the main cause of mortality due to rheumatic fever. and tricuspid valve disease. Mitral valve involvement
Management of chorea: The patient as well as the parents manifests predominantly as mitral regurgitation (MR) and
are reassured and told about the self-limiting course of much less commonly as mitral stenosis (MS). Aortic valve
the disease. The signs and symptoms of chorea do not and tricuspid valve involvement presents as aortic (AR)
respond well to anti-inflammatory agents or steroids. and tricuspid regurgitation (TR), respectively. Rheumatic
Supportive measures such as rest in a quiet room and aortic stenosis (AS) is very rare in childhood or adolescence.
medications such as haloperidol, diazepam and
carbamazepine are effective. Mitral Regurgitation
Mitral regurgitation (MR) is the chief manifestation
Prevention of Rheumatic Fever (80-85%) of acute and previous rheumatic carditis.
Primary prevention requires identification of streptococcal
sore throat and its prompt treatment with penicillin. For Hemodynamics
primary prevention, it is necessary to educate the Mitral regurgitation results in a systolic leak of blood to
community regarding the consequences of streptococcal the left atrium. The regurgitant blood reaches the left
pharyngitis. Logistically, this may be difficult since it atrium during ventricular systole at almost systolic
requires (i) prompt identification of sore throat, (ii) rapid pressure. However, during diastole it can pass freely
confirmation of a streptococcal etiology and (iii) availability across the mitral valve. Thus, although the left atrial
of penicillin. Recent data indicates that rheumatic fever pressure increases during systole, it drops during diastole.
may follow episodes of asymptomatic streptococcal The mean left atrial pressure, therefore, stays normal or is
pharyngitis. Primary prevention can only be possible by only slightly increased. There is only a minimal increase
using an antistreptococcal vaccine, which is not available. in pulmonary venous pressure and no pulmonary
Secondary p revention consists in giving long-acting congestion. The increased volume of blood handled by
benzathine penicillin. The dose is 1.2 million units once the left atrium and left ventricle results in an increase in
every 3 weeks or 0.6 million units every alternate week. the size of both these chambers. Mitral regurgitation
The injection is painful and often administered on provides two exits for the left ventricular blood-forward
weekends to avoid school absence. While the responsi flow through the aortic valve into the systemic circulation
bility of continuing penicillin prophylaxis is on parents, and backward leak into the left atrium. The forward output
the physician should explain the seriousness of the becomes insufficient during exertion. This decrease in the
problem and need for prolonged treatment (Table 16.17). systemic output results in fatigue, the commonest
Patient without proven carditis should receive symptom of significant MR. Absence of pulmonary
prophylaxis for 5 years after the last episode, or until they congestion prevents occurrence of dyspnea unless the MR
are 18-yr-old (whichever is longer). Patient with carditis is severe or the left ventricular myocardium is failing. With
(mild mitral regurgitation or healed carditis) should failing left ventricle, the left ventricular diastolic pressure
receive prophylaxis for 10 years after the last episode, or increases, the left atrial and pulmonary venous pressure
at least until they are 25-year-old (whichever is longer). increase and pulmonary congestion appears. There is an
Patients with established RHO or following valve surgery increase in pulmonary arterial pressure and features of
or balloon valvotomy should receive lifelong prophylaxis. pulmonary arterial hypertension appear. Thus presence
Some cardiologists recommend discontinuation of of features of pulmonary arterial hypertension in a patient
prophylaxis after the age of 40 years, since the likelihood having pure MR suggests (i) severe MR or (ii) failing left
of recurrence beyond this age is minimal. ventricular myocardium.
Disorders of Cardiovascular System 1435-
the pulse pressure, the more severe the aortic leak. The cular septal defect, ruptured sinus of Valsalva and
diastolic blood pressure may be recorded as zero with congenital aortic valve disease. As a rule congenital aortic
severe AR. Prominent carotid pulsations (Corrigan sign), valve disease is either a leaking bicuspid aortic valve or
visible arterial pulsations over extremity vessels (dancing aortic stenosis. Pure congenital AR is extremely rare. Other
peripheral arteries) and visible pulsations of the conditions that may result in AR include Marfan
abdominal aorta are present. Nodding of head may be syndrome, Hurler syndrome and Takayasu aortoarteritis.
present with each systole (de Musset sign) in severe AR.
Arteriolar pulsations may be seen over the nail bed, uvula, Management
lips, ear lobes and in the eye grounds. There is also Mild to moderate AR is well tolerated for years. There is
exaggeration of the systolic pressure difference between role for therapy with calcium channel blockers. Significant
the brachial and femoral arteries (Hill sign). Normally, AR, if associated with either chest pain or left ventricular
the difference between the pressures in brachial artery and failure, should be treated surgically. Surgical treatment
femoral artery is less than 20 mm Hg, the femoral systolic consists of aortic valve replacement either by homograft
pressure being higher. Systolic pressure difference or prosthetic valve; valve repair is not feasible for
between 20 to 40 mm Hg suggests mild AR, 40 to 60 mm Hg rheumatic AR. Better surgical results are obtained before
moderate AR, and more than 60 mm Hg severe AR. onset of significant ventricular dysfunction.
Stethoscope over the brachial or the femoral artery shows Patients planned for valve replacement should be
pistol shot sounds in severe AR. A systolic murmur may screened for: (i) rheumatic activity; (ii) ability of the patient
be heard, if pressure is applied to partially occlude the and the family to monitor lifelong anticoagulation. Aortic
artery proximal to the chest piece, and diastolic murmur valve replacement has fewer long-term complications
if pressure is applied distally; the combination of systolic when compared to mitral valve replacement.
and diastolic murmurs is the Duroziez sign.
The apex is displaced downward and outward and is Tricuspid Regurgitation (TR)
forcible or heaving. A diastolic thrill is unusual. The first
sound is soft and the aortic component of the second sound Features indicative of TR are seen in 20 to 50% patients of
may be audible or may be masked by the regurgitant RHD in children. It is often difficult to determine whether
diastolic murmur. The murmur of AR is a high-pitched, TR is organic (due to involvement of the tricuspid valve
decrescendo diastolic murmur starting with the aortic by the rheumatic process) or functional (due to pulmonary
component of the second sound. The intensity and the hypertension).
length of the murmur do not correlate with the severity
of AR. The murmur is heard along the left sternal border Hemodynamics and Clinical Features
and may radiate to the apex. With large aortic leaks there TR results in a systolic backflow of blood from the right
is also an ejection systolic murmur at the second right ventricle to the right atrium. The systolic leak thus results
interspace, conducted to the neck and not infrequently in a systolic murmur and volume load of the right atrium
associated with a systolic thrill. The systolic murmur is as well as the right ventricle. As a rule, almost all patients
the result of a large stroke volume, passing across rough who have TR also have features of pulmonary arterial
valves. It does not indicate aortic stenosis, if the pulse hypertension. The systolic backflow under pressure results
pressure is wide and the carotid upstroke is brisk. in a prominent systolic wave, the V wave, in the jugular
The electrocardiogram shows increase in left ventricular venous pulse as well as the liver. Both the systolic as well
voltages with deep S waves in Vl and tall R waves in V6. as the diastolic murmurs at the tricuspid valve become
There are also deep Q waves in left chest leads accom louder during inspiration. In patients of rheumatic heart
panied with tall T waves, the diastolic overloading pattern disease, the TR may be associated either with MS or with
of the left ventricle. Thoracic roentgenogram shows MR. If the TR is associated with MS, it may be either
cardiac enlargement of the left ventricular type and dilated organic or functional due to pulmonary arterial hyp er
ascending aorta. Echocardiogram identifies enlarged left tension. If, on the other hand, the TR is associated with
ventricle, dilated aorta and flutter of anterior mitral leaflet. dominant or pure MR it is likely organic.
Doppler echo can quantify the severity of AR. There are no specific symptoms of TR. It is possible
that with onset of TR, the dyspnea may be relieved to some
Differential Diagnosis extent in patients of MS. The patients may give history of
The differential diagnosis of rheumatic AR includes two pain in right hypochondrium due to a congested liver and
sets of conditions: (i) conditions associated with a wide of fatigue due to a decrease in systemic output. In addition
pulse pressure like patent ductus arteriosus, arteriovenous to features of TR, there are signs of pulmonary arterial
fistulae, ventricular septal defect with AR, ruptured sinus hypertension and those of mitral valve disease. In
of Valsalva, anemia and thyrotoxicosis, (ii) conditions association with MS, severe TR may result in marked
associated with a non-rheumatic regurgitant diastolic dilatation of the right ventricle and the whole of the
murmur like pulmonary regurgitation, AR with ventri- anterior surface, including the apex may be formed by
Disorders of Cardiovascular System 1439-
the right ventricle. In such patients, the apex beat is not Doppler echocardiography: a scientific statement from the
only displaced outward but also downward. This should American Heart Association. Circulation. 2015;131:1806-18.
• Bland EF, Jones TD. Rheumatic fever and rheumatic heart disease.
not be mistaken for left ventricular enlargement. In these A twenty year report on 1000 patients followed since childhood.
cases, the pansystolic murmur of TR may be heard from Circulation 1951; 42:836.
the lower left sternal border to the apex. Since the left • Narula J, Virmani R, Reddy KS, Tandon R. Rheumatic fever. Amer
ventricle is displaced backwards, the MS murmur may Registry Path AFlP. Washington DC, 1999.
be audible only in the axilla or may not be made out at all. • Rheumatic fever and rheumatic heart disease. Report of a WHO
expert consultation. World Health Organization, Geneva, 2004
It is not uncommon for these patients to be diagnosed as (Technical Report Series No. 923).
those of MR. Besides clinical signs of TR, the electro
cardiogram is helpful in diagnosis. Patients of TR of this INFECTIVE ENDOCARDITIS
severity almost always show severe right ventricular
hypertrophy in the electrocardiogram. Infection of the endocardial lining of the heart is called
infective endocarditis, and may involve the endocardium
Management of the valves, the mural endocardium or the endothelium
Decongestive measures help reduce the severity of TR. of blood vessels (infective endarteritis). The commonest
Further management depends on the associated mitral site of infection is a diseased valve from where the
valve lesion. TR may resolve following mitral valvotomy. infection can spread along the endothelium.
In patients undergoing surgery for the MR, the tricuspid
Etiopathogenesis
valve can be inspected and tricuspid annuloplasty or
repair performed, if needed. Infective endocarditis (IE) predominantly occurs in a
diseased heart. The commonest substrate is a damaged
Clinical Problems in Patients with endothelium or endocardium resulting from contact with
Rheumatic Heart Disease a high velocity jet together with the presence of a
Two major problems that clinicians face in patients of RHD significant bacteremia. Endocarditis can occur following
are discussed below. a surgical shunt as in Blalock-Taussig shunt. Other
congenital lesions, associated with endocarditis are VSD,
Active or Inactive Rheumatic Fever PDA, tetralogy of Fallot, aortic stenosis and mitral
A lot of judgment or personal bias is involved in this regurgitation. Examples of conditions seldom associated
decision. The diagnosis of activity rests on the Jones with IE include atrial septal defect and isolated pulmonary
criteria. Presence of cardiac involvement cannot be used valve stenosis.
as a major criterion since carditis may be the result of a Infective endocarditis occurs over the mitral or aortic
previous attack of rheumatic fever. However, presence of valves in patients with rheumatic heart disease. Patients
a pericardia! friction rub is evidence of active carditis. If with prosthetic valves or those who have had a recent
the patient has documented cardiac findings, then the cardiac operation are also especially prone to endocarditis.
appearance of a new murmur or a significant increase in Infections anywhere in body like boils or furuncles, tooth
a pre-existing murmur suggests active rheumatic fever. abscess, ear infection, urinary tract infection or
History of arthralgia or arthritis within a period of less osteomyelitis may result in endocarditis. Although
than 12 weeks is suggestive of active rheumatic fever, interventions like dental procedures, genitourinary
especially if associated with high sedimentation rate and procedures or bronchoscopy can be followed by IE, it is
ASO titers. Despite congestive cardiac failure, it is unusual uncommon to be able to identify the predisposing event.
for the sedimentation rate to be normal in a patient of Perhaps the most important preventable cause of
active rheumatic fever. Patients with rheumatic activity endocarditis is poor dental hygiene. Parenteral drug abuse
show elevated ASO titers, although there are problems in is a frequent cause of right-sided endocarditis involving
interpretation of borderline values. the normal tricuspid or the pulmonary valve. Occasionally,
it can result in mitral and/ or aortic valve disease as well.
In a Febrile Patient, Is it Active Rheumatic Fever or The pathogenesis of endocarditis depends on the
Infective Endocarditis? invasiveness and virulence of the infective organisms. The
At times separation of rheumatic activity from infective infection generally starts at a jet lesion, where the high
endocarditis can be difficult. The arguments used above pressure jet strikes the endocardium or the endothelium.
for separating active from inactive rheumatic fever can The right ventricular mural endocardium or the tricuspid
be used for diagnosis of active rheumatic fever. A detailed valve in VSD, aortic endothelium in AS or coarctation of
description of endocarditis follows. the aorta, ventricular surface of the aortic valve in AR are
the usual sites. Endocarditis results in immune-mediated
Suggested Reading vasculitis and thrombocytopenia.
• Gewitz MH, Baltimore RS, Tani LY, et al. Revision of the Jones Bacteremia resulting from an infection such as a boil,
criteria for the diagnosis of acute rheumatic fever in the era of furuncle, otitis media or initiated by an intervention such
440 Essential Pediatrics
valves. Incidence of embolism is high since the fungal of fingers or toes due to obstruction of blood supply.
vegetations tend to be very large. Despite intensive Damage to the vasa vasorum of blood vessels due to
therapy, mortality is high. vasculitis may result in the formation of mycotic aneurysms
that can rupture and result in massive bleeding. The
Laboratory Diagnosis kidneys suffer from embolic infarct with hematuria and
Blood culture is essential for diagnosis. A positive blood focal or diffuse membranoproliferative glomerulonephritis
culture in a patient with underlying heart disease, resulting in albuminuria and microscopic hematuria. The
suspected to have endocarditis is confirmatory. Three sets findings of IgG, IgM and complement deposits on the
of cultures, each containing adequate volumes of blood, glomerular basement membrane indicate that it is an
taken every half-hour are appropriate and detect 95% immune complex nephritis. Renal insufficiency tends to
cases. The commonest cause for negative cultures is prior appear beyond three weeks of the onset of endocarditis and
antibiotic therapy or unsatisfactory culture technique. is progressive until the endocarditis is cured; hematuria
Infection with unusual organisms, anaerobic organisms can persist for 3-6 months. Even advanced renal
and fungi require special mediums and incubation for insufficiency tends to regress and renal function returns to
2-3 weeks. Arterial sampling does not offer any advantage normal after the endocarditis has been cured.
over venous samples. Other investigations, which provide
supportive evidence for the diagnosis, include: (i) normo Treatment
cytic normochromic anemia, (ii) moderately elevated total The principles of management consist of: (i) identification
leukocyte count, (iii) reduced platelets, (iv) elevated of organism and its antibiotic sensitivity; and (ii) prompt,
sedimentation rate and C-reactive protein, and (v) micro appropriate and prolonged antimicrobial treatment to cure
scopic hematuria and albuminuria. and prevent relapse. If the blood culture is positive, the
choice of antibiotics is dictated by the antibiotic sensitivity.
Echocardiography If the culture is negative, empirical therapy covering a
Echocardiography is a valuable diagnostic tool, especially wide range of organisms is necessary. If the culture is
in patients with culture negative endocarditis. positive, the culture plate should not be discarded. After
Complications like ruptured chordae, perforated cusps starting the antibiotic treatment, patient's serum diluted
and flail cusps can be identified. Vegetations more than to 1:8 parts or more should be used to determine if it
2 mm can be identified on echocardiography, but its inhibits the growth of the organism in subculture, to
sensitivity is dependent on the site of involvement. For indicate the efficacy of treatment. Common organisms
aortic and mitral valves, the sensitivity is more than 90%, causing endocarditis, antibiotic of choice and duration of
while for tricuspid and pulmonary valves, it is 70%. The treatment is shown in Table 16.18. Over the last 2-3
presence of vegetations has high negative as well as decades are, the threshold for surgery for treatment of
positive predictive value for confirming the diagnosis of endocarditis is lowered considerably. Surgery is indicated,
infective endocarditis. Transesophageal echocardiography if response to antibiotics is suboptimal, in presence of large
is useful for diagnosing prosthetic valve endocarditis and vegetation, damage to valve apparatus with severe or
valve ring abscess. refractory heart failure and for fungal endocarditis.
Fungal endocarditis: Fungal endocarditis is resistant to
Complications therapy. Therefore, after 2 to 3 weeks of appropriate
Damage to valve cusps or perforation and rupture of treatment (amphotericin B), the patient should be operated
chordae tendinae might result in acute regurgitant lesions to remove the fungal mass. The antifungal agents should
and hemodynamic deterioration. Migration of vegetations be continued postoperatively for a minimum of 6 weeks.
may result in embolic neurological deficit, renal infarcts Relapse following apparently successful treatment can
with hematuria, mesenteric infarct and melena, and loss occur even up to 2 years.
Table 16.18: Choice of antibiotics and duration of treatment for infective endocarditis
Organism Option I Option II Duration, weeks
Streptococcus viridans Penicillin, aminoglycoside Ceftriaxone, aminoglycoside 4
Group A streptococci Penicillin, aminoglycoside Ceftriaxone, aminoglycoside 4
Streptococcus faecalis Ampicillin, aminoglycoside Vancomycin, aminoglycoside 4-6
Staphylococcus aureus Cloxacillin/cefazolin, aminoglycoside Vancomycin, aminoglycoside 6
Escherichia coli Ceftriaxone, aminoglycoside Ampicillin, aminoglycoside 6
Pseudomonas spp. Ticarcillin, aminoglycoside Meropenem, aminoglycoside 6
Culture negative Ampicillin, aminoglycoside Ampicillin, aminoglycoside 6
The choice of antibiotics should ideally be guided by culture results and organism sensitivity
442 Essential Pediatrics
Culture negative endocarditis: Patients with culture are repeated at least for 2 more doses after the
negative endocarditis need to be treated empirically. The procedure
choice of treatment is dictated by circumstances ii. Gastrointestinal surgery: Add metronidazole
anticipating the most likely organism. If the patient seeks Infective endocarditis is a life-threatening disease with
help late and has significant renal insufficiency, the significant mortality and morbidity. Treating physicians
medication dose might need to be modified. should advise patients and parents regarding prevention
of endocarditis. The maintenance of good oral hygiene is
Prophylaxis
encouraged. Careful attention to prophylaxis, when
There have been major changes in the recommendations indicated, is useful.
for prevention of endocarditis. Patients with congenital
heart defects such as ventricular septal defect, bicuspid Suggested Reading
aortic valve and valvar pulmonary stenosis do not • Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective
routinely require prophylaxis. According to the guidelines endocarditis. Guidelines from American Heart Association.
of the American Heart Association, since the absolute Circulation 2007;116(15):1736-54.
lifetime risk of endocarditis is small, prophylaxis is only
recommended for patients with conditions associated with MYOCARDIAL DISEASES
increased risk of adverse outcome from endocarditis Myocarditis
(Table 16.19). The focus of prophylaxis has shifted from
prophylactic antibiotics for a dental procedure to the Myocarditis is chiefly caused by ECHO, Coxsackie B,
prevention of dental caries, which reduces the incidence rubella, herpes and influenza viruses. Diphtheritic
of bacteremia from daily activities and is, therefore, more myocarditis is occasionally noted in South Asia. The
important. These guidelines need validation in developing presentation may be abrupt, with cardiovascular collapse,
countries where oral hygiene is unsatisfactory and regular or insidious development of heart failure. Arrhythmias
dental health screening is not instituted in the majority. and conduction disturbances may be present. Examination
Antibiotic recommendations for those who need shows cardiac enlargement, tachycardia, muffled heart
prophylaxis are as follows: sounds and features of congestive cardiac failure. The
electrocardiogram shows low voltages, and nonspecific
Dental Treatment ST-T changes. Chest X-ray reveals cardiac enlargement
i. Penicillin V 2 g given orally on an empty stomach with pulmonary venous congestion.
1 hour before dental treatment, followed by 0.5 g every Treatment includes management of congestive failure.
6 hours for 3 days, or Digoxin should be used cautiously, preferably in half to
ii. Crystalline penicillin G 1,000,000 U mixed with 600,000 three-quarters the standard dose. Steroids are of uncertain
U of procaine penicillin 30-60 min before dental value and should be avoided during acute viremia. ACE
treatment, followed by oral penicillin as above, or inhibitors are a useful adjunct to therapy. The utility of IV
iii. Single dose of amoxicillin 50 mg/kg orally 1 hour immunoglobulins is not proven. Severe heart failure may
before the procedure require admission in an intensive care unit and mechanical
iv. Patients with prosthetic heart valves: Injectable ventilation. A variable proportion of children with
penicillin with streptomycin or gentamicin IM 1 hour myocarditis recover completely.
before the procedure.
Cardiomyopathies
Genitourinary and Gastrointestinal Procedures The term cardiomyopathy is an intrinsic disease of the
i. Amoxicillin 25 mg/kg by mouth 1 hour before, with myocardium which is not associated with a structural
gentamicin 2 mg/kg IM 30 min before procedure; both deformity of the heart. It is considered primary cardiomyo
pathy when the etiology is unknown, and secondary, if
Table 16.19: Conditions where antibiotic prophylaxis is the myocardial disease is attributed to a systemic disease.
definitely recommended Myocardial diseases are classified clinically as (i) dilated,
Prosthetic cardiac valve; prosthetic material used for valve repair (ii) restrictive, and (iii) hypertrophic cardiomyopathy.
Past history of infective endocarditis
A significant proportion of patients have correctible
causes of left ventricular dysfunction that mimics dilated
Uncorrected cyanotic heart disease, palliative shunts and
conduits
cardiomyopathy (Table 16.20).
During first 6 months following complete surgical repair of Dilated Cardiomyopathy
congenital heart disease
Dilated cardiomyopathy (DCM) is the commonest form
Repaired congenital heart disease with residual defects at or
adjacent to the site of repair
of myocardial disease. The onset of cardiac failure may
be acute or insidious. Cardiomegaly and S3 gallop are
Cardiac transplantation recipients with cardiac valvulopathy
present. Murmur of MR and uncommonly, that of
Disorders of Cardiovascular System 1443-
tricuspid regurgitation, may be present. The patients are Anomalous Left Coronary Artery
prone to embolic phenomena. The electrocardiogram from Pulmonary Artery {ALCAPAJ
shows non-specific ST and T changes with or without left ALCAPA should be considered in a patient with heart
ventricular hypertrophy, conduction disturbances, failure with or without a murmur suggesting MR and a
arrhythmias or pseudo-infarction pattern. Chest X-ray
pattern on electrocardiogram that suggests anterolateral
shows cardiomegaly with pulmonary venous hypertension.
myocardial infarction (Fig. 16.45). Echocardiography
Echocardiogram confirms dilated ventricular cavity
shows a large right coronary artery and absence of the
without hypertrophy of the left ventricle or the septum;
origin of left coronary artery from the aorta. The left
left ventricular contractility is reduced.
coronary artery is seen to arise from the pulmonary artery
Treatment consists of decongestive therapy with
and shows flow in the reverse direction in the left anterior
vasodilators, especially ACE inhibitors. Beta-blockers
descending artery and the left circumflex artery. This flow
control the heart rate and reduce catecholamine-induced
reversal results from collateral flow into the left coronary
vasoconstriction. Carvedilol, a beta-blocker with
system from the right coronary artery. Angiography is
peripheral vasodilator effect, is useful in management of
rarely necessary for the diagnosis. The treatment is
CCF, especially in patients with disproportionate
surgical and requires mobilization and translocating the
tachycardia. The starting dose is 0.1 mg/kg/day once
origin from pulmonary artery to aorta.
daily, which is gradually increased to 0.5 mg/kg/day.
Gradual improvement occurs in a significant
Restrictive Cardiomyopathy [RCMJ
proportion. The prognosis for individual patients cannot
be predicted and treatment should continue for prolonged It is relatively uncommon in children. Restriction to
periods. Despite aggressive therapy, about one-third of ventricular filling is usually associated with either
children with cardiomyopathy continue to deteriorate and endomyocardial fibrosis or endocardial fibroelastosis with
eventually become refractory. Intermittent (weekly or bi a normal or smaller than normal left ventricle.
weekly) dobutamine or levosimendan infusions are useful Endomyocardial fibrosis was previously endemic in
in some patients. It is important to be aware of a number Kerala, but is now rare. There is dense fibrosis in the apical
of correctable conditions that can mimic cardiomyopathy and inflow regions of the left and right ventricles. Papillary
(Table 16.24). Clues to these conditions are obtained on muscles and chordae may be tethered by the connective
clinical and laboratory findings, or ECG (Fig. 16.44). tissue, resulting in severe mitral or tricuspid regurgitation.
444 Essential Pediatrics
Fig. 16.44: Pompe disease with biventricular hypertrophy. Note the characteristically tall QRS voltages, and T wave inversion
-- -'
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Fig. 16.45: ECG of an infant with heart failure and ventricular dysfunction. The leads I, aVL and V6 show q waves and subtle ST
segment elevation suggesting myocardial infarction. The echocardiographic diagnosis of anomalous left coronary artery from
pulmonary artery was confirmed at surgery.
Patients with predominant left-sided involvement have involvement, patients present with fatigue, pedal edema
symptoms of dyspnea, orthopnea, hemoptysis and embolic and ascites. There is cardiomegaly with prominent cardiac
phenomena. On examination, there is cardiomegaly with pulsations; S3 gallop and TR murmur may be present.
or without findings of MR. With predominant right-sided Treatment consists of decongestive therapy.
Disorders of Cardiovascular System 1445-
shows an echo-free space behind the posterior left children and adolescents. Systemic hypertension is rare
ventricular wall. Evidence of right atrial or right in infants and young children, but when present usually
ventricular diastolic collapse indicates a hemodynamically due to an underlying disease (secondary hyp ertension).
significant effusion. Pericardiocentesis is done to The prevalence of essential hypertension increases with
determine the etiology and relieve cardiac tamponade, if age. Approximately 3-4% of children and adolescents
present. Treatment will depend on the etiology. Surgical have hyp ertension and 10% have elevated blood pressure.
drainage is indicated, if pyopericardium is suspected.
Etiology
Chronic Constrictive Pericarditis
The etiology of essential hypertension is multifactorial.
Constrictive pericarditis is not uncommon in our country, Obesity, insulin resistance, activation of sympathetic
following tuberculous infection and less commonly, nervous system, disorders in sodium homeostasis and
following pyogenic pericarditis. Fibrous thickening of renin-angiotensin system, vascular smooth muscle
both layers of the pericardium encases the heart and structure and reactivity, uric acid levels, genetic factors
restricts filling of both the ventricles equally; calcification and fetal programming have been implicated. There is
is rare in childhood. The myocardium is not involved often a history of hyp ertension in the parents.
initially, but the fibrous process may infiltrate the myo Approximately 90% of secondary hypertension in
cardium. Dyspnea, fatigue and progressive enlargement children are due to renal or renovascular abnormalities.
of the abdomen are common. The major renal causes are chronic glomerulonephritis,
Jugular venous pressure is always elevated with equally reflux or obstructive nephropathy, polycystic or dysplastic
prominent 'a' and 'v' waves and a prominent 'y' descent. renal diseases and renovascular hypertension. Coarctation
Inspiratory filling of neck veins (Kussmaul sign) is seen of the aorta and Takayasu arteritis are leading vascular
in about one-half. Liver is enlarged and pulsatile; ascites causes. Hyperthyroidism, hyperparathyroidism, congenital
with unilateral or bilateral pleural effusion is common. adrenal hyperplasia, Cushing syndrome, primary
Splenomegaly may also be present. Pulse is fast and of aldosteronism, pheochromocytoma and neuroblastoma
low volume and pulsus paradoxus may be present. The are uncommon.
precordium is quiet with a normal-sized heart. First and Transient or intermittent hyp ertension may be caused
second sounds are normal. An early third heart sound by postinfectious glomerulonephritis, rapidly progressive
(pericardial knock) is commonly heard. The EKG shows (crescentic) glomerulonephritis, Henoch-Schonlein purpura,
low voltage in 75% patients and non-specific ST-T changes hemolytic uremic syndrome, acute tubular necrosis, and
in all cases. Normal electrocardiogram is against the diag renal trauma. Raised intracranial pressure, Guillain-Barre
nosis of constrictive pericarditis. Occasionally, there is right syndrome, bums, Stevens-Johnson syndrome, porphyria,
axis deviation or right ventricular hypertrophy pattern. poliomyelitis, encephalitis, drugs (e.g. sympathomimetic
The chest X-ray shows normal-sized heart with ragged agents, steroids, cyclosporine), heavy metal poisoning
or shaggy borders and prominent superior vena cava (e.g. lead, mercury) and vitamin D intoxication may result
merging with the right atrial margin. The lungs may show in acute elevation of blood pressure.
pleural effusion and plate atelectasis. Hemodynamic
studies reveal elevation of right atrial mean pressure, right Definition and Staging
ventricular end-diastolic pressure, pulmonary artery The American Academy of Pediatrics (AAP) clinical
diastolic pressure and the pulmonary artery wedge practice guidelines for screening and management of high
pressures, which are identical. The right ventricular end blood pressure in children and adolescents (2017) provide
diastolic pressure is more than one-third of the systolic revised normative data on distribution of blood pressure
pressure. The cardiac index may be normal or reduced, in normal weight children. Hypertension is defined as
but the stroke volume is low. In some cases, therapy with average systolic blood pressure (SBP) and/or diastolic
digitalis may improve the hemodynamics indicating blood pressure (DBP) that is 95th percentile for age, sex
presence of myocardial dysfunction. and height on three different occasions. Elevated blood
Surgical decortication of the pericardium results in pressure is defined as SBP or DBP that are 90th percentile
normalization of the hemodynamic abnormalities in most but <95th percentile. Adolescents with blood pressure
cases. Some cases of long-standing constrictive pericarditis between 120/80 and 129/ <80 mm Hg are also considered
with myocardial dysfunction may improve slowly or have as having elevated blood pressure while hypertension is
residual myocardial dysfunction. A full course of defined by blood pressure >130/80 mm Hg in this age
antitubercular treatment often follows pericardiectomy if group. Children with blood pressure between the 95th
the cause is not clear. percentile and 95th plus 12 mm Hg are classified as stage
I hyp ertension and children with blood pressure above
SYSTEMIC HYPERTENSION
95th plus 12 mm Hg have stage II hypertension.
Essential (primary) hypertension, the most common form Figures 16.46 and 16.47 indicate blood pressure cut off for
of hyp ertension in adults, is increasingly recognized in stage I and stage II hyp ertension in girls and boys with
Disorders of Cardiovascular System 1447-
50
40
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30
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a -+ 9oth DBP -o- 95th DBP � 95th+12 mm Hg DBP
UV
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Fig. 16.46: Blood pressure levels for boys at 50th percentile for height. Chart depicting 90th (closed diamonds), 95th (open
squares) and 95th + 12 mm Hg (open triangles) percentile values for (a) systolic and (b) diastolic blood pressures, representing cut
off values for the diagnosis of elevated blood pressure and stage I and stage II hypertension, respectively, in boys (Based on
American Academy of Pediatrics clinical practice guidelines for screening and management of high blood pressure in children
and adolescents, 2017)
448 I Essential Pediatrics
150
140
:r -
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0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
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50
40
0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Fig. 16.47: Blood pressure levels for girls at 50th precentile for height. Chart depicting 90th (closed diamonds), 95th (open squares)
and 95th + 12 mm Hg (open triangles) percentile values for (a) systolic and (b) diastolic blood pressures, representing cut off
values for the diagnosis of elevated blood pressure and stage I and stage II hypertension, respectively in girls (Based on American
Academy of Pediatrics clinical practice guidelines for screening and management of high blood pressure in children and
adolescents, 2017)
Disorders of Cardiovascular System
Table 16.22: Screening blood pressure cut-offs useful for screening for hypertension in children
I 449 -
Age 1 2 3 4 5 6 7 8 9 10 11 12 >13
Girls SPB 98 101 102 103 104 105 106 107 108 109 111 114 120
DBP 54 58 60 62 64 67 68 69 71 72 74 75 80
Boys SBP 98 100 101 102 103 105 106 107 107 108 110 113 120
DBP 52 55 58 60 63 66 68 69 70 72 74 75 80
stature at median for age. Simplified tables, which can be activities, including sleep. ABPM is more accurate in
used in office practice, to define patients who need making a diagnosis of hypertension, and its parameters
evaluation are available (Table 16.22). Blood pressure cut correlate more strongly with end orange damage, than
offs identifying children in the outpatient who need casual blood pressure. ABPM is recommended in children
further evaluation are provided in Table 16.22. with high risk of hypertension (chronic kidney disease,
diabetes mellitus, obstructive sleep apnea, preterm
Measurement of Blood Pressure children and children with obesity), where clinic blood
Blood pressure can be measured by auscultation, pressure might be normal but ambulatory blood pressure
palpation, oscillometry and Doppler ultrasound. While is high (masked hypertension) or vice-versa (white coat
oscillometric devices are readily available and easy to use, hypertension).
they are susceptible to artifacts and require calibration.
Hence, the auscultatory method preferred for confirming Clinical Features
the diagnosis of hypertension. Blood pressure should be Hypertension in children is usually asymptomatic unless
measured after a period of adequate rest (3-5 min), twice blood pressures are high or sustained. Symptoms are
on each occasion in the right arm in seated position. The common with secondary hypertension. Headache,
stethoscope is placed over the brachial artery pulse, below dizziness, irritability, epistaxis, anorexia, visual changes
the bottom edge of the cuff. An appropriate selection of and seizures occur with significant elevations of blood
cuffs is necessary (Table 16.23). Cuffs should have a pressure. Marked increase in blood pressure may result
bladder width of approximately 40% of the arm circum in cardiac failure, pulmonary edema and renal
ference midway between the olecranon and acromion. The dysfunction. Hypertensive encephalopathy presents with
bladder should cover at least two-thirds of the upper arm vomiting, ataxia, stupor and seizures. Hypertensive crisis
length and 80-100% of its circumference. may present with decreased vision, symptoms of
The cuff is inflated rapidly to occlude the brachial artery encephalopathy, cranial nerve palsies, cardiac failure and
(at least 20-30 mm Hg above expected SBP). The cuff is rapid worsening of renal function. Eye examination shows
deflated slowly at the rate of 2-3 mm Hg per second while papilledema or retinal hemorrhages. Subclinical target
auscultating at the cubital fossa. Systolic pressure is organ injury may occur in asymptomatic children and
indicated by the appearance of Korotkoff sounds (phase include left ventricular hypertrophy, increased carotid
I) and diastolic pressure by its disappearance (phase V). intima media thickness, retinopathy and microalbuminuria.
Ambulatory blood pressure monitoring (ABPM) is a Children with chronic renal disease present with polyuria,
procedure where the child wears a device that records blood polydipsia, pallor, weight loss and growth retardation.
pressure at regular intervals (usually every 20-30 min),
through a 24-hr period while the child performs regular Evaluation
Table 16.23: Recommended dimensions for Children with confirmed hypertension need evaluation
blood pressure cuff bladders to identify potential causes, identify comorbidities and
Age group Width (cm) Length (cm) Maximum arm extent of target organ damage. Patients require a detailed
circumference (cm) history and physical examination. The history should
Newborn 4 8 10 include sleep and treatment history, smoking and alcohol
Infant 6 12 15 intake, drug abuse and family history (early cardiovascular
diseases, hypertension, diabetes, dyslipidemia or renal
Child 9 18 22
diseases). The birth history and growth patterns are
Small adult 10 24 26 elicited. Examination should focus on identification of
Adult 13 30 34 pallor, edema, syndromic fades, ambiguous or virilized
Large adult 16 38 44 genitalia, rickets, goiter, and skin changes (cafe au lait
Thigh 20 42 52 spots, neurofibromas, rash, striae). Examination of eyes
is done for proptosis, extraocular muscle palsies and
Maximum arm circumference is calculated such that the largest arm
would still allow bladder to encircle arm by at least 80% (Adapted from fundal changes. Detailed examination is done for
Fourth Task Force report) asymmetry of peripheral pulses, upper and lower limb
4so I Essential Pediatrics
blood pressures, cardiomegaly, heart rate, cardiac rhythm The goal of therapy for children and adolescents with
abnormalities, murmurs and pulmonary edema. hypertension is to reduce blood pressure below 90th
Abdominal examination may show hepatomegaly, percentile and <130/80 mm Hg in adolescent, except in
abdominal mass or epigastric or renal bruit. presence of chronic kidney disease, where or target organ
Laboratory evaluation includes estimation of blood damage, when the goal is to reduce blood pressure to less
levels of creatinine and electrolytes and urinalysis. Renal than 50 to 75th percentile. Pharmacotherapy is done in a
ultrasound may identify a mass, scars, congenital stepped-care approach and usually starts with a low dose
anomalies or disparate renal size. The evaluation of of a single agent (step 1). If blood pressure control is not
comorbidities requires fasting lipid profile and glucose achieved, the dose is titrated 4-6 weeks until blood
levels to identify dyslipidemias, metabolic syndrome and pressure goals are achieved or the maximum dosage for
diabetes mellitus. Children with history of sleep the drug is reached (step 2). If adequate blood pressure
disordered breathing may benefit from polysomnography. control is not achieved with a single agent, a second agent
An echocardiogram is used to identify left ventricular with a complementary mechanism of action should be
hyp ertrophy and screen for coarctation of aorta. Children added and dose titrated until adequate control or dosage
with suspected renovascular hypertension are limit is reached (step 3). If adequate blood pressure control
investigated by Doppler studies or angiography. is not achieved with a two-drug regime, a third agent from
Investigations like plasma renin and aldosterone, plasma/ a different drug class should be added (step 4).
urine steroid levels and plasma/urine catecholamines are In the case of hyp ertensive emergencies, the safest way
rarely required. is to lower blood pressure up to -95th percentile by using
a medication that is administered by continuous
intravenous infusion in an intensive care unit. In general,
Treatment the pressure should be reduced by up to 25% over the
The treatment of hypertension in children and adolescents first 8 hours (10% in the first hour), followed by remainder
has two components, therapeutic lifestyle interventions and planed reduction over next 12-24 hours. Too rapid a
pharmacotherapy. Weight reduction, increased physical reduction in blood pressure may lead to cerebral ischemia.
activity and dietary interventions are the major therapeutic Drug choices include labetalol, nicardipine and sodium
lifestyle interventions. Weight reduction in overweight nitroprusside. Nicardipine is preferred in children due to
children results in significant reduction of blood pressure, its efficacy and safety, but is not easily available
and decreases other cardiovascular risk factors like (Table 16.25). Many patients in hypertensive crisis are
dyslipidemia and insulin resistance. Current physical volume depleted because of a combination of decreased
activity recommendations for children include 30 to 60 oral intake and pressure natriuresis. Volume repletion in
minutes per day at least 3 to 5 days per week or more of such conditions will help restore tissue perfusion and
moderate intensity aerobic exercise plus limitation of prevent a precipitous fall in blood pressure that may occur
sedentary activity to less than 2 hours per day. Children with intravenous antihypertensive therapy.
with hypertension may benefit from a dietary approach to
stop hypertension (DASH) diet which incorporates Prevention
increased intake of fresh fruits and vegetables, fiber, non Prevention of high blood pressure in children can be
fat dairy and whole grain as well as a reduction in sugar achieved by preventing childhood obesity. Regular
and salt consumption. The recommendation for adequate physical activity, consumption of fruits and vegetables,
sodium intake is 1.2 g/day for children 4 to 8 years old and moderate salt intake and limited consumption of
1.5 g/day for older children. processed food items and animal fats, and reducing
Children with symptomatic essential hypertension, sedentary activities will aid in lowering the prevalence of
hypertension associated with chronic kidney disease, high blood pressure in children.
diabetes-associated hypertension, evidence of target-organ
damage (left ventricular hypertrophy), or failed non Suggested Reading
pharmacologic interventions require pharmacologic • National High Blood Pressure Education Program Working Group
on High Blood pressure in Children and Adolescents. The fourth
therapy. Agents approved for management of hypertension report on the diagnosis, evaluation and treatment of high blood
include angiotensin-converting enzyme (ACE) inhibitors, pressure in children and adolescents. Pediatrics. 2004;114(2 Suppl
angiotensin receptor blockers (ARB), beta blockers, 4th Report): 555-76.
calcium channel blockers and diuretics (Table 16.24). ACE • Raj M, Sundaram KR, Paul M, Deepa AS, Kumar RK.,Obesity in
children - time trends and relationship with hypertension, Natl
inhibitors, calcium-channel blockers and thiazide diuretics Med J India, 2007;20:288-93.
should be used as first-line drugs in children. ACE
inhibitors or ARB are preferred in patients with diabetes
PULMONARY ARTERIAL HYPERTENSION
or chronic kidney disease, however, these agents should
be used carefully in girls of childbearing age due to risk Pulmonary arterial hypertension (PAH) is defined as
of injury to the developing fetus. resting mean pulmonary arterial pressure greater than
Disorders of Cardiovascular System 1451-
In some situations, it may be possible to affect a complete childhood dilated cardiomyopathy, especially if the heart
cure. rate is relatively fixed.
Clinical Features Underlying conditions: A number of congenital and
acquired heart diseases and certain systemic conditions
Irregular heart rate: The commonest cause of an irregular are known to be associated with cardiac arrhythmias
heart rate is physiological sinus arrhythmia. This can be
(Table 16.28). Ventricular and supraventricular arrythmias
recognized by an increase in heart rate with inspiration
can follow cardiac surgery for correction of CHO.
and decrease with expiration. Sinus arrhythmia is usual
Operations resulting in scar formation in the right
following a febrile illness and by drugs that increase vagal
tone (such as digoxin). It is readily abolished by exercise. ventricle, such as repair of tetralogy of Fallot, are known
Irregularities of rhythm are commonly seen in premature to be associated with ventricular tachycardia. The Fontan
infants especially bradycardia associated with periodic operation for single ventricle physiology or the Senning
apnea. Common causes of heart rate irregularity in or Mustard procedure for transposition is known to result
children include atrial and ventricular premature beats in a particularly high incidence of re-entrant atrial
and conduction disturbances (Table 16.27). arrhythmias. Organophosphate exposure, tricyclic anti
depressant overdose, digoxin toxicity, antiarrhythmic
Inappropriate heart rate: A heart rate that is inappropriately
drug treatment and substance abuse can be associated
fast or slow for the clinical condition or physiological state
with a variety of arrhythmias.
should arouse the suspicion of an underlying arrhythmia.
Inappropriately slow heart rate in a child with fatigue, Syncope: The commonest cause of syncope in children is
giddiness or syncope should arouse the suspicion of mediated via the autonomic nervous system, known as
complete heart block. Inappropriately fast rates suggest the neurocardiogenic syncope or vasovagal syncope. A
tachyarrhythmias such as SVT. fraction of syncopal episodes result from cardiac
arrhythmias. Life-threatening ventricular tachycardia (VT),
Unexplained heart failure: Incessant arrhythmias such as
as associated with long QT syndrome characteristically
ectopic atrial tachycardia (EAT), permanent junctional re
results in syncope. It is important to differentiate them
entrant tachycardia (PJRT) and some forms of ventricular
from vasovagal episodes. Vasovagal syncope occurs in
tachycardia can present as heart failure. At the time of
specific situations like prolonged standing in a hot
initial evaluation, the heart rates may not be inappropriate
environment, sight of blood, painful stimulus, emotional
for the degree of heart failure. Diagnosis may be missed
stress or following a recent illness. Syncopes secondary
and requires a high index of suspicion. These conditions
to arrhythmia are sudden, unpredictable, paroxysmal and
should be considered in the differential diagnosis of
usually have no predisposing cause or premonition.
Table 16.26: Clinical features in arrhythmias Duration of syncope depends upon the duration of
Irregular heart beat
Heart rate that is inappropriate for the clinical condition Table 16.28: Arrhythmias suggestive of
specific congenital heart disease
Unexplained heart failure
Sick sinus syndrome
Syncope, palpitations, chest discomfort
Sinus venosus, atrioventricular canal defect, Holt Oram
Underlying cardiac anomaly known to be associated with syndrome with atrial septal defect (ASD)
rhythm disorders
Narrow ORS tachycardias
Family history of sudden cardiac events Ebstein anomaly; corrected transposition with Ebstein
anomaly
Table 16.27: Causes of irregular heart beat Atrioventricular canal defect, ASD, pulmonic stenosis, total
Sinus arrhythmia anomalous pulmonary venous connection, tricuspid atresia
Other common and usually benign causes Atrial fibrillation and flutter
Congenital mitral stenosis, total anomalous pulmonary
Supraventricular (atrial and junctional) premature beats venous connection, coronary AV fistula
Ventricular premature beats
WPW and pre-excitation syndromes
Transient conduction disturbances (Wenckebach type),
Ebstein anomaly; corrected transposition with Ebstein
atrioventricular and sinoatrial blocks
anomaly
Transient bradycardia in a premature infant
Wide ORS tachycardias
Uncommon but potentially serious causes Anomalous left coronary artery from pulmonary artery,
Mobitz type II heart block coronary AV fistula, arrhythmogenic right ventricle, atrio
Ectopic atrial tachycardia; multifocal atrial tachycardia ventricular conduction defects, corrected transposition of
Polymorphic ventricular tachycardia and Torsades great arteries; Ebstein anomaly
Atrial fibrillation, with or without WPW syndrome Postoperative patients
Atrial flutter with variable conduction Supraventricular, ventricular arrhythmias
454 I Essential Pediatrics
arrhythmia. Some forms of long QT syndromes and Diagnostic Workup of Suspected Arrhythmia
catecholaminergic tachycardia are precipitated by Attempts should be made to answer all the questions listed
exercise. Ventricular tachycardia secondary to Brugada in Table 16.29. This will allow the specific treatment
syndrome may be precipitated during febrile illness. strategy to be initiated. A 12-lead EKG should be obtained
Syncope during exertion is potentially serious and may and cardiac rhythm monitoring should be initiated as
suggest specific arrhythmic substrates such as quickly as possible.
catecholaminergic ventricular tachycardia and long QT
syndrome. Management of Hemodynamic Instability
Palpitations and chest discomfort: Older children may Extreme hemodynamic instability is relatively rare in
complain of episodic palpitations. Not infrequently, they childhood arrhythmias, particularly in absence of struc
have a sensation of chest discomfort or pain during tural heart disease. Hemodynamic instability necessitates
tachyarrhythmia. emergency treatment. Most unstable tachyarrhythmias are
broad QRS. Unstable narrow QRS tachycardias are quite
Basic Electrophysiology Concepts uncommon, especially in the absence of structural heart
Arrhythmia that originates at or above the bundle of disease. Low energy (0.5-2 J /kg) synchronized DC
His has narrow QRS morphology; that below this level cardioversion should be performed. If and when possible,
(Purkinje fibers, ventricular muscles) have wide QRS cardioversion should always be preceded by administra
morphology. Majority of tachycardia in children are tion of a short-acting benzodiazepine such as midazolam
regular. Common irregular tachycardias are ectopic (0.1-0.2 mg/kg/dose). Emergency treatment options for
atrial tachycardia, multifocal atrial tachycardia, atrial bradyarrhythmia are shown in Table 16.30.
flutter with varying conduction, atrial fibrillation (rare Diagnosis and Management of Tachyarrhythmia
in children) and ventricular fibrillation. During a
regular narrow QRS tachycardia, if a P wave is A combined strategy that simultaneously addresses both
identified and has normal morphology, axis and 1:1 P diagnosis and treatment is appropriate. This is determined
and QRS relation, it suggests sinus tachycardia. Absence by the QRS duration on the initial EKG and presence or
of any of the three suggests supraventricular absence of hemodynamic instability. Based on the QRS
tachyarrhythmia. duration, arrhythmias can be classified as narrow and
wide. This is a useful practical classification and serves as
Re-entrant vs automatic tachyarrhythmias: Tachyarrhy an excellent guide to initial treatment. Age specific normal
thmia is generally considered to result from one of the values for QRS duration are given in Table 16.31. As a
three mechanisms: Re-entry, increased automaticity and preliminary step, sinus tachycardia should be excluded.
triggered activity. In children, the first two mechanisms Rates as high as 240/min are occasionally recorded during
account for most important arrhythmias. Clinical and EKG sinus tachycardia. There is always an underlying cause
features together with response to certain medications and for sinus tachycardia and this is usually apparent during
maneuvers help distinguish re-entrant tachyarrhythmia
from those due to increased automaticity. Re-entrant Table 16.29: Initial assessment of arrhythmia
arrhythmias characteristically have a relatively sudden Can the clinical condition result from a cardiac arrhythmia?
onset and termination. Successful termination with DC Is there hemodynamic instability?
cardioversion or overdrive pacing (pacing at rates faster
Is the arrhythmia incessant or episodic?
than the arrhythmia rate) strongly suggests a re-entrant
mechanism. Automatic arrhythmias characteristically Is this a re-entrant arrhythmia or does it involve an automatic
focus?
have a relatively slow onset. Gradual acceleration (warm
up) to the peak rates may be demonstrable at onset and Where is the arrhythmic focus or circuit located?
gradual deceleration (cool down) at termination is seen. Is there an underlying structural heart disease?
Table 16.31 : Normal QRS duration at various age groups Table 16.32: Causes of narrow QRS tachycardia
Age group QRS duration in seconds Site Re-entrant arrhythmias Automatic arrhythmias
0-6 months 0.03-0.07 (0.05) Sinus node Sinus node re-entry Sinus tachycardia
1-5 years 0.04-0.08 (0.06) Atrium Intra-atrial re-entrant Ectopic atrial
arrhythmias following tachycardia
10-15 years 0.04-0.09 (0.07)
cardiac surgery Multifocal atrial
>15 years 0.06-0.09 (0.08) (Fontan, Senning tachycardia
Values represent range (mean) operations)
Atrial flutter
Stable narrow ORS tachycardia Atrial fibrillation
adenosine 140 µg/kg bolus AV node AV node re-entry Junctional ectopic
tachycardia
Accessory Atrioventricular
Failure of the tachycardia to
terminate after adenosine pathway re-entry involving
concealed or manifest
(WPW) pathway
AVNRT Permanent junctional
AVRT
re-entrant tachycardia
Beta blockade,
digoxin, preliminary diagnostic workup (Table 16.33). If a patient
Digoxin,
amiodarone is seen during an episode of tachyarrhythmia, all attempts
beta blockade, should be made to obtain quality data before terminating
amiodarone the arrhythmia. Information that should be specifically
sought includes the P wave morphology and P-QRS
Fig. 16.48: Management algorithm for stable narrow QRS
tachycardia. AVNRT atrioventricular nodal re-entrant relationship. P waves that appear normal during the
tachycardia; AVRT atrioventricular re-entrant tachycardia tachyarrhythmia suggest sinus tachycardia. Ectopic atrial
tachycardia is suggested by abnormal P wave morphology.
the initial evaluation. Fever, circulatory failure, extreme Inverted P waves may be seen when atria are activated in
dehydration, accidental ingestion of drugs and toxic a retrograde fashion as in the case of re-entrant
substances are common examples. Figure 16.48 depicts a tachyarrhythmia involving accessory pathways (AV re
useful treatment algorithm. entrant tachycardia) (Fig. 16.49). Often P waves are not
Narrow QRS tachycardia: Most narrow QRS tachycardias clearly seen on baseline EKG but are unmasked by
(Table 16.32) are reasonably well tolerated and allow a adenosine. Evidence of 2:1 AV conduction as suggested
� ,.,
-.....r
2+1 '-•
t-+-t- " -+-t-1+••• 1-•
1+- i ! Ei
+-11-I .....-tt-t-ll
T C RS !� 8 2 • •• I I '8 2 : 2 I 1 •"��
�
-t -1 +--+- +-
+'�_E t- +1-11-+--t-t--+-;-+-t-
• •
' '
I I I T A
rr ,.. r ,-
I
i
J
L
I I I '-
I - 'j
,-�=
=;....,.: � --· - -_.: :-;: -�
-
-=- :::.: . - ·: _- - -..-.. - - :. -��. - � ;;.;..-:: � � --:-"! - - - - .. � .:-
I I I I I
H-+�-1--+ --
Fig. 16.49: Six-lead ECG. Adenosine was administered to a child with regular narrow QRS supraventricular tachycardia. Note the
tachycardia terminates with a P wave. Note delta waves with short PR interval that is prominently seen in lead I
by a 2:1 P-QRS ratio during a narrow QRS tachycardia Wide QRS tachycardia: Wide QRS complex tachycardias
indicates atrial flutter (Fig. 16.50). Evidence of complete usually result from foci or circuits in the ventricles. Some
AV dissociation (no consistent P-QRS relationship) supraventricular tachycardias can also result in a wide
indicates junctional ectopic tachycardia. QRS configuration. The overall approach is quite similar
to narrow QRS tachycardias, with identification of P
Adenosine administration acts by producing a marked waves, defining P-QRS relationship and determining the
slowing of AV node conduction (Table 16.33). The effect QRS axis configuration (Fig. 16.52).
of adenosine lasts for a few seconds. Side effects are short Demonstrable AV dissociation (inconsistent P-QRS
lived and include flushing, chest pain and dyspnea. relation) suggests ventricular tachycardia (VT). In most
Adenosine needs to be administered rapidly followed by situations, however, it is not easy to distinguish VT from
rapid push of normal saline as a bolus. The recommended SVT. If the patient is stable, administration of adenosine
dose is 50-300 µg/kg. Most re-entrant tachycardias, where will terminate or unmask SVT. If there is no response,
AV node is a part of the circuit (AV node re-entrant treatment for VT should be initiated. In stable patients, it
tachycardia, AV re-entrant tachycardia), will be terminated is better to initiate pharmacologic treatment of VT before
by adenosine. Atrial flutter is seldom terminated by considering cardioversion since the response to initial
adenosine. The transient AV block that results from treatment can help decides long-term therapy. Lignocaine
adenosine administration can unmask flutter waves on is the initial choice; procainamide is an effective
the EKG thereby confirming the diagnosis (Fig. 16.51). alternative; others include amiodarone, sotalol, mexeletine
Similarly transient slowing of AV conduction can unmask and flecanide.
ectopic atrial tachycardia. If adenosine is not available, Unstable wide QRS tachycardia: Wide QRS tachycardia
vagal maneuvres can be attempted. For infants and young with hemodynamic instability is a medical emergency.
children, an ice filled plastic bag placed on the face is the Synchronized cardioversion (0.5-2 J /kg) should be
most effective vagal maneuver. Older children can be performed immediately. For pulseless patients, CPR
encouraged to perform the Valsalva maneuver or carotid should be initiated. Subsequent treatment should follow
sinus massage can be attempted. Eyeball pressure is standard guidelines recommended for pulseless patients
contraindicated in infants. with VT (Fig. 16.53).
Disorders of Cardiovascular System 1457-
Fig. 16.50: Atrial flutter: Regular narrow QRS tachycardia at a heart rate of 150/min. Heart rate was fixed at 150/min for several
hours that was suggestive of underlying arrhythmia. P waves were abnormally broad and tall
. l !"
•·-
r•
1,
-
,c
t
- I
" I
r
14,
� I "-.1 ti,,, If I" i'\ " II � li,'\ V t I '\ I"\
r
Ill II '\/1 rv (�I ,.,, j I I jl'\ i.J IJ �� f..
f
J 11 J " \i n
IY "
\.
''
" I
,I..' \. ., -
I I
I ,_, I J
�It "
1 f J I
V ir ' It
f'I
/I\ II.. 1 '\1 /\" 1/i( "
",I Ml
I f\ I
I\ "'
l( J
f �
. 'i/'" i( 1.,/ \ V
� ,\1 � II V I V
'- I I --
Fig. 16.51 : Response to adenosine administration to a child with atrial flutter. Note the unmasking of flutter waves that are prominently
seen in lead II and Ill. P rate was 300/min. Before administration of adenosine, there was 2: l AV conduction. The blocked P waves
were hidden within the QRS complexes. After administration of adenosine, AV block increased and AV conduction block increased
to 4: 1 unmasking the flutter waves
4sa I Essential Pediatrics
n �/\ �/\'--11�'
Intra-cardiac
Obesity: Obesity influences major cardiovascular risk
- "-V '--1) factors such as dyslipidemia, hypertension, glucose
intolerance and inflammation. Emerging cardiovascular
Surface risk factors like carotid intima media thickness as well as
Fig. 16.52: Wide QRS tachycardia resulting from a re-entrant carotid elasticity has also shown strong association with
circuit involving an accessory pathway in a patient with right childhood obesity. Childhood obesity is managed by a
bundle branch block. Surface ECG, can be mistaken for combination of increased physical activity and dietary
ventricular tachycardia. ECG of the top two rows has been interventions.
obtained directly from the atrium using postoperative atrial wires
as electrodes. The bottom strip is the surface ECG from a Hypertension: Primary or essential hyp ertension is the
monitoring lead. Conversion to sinus rhythm after adenosine is most common form of hypertension in older children and
seen in the last four complexes on the right. a artial contraction, adolescents. Childhood obesity is associated with
P p wave hypertension in children, which often tracks into adulthood.
Dyslipidemia: Screening for dyslipidemia is recommended
Wide QRS tachycardia
for children whose parents and/or grandparents required
coronary artery bypass-surgery or balloon angioplasty
before 55 years, those with family history of myocardial
infarction, angina pectoris, peripheral or cerebrovascular
disease, or sudden death before 55 years, and those whose
parents have dyslipidemia. Youth with dyslipidemia are
treated with a diet low in total and saturated fats and
• If 1: 1 P-QRS relation, try adenosine
• If AV dissociation IV lignocaine
cholesterol. The intake of complex carbohydrates is
1 mg/kg or IV amiodarone 45 mg/kg increased, whereas that of simple sugars is decreased.
• If no response, DC shock Drug therapy is used in patients with significantly
CPR = Cardiopulmonary resuscitation elevated LDL-cholesterol.
Fig. 16.53: Management of wide QRS tachycardia Diabetes mellitus: Diabetes mellitus is associated with
cardiovascular complications, which develop early in
Irregular wide QRS tachycardia: Sustained and irregular childhood and adolescence. Endothelial dysfunction seen
wide QRS tachycardia is uncommon and usually suggests in both types of diabetes is recognized to aggravate
a diagnosis of Wolf-Parkinson-White (WPW) syndrome cardiovascular risk in later life. Optimal daily and long
with atrial fibrillation. In presence of hemodynamic term glycemic control, maintenance of blood pressure and
instability, synchronized cardioversion (1-2 J/kg) is lipid levels in the normal values for age, regular exercise,
indicated. If the patient is stable, procainamide infusion healthy diet and avoidance of smoking are necessary.
may be tried.
Tobacco consumption: Mechanisms by which smoking
Once the arrhythmia has been managed, recurrences exerts its detrimental effects on cardiovascular system
need to be prevented. Most childhood arrhythmias include endothelial dysfunction, increased oxidative
warrant evaluation by a pediatric cardiologist for follow stress, increased arterial stiffness, alterations in lipoprotein
up care and to plan definitive treatment. An echo metabolism and induction of prothrombotic state. School
cardiogram, Holter test (24 hours ambulatory EKG based campaigns to prevent smoking and chewing tobacco
recording) and esophageal electrophysiologic study is are appropriate tools to contain this public health concern.
often required. Invasive intracardiac electrophysiologic Parents should be role models to children by avoiding or
study is combined with radiofrequency (RF) ablation. quitting smoking and chewing tobacco.
Most accessory pathways are now treated by radio Early atherosclerotic disease has been documented in
frequency ablation, especially in older children (>4-year certain conditions in children. The risk category, group of
old). For younger children, RF ablation is reserved for diseases in each category and the prevention oriented
refractory situations. treatment targets are shown Table 16.34.
Disorders of Cardiovascular System 1459-
Suggested Reading
1. Raj M. Obesity and cardiovascular risk in children and adolescents. 2. Raj M, Sundaram KR, Paul M, et al. Obesity in children: time trends
Indian J Endocrinol Metab 2012; 16:13-19. and relationship with hypertension. Natl Med J India 2007; 20:288-93.
Chapter
RENAL ANATOMY AND PHYSIOLOGY (Fig. 17.1). Six to eight distal tubules join to form the
collecting ducts that finally enter the renal pelvis.
Each kidney is composed of approximately a million
nephrons, each consisting of a glomerulus and renal The early part of the distal tubule on its ascent from the
tubule. The glomerulus is made of a tuft of capillaries and medulla to the cortex lies near the glomerulus of the same
a central region of mesangium. The capillaries arise from nephron. The cells of the tubule in contact with the afferent
the afferent arteriole and join to form the efferent arteriole. arteriole are denser than the rest and called macula densa.
The capillary wall consists of fenestrated endothelium, The smooth muscle cells of the afferent arteriole, in this
glomerular basement membrane and foot processes region, contain prominent cytoplasmic granules that are
(podocytes) of visceral epithelial cells. The basement the site of renin activity. The juxtaglomerular apparatus
membrane is made of type IV collagen, laminin and GGA) is composed of afferent and efferent arterioles, the
heparan sulfate proteoglycan. The Bowman space leads macula densa and lacis cells located between these
into the proximal tubule that has an initial convoluted structures. The JGA is involved in systemic blood pressure
portion, then the straight segment, descending and regulation, electrolyte homeostasis and tubuloglomerular
ascending limbs of the loop of Henle and the distal tubule feedback.
Connecting tubule
rn,1a1000,01,1,,
tubule
,nn
Proximal convoluted tubule
Na• (50%) Cortical collecting duct
K + (65-70%)
Thick ascending Na• (2-3%)
loop of Henle K + (2-5%)
Proximal straight tubule
Na•(15%)
Na• (20%)
K + (20-25%)
Medullary collecting duct
Fig. 17. l: Renal tubular handling of sodium and potassium. The major sites of reabsorption are shown, with percentage of filtered
cation in parenthesis
460
Disorders of Kidney and Urinary Tract 1461-
3 Na•
-------------T-...
I
I
I
I
I
I
I
I I Na•
I �-+
I Carbonic
1 anhydrase
Carbonic I
anhydrase't'
t------... Hco3
,
I
H 2 0 + CO 2 - - - - - - - - - - - - - J
r�
lumen fluid lumen fluid
H2 0
H+ + ow 3 Na•
+ Na•
Carbonic �
CO 2 anhydrase
ENaC Aldosterone
y
+
H+
-._�MR
receptor
K+
�K +
a b
c1---------------
to a maximum of 700-800 mOsm/kg whereas the older to posterior urethral valves. Persistent dribbling indicates
child can achieve 1200-1400 mOsm/kg. Growing babies abnormal ureteric insertion distal to bladder neck. Infants
utilize most of the protein available for growth rather than with meningomyelocele should be evaluated for bladder
catabolize to urea. Decreased production and excretion dysfunction. Dysuria, flank pain and ureteric colic suggest
of urea result in a relatively hyposmolar interstitium and UTI or urinary tract calculi.
reduced urinary concentration. The newborn can dilute
urine to a minimum of 50 mOsm/kg, like an older child. Polyuria, Po/ydipsia
However, the time taken to excrete a water load is longer. Impaired urinary concentration is a feature of obstructive
Thus, delayed feeding and overdiluted or concentrated uropathy and primary or secondary tubulointerstitial
feeds are potentially harmful. disorders. Polyuria is also present in conditions associated
with deficiency or resistance to antidiuretic hormone,
Maturation of Renal Function diabetes mellitus, hypokalemia (e.g. distal renal tubular
Renal function continues to improve during the first two acidosis) and hypercalcemia.
years of life, at the end of which, various parameters of
renal function approach adult values, if corrected to Enuresis
standard surface area. Structural growth parallels the Primary monosymptomatic enuresis needs to be distin
functional maturation. guished from patients with dysfunctional voiding. Most
children with nocturnal enuresis have no evidence of renal
Suggested Reading disease. Urinalysis and culture are recommended in
• De Curtis M, Rigo J. Nutrition and kidney in preterm infant. patients with secondary enuresis.
J Matern Fetal Neonatal Med 2012;25 51:55-9.
• Lowenstein J, Grantham JJ. The rebirth of interest in renal tubular Hypertension
function. Am J Physiol Renal Physiol. 2016;310:F1351-5.
• Kastl JT. Renal function in the fetus and neonate-the creatinine
Assessment of blood pressure is necessary in all children,
enigma. Semin Fetal Neonatal Med 2017;22:83-89. and especially those with disorders of the kidneys or
urinary tract. Symptomatic hypertension is chiefly due to
DIAGNOSTIC EVALUATION a renal parenchymal or renovascular cause; endocrine
conditions are uncommon.
Clinical Features of Renal Disease
Hematuria Growth Retardation, Anemia
Gross hematuria in acute GN is typically smoky brown Physical retardation is a feature of advanced chronic
or cola colored. Bright red blood suggests a nonglomerular kidney disease (CKD, stages 3-5) and tubular disorders.
cause, as in renal or vesical calculi. Gross hematuria is Normocytic normochromic anemia is striking in patients
rare in UTI. Other conditions which might impart a red with advanced CKD. Patients with unexplained anemia
color to urine include hemoglobinuria, myoglobinuria, should be evaluated for a renal disease.
porphyria and ingestion of beetroot.
Abdominal Mass
Edema Multicystic renal dysplasia, polycystic kidneys, renal vein
Acute GN presents with facial puffiness and gross thrombosis, hydronephrosis (due to pelviureteric or lower
hematuria; the edema does not pit readily on pressure. If urinary tract obstruction) and Wilms' tumor may result
fluid intake is not restricted, the edema may increase and in palpable masses.
involve hands, feet and legs. In nephrotic syndrome,
edema develops insidiously, starting with eyelid puffiness Examination of Urine
most noticeable in the morning. Over a period of several Urinalysis is an important step for diagnosis of renal
days, there is pitting edema over the feet and legs. Facial disease. Evaluation includes microscopic examination of
swelling is often mistaken for allergy or insect bite. the uncentrifuged as well as centrifuged specimen and
semiquantitative or quantitative detection of different
0/iguria substances.
Oliguria, defined as urine volume less than 0.5 mL/kg/ hr,
commonly results from gastroenteritis and hypo-volemia. Collection of Specimen
Oliguria is an important feature of moderate or severe The first morning specimen is preferred since it is
acute GN, acute tubular necrosis and conditions causing relatively concentrated. While a clean container is
severe glomerular injury (e.g. HUS, vasculitis). sufficient, specimens for culture should be collected in a
sterile container. After cleaning the perineum with soap
Abnormalities of Micturition and water, a 'clean catch' sample is collected. If facilities
A poor urinary stream in boys, especially in presence of a for immediate processing are not available, the specimen
full bladder, suggests obstruction, most commonly due is stored at 4 °C for 12-14 hours.
-464 Essential Pediatrics
C d
Fig. 17 .4: Appearance of casts on urine microscopic examination. [a) White blood cell casts; [b) Red blood cells casts,
(c) Hyaline cast; [d) Granular cast
Disorders of Kidney and Urinary Tract 1465-
L R
a
Time in minutes
Fig. 17 .5: (a] 99mTc-DMSA scintigraphy showing midzonal scars and loss of volume in the right kidney. The left kidney is normal;
(bl Renal dynamic scan with diuretic was performed in a 6-week-old newborn with isolated left hydronephrosis. The excretion of the
tracer on the left side is sluggish and unchanged with administration of diuretic, suggesting an obstructive pattern of excretion, as
seen with pelviureteric junction obstruction
• Schwartz GJ, Munoz A, Michael F, et al. New equations to estimate not infrequent. Gross hematuria is rare in acute pyelo
GFR in children with CKD. J Am Soc Nephrol 2009;20:629-37 nephritis. Conditions that cause persistent microscopic
• Utsch B, Klaus G. Urinalysis in children and adolescent. Dtsch
Arztebl Int. 2014;111:617-25.
hematuria include idiopathic hypercalciuria, benign
familial hematuria, Alport syndrome, IgA nephropathy
and membranoproliferative GN.
HEMATURIA
The presence of blood in urine imparts it a color, which Diagnostic Evaluation
includes various shades of deep red, smoky brown, cola A history of pain in the flank or suprapubic region, dysuria
color and faint pink. Parents may mistake very concen and edema should be obtained. Physical examination
trated urine for that containing blood. Microscopic includes assessment of growth and features of acute or
examination of urine will show red blood cells. Reagent chronic kidney disease such as edema, hypertension,
coated dipsticks detect free hemoglobin and myoglobin. unexplained pallor, bony abnormalities and abdominal
Red urine may be present in porphyria and following mass. An audiogram and a detailed eye examination may
beetroot ingestion. Urine appears orange-colored after be needed. Figure 17.6 shows an algorithm for evaluation
administration of rifampicin or pyridium. Uric acid and of patients with hematuria.
xanthine crystals may also impart a pink tinge to the nappy. A fresh specimen is examined for red cells, red cell casts
In children, the commonest cause of gross hematuria is and protein. Absence of large number of red cells in bloody
postinfectious GN (Table 17.2). Urinary tract stones are urine suggests hemoglobinuria (intravascular hemolysis)
I Red urine I
+
Urine dipstick, microscopy
Urinalysis >5 RBC/high power field
No
I Pigmenturia, drugs J
24 hours urine protein and creatinine Urine spot calcium, creatinine, protein, urate
ASO, anti-DNAse B 24 hours urine calcium, urate, protein, creatinine
ANA, anti-dsDNA, ANCA Urine culture
Blood albumin, cholesterol Spiral CT abdomen
Coagulation screen
Renal Doppler, magnetic resonance venography
Fig. 17.6: Approach to evaluation of a patient with hematurta. The initial step in evaluation attempts to distinguish glomerular from
nonglomerular causes of hematuria (see Table 17.3). Estimation of complement C3 is an important screening test for postinfectious
glomerulonephritis. Patients with persistent glomerular hematuria might require kidney biopsy and/or screening for familial causes. ASO
antistreptolysin O; ANA antinuclear antibody; anti-dsDNA anti-double-stranded DNA antibody; ANCA antineutrophil cytoplasmic antibody
or myoglobinuria. In glomerular disease, urine shows A plain X-ray film of the abdomen and abdominal
dysmorphic red cells, of different shapes, whereas in ultrasound is done to exclude major renal and urinary tract
bleeding from renal pelvis or the lower urinary tract, the anomalies and calculi. Blood levels of creatinine are
red cells maintain normal morphology (Fig. 17.7 and measured; specialized blood tests depend on the likely
Table 17.3). Presence of significant proteinuria (2+ or clinical etiology. Surgical conditions that cause hematuria
more) and/or red cell casts suggests glomerular disease. can be diagnosed by appropriate imaging. Invasive
Hypercalciuria should be screened by determination of procedures such as cystoscopy are rarely indicated.
urinary calcium to creatinine ratio on one or more random In a significant proportion, isolated microscopic
samples. hematuria spontaneously disappears over a period of
several years. Other family members may have similar
urinary abnormalities. If there is no family history, a renal
biopsy is not urgently indicated and the patient kept under
observation.
Renal Biopsy
Renal biopsy should be done, if hematuria is associated
with persistent or heavy (3+ or more) proteinuria, history
of renal disease in the family or evidence of chronic kidney
disease in the patient, or if renal impairment or hyper
tension are seen on follow-up. A biopsy is also considered
in children showing persistent microscopic hematuria for
two or more years even in the absence of the above
Fig. 17.7: Phase contrast microscopy showing dysmorphic red features. This procedure is necessary to diagnose IgA
cells (arrowhead). Normal red cells are also seen (arrow) nephropathy, Alport syndrome, thin basement membrane
468 Essential Pediatrics
disease (typically presents as familial benign hematuria) changes. Persistent and heavy proteinuria, especially if
and chronic GN. The biopsy is evaluated by light, associated with hematuria, should be promptly evaluated.
immunofluorescence and electron microscopy.
Quantitation of Proteinuria
Alport Syndrome
Protein excretion at 100-1000 mg/m2 / day indicates mild
This condition is inherited in an X-linked manner, although to moderate proteinuria; more than that is heavy
autosomal transmission is known. Mutations in the gene (nephrotic range) proteinuria. Accurate quantitative
encoding alpha subunit of collagen IV (COL4A) result in measurements of 24 hours urinary protein are not needed,
persistent microscopic hematuria, moderate proteinuria if semiquantitative tests are done on a concentrated (first
and progressive kidney failure. A significant proportion morning) specimen. Normally, the protein to creatinine
show high frequency sensorineural deafness; ocular defects ratio, in the first morning urine specimen, is below
(lenticonus, cataract, macular changes) are often associated. 0.2 (mg/mg); a ratio of 0.2-2 indicates mild to moderate
Ultrastructural examination of renal biopsy shows variable and >2 heavy proteinuria. The latter usually corresponds
thickness of glomerular basement membrane with lengths to 3+ or 4+ reaction on boiling or dipstick test.
of marked attenuation to areas of lamination. Therapy is Important causes of asymptomatic proteinuria include
supportive, including the use of angiotensin-converting orthostatic proteinuria, chronic glomerular diseases, reflux
enzyme inhibitors. The majority of male patients (X-linked nephropathy, renal hyp oplasia and rarely renal tubular
illness; hemizygous mutations in COL4A5 gene) show disorders (Table 17.4). In orthostatic (postural) proteinuria,
progression to end stage kidney disease. The course the
illness in patients with autosomal recessive illness (mutation Table 17.4: Conditions presenting with proteinuria
in COL4A3 or COL4A4) is also rapid. Glomerular proteinuria
Nephrotic syndrome (minimal change disease, focal segmental
Suggested Reading
glomerulosclerosis, congenital nephrotic syndrome)
• Fiorentino M, Bolignano D, Tesar V, et al; ERA-EDTA Immuno
Membranous
nephrology working group. Renal biopsy in 2015-from epidemiology
to evidence-based indications. Am J Nephrol. 2016;43:1-19. Hepatitis B and C nephropathy, HIV nephropathy
• Hicks J, Mierau G, Wartchow E, Eldin K. Renal diseases associated Reflux nephropathy
with hematuria in children and adolescents: a brief tutorial. Amyloidosis
Ultrastruct Pathl 2012; 36:1-18.
• Indian Pediatric Nephrology Group. Consensus statement on Associated hematuria: Postinfectious glomerulonephritis, lgA
evaluation of hematuria. Indian Pediatr 2006;43:965-73. nephropathy, Henoch-Schonlein nephritis, lupus nephritis, C3
glomerulopathy, Alport syndrome
PROTEINURIA Nonglomerular proteinuria
The glomerular capillaries provide an effective barrier to Drug induced nephropathy (analgesics)
filtration of proteins. Small amounts of protein are filtered Heavy metal nephropathy (e.g. gold, lead, cadmium)
but almost completely reabsorbed by the proximal tubule. Renal tubular acidosis
Detection of more than trace amounts of protein in the urine Interstitial nephritis, pyelonephritis
is abnormal. However, the degree of proteinuria does not Intermittent or transient proteinuria
always reflect the severity of glomerular abnormality. Postural (orthostatic)
Massive proteinuria occurs in minimal change nephrotic Fever
syndrome, in which glomeruli are normal or show mild Exercise
Disorders of Kidney and Urinary Tract 1469-
protein is absent in urine specimen collected after Table 17.6: Indications for renal biopsy in acute glomerulo
overnight recumbence. Continued follow-up is necessary nephritis
until proteinuria disappears. Systemic features. Fever, rash, joint pain, heart disease
A renal biopsy is indicated in presence of persistent or Absence of serologic evidence of streptococcal infection;
heavy proteinuria. Long-term observ�tion is necessar)'.' to normal levels of C3 in the acute stage of illness
monitor clinical course and renal function. The underlymg Mixed features of glomerulonephritis and nephrotic syndrome
cause is treated, where possible. Low salt diet and High blood levels of urea or presence of anuria requiring dialysis
prolonged treatment with angiotensin-converting enz):Ile (rapidly progressive GN)
inhibitors or angiotensin receptor blockers are effective
Delayed resolution
in reducing glomerular proteinuria.
Oliguria, hypertension and/or azotemia persisting past
7-10 days
Suggested Reading Gross hematuria persisting past 3-4 weeks
• Rademacher ER, Sinaiko AR. Albuminuria in children. Curr Opin Nephrotic range proteinuria beyond 2 weeks
Nephrol Hyperten 2009;18:246-51 Low C3 levels beyond 12 weeks
• Vogt B. Nephrology update: glomerular disease in children. FP
Essent. 2016;444:30---40.
Persistent proteinuria beyond 6 months
Poststreptococcal Glomerulonephritis
Clinical Features
Poststreptococcal GN affects school-age children, more
Acute GN following infection by group A beta-hemolytic
commonly boys and is uncommon below 3 yr. Subclinical
streptococci is a common disorder. Streptococcal infection
episodes are more common than overt disease, especially
of the throat or skin precedes the onset of nephritis by 1
during epidemics. The onset is rapid, with puffiness
to 4 weeks. Only a few strains of streptococci are
around the eyes and pedal edema. Urine is cola-colored;
hematuria is brief, often lasting only a few hours and does
Table 17.5: Etiology of the acute nephritic syndrome not persist beyond 1-2 weeks. While the degree of oliguria
Postinfectious correlates with the disease severity, anuria is uncommon.
Hypertension, present in over half the patients, resolves
Streptococci, staphylococci, pneumococci, meningococci,
Treponema pallidum, Salmonella, leptospira
with loss of edema. Atypical presentations include (i)
convulsions due to hypertensive encephalopathy; (ii) left
Plasmodium malariae, P. falciparum, toxoplasma, filaria
ventricular failure and pulmonary edema, due to
Hepatitis B and C, cytomegalovirus, parvovirus, Epstein-Barr
malignant hypertension and hypervolemia; (iii) acute
virus, coxsackievirus, echovirus, varicella
kidney injury; and (iv) nephrotic syndrome.
Associated with severe infections; infection of shunts,
prostheses, bacterial endocarditis
Laboratory Findings
Systemic vasculitis
Urine shows 1-2+ protein with red cells, and red cell and
Henoch-Schonlein purpura
granular casts. White cells indicate glomerular inflam
Microscopic polyarteritis, Wegener granulomatosis mation and should not be regarded as evidence of UTI.
Others Hemodilution may result in normocytic anemia; ESR is
Membranoproliferative glomerulonephritis raised. Blood levels of urea and creatinine are elevated
lgA nephropathy reflecting renal impairment; hyponatremia and hyper
Hereditary nephropathy kalemia occur with continuing oliguria. Chest X-ray may
Systemic lupus erythematosus
show prominent vascular markings suggesting hyper
volemia.
410 I Essential Pediatrics
Fig. 17 .8: (a) Poststreptococcal GN. Moderately severe proliferation and exudative changes with infiltration of neutrophils. A few
open capillary lumina are seen; (bl lmmunofluorescence examination showing extensive fine granular deposition of lgG along
the capillary wall and in mesangium with a starry sky appearance
Serologic evidence for streptococcal infection is present enzyme inhibitors carry risk of hyperkalemia. Patients
in most patients with pharyngitis, though antibiotic with hypertensive emergencies need prompt treatment
therapy may blunt this response. ASO titer is increased in with IV nitroprusside or labetalol.
more than 80% patients; anti-DNase B is elevated in cases Left ventricular failure: Hypertension should be
of streptococcal skin infection. The titers decrease within controlled and IV frusemide given to induce diuresis,
4-6 weeks. The level of serum C3 is low in 90% patients leading to improvement in heart failure. If diuresis is not
but normalizes by 8-12 weeks. Persistent low C3 levels noted, dialysis is initiated. Respiratory support with
indicate other forms of GN. positive end-expiratory pressure may be needed.
Management Prolonged oliguria: Treatment, as outlined above, should
Patients with mild oliguria and normal blood pressure be continued and levels of blood urea, creatinine and
can be managed at home. Close attention to blood pressure electrolytes monitored. Dialysis is required in children
and dietary intake is essential. Treatment with penicillin with severe renal failure and prolonged oligoanuria, fluid
has no effect on the course of the disease, but may be given, overload and life-threatening electrolyte disturbances.
if active pharyngitis or pyoderma is present. The principles Occurrence of secondary infections should be avoided.
of management of patients with severe oliguria and acute
kidney injury are discussed later. Outcome and Prognosis
Diet: The intake of sodium, potassium and fluids is Acute poststreptococcal GN has an excellent prognosis in
restricted until blood levels of creatinine reduce and urine childhood. The symptoms begin to resolve in the first week
output increases. Overhydration may increase the risk of with loss of edema and fall in blood pressure. Gross
hypertension and precipitate left ventricular failure. hematuria and significant proteinuria disappear within
Patients with azotemia require accurate measurement of 2 weeks, although microscopic hematuria and slight
urine output and daily weight, and restriction of fluid proteinuria may persist for several months. Hypertension
intake to an amount equal to insensible losses and 24 hr subsides within 2-3 weeks, but rarely may persist for
urine output. several weeks. Patients with acute GN of nonstreptococcal
etiology have variable and unpredictable outcome. These
Diuretics: Patients showing modest edema are treated cases need close follow-up over several years with periodic
with oral frusemide at a dose of 1-3 mg/kg; the edema urinalyses and measurements of blood pressure.
disappears with the return of renal function. Therapy with
IV frusemide (2--4 mg/kg) is necessary in patients with Renal biopsy: A biopsy is rarely indicated in those
pulmonary edema. suspected to have poststreptococcal GN except when
Hypertension: Mild hypertension may be controlled by renal function is severely impaired beyond 7-10 days or
restriction of salt and water intake. Effective anti serum C3 remains depressed beyond 12 weeks. Patients
hypertensive agents include amlodepine, nifedipine or with features of a systemic illness (e.g. systemic lupus)
diuretics. Beta-blockers and angiotensin-converting require a kidney biopsy (Table 17.6).
Disorders of Kidney and Urinary Tract 1471-
Crescentic Glomerulonephritis
Rapidly progressive GN (RPGN) is defined as an acute
nephritic illness accompanied by rapid loss of renal
function over days to weeks. The histopathological
correlate is the presence of crescents (crescentic GN)
involving 50% or more glomeruli (Fig. 17.9) suggesting
severe glomerular injury. The chief forms of RPGN are:
(i) immune complex crescentic GN (immunofluorescence
showing immunoglobulin and C3 deposits; normal or low
C3), (ii) pauci-immune crescentic GN (related to small
vessel vasculitis; positive antineutrophil cytoplasmic
antibodies; scant immune deposits) and (iii) anti
glomerular basement membrane GN (with anti-GBM
antibodies; linear IgG deposits). There is satisfactory
clinicopathologic correlation and patients with extensive Fig. 17 .10: Henoch-Sch6nlein purpura in a 6-year-old girl
histological changes have poor outcomes. Renal biopsy admitted with severe abdominal pain. Note purpuric rash over
should be performed in all patients with severe nephritic the lower limbs
features, which do not resolve within 1-2 weeks.
The outcome is related to histological severity and patient may present with nephritic or nephrotic syndrome,
prompt institution of therapy. Satisfactory results have hypertension, azotemia and crescentic GN. Therapy with
been obtained with initial administration of IV and oral a combination of oral/IV corticosteroids and cyclophos
corticosteroids and IV cyclophosphamide, followed by phamide initially, followed by maintenance steroids and
maintenance immunosuppression for 2-3 years. Prompt azathioprine is recommended. Long-term outcome
plasmapheresis is recommended for patients with pauci depends on the severity of renal manifestations.
immune crescentic GN and Goodpasture syndrome.
lmmunoglobulin A Nephropathy
Nephritis in Henoch-Schonlein Purpura Predominant deposition of IgA in the glomeruli, chiefly
Henoch-Schonlein purpura (HSP) is the most common in the mesangium and occasionally in capillary walls is
vasculitis in children (Fig. 17.10). Mild renal involvement characteristic. The usual clinical manifestation is
indicated by microscopic hematuria and mild proteinuria recurrent episodes of gross hematuria following upper
is common. Serum IgA levels may be elevated. Renal respiratory infections; each episode lasts for 2-5 days.
biopsy shows mesangial proliferation with mesangial An acute nephritic or nephrotic syndrome is rarely the
deposition of IgA. Most patients recover without any initial manifestation. Renal histology shows mesangial
specific treatment. However, long-term observation is proliferation of varying severity. Patients with
necessary to detect insidious renal damage. Rarely, a hematuria and non-nephrotic proteinuria are treated
using angiotensin-converting enzyme inhibitors.
Therapy with corticosteroids and alkylating agents is
indicated in patients with nephrotic range proteinuria,
deranged renal function or those with severe
histological changes.
Lupus Nephritis
Patients with systemic lupus erythematosus variably
present with asymptomatic proteinuria and/or hematuria,
acute nephritic syndrome and nephrotic syndrome. Renal
biopsy may show almost normal glomeruli, focal or diffuse
proliferative GN or membranous nephropathy. Immuno
fluorescence studies show mesangial and capillary wall
deposits of all immune reactants (full-house deposition).
Antinuclear and double-stranded DNA autoantibodies are
present in most cases with lupus nephritis; C3 levels are
reduced.
Remissions and relapses and progressive renal damage
Fig. 17. 9: Large cellular crescent with compression of glomerular are characteristic. Infections and end stage renal disease
tuft (Masson trichome x 200) are the chief cause of mortality.
472 Essential Pediatrics
Fig. 17.11: (a) Renal histology in a 4-year-old boy with steroid-dependent nephrotic syndrome. There is normal morphology of
glomerular capillary loops, mesangial matrix and cells suggestive of minimal change disease; (b) Histological features in a
6-year-old girl with steroid-resistant nephrotic syndrome secondary to focal segmental glomerulosclerosis. Note the hilar sclerosis
involving large areas of the glomerulus and adhesions to the Bowman's capsule
immunity, which through yet undefined mechanisms increasing edema, urine output may fall. The blood
alters the permselectivity of the glomerular filter, resulting pressure is usually normal; sustained elevation suggests
in proteinuria. A significant proportion of patients shows the possibility of significant glomerular lesions. The
Th2 polarization; some also show perturbation in the T bloated appearance and relative well-being of the child is
regulatory /Thl7 axis. misleading and after the loss of edema, severe muscle
wasting is revealed. Infections may be present at the onset
Clinical Features and during relapses.
The onset is insidious with edema first noticed around
the eyes and subsequently on legs. It is soft and pits easily Laboratory Findings
on pressure. Gradually, edema becomes generalized, with Urine examination shows heavy (3 -4+) proteinuria. Gross
ascites, hydrothorax and hydrocele (Fig. 17.12). With hematuria or persistent microscopic hematuria suggests the
likelihood of significant glomerular lesions; hyaline and
granular casts are present. Serum albumin is low and values
below 1 g/dL are often obtained. Hypercholesterolemia
may impart a milky appearance to the plasma. Blood urea
and creatinine values are within the normal range except
when there is hypovolemia and fall in renal perfusion.
Blood levels of IgG are low and those of IgM elevated;
C3 level is normal. The severity of glomerular damage is
reflected in the passage of proteins of large molecular
weight, chiefly globulin.
Evaluation at onset of nephrotic syndrome includes:
(i) urinalysis for proteinuria, red cells, casts; (ii) blood
levels of urea, creatinine, albumin, cholesterol; (iii)
complete blood counts; and (iv) tuberculin test. Depen
ding on clinical and laboratory findings, the following
additional tests may be required: (i) C3 and antistrepto
lysin O (if gross or persistent microscopic hematuria); (ii)
chest X-ray (positive tuberculin test or history of contact
Fig. l 7.12: An 8-year-old boy with steroid-dependent nephrotic with tuberculosis); (iii) hepatitis B surface antigen (recent
syndrome. Anasarca is seen affecting upper limbs (including jaundice, raised levels of transaminases); (iv) antinuclear
dorsa of hands), trunk and ascites. Note the cushingoid features antibodies (suspected systemic lupus erythematosus); and
and striae on lower abdominal wall and upper legs (v) urine culture (suspected urinary tract infection).
474 I Essential Pediatrics
A renal biopsy is not required to confirm the diagnosis Table 17.8: Definitions regarding course of nephrotic syndrome
of MCNS prior to starting treatment. A biopsy is recom Remission: Urine albumin nil or trace (or proteinuria <4 mg/
mended in children with atypical features at the onset (age m2/hr) for 3 consecutive early morning specimens
below 12 months, gross or persistent microscopic hema
Relapse: Urine albumin 3+ or 4+ (or proteinuria >40 mg/m2/hr)
turia, low blood C3, hypertension or impaired renal for 3 consecutive early morning specimens, having been in
function). Patients who continue to show nephrotic range remission previously
proteinuria despite appropriate steroid therapy require a
Frequent relapses: Two or more relapses in initial six months
biopsy to determine the underlying disorder. or four or more relapses in any 12 months
Steroid dependence: Two consecutive relapses when on
Management of Initial Episode
alternate day steroids or within 14 days of its discontinuation
The child should receive a high protein diet. Salt is restric Steroid resistance: Absence of remission despite therapy with
ted to the amount in usual cooking with no extra salt given. daily prednisolone at a dose of 60 mg/m2/day for 4 weeks and
Any associated infection is treated. Patients should be alternate day for next 4 weeks
screened for tuberculosis. Diuretics are administered, only
if edema is significant. They should be used cautiously and Management of Relapse
overzealous fluid loss avoided. Frusemide (1-4 mg/kg/
day in 2 divided doses) alone or with an aldosterone Relapses are often triggered by minor infections.
antagonist, spironolactone (2-3 mg/kg/day in 2 divided Symptomatic therapy of infectious illness might result in
doses) is adequate. Therapy with corticosteroids results in remission of low grade (1-2+) proteinuria. However,
abolition of proteinuria (remission) usually by 10-14 days, persistence of 3-4+ proteinuria requires treatment for relapse.
diuresis and loss of edema. Prednisolone is given at a dose of 60 mg/m2 / day until
protein is negative/trace for three consecutive days, and then
The first episode of nephrotic syndrome should be on alternate days at a dose of 40 mg/m2 for 4 weeks. Thus,
treated adequately, both in terms of dose and duration of treatment for a relapse usually lasts for � weeks.
corticosteroids, since this is considered an important
The first 2-3 relapses are treated in the manner described
determinant of long-term course. Only prednisolone and
above. Once the pattern of relapses is known, therapy is
prednisone are of proven benefit in the treatment of individualized. Patients with infrequent relapses continue
proteinuria. Either of these agents is given at a dose of to receive treatment for individual relapses as outlined
60 mg/m2/day (maximum 60 mg) in single or divided
above.
doses for 6 weeks, followed by 40 mg/m2 (maximum
40 mg) as a single morning dose on alternate days for the Frequent Relapses and Steroid Dependence
next 6 weeks. Therapy with corticosteroids is then
stopped. Extending initial therapy beyond 12 weeks Patients with frequent relapses or steroid dependence
increases the risk of corticosteroid toxicity without require prolonged treatment in order to maintain disease
significant benefits, and is not recommended. remission.
Long-term Alternate Day Prednisolone
Parent Education Following treatment of a relapse, the dose of prednisolone
The parents should be explained about the disease and is tapered to maintain the patient in remission; usually a
the usual outcome and their cooperation ensured. They small dose is given on alternate days for 9-18 months
are taught how to examine urine for protein, which (Table 17.9). This strategy is effective in maintaining
should be done periodically to detect a relapse early. remission in many patients. Since infections precipitate
During the periods of remission, no dietary restrictions relapses, administering the same small dose daily for
are imposed. 5-7 days starting at onset of infections may prevent
relapses. Relapses, while on this therapy, are treated as
Subsequent Course described above. Patients with repeated relapses, while
A small proportion of patients have only a single episode on long-term therapy, should be considered for treatment
of the illness, while the majority shows relapses. Some with a steroid- sparing agent.
patients have three or less relapses in a year (infrequent
relapsers), while others have four or more relapses Steroid-Sparing Agents
(frequent relapsers) (Table 17.8). About 15% remain in The additional use of an alternative agent should be
remission while on prednisolone therapy and relapse considered in patients with: (i) prednisolone threshold (for
whenever the dose is reduced or within 2 weeks of its maintaining remission) higher than 0.5-0.7 mg/kg on
discontinuation (steroid dependent). About 10% patients alternate days, or (ii) features of corticosteroid toxicity
either do not respond to the initial treatment with (growth failure, hypertension, cataract). The agents used,
prednisolone, or do so transiently and later cease to usually in successive order, are listed below and in
respond (steroid resistant). Table 17.9.
Disorders of Kidney and Urinary Tract 1475-
• Preferred earlier, if relapses are life-threatening (associated with peritonitis, other serious infections or thrombosis) or in presence of significant
steroid toxicity
Levamisole: This immunomodulator is effective in steroid-sparing agents or show high steroid threshold with
reducing relapses in patients with frequent relapsing or steroid toxicity. Cyclosporine A or tacrolimus is
steroid-dependent nephrotic syndrome. After inducing administered, in two divided doses, for 12-24 months
remission, levamisole is administered at a dose of 2- aiming for respective trough levels of 80-120 ng/mL and
2.5 mg/kg on alternate days. Alternate day prednisolone 3-7 ng/mL. Both agents have strong steroid-sparing
is given in decreasing doses, until a dose of 0.3-0.5 mg/ potential, with steroid discontinuation achieved in most
kg is reached, for 3-6 months; it is occasionally possible patients over 6-9 months.
to discontinue steroids altogether. Treatment with Adverse effects are common and include acute and
levamisole is given for 1-2 year or longer. The chief side chronic nephrotoxicity. A renal biopsy is done after
effect is leukopenia, which should be monitored every 2-3 years of continuous therapy. Patients receiving
2 months; others include flu-like symptoms and rash. cyclosporine have cosmetic side effects (hirsutism, gum
hyperplasia), hypertension and hypercholesterolemia.
Cyclophosphamide: Treatment with cyclophosphamide Treatment with tacrolimus is associated with risk of
and alternate day prednisolone is effective in many hyperglycemia, elevated transaminases, diarrhea, tremors,
patients with frequent relapsing or steroid-dependent headache and seizures.
nephrotic syndrome. A 12-week course of treatment may
induce long-lasting remission in 30-40% cases. Side effects Rituximab: This monoclonal anti-CD20 antibody has been
include leukopenia, nausea and vomiting; a high fluid used with success in patients with steroid dependent
intake is ensured to prevent hemorrhagic cystitis. There nephrotic syndrome, with remission lasting 6-18 months.
is risk of gonadal toxicity and malignancies, although at This agent appears to be useful in patients who fail to
the doses and duration used, these risks are minimal. The respond or show toxicity with other therapies.
alkylating agent, chlorambucil has significant additional
toxicities and a low margin of safety, and is not Complications in Nephrotic Syndrome
recommended. The patient should be maintained in remission, as far as
Mycophenolate mofetil: Prolonged treatment with this possible. Relapses should be promptly treated so that the
agent is useful in reducing relapse rates and corticosteroid child does not develop more than minimal edema.
sparing. The lack of renal, hemodynamic and metabolic Edema
toxicity makes it an alternative to calcineurin inhibitors.
Edema is controlled with salt restriction and oral hydro
Chief side effects include gastrointestinal discomfort,
chlorothiazide or frusemide for a few days. Salt must
diarrhea and leukopenia. The dose of the medication is
not be totally stopped and the usual amounts used in
600-1000 mg/m 2/day or 20-25 mg/kg/day in two
cooking should be allowed. For massive edema, higher
divided doses for 12-36 months. Tapering doses of
doses of frusemide along with spironolactone are needed.
prednisolone are given for -6 months.
Infusion of albumin is necessary in cases where serum
Cyclosporine and tacrolimus: Therapy with either of these albumin levels are low causing poor renal perfusion and
agents is indicated in patients that fail to benefit with other oliguria.
476 I Essential Pediatrics
treatment is the achievement of complete remission, although ultrastructural abnormalities of the glomerular
occurrence of partial remission is also satisfactory. Patients basement membrane are present at birth. Elevated levels
who respond to treatment do so within 3-6 months. of alpha-fetoprotein (AFP) in maternal serum and
Adjunctive therapy with angiotensin-converting amniotic fluid enable antenatal screening. The clinical
enzyme inhibitors (e.g. enalapril 0.3-0.6 mg/kg/day, course is complicated by failure to thrive, recurrent
ramipril 6 mg/m2/day) is associated with decrease in infections, hypothyroidism and progression to renal
proteinuria and control of hypertension. Adverse effects failure by 2-3 years.
include dry cough, hyperkalemia and decline in renal Patients with Denys-Drash syndrome show mutations
function. Angiotensin receptor blockers (e.g. losartan, in the WTl gene, congenital nephrotic syndrome, male
valsartan) may be used in case of persistent dry cough pseudohermaphroditism and high risk of bilateral Wilms'
with ACE inhibitors, or as add-on therapy for better tumor. Renal histology is characterized by diffuse
antiproteinuric effect. Therapy with HMG coenzyme-A mesangial sclerosis and there is progressive renal failure.
reductase inhibitors is advised for subjects with persistent Other causes of congenital nephrotic syndrome include
hypercholesterolemia. infections (congenital syphilis, cytomegalovirus disease,
Hypertension must be controlled and infections mana toxoplasmosis) and mutations in PLCEl or NPHS2 genes;
ged appropriately. Edema is minimized with judicious use rarely renal histology may be normal (minimal change
of diuretics. The use of intravenous albumin is indicated in nephrotic syndrome) or show focal segmental glomerulo
cases with (i) symptomatic hypovolemia, (ii) symptomatic sclerosis. Therapy of patients with congenital nephrotic
edema or (iii) marked ascites that is causing respiratory syndrome includes appropriate nutrition, control of
compromise. In cases with hypovolemia, 10-20 mL/kg of edema, thyroxin supplements and reduction of proteinuria
4.5-5% albumin should be infused. Severe symptomatic through ACE inhibitors and/or indomethacin.
edema or ascites may be treated with 0.75-1 g/kg of 20% Regular use of IV albumin infusions (every 2-3 weeks)
albumin, infused over 2 hours, to expand the circulating avoids marked hypoalbuminemia and reduces the need
volume followed by frusemide 1 mg/kg. Close monitoring for hospitalization for managing anasarca.
is essential to avoid fluid overload and pulmonary edema.
Suggested Reading
Congenital Nephrotic Syndrome • Ellis D. Pathophysiology, evaluation, and management of edema
Congenital nephrotic syndrome present in the first in childhood nephrotic syndrome. Front Pediatr 2016; 3:111.
3 months of life with anasarca, hypoalbuminemia and • Gulati A, Bagga A, Gulati S, on behalf of the Indian Society of
oliguria. The etiology of congenital nephrotic syndrome Pediatric Nephrology. Guidelines for management of children with
steroid resistant nephrotic syndrome. Indian Pediatr 2009; 46:35-47.
is heterogeneous. The 'Finnish' form of the disease is
• Indian Pediatric Nephrology Group. Indian Academy of Pediatrics.
inherited in an autosomal recessive manner, with Management of steroid sensitive nephrotic syndrome. Revised
mutations in the gene encoding nephrin (NPHS1). The guidelines. Indian Pediatr 2008; 45:203-14.
characteristic renal histology with microcystic dilation • Sinha A, Menon S, Bagga A. Nephrotic syndrome: State-of-the
of proximal tubules is seen after a few months of life, art. Curr Pediatr Rep 2015; 3:43-61.
41a I Essential Pediatrics
The patient may be asymptomatic and the disease detected Urinary tract infection (UTI) is a common medical problem
on routine urine examination. Others may show failure in children, affecting 3-10% girls and 1-3% boys. They
to thrive, persistent anemia, moderate to severe hyper are an important cause of morbidity and might result in
tension, edema, nocturia, microscopic or gross hematuria, renal damage, often in association with vesicoureteric
bone pains and deformities. reflux (VUR). During infancy, UTis are equally common
in boys and girls because the route of infection is often
Differential Diagnosis hematogenous and boys have a higher incidence of
urinary tract anomalies. Beyond infancy, the incidence is
It might be difficult to distinguish chronic from acute GN.
higher in girls.
The presence of anemia, growth retardation, hypertensive
retinopathy, left ventricular hypertrophy and radiological Microbiology
skeletal changes indicate impaired renal function of long
duration. Examination of the renal biopsy is valuable. UTis are chiefly caused by E. coli the predominant
Urinalysis shows proteinuria, hematuria, white cells and periurethral flora, others include Klebsiella, Enterobacter
casts. Urine specific gravity is fixed and low (around 1.010). and Staphylococcus saprophyticus. Proteus and Pseudomonas
Blood urea and creatinine levels are raised and the infections occur following obstruction or instrumentation;
glomerular filtration rate less than 30 mL/min/1.73 m2 • Candida infection occurs in immunocompromised children
Ultrasonography shows small kidneys with regular outline. or after prolonged antimicrobial therapy.
There is no specific treatment for chronic GN. Treatment Recurrent UTis are observed in 30-50% children, usually
with immunosuppressive drugs does not offer any benefit. within 3 months of the first episode. Predisposing factors
The blood pressure should be controlled and infections for recurrent UTI include female sex, age below 6 months,
treated. If renal function is compromised, the treatment is obstructive uropathy, severe vesicoureteric reflux (VUR),
that of advanced chronic kidney disease. voiding dysfunction, constipation and repeated
catheterization, e.g. for neurogenic bladder. Children
with malnutrition and those receiving immuno
INTERSTITIAL NEPHRITIS suppressive therapy are also susceptible.
This is focal or diffuse inflammatory reaction of renal
interstitium with secondary involvement of tubules and Clinical Features
rarely, glomeruli. Acute interstitial nephritis is usually due Neonates show features of sepsis with fever, vomiting,
to infections or drugs (e.g. ampicillin, cephalosporins). diarrhea, jaundice, poor weight gain and lethargy. The
Common causes of chronic interstitial nephritis include older infant has unexplained fever, frequent micturition
urinary tract obstruction and vesicoureteric reflux. and occasionally convulsions. Gross hematuria is
Interstitial nephritis may be a feature of a systemic uncommon. The presence of crying or straining during
disorder (e.g. systemic lupus, vasculitis, associated with voiding, dribbling, weak or abnormal urine stream and
uveitis); autoantibodies to tubular basement membrane palpable bladder suggest urinary obstruction.
are found in some cases. It is difficult to distinguish between infection localized
The clinical features are nonspecific and include to the bladder (cystitis) and upper tracts (pyelonephritis).
abdominal pain, anorexia, pallor, headache and edema. The distinction is not necessary since most UTI in children
Hypertension is absent. The presence of progressive renal below 5 years of age involve the upper tracts. Patients with
Disorders of Kidney and Urinary Tract 1479-
high fever (>39°C), systemic toxicity, persistent vomiting, Table 17.11: Antimicrobials for treatment of UTI
dehydration, renal angle tenderness or raised creatinine are Medication Dose (mg/kg/day)
considered as complicated. Patients with low grade fever,
dysuria, frequency and urgency and absence of symptoms Parenteral
of complicated UTI are considered to have simple UTI. This Ceftriaxone 75-100, in 1-2 divided doses IV
distinction is important for purposes of therapy. Cefotaxime 100-150, in 2-3 divided doses IV
Important features on evaluation include history of Amikacin 10-15, single dose IV or IM
straining at micturition, incontinence or poor urinary Gentamicin 5-6, single dose IV or IM
stream, voiding postponement and surgery for meningo Coamoxiclav 50-75 of amoxicillin, in 2 divided doses IV
myelocele or anorectal malformation. Finding of palpable Oral
kidney(s), distended bladder, tight phimosis or vulval
Cefixime 8-10, in 2 divided doses
synechiae and neurological deficit in lower limbs suggest
Coamoxiclav 30-50 of amoxicillin, in 2 divided doses
a predisposing cause.
Ciprofloxacin 10-20, in 2 divided doses
Diagnosis Ofloxacin 15-20, in 2 divided doses
Cephalexin 50-70, in 2-3 divided doses
The diagnosis of UTI is based on growth of significant
number of organisms of a single species in the urine. or following treatment, unless symptoms fail to resolve
Significant bacteriuria is a colony count of > 105 / mL of a despite 72 hours of therapy symptoms recur, or
single species in a clean catch sample. Urine may be
contamination of the initial culture is suspected.
obtained by suprapubic bladder aspiration or urethral
catheterization in children below 2 years. Any colonies Imaging Studies
on suprapubic aspiration and >50,000/mL on urethral
Following treatment of the first episode of UTI, plans are made
catheterization are considered significant. The occurrence
for evaluation of the urinary tract. The aim of imaging studies
of significant bacteriuria in absence of symptoms is termed
asymptomatic bacteriuria. is to identify urologic anomalies that predispose to
pyelonephritis, such as obstruction or vesicoureteric
The presence of > 10 leukocytes per mm 3 in fresh reflux, and detect evidence of renal scarring. Renal
uncentrifuged sample, or >5 leukocytes per high power ultrasonography is useful in detecting hydronephrosis or
field in centrifuged sample is useful for screening. Dipstick anomalies of the urinary bladder and may be performed
examination, combining leukocyte esterase and nitrite, has even during therapy for UTI. Micturating cystourethrogram
moderate sensitivity and specificity for detecting UTI. is necessary for the diagnosis and grading of VUR
(Fig. 17.13) and defines urethral and bladder anatomy.
Treatment This procedure may be performed 2-4 weeks after
Once UTI is suspected, a urine specimen is sent for culture treatment of the UTI. DMSA scintigraphy detects cortical
and treatment started. Infants below 3 months of age and scars, which are regions of decreased uptake with loss of
children with complicated UTI should initially receive parenteral renal contours or presence of cortical thinning with
antibiotics. The initial choice of antibiotics is empiric and is decreased volume (Fig. 17.Sa). In order to distinguish scars
modified once culture result is available. While a third from reversible changes of pyelonephritis, this procedure
generation cephalosporin is preferred, therapy with a is done 3-4 months after therapy for UTI.
single daily dose of aminoglycoside is also safe and These investigations should be performed judiciously,
effective (Table 17.11). Once oral intake improves and such that sufficient evaluation is done but at minimum
symptoms abate, usually after 48-72 hours, therapy is risks of radiation exposure. The recommendations of the
switched to an oral antibiotic. The duration of treatment for Indian Society of Pediatric Nephrology on evaluation
complicated UTI is 10-14 days. Older infants and patients following the first UTI are summarized in Table 17.12. All
with simple UTI should receive treatment with an oral infants (<1 year) require evaluation using ultrasonography,
antibiotic for 7-10 days. Adolescents with cystitis may MCU and DMSA scan, since they are at the highest risk of
receive shorter duration of antibiotics, lasting 72 hours. UTI recurrence and scarring. Early detection of high grade
Patients with asymptomatic bacteriuria do not require treatment. VUR or obstructive uropathy allows interventions to
All children with UTI are encouraged to take enough prevent progressive kidney damage. Imaging is less
fluids and empty the bladder frequently. Routine aggressive in older children, but patients with recurrent
alkalization of the urine is not necessary. With appropriate UTI require detailed evaluation for anomalies.
therapy, fever and systemic toxicity reduce and urine
culture is sterile within 24-36 hours. Failure to obtain such Preventing Recurrent UTI
results suggests either lack of bacterial sensitivity to the Prophylactic antibiotics are administered to young infants
medication or presence of an underlying anomaly of the until results of imaging are available. The medication used
urinary tract. A repeat urine culture is not required during should be effective, nontoxic and not alter the gut flora or
-480 Essential Pediatrics
T able 17.12: Evaluation following the first episode of urinary • Okarska-Napierala M, Wasilewska A, Kuchar E. Urinary tract
infection in children: Diagnosis, treatment, imaging-comparison
tract infection
of current guidelines. J Pediatr Urol 2017:S1477-5131:30353-4.
Age Evaluation* • Traisman ES. Clinical management of urinary tract infections.
Below 1 year Ultrasound Pediatr Ann 2016;45:elOB--11.
Micturating cystourethrogram (MCU)
Dimercaptosuccinic acid (DMSA) renal scan VESICOURETERIC REFLUX
1-5 years Ultrasound
Vesicoureteric reflux (VUR) refers to the retrograde flow
DMSA scan
MCU, if ultrasound or DMSA scan is abnormal
of urine from bladder to ureters and pelvis at rest or during
micturition. Pathogenic organisms that might be present in
Above 5 years Ultrasound
the bladder can gain access to the renal parenchyrna, ini
If ultrasound abnormal: MCU and DMSA scan
tiate inflammation and renal scarring (reflux nephropathy).
*Patients with recurrent UTI need d et ailed ev aluation with VUR may be an isolated anomaly (primary) or associated
ultrasonography, DMSA scan and MCU
with other anomalies of the urinary tract (secondary).
VUR is present in 30-35% of children with febrile UTI
Table 17.13: Antimicrobials for prophylaxis of urinary tract infections and is a major risk factor for acute pyelonephritis and
Medication Dose (mg/kg/day) Remarks reflux nephropathy. The latter may result in hypertension,
Cotrimoxazole 1-2 of Avoid in infants renal insufficiency and cause morbidity during pregnancy.
trimethoprim <3-mo-old, glucose- Two techniques are commonly used to detect VUR. The
6-phosphate radiocontrast MCU is commonly used since in addition
dehydrogenase to showing VUR it provides excellent anatomical details
{G6PD) deficiency (Fig. 17.13). The severity of VUR is graded from I to V
Nitrofurantoin 1-2 May cause vomiting (Fig. 17.14). Isotope radionuclide cystography is more
and nausea; avoid sensitive for detecting VUR and causes less radiation
<3-mo-old, G6PD exposure but provides fewer anatomical details.
deficiency, renal
insufficiency Management
Cephalexin 10 Drug of choice in first The proposed guidelines for management of VUR are
3-6 months of life outlined in Fig. 17.15. Randomized trials suggest that
Cefadroxil 5 Alternative agent antibiotic prophylaxis have a modest benefit in reducing
in early infancy the risk of recurrent UTI. Continuous antibiotic
Usually given as single bedtime dose prophylaxis is recommended as the initial treatment for
all children with VUR since it reduces periurethral
induce bacterial resistance (Table 17.13). The medication is colonization and, thereby, the risk of recurrent UTI.
given as a single bedtime dose. Long-term antibiotic Cotrimoxazole or nitrofurantoin is given as a bedtime
prophylaxis is also recommended in patients with VUR and dose. Since the risk of recurrent UTI and renal scarring is
in those with frequent febrile UTI (3 or more episodes in a
year), even if the urinary tract is normal.
Circumcision reduces the risk of recurrent UTI in infant
boys, and might have benefits in patients with high grade
VUR. Children with recurrent UTI and/ or VUR might
have dysfunctional voiding and require appropriate
advice. Constipation should be managed with dietary
modifications and medications as required. Some patients
may require bladder retraining, anticholinergic medi
cations and/ or clean intermittent catheterization.
Suggested Reading
• American Academy of Pediatrics, Subcommittee on Urinary tract
infections. Urinary tract infection: Clinical practice guideline for
the diagnosis and management of the initial UTI in febrile infants
and young children 2 to 24 months. Pediatrics 2011;128:593-610.
• Garcia-Roig ML, Kirsch AJ. Urinary tract infection in the setting of
vesicoureteral reflux. FlOOORes. 2016 June 30;5.
• Indian Society of Pediatric Nephrology. Revised statement on Fig. 17 .13: Mlcturating cysotourethrogram showing bilateral
management of urinary tract infections. Indian Pediatr 2011; grade V vesicoureteric reflux in a girl with recurrent UTI. Note the
48:709-17. dilatation, tortuosity of ureters and cupping of the calyces
Disorders of Kidney and Urinary Tract 1481-
• •
imaging is performed, if ultrasonography is abnormal.
Grades I and II Grades Ill to V
Outcome
Antibiotic prophylaxis Antibiotic prophylaxis till 5-year-old
till 1-year-old Continue beyond 5 years, if bowel Primary VUR tends to resolve by 6-10 years of age. Factors
bladder dysfunction is present favoring resolution are younger age and low grade and
unilateral VUR. The rate of resolution is 70-90% for grades
Breakthrough febrile UTI
Consider surgery I
I-III and 10-35% for higher grades.
Reflux Nephropathy
Fig. 17 .15: Management of vesicoureteric reflux. Medical This is characterized by renal cortical scarring, pre
therapy is based on the principle that VUR resolves over time, dominantly at the poles. The underlying calyces lose their
and prophylactic antibiotics maintain urine sterility and prevent normal concave shape and show clubbing. Such scarring
infections while awaiting spontaneous resolution. Reflux takes occurs early in life when the kidneys are still growing.
longer to resolve, if associated with bowel bladder dysfunction Reflux nephropathy is an important cause of hypertension
or if high grade reflux is present; such patients require prolonged and end stage renal disease in children.
prophylaxis. Surgical correction of VUR is indicated, if break
through infections occur, since significant parenchymal injury
Suggested Reading
may occur with pyelonephritis
• Neveus T, von Gontard A, Hoebeke P, et al. The standardization
of terminology of lower urinary tract function in children and
low after 4-5 years of age, prophylaxis may be adolescents: report from the standardization committee of the
discontinued in children older than 5 years with normal International Children Continence Society. J Urol 2006;176:314-24.
bowel and voiding habits, even if mild to moderate reflux • Peters CA, Skoog SJ, Arant BS, et al; American Urological
persists. Association Education and Research. Summary of the AUA
guideline on management of primary vesicoureteral reflux in
Other measures to be instituted include a liberal fluid children. J Urol 2010;184,1134-44.
intake, regular and complete bladder emptying and local • Skoog SJ, Peters CA, Arant BS, et al. American Urological
toilet. Constipation should be avoided. A close follow-up Association Education and Research. Pediatric vesicoureteral reflux
is required for occurrence of breakthrough UTI. guidelines panel summary report: Clinical practice guidelines for
The indications for surgical correction of primary VUR screening siblings of children with vesicoureteral reflux and
neonates/infants with prenatal hydronephrosis. J Urol 2010;
are limited and include poor compliance or intolerance to 184:1145-51.
medical treatment. Patients with grades III to V reflux may • Yeung CK, Chowdhary SK, Sreedh B. Minimally invasive
be offered surgical repair, if they have breakthrough management for vesicoureteral reflux in infants and young
febrile UTI, if parents prefer surgical intervention to children. Clin Perinatol 2017;44:835-49.
482 Essential Pediatrics
ACUTE KIDNEY INJURY back into the circulation across the damaged tubular
epithelium and tubular obstruction from impaction of
Acute kidney injury (AKI) or acute renal failure (ARF)
casts and cellular debris results in oliguria. While early
denotes an acute impairment of renal function resulting
stages are rapidly reversible by infusion of fluids,
in retention of nitrogenous wastes and other metabolic
prolonged or severe ischemia may lead to acute tubular
derangements. Oliguria or anuria is a prominent feature,
necrosis. Nephrotoxic agents cause uniform epithelial
though rarely urine output may be normal.
damage, especially in the proximal tubules, without
disruption of tubular basement membrane.
Definition and Classification In acute tubular necrosis, examination may be normal
In the absence of a standard definition of ARF, the term except for dehydration. The oliguric phase lasts about
acute kidney injury (AKI) is proposed to reflect the entire 3-10 days, during which period the biochemical and
spectrum of the disorder. Patients are diagnosed to have clinical abnormalities gradually worsen, more rapidly if
AKI, if there is abrupt reduction in kidney function, infection, trauma and bleeding are associated. Subse
defined as either (i) absolute increase in serum creatinine quently, urine output increases steadily. A diuretic phase
of more than or equal to 0.3 mg/dL over 48 hours, or a may be observed, usually lasting for a week, during which
percentage increase of more than or equal to 50% from large amounts of water and electrolytes may be lost.
baseline in last 7 days, or (ii) reduction in urine output
(less than 0.5 mL/kg/hr for >6 hours). The inclusion of Approach to Evaluation
both an absolute and a percentage change in creatinine History provides clues to the underlying cause of AKI. It
allows for variations related to age, gender and body mass is important to examine for prerenal factors that lead to
index. Table 17.14 shows the classification of AKI. renal hypoperfusion. A history of diarrhea, vomiting, fluid
or blood loss is taken and assessment of fluid intake in
Incidence and Etiology the previous 24 hours made. In patients with nephro
The etiology of AKI is classified as prerenal, intrinsic renal toxicity or intravascular hemolysis, urine output is often
or postrenal (Table 17.15). The chief causes of AKI include not diminished (nonoliguric renal failure).
acute tubular necrosis (ATN) secondary to hypovolemia, Laboratory evaluation (Table 17.16) includes blood
sepsis and nephrotoxic agents, acute glomerulonephritis counts and estimation of blood levels of urea, creatinine,
and hemolytic uremic syndrome (HUS). Postrenal failure electrolytes, pH and bicarbonate and urinalysis. In
is consequent to mechanical obstruction in the collecting prerenal azotemia, the renal tubular function is intact and
system. In developing countries, common causes include reabsorption of water and sodium is increased. The urine
septicemia with multiorgan failure, HUS, gastroenteritis is concentrated with low sodium content. Impaired
with dehydration, postinfectious and crescentic GN and tubular function in intrinsic renal failure results in
intravascular hemolysis. In developed countries, AKI increased sodium excretion and failure to concentrate
follows major surgical procedures, HUS and severe urine. Determination of urine sodium and osmolality and
systemic infections. fractional excretion of sodium help in differentiating
functional oliguria (prerenal) from established (intrinsic)
Pathophysiology renal failure. Ultrasonography is a useful imaging tool in
renal failure since it allows visualization of the pelvi
Prerenal failure is secondary to systemic hypovolemia or calyceal system and assessment of the renal size, structural
renal hypoperfusion, where renal tubular injury leads to anomalies and calculi, and does not depend on renal function.
marked decline in glomerular filtration and renal blood Most patients with AKI do not require a renal biopsy.
flow, often by 50 to 75%. Leakage of glomerular filtrate Indications for biopsy are: (i) rapidly progressive or
Table 17.14: Staging of acute kidney injury (AKI), based on KDIGO criteria*
Stage Serum creatinine Urine output
1 Increase in serum creatinine of �0.3 mg/dL over Less than 0.5 mUkg per hour for >6 hours
48 hours or �150% to 200% (1.5- to 2-fold) from
baseline in last 7 days
2 Increase in serum creatinine to more than 200% Less than 0.5 mUkg per hour for >12 hours
to 300% (>2- to 3-fold) from baseline
3** Increase in serum creatinine to more than 300% Less than 0.3 mUkg per hour for 24 hours, or anuria for 12
hours (>3-fold) from baseline (or serum creatinine
�4.0 mg/dL with acute increase of �0.5 mg/dL)
*Only one criterion (creatinine or urine output) should be fulfilled to qualify for a stage
**Patients receiving renal replacement therapy (RRT) are considered in stage 3
KDIGO: Kidney Disease Improving Global Outcomes
Disorders of Kidney and Urinary Tract 1483-
Table 17.15: Important causes of acute kidney injury Table 17.16: Investigations in patients with acute kidney injury
Prerenal failure Complete blood counts
Hypovolemia (dehydration, blood loss, diabetic ketoacidosis) Blood: Urea, creatinine, sodium, potassium, calcium,
T hird space losses (septicemia, nephrotic syndrome) phosphate, pH, bicarbonate
Congestive heart failure Urinalysis; culture
Perinatal asphyxia Urine: Sodium, osmolality, fractional excretion of sodium
Drugs (ACE inhibitors, diuretics) Chest X-ray (for fluid overload, cardiomegaly)
Intrinsic renal failure Abdominal ultrasonography
Acute tubular necrosis Investigations to determine cause
Prolonged prerenal insult (see above) Peripheral smear examination, platelet and reticulocyte count,
Medications: Aminoglycosides, radiocontrast, NSAIDs complement (C3), LOH levels; stool shigatoxin (suspected
Exogenous toxins: Diethylene glycol, methanol hemolytic uremic syndrome)
lntravascular hemolysis, hemoglobinuria Blood ASO, C3, antinuclear antibody, antineutrophil cytoplasmic
Tumor lysis syndrome antibody (suspected acute, rapidly progressive GN)
Hemolytic uremic syndrome: Infection associated, atypical Doppler ultrasonography (suspected arterial, venous
Glomerulonephritis (GN) thrombosis)
Postinfectious GN Renal biopsy (specific diagnosis feasible)
Systemic disorders: SLE, Henoch-Schonlein syndrome,
microscopic polyangiitis includes measurement of blood pressure, search for signs
Membranoproliferative GN of congestive heart failure, fluid overload, acidosis and
Interstitial nephritis (drug-induced, idiopathic) anemia. Complications such as dehydration or fluid
Bilateral renal vessel occlusion (arterial, venous) overload, hypertension, heart failure, severe anemia,
Postrenal failure
hyperkalemia and acidosis require urgent treatment.
Posterior urethral valves, urethral stricture Fluid Repletion
Bilateral pelviureteric junction obstruction
Prerenal ARF responds to fluid replacement with
Ureteral obstruction (stenosis, stone, ureterocele)
improved renal perfusion and increased urine output.
Neurogenic bladder
Dehydration is corrected by infusion of 20-30 mL/kg of
NSAIDs: Nonsteroidal anti-inflammatory drugs; SLE: Systemic lupus normal saline or Ringer's lactate over 45-60 min. If
erythematosus hemorrhage accounts for vascular collapse, blood
transfusion should be given. Potassium should not be
nonresolving glomerulonephritis; (ii) AKI associated with administered until urine flow is established; care is taken
underlying systemic disorder, e.g. lupus erythematosus, to avoid overhydration. Patients with renal hypoper
Henoch-Schonlein purpura; (iii) suspected interstitial fusion, in whom the only reason for oliguria is intra
nephritis; (iv) clinical diagnosis of acute tubular necrosis vascular volume depletion, respond to fluids with increase
or HUS, if significant dysfunction persists beyond 2-3 in urine output (-2 mL/kg over 2-3 hours). Appropriate
weeks; (v) underlying cause of AKI not apparent on fluid therapy should be continued. However, if no diuresis
clinical features and investigations. Patients with severe occurs despite correction of dehydration, frusemide
azotemia might require dialysis prior to biopsy to reduce (1-2 mg/kg IV) may be given. If these measures fail to
the risk of bleeding. Figure 17.16 indicates representative induce diuresis, a diagnosis of AKI is likely.
diagnoses on histology.
Occasionally, a patient with undetected chronic kidney Fluid Restriction
disease may present for the first time with acute onset of In patients with AKI, fluid retention may result from
oliguria. History of previous renal disease may be present. excessive oral or parenteral fluids, and leads to edema,
The presence of the following suggests the possibility of hypertension and heart failure. Daily fluid requirement
chronic kidney disease: (i) retarded physical growth, is restricted to insensible water losses (300-400 mL/m2),
(ii) severe anemia, (iii) hypertensive retinopathy, urine output and extrarenal fluid losses. This is usually
(iv) hypocalcemia, hyperphosphatemia and high para given orally; intravenous fluids are not required.
thormone, (v) radiologic features of mineral bone disease Intake-output monitoring, daily weight, physical exami
and (vi) small kidneys on imaging. nation and serum sodium guide fluid management. If fluid
in an appropriate volume and composition is given, the
Management patient should lose 0.5-1% of weight every day and serum
Prompt clinical and laboratory evaluation is necessary. sodium should stay within normal range. A rapid weight
Management includes treatment of life-threatening loss and rising sodium suggest inadequate fluid
complications, maintenance of fluid and electrolyte balance replacement, while absence of weight loss and low serum
and nutritional support. Evaluation for complications sodium indicate fluid excess.
484 Essential Pediatrics
Fig. 17 .16: Photograph of kidney biopsy showing (a) Acute tubular necrosis/injury in the form of simplification of proximal tubular
epithelium along with fine granular casts in some tubular lumina (H & E 200x); (bl Patch of acute cortical necrosis involving glomeruli,
tubules and interstitium with adjacent relatively preserved cortical parenchyma (H & E 40x); (c) Thrombotic microangiopathy, suggested
by glomeruli with marked endothelial swelling, capillary lumina occluded by fibrin thrombi and mesangiolysis; (d) Thrombotic
microangiopathy, suggested by glomeruli showing endothelial swelling and detachment widened subendothelial spaces, and
arterioles showing intimal hyperplasia, endothelial swelling and lumen occluded by platelet thrombi (arrow)
Dopamine at low doses causes renal vasodilatation and interstitial nephritis is suspected, the offending agent
may induce a modest natriuresis and diuresis. However, should be withdrawn and oral corticosteroids given.
it has no beneficial effect on the outcome of AKI, and may
be associated with transient tachyarrhythmia or tissue Dialysis
ischemia. Hence, its use for prevention or treatment of
acute tubular necrosis is not recommended. The role of AKI requiring dialysis can be managed with multiple
other medications, including fenoldopam, atrial natriuretic modalities, including peritoneal dialysis, intermittent
peptide and calcium channel blockers is investigational. hemodialysis and continuous hemofiltration or hemodia
filtration. The purpose of dialysis is to remove endogenous
Treatment of Complications and exogenous toxins and maintain fluid, electrolyte and
acid-base balance until renal function recovers.
In a child with ARF, immediate attention is directed
towards detection and management of life-threatening Indications for dialysis include persistent hyperkalemia
complications. Table 17.17 lists important complications (>6.5 mEq/L), fluid overload (pulmonary edema, severe
and measures for their management. Children with hyp ertension), uremic encephalopathy, severe metabolic
pulmonary edema and congestive cardiac failure may acidosis (bicarbonate <10-12 mEq/L) and hyponatremia
require endotracheal intubation and assisted ventilation. ( <120 mEq/L) or hyp ernatremia. The decision to institute
Severe acidosis is treated by administration of sodium dialysis should be based on assessment of the patient and
bicarbonate, and, if persistent, dialysis. keeping in view the likely course of AKI. Dialysis should
Infections, including respiratory and urinary tract, begin early to prevent life-threatening complications.
peritonitis and septicemia, are important causes of death. The choice of dialysis modality is influenced by several
Procedures should be performed with aseptic techniques, factors, including goals of dialysis, the advantages and
IV lines carefully watched, skin puncture sites cleaned, disadvantages of each modality and institutional resources
and long-term catheterization of the bladder avoided. (Table 17.18).
Specific Therapy Peritoneal dialysis: Peritoneal dialysis does not require
Patients with atypical HUS benefit from plasma exchanges. vascular access and sophisticated equipment and is easy to
Immunosuppressive medications and plasma exchange perform even in neonates. It is often the initial renal
are useful in dialysis-dependent patients with vasculitis, replacement therapy of choice in sick and unstable infants.
crescentic GN or systemic lupus erythematosus. If Peritoneal access is obtained using a stiff catheter and trocar,
or a soft silastic catheter (see Chapter 29). The abdominal The most important complication is peritonitis.
skin is prepared as for a surgical procedure. Dialysis fluid Meticulous aseptic precautions will minimize its incidence.
is infused 30-50 mL/kg, left in the peritoneal cavity for 30- Stiff catheters should be removed after 48-72 hours, beyond
60 min and then drained using siphon effect (Fig. 17.17a). which the risk of infection is very high. The risk of injury
Initially 30-40 cycles are carried out. Commercially available to viscera and infections is considerably less with soft
dialysates are lactate based and with a dextrose concentration silastic (Tenckhoff or Cook) catheters, which, therefore, can
of 1.7%. In patients with fluid overload, the concentration be used for prolonged periods. While the standard
of dextrose is increased to 2.5--3% to facilitate ultrafiltration. (double-cuff) Tenckhoff catheter needs to be placed
Potassium is not added in the first 5-10 cycles, to enable surgically, a temporary (peel away) catheter is inserted
correction of hyperkalemia. Later, 3-4 mEq/L potassium bedside. The use of an automated cycler is preferred to
chloride is added to the dialysate. The results of peritoneal manual peritoneal dialysis.
dialysis are gratifying. In acute tubular necrosis, often a single
Hemodialysis: Hemodialysis is efficient for correction of
dialysis is adequate. The procedure can be repeated, if
fluid and electrolyte abnormalities. It is expensive to
necessary.
Hemodialysis machine
Solution bag
Pure
+- water
i !
0 0
Dextrose Blood I
!
---1
06 pump :I--------
Drain :I Fresh
0 dialysate
Drainage bag 0
0 C:,. ----------------------------------------------
0 0 C:,.
0 6
b
a 0 0
Fig. 17.17: Modalities of dialysis for acute kidney injury. (a) Peritoneal dialysis is based on solute exchange and water transfer
across the peritoneal membrane, driven by the concentration gradient and high dextrose content of the dialysate. (b) Hemodialysis
requires blood to be pumped outside the body via a large bore double lumen catheter, followed by the exchange of solute and
ultrafiltration of water across a synthetic hemodialyser membrane into a dialysate; the purified blood is then returned into the
bloodstream via the same catheter
Disorders of Kidney and Urinary Tract 1487-
institute, and requires expertise and skilled nursing. The volemia secondary to dehydration, intraventricular
procedure might not be suited for patients with hemo hemorrhage, heart disease and postoperatively, (iii) sepsis
dynamic instability, bleeding tendency and in young with hypoperfusion; (iv) delayed initiation and inadequacy
children with difficult vascular access. of feeding in early neonatal period; (v) increased insensible
The equipment required are the hemodialysis machine, losses (due to phototherapy, radiant warmers, summer
pediatric dialyzer with tubings and dialysate fluid heat), twin-to-twin transfusions and placental hemorrhage;
(Fig. 17.17b). These dialyzers are available in different sizes (vi) nephrotoxic medications, e.g. aminoglycosides,
(0.5-1.5 m2) and selection depends upon patient size and indomethacin; maternal intake of AC E inhibitors,
ultrafiltrate properties. Vascular access is necessary for nimesulide; and (vii) renal vein thrombosis, e.g. in infants
removing and returning large quantities of blood required of diabetic mothers, severe birth asphyxia, dehydration,
for the procedure. This is usually achieved using a double polycythemia and catheterization of umbilical veins. AKI
lumen catheter inserted into the internal jugular, femoral may occasionally be the first manifestation of a congenital
or subclavian vein. Most children are maintained on a anomaly of the urinary tract.
hemodialysis regimen of 3-4 hours, three times a week. Renal failure is suspected in the presence of oliguria
Sick patients with fluid overload benefit from daily (urine output <0.5 mL/kg/hr) or blood creatinine >1.2 mg/
dialysis initially. dL. Serum creatinine levels are high at birth (reflecting
maternal levels) and decrease to below 0.5 mg/dL by 5-7
Continuous renal replacement therapies (CRRT): CRRT is
days of age. Failure of reduction or rise of serum creatinine
any extracorporeal blood purification therapy intended to
indicates impaired renal function.
substitute for impaired renal function over an extended
period of time and applied for, or aimed at being applied The principles of management are similar to that for
for, 24 hours a day. Various modalities include [continuous older children. Fluid should be limited to insensible
arteriovenous hemofiltration (CAVH)], [continuous (30 mL/kg/day for full-term, 50-100 mL/kg/day for
venovenous hemofiltration (CVVH)], continuous veno preterm neonates), gastrointestinal and renal losses.
venous hemodiafiltration (CVVHDF) and slow continuous Extremely premature neonates nursed in radiant warmers
ultrafiltration (SCUF). These therapies are useful when large require extra fluids. Systolic blood pressure more than
amount of fluids have to be removed in sick and unstable 95-100 mm Hg may need treatment.
patients. CVVH is preferred modality in AKI secondary to Extra care should be taken while dialyzing neonates;
major surgical procedures, bums, heart failure and septic peritoneal dialysis is technically easier and preferred.
shock, especially when conventional hemodialysis or However, sudden distention of peritoneal cavity may
intermittent peritoneal dialysis is not possible. cause respiratory embarrassment or apnea. Hypothermia
should be avoided by carefully warming the dialysis fluid.
Slow long extended daily dialysis (SLEDD): Sick patients A number of drugs are dialyzable and appropriate
often benefit from hybrid treatments that combine the amounts should be added to supplement for their losses.
advantages of CRRT and feasibility of hemodialysis. SLEDD
is done daily for an extended but limited period (8-10 hours) Suggested Reading
using low dialysate flow rates and at the same time • Ciccia E, Devarajan P. Pediatric acute kidney injury: prevalence,
minimizing the cost and technical complexities of CRRT. impact and management challenges. Int J Nephrol Renovasc Dis
2017; 10:77-8.
Outcome • Jetton JG, Askenazi DJ. Update on acute kidney injury in the
AKI carries a mortality of 20-40%, chiefly related to the neonate. Curr Opin Pediatr 2012; 24:191-6.
• Moore PK, Hsu RK, Liu KD. Management of acute kidney injury:
underlying etiology and duration of renal failure. Patients Core curriculum 2018. Am J Kidney Dis 2018; 72:1-13.
with septicemia and HUS with prolonged anuria are • Ricci Z, Goldstein SL. Pediatric continuous renal replacement
associated with poor prognosis. The outcome in crescentic therapy. Contrib Nephrol 2016; 187:121-30.
GN and vasculitis depends on the severity of the renal • Selewski DT, Goldstein SL. The role of fluid overload in the
injury and promptness in initiation of specific therapy. prediction of outcome in acute kidney injury. Pediatr Nephrol. 2018;
The outlook is satisfactory in acute tubular necrosis 33:13-24.
without complicating factors. Other factors associated
with poor outcome include delayed referral, presence of HEMOLYTIC UREMIC SYNDROME
complicating infections and cardiac, hepatic or respiratory Hemolytic uremic syndrome is a heterogeneous group of
failure. Maintenance of nutrition and prevention of disorders that are a common cause of AKI in children.
infections is crucial in improving outcome. They are characterized by microangiopathic hemolytic
anemia, thrombocytopenia and acute renal insufficiency.
Acute Renal Failure in Newborn Two broad subgroups are recognized; the first is more
Newborns are at high risk of AKI. Important causes common, occurs in young children and is associated with
include: (i) perinatal hypoxemia, associated with birth shigatoxin producing enteropathogens (shigatoxin
asphyxia or respiratory distress syndrome; (ii) hypo- associated HUS), whereas the second is uncommon, affects
488 I Essential Pediatrics
children of all ages and is associated with abnormalities (Figs 17.16c and d). The capillary lumen is narrowed by
of the alternative complement pathway (complement swollen endothelial cells, blood cells and fibrin thrombi.
associated or atypical HUS). Arterioles may show similar changes. Patchy or extensive
renal cortical necrosis may be present. HUS is diagnosed
Shigatoxin-Associated HUS on clinical and laboratory features, and a renal biopsy is rarely
Verotoxin-producing E. coli (in North America and required.
Europe; most commonly 0157: H7; 0104:H4 in a recent Treatment
epidemic) and Shigella dysenteriae 1 (in south Asia) cause
the diarrheal prodrome preceding HUS. Cytotoxin Treatment includes management of complications of renal
mediated injury to endothelium in the renal micro failure, treatment of hypertension and correction of
vasculature leads to localized coagulation and fibrin anemia. Proper nutrition must be ensured. Peritoneal or
deposition. As red cells and platelets traverse these hemodialysis may be necessary to prevent complications
damaged vessels, they are injured and sequestered. of renal insufficiency. Repeated plasma exchange with
Though the brunt of the microvascular injury is on the infusion of fresh frozen plasma is recommended for
kidney, other organs especially the brain may be affected. patients with atypical HUS. Plasma exchanges are initiated
Since chiefly shigatoxins 1 and 2 are implicated, the illness as early as possible, performed daily until hematological
is also called shigatoxin E. coli-related hemolytic uremic remission, and then less frequently. Patients with anti
syndrome (STEC-HUS). factor H antibodies benefit from immunosuppression with
agents that reduce antibody production. The use of
Atypical HUS eculizumab, a high affinity monoclonal antibody targeted
against CS, benefits patients with HUS associated with
This condition often lacks the prodromal history of activation of the complement cascade. While effective in
diarrhea or dysentery, but may be triggered by minor ensuring hematological and renal remission, the
infections. The onset may be insidious or present with a medication is not available in the country.
rapidly progressive illness. Microangiopathic lesions
chiefly affect interlobular arteries and result in severe Outcome
hypertension and progressive renal insufficiency.
Predisposing factors include mutations in regulators of Mortality during the acute episode of shigatoxin
the complement pathway (factors H, I and B, C3, associated HUS is low. On follow-up, 20-30% patients
membrane cofactor protein and thrombomodulin), and show varying degree of residual renal damage. Factors
antibodies against complement factor H. suggestive of poor outcome include oligoanuria for more
than 2 weeks, severe neurological involvement and
Clinical and Laboratory Features presence of cortical necrosis. The acute and long-term
outcome in atypical HUS is unsatisfactory, though the
Children of all ages may be affected. Following a prognosis has improved with supportive measures.
prodrome of acute diarrhea, dysentery or a febrile illness, Recurrent episodes of HUS may occur, including in the
patients show sudden onset of pallor and oliguria. Blood allograft after renal transplantation.
pressure may be high. Focal or generalized seizures and
alteration of consciousness are common. Many patients Suggested Reading
do not show a prodromal illness.
• Ariceta G, Besbas N, Johnson S, European Pediatric Study Group
The blood film shows broken and distorted red cells, for HUS: Guideline for the investigation and initial therapy of
increased reticulocyte count and high blood levels of LOH. diarrhea negative hemolytic uremic syndrome. Pediatr Nephrol
Coombs' test is usually negative except in S. pneumoniae 2009, 24:687-96.
associated HUS where the test is positive. Thrombo • Fakhouri F, Zuber J, Fremeaux-Bacchi V, Loirat C. Haemolytic
uraemic syndrome. Lancet. 2017; 390(10095):681-696.
cytopenia is usually present; neutrophilic leukocytosis is
• Loirat C, Fremeaux-Bacchi V. Atypical hemolytic uremic syndrome.
seen in patients with shigellosis. Urine shows microscopic Orphanet J Rare Dis 2011; 8:6-60.
hematuria and mild proteinuria. Blood levels of urea and • Walsh PR, Johnson S. Treatment and management of children with
creatinine reflect the severity of renal failure. In patients haemolytic uraemic syndrome. Arch Dis Child 2017; doi: 10.1136/
with STEC-HUS, establishing etiology requires either stool archdischild-2016; 311-377.
culture or PCR for STEC or ELISA for shigatoxin. Serum
complement C3 levels are low in some patients with CHRONIC KIDNEY DISEASE
atypical HUS. Detailed analysis of components of the Chronic kidney disease (CKD) is defined as kidney
alternative complement pathway and its regulators is damage lasting for at least 3 months, as characterized by
recommended in all patients with atypical HUS. structural or functional abnormalities of the kidney with
On renal biopsy, the endothelial cells are swollen and or without decreased glomerular filtration rate (GFR).
separated from the basement membrane with accu Abnormalities may include structural malformations (e.g.
mulation of foamy material in the subendothelial space hydronephrosis, single kidney), pathological conditions
Disorders of Kidney and Urinary Tract I 489 -
(e.g. focal segmental glomerulosclerosis) and markers of frequent passage of urine, nocturia and increased thirst.
kidney damage such as abnormal urinalysis (hematuria, Anemia that is usually normocytic and normochromic is
proteinuria) or biochemistry (persistently increased serum chiefly due to reduced renal erythropoietin production.
creatinine). CKD is divided into 5 stages, based on level Mild hemolysis and blood loss from gastrointestinal tract
of GFR estimated from level of serum creatinine and height may also contribute.
using the modified Schwartz formula (Table 17.19). Since Resistance to the action of growth hormone, the levels
renal maturation increases from infancy to reach adult of which are increased, is considered to be responsible
values at the age of 2 years, CKD stages apply only to for growth failure. Anorexia, malnutrition and skeletal
children beyond >2-year-old. Terms such as chronic renal deformities contribute to growth retardation. Abnormalities
failure and end stage renal disease are avoided. Important in metabolism of calcium and phosphate and bone disease
conditions resulting in CKD are listed in Table 17.20. results from hyp erphosphatemia, lack of renal formation
Congenital abnormalities of the kidney and urinary tract of 1, 25-dihydroxyvitamin D3 , deficiency of calcium,
(CAKUT) are the leading causes of CKD in childhood. chronic acidosis and secondary hyp erparathyroidism.
The blood pressure may be increased and optic fundi
Pathophysiology and Clinical Features
show hypertensive retinopathy. Severe proximal muscle
The term CKD implies permanent decrease in renal weakness, peripheral neuropathy, itching, purpura and
function. Most children with CKD stage 1-3 (GFR more pericarditis are late features. Infections are common and
than 30 mL/min/1.73 m2) are asymptomatic; reduction may acutely worsen renal function.
of GFR below this level is associated with symptoms.
Regardless of the etiology, once there is a critical loss of nephron Investigations
mass, the renal failure is progressive and manifests with similar
The patient should be investigated to find the cause of
symptoms. Loss of urinary concentrating ability results in
renal failure and detect reversible factors (e.g. urinary tract
obstruction, UTI, severe hyp ertension, drug toxicity and
Table 17.20: Common causes of chronic kidney disease dehydration). Appropriate imaging studies are done.
Glomerulonephritis: Idiopathic (e.g. focal segmental glomerulo Blood counts and levels of urea, creatinine, electrolytes,
sclerosis); secondary (systemic lupus erythematosus, lgA pH, bicarbonate, calcium, phosphate, alkaline phos
nephropathy, microscopic polyarteritis, Henoch-Schonlein phatase, parathormone (PTH), protein and albumin are
purpura) obtained. Levels of ferritin and transferrin saturation are
Reflux nephropathy: Primary, secondary obtained in patients with anemia. GFR can be estimated
based on serum creatinine and height (p 465); its accurate
Obstructive uropathy: Posterior urethral valves, pelviureteric
assessment by creatinine clearance or radionuclide
junction obstruction, renal stones
methods is rarely necessary.
Developmental anomalies: Bilateral renal hypoplasia, dysplasia
Familial nephropathy: Nephronophthisis, Alport syndrome, Management
polycystic kidneys
Optimal management of CKD involves a team approach
Others: Hemolytic uremic syndrome, amyloidosis, renal vein involving pediatric nephrologist, specialist nurse,
thrombosis, renal cortical necrosis dietitian, social worker and orthopedic surgeon. The
490 I Essential Pediatrics
management of CKD focuses on the following principles: sodium requiring its supplementation. Children with
(i) Treatment of reversible conditions; (ii) Retarding the chronic glomerulonephritis retain sodium and water,
progression of kidney disease, with particular attention which contributes to hyp ertension. These patients require
to control of hypertension and proteinuria; (iii) Anticipa salt and water restriction and may benefit from diuretics.
tion and prevention of complications of CKD; (iv) Optimal
management of complications, including anemia, mineral Potassium: Renal regulation of potassium balance is
bone disease, malnutrition, growth failure and metabolic maintained until very late, but the capacity to rapidly
acidosis; and (v) Identification of children in whom renal excrete a potassium load is reduced. Dietary items with
replacement therapy (RRT) is anticipated; adequate large potassium content should be avoided.
counseling and preparation of the family for RRT. Calcium and phosphorus: Calcium supplements are given
At the initial stages, management aims at maintaining as calcium carbonate or acetate. Excessive consumption
nutrition and retarding progression of the renal failure. of dairy products should be avoided to restrict phosphate
Later, treatment of complications and renal replacement intake.
therapy in the form of dialysis or transplantation is required.
Vitamins: Vitamins B1, B2, folic acid, pyridoxine and B12
Treatment of Reversible Renal Dysfunction are supplemented.
Common conditions with potentially recoverable kidney
function include an obstruction to the drainage, recurrent Hypertension
urinary tract infections with vesicoureteric reflux and Hypertension in patients with proteinuria and glomerular
decreased renal perfusion due to renal arterial stenosis. filtration rate >30 mL/min/1.73 m2 should preferably be
Care should be taken to avoid AKI that may follow the treated with angiotensin-converting enzyme inhibitors
administration of nephrotoxic drugs, herbal medications (e.g. enalapril). Beta-adrenergic blockers (atenolol) and
and radiocontrast agents, and occur with hypoxic injury calcium channel antagonists (nifedipine, amlodipine) are
due to inadequate hydration during or following surgery. also effective; the latter are the preferred initial choice in
Retarding Progression of Renal Failure CKD stage 4-5 (GFR <30 mL/min/1.73 m2). Treatment
with loop diuretics is beneficial in those with fluid
Hypertension and proteinuria lead to increased intra overload. Patients with severe hypertension, uncontrolled
glomerular perfusion, adaptive hyperfiltration and pro with the above medications, may require additional
gressive renal injury. Hypertension should be adequately therapy with clonidine or prazosin.
controlled. Long-term therapy with angiotensin
converting enzyme inhibitors has been shown to reduce Anemia
proteinuria and may retard progression of renal failure. Anemia generally develops when the GFR falls below
Strict control of blood pressure to 50th to 75th centile for 30 mL/min/1.73 m2 • Iron deficiency, indicated by low
age, gender and height, is useful in delaying progression. levels of transferrin saturation ( <20%) and ferritin
Children with proteinuria should be treated with an ACE ( <100 ng/ dL), is the most common underlying
inhibitor or an angiotension receptor blocker (ARB) contributing factor. Therapy with iron (elemental iron
because of their antiproteinuric effect. Therapy with lipid 4-6 mg/kg per day) should be initiated in such cases. Iron
lowering agents and correction of anemia, shown to be replete patients with pernicious anemia should receive
useful in retarding progression of CKD in adults, may also therapy with recombinant human erythropoietin
have utility in children. 50-150 U/kg/dose given subcutaneously or intravenously
Diet 2-3 times a week. The dose of erythropoietin should be
adjusted to achieve target hemoglobin of 11-12 g/dL.
Careful attention to diet is essential. Recommended daily
Patients should receive iron and micronutrient supple
amounts of calories should be ensured. A diet high in
ments concomitantly. Patients on hemodialysis should
polyunsaturated fats, such as com oil and medium chain
receive intravenous iron supplementation. Inadequate
triglycerides and complex carbohydrates is preferred.
response to erythropoietin may occur due to iron, folate
Water restriction is usually not necessary, except in ESRD
or vitamin B 12 deficiency, chronic infection, aluminum
or presence of fluid overload. Excessive use of diuretics,
toxicity and severe hyperparathyroidism. Patients with
overzealous restriction of salt and gastroenteritis may lead
hemoglobin level below 6 g/dL should receive leukocyte
to dehydration that should be corrected.
poor, packed red cell transfusions. Blood is transfused slowly,
Proteins: The protein intake should be 1-2 g/kg/day; since it may aggravate hypertension and heart failure.
proteins consumed should be of high biologic value.
Restriction of protein intake is not required. Infections
Sodium: Since renal regulation of sodium reabsorption is Urinary tract and other infections should be promptly
impaired, its dietary intake needs to be individualized. treated with effective and least toxic drugs. The dosage of
Some infants are polyuric and lose large amounts of most drugs requires modification (reduction of dosage
Disorders of Kidney and Urinary Tract 1491-
and/or increase in dosing interval), depending on the hypocalcemia, hyperphosphatemia and raised levels of
severity of renal failure. alkaline phosphatase and PTH. X-rays reveal changes
suggestive of rickets. Radiologic features of secondary
Growth hyp erparathyroidism are initially seen in the phalanges
Optimization of caloric and protein intake and treatment and clavicles.
of mineral bone disease is important. Administration of The goals of early intervention are to maintain normal
recombinant human growth hormone at 0.024-0.070 mg/ bone mineralization and growth, avoid hyperphospha
kg subcutaneously once a day, 6-7 times a week (max 0.35 temia and hypocalcemia, and prevent or reverse increased
mg/kg/week) improves growth velocity in children with PTH secretion. Treatment is based on dietary restriction of
chronic renal failure. Early recognition and management phosphate, and administration of phosphate binders and
of malnutrition, mineral bone disease, metabolic acidosis vitamin 0. When serum phosphate exceeds the target
and electrolyte disturbances should take precedence over range, phosphate containing food (e.g. dairy products) are
the institution of therapy with growth hormone. The goal restricted. Oral phosphate binders, calcium carbonate or
of therapy is to achieve the patient's genetic height acetate (0.5-1 g/day with meals) reduce intestinal
potential. absorption of dietary phosphate. Since aluminum
accumulation may increase the risk of bone disease and
Mineral Bone Disease encephalopathy, prolonged administration of aluminum
Mineral bone disease (MBO) is a serious problem in hydroxide as a phosphate binder is avoided. Sevelamer, a
children as it occurs during the period of active growth calcium and aluminum free ion-exchange resin that binds
(Fig. 17.18). Its prevention and adequate treatment is phosphorus within the intestinal lumen, is a safe and
crucial. The proximal nephron is the chief site of synthesis effective alternative to calcium containing phosphate
of 1,25-dihydroxyvitamin 03 (calcitriol), the most potent binders.
metabolite of vitamin 0. Its decreased production is an The first steps in managing elevated levels of PTH in
important factor in the pathogenesis of secondary children with CKO are correction of underlying
hyp erparathyroidism in CKO. Recent studies also show a nutritional deficiency of vitamin O deficiency and
high incidence of vitamin O deficiency among children management of hyperphosphatemia. If the PTH still
with CKO. With reduction of renal function, phosphate remains elevated after these measures, therapy with
balance is initially maintained by its increased excretion activated vitamin O should be started. Vitamin O analogs
from the normal nephrons. However, when the GFR falls with short half-life (calcitriol, 20-50 ng/kg/day or la.
below 25%, blood phosphate levels rise. hydroxy 03, 25-50 ng/kg/day) are preferred. Excessive
The symptoms of are vague and nonspecific. Bone pain, vitamin O intake may cause hypercalcemia, hyper
muscle weakness, growth retardation and skeletal calciuria and elevation of calcium phosphorus product,
deformities are prominent. Blood examination shows which should be monitored.
Osteotomy may be required to correct bony deformities.
Immunization
Patients with CKO should receive all routine vaccines.
Apart from the regular immunization, children with CKO
should also receive vaccines against pneumococcal,
chickenpox and hepatitis A and B infections, especially if
prepared for transplantation. Immunization is scheduled
so as to complete live vaccinations prior to transplantation.
Primary as well as booster doses of inactivated vaccines
can be given 6 months after transplant.
Long-term Care
The rate of progression of chronic renal injury is variable.
In some disorders (e.g. hemolytic uremic syndrome,
crescentic GN), stage V CKO is present within a few weeks
or months. In others (e.g. reflux nephropathy and some
forms of chronic GN), the decline in renal function is slow.
Fig. 17 .18: Mineral bone disease associated with hyper Patients showing a rapid deterioration of renal function
phosphatemia and secondary hyperparathyroidism in a 12-year should be evaluated for potentially reversible complications
old girl on chronic hemodialysis. Note the osteopenia and bone (infection, urinary outflow obstruction, fluid loss,
resorption in terminal phalanges of the fingers hypertension and use of nephrotoxic drugs).
492 Essential Pediatrics
Suggested Reading
• Bertram JF, Goldstein SL, Pape L, et al. Kidney disease in children:
latest advances and remaining challenges. Nat Rev Nephrol.
2016;12:182-91.
• Gallibois CM, Jawa NA, Noone DG. Hypertension in pediatric
patients with chronic kidney disease: management challenges. Int
J Nephrol Renovasc Dis. 2017; 10:205-213.
• Hanudel MR, Salusky IB. Treatment of pediatric chronic kidney
disease-mineral and bone disorder. Curr Osteoporos Resp
2017;15:198-206.
• K/DOQI clinical practice guidelines for nutrition in children with
CKD: 2008 Update. Am J Kidney Dis 2009;53:511-104.
• Rees L, Shroff RC. Phosphate binders in CKD: chalking out the
differences. Pediatr Nephrol 2010;25:385-94
• Staples A, Wong C. Risk factors for progression of chronic kidney
disease. Current Opin Pediatr 2010;22:161-9.
Fig. 17 .19: Hemodialysis in a patient with end-stage renal dis
ease. Note the vascular access through a catheter in the internal
RENAL REPLACEMENT THERAPY jugular vein, hemodialysis machine and the dialyzer (solid arrow)
Preparation of a child for end stage care should be discussed
in advance with the family members. The financial fistula or graft, or a double lumen indwelling catheter in
resources and the family support available should be a central vein (internal jugular vein preferred). Dialysis is
addressed. Initiation of dialysis should be considered when done for 3-4 hours/session, with a frequency of 3
the glomerular filtration rate (GFR) falls below 12 mL/min/ sessions/week. During a hemodialysis session, blood is
1.73 m2 body surface area and is strongly recommended circulated through an extracorporeal circuit that includes
when the GFR is <8 mL/min/1.73 m2• However, the well a hollow fiber dialyzer (artificial kidney) (Fig. 17.19). Anti
being of the patient is more important than the estimated coagulation of the circuit is achieved by systemic
GFR for deciding when dialysis should begin. The presence heparinization. The procedure requires technical expertise
of fluid overload, hypertension, gastrointestinal symptoms, and need for continuous monitoring.
growth retardation and neurological consequences of
uremia influence the decision to initiate RRT. Renal Transplantation
The different forms of renal replacement therapy are The feasibility and efficacy of renal transplantation as
chronic peritoneal dialysis, hemodialysis and renal standard therapy for ESRD in children is well established.
transplantation. In children with stage V CKD (ESRD), Advances in surgical skills, availability of better immuno
transplantation is the desired form of therapy. While suppressive medications and ability to prevent and treat
chronic dialysis is life sustaining, it is inferior to renal infections, have improved the short- and long-term
transplantation in providing adequate renal replacement. outcome. The usual immunosuppressive therapy is a
Transplantation is associated with significant survival combination of a calcineurin inhibitor (cyclosporin or
advantage, decreased risks of hospitalization and tacrolimus), purine synthesis inhibitor (azathioprine or
improved quality of life. mycophenolate mofetil) and prednisolone. Long-term
allograft survival is better with live compared to deceased
Chronic Peritoneal Dialysis (PD) donors. Following successful renal transplantation, the
Chronic PD is done through a Tenckhoff catheter tunneled child can lead a normal life and resume physical activity
through the abdominal wall into the peritoneum. Chronic and schooling. The allograft survival varies between 10
PD can be done manually (ambulatory PD) or with the and 20 years.
help of an automatic cycler (cyclic PD). The duration of
dialysis is usually 10-12 hours a day during which 4--6 Suggested Reading
cycles are performed. Chronic PD is preferred to chronic • Auron A, Brophy PD. Pediatric renal supportive therapies: the
hemodialysis since it is done at home, without the need changing face of pediatric renal replacement approaches. Curr Opin
Pediatr 2010;22:183-8.
for hospital visits. Patients on chronic PD have less restric • Holmberg C, Jalanko H. Long-term effects of paediatric kidney
tion on fluid and caloric intake; control of hypertension is transplantation. Nat Rev Nephrol, 2016;12:301-11.
better and hematocrit is maintained. The success of chronic • http://www.kidney.org/professionals/kdoqi/
PD, however, relies upon the motivation of families to
carry out the procedure. DISORDERS OF RENAL TUBULAR TRANSPORT
In comparison to glomerular diseases, tubular disorders
Chronic Hemodialysis (HD) are less common. Early and correct diagnosis is essential
HD is mostly carried out in the hospital setting. These since specific management is possible in many cases. The
children require vascular access either an arteriovenous diagnosis of a primary tubular disorder implies that there
Disorders of Kidney and Urinary Tract 1493-
is no significant impairment of glomerular function or Table 17.21: Presenting features in tubular disorders
tubulointerstitial inflammation. A tubular disorder may be Growth retardation, failure to thrive
congenital or acquired and involve a single function of a
Delayed gross motor milestones
tubule (renal glucosuria, nephrogenic diabetes insipidus)
or multiple functions (Fanconi syndrome). Polyuria, excessive thirst
Recurrent episodes of dehydration, vomiting, fever
Initial Evaluation Rickets, bone pains
Children with primary defects in tubular function usually Episodic weakness
present during infancy. Table 17.21. shows important Constipation
clinical features of patients with such disorders. Most renal Craving for salt and savory foods
tubular disorders can be diagnosed following careful
interpretation of urine and plasma biochemistry, key
glomerular filtration rate. Patients with distal RTA are
investigations are listed in Table 17.1.
unable to excrete ammonium(NH;) ions adequately, and
Renal Tubular Acidosis (RTA) the urine pH cannot reach maximal acidity (i.e. remains
>5.5) despite acidemia, indicating low H+ concentration
RTA encompasses conditions characterized by a defect of in the collecting duct. Hypokalemia is caused by increased
renal acidification, which result in hyperchloremic
urinary losses of potassium and aldosterone stimulation
metabolic acidosis and inappropriately high urine pH
by urinary Na+ loss and volume contraction, leading to
Defects in tubular transport result in reduced proximal further increase in tubular K+ secretion.
tubular reabsorption of bicarbonate (HC03), the distal
secretion of protons (hydrogen ion, H+) or both, leading The condition is often sporadic, but may be inherited
(dominant, recessive or X-linked). Important forms are
to impaired capacity for net acid excretion and persistent
hyperchloremic metabolic acidosis. The plasma anion gap listed in Table 17.22. The disease may be associated with
[Na+ -(CI-+ HC03)] is in the normal range(8-12 mEq/L). systemic diseases(systemic lupus erythematosus, Wilson
The renal function is normal or only mildly impaired. disease) or secondary to renal disease (obstructive
uropathy, reflux nephropathy) or drug toxicity (lithium,
Two main forms are recognized: Distal RTA (type 1) analgesics, amphotericin B).
and proximalRTA(type 2). Another variety(type4) distin
guished by the presence of hypoaldosteronism and Presenting features: Children present with failure to thrive,
hyp erkalemia is less common in children. polyuria, polydipsia, hypokalemic muscle weakness and
rickets. Ultrasonography may show nephrocalcinosis
Distal RTA (Fig. 17.20).Patientswithincompleteformsof distalRTAmay
Distal (type 1) RTA is due to defective secretion of H+ in present with nephrolithiasis or incidentally detected
the distal tubule, in the absence of significant decrease in nephrocalcinosis.
Table 17.22: Inherited forms of renal tubular acidosis (RTA)
Type of RTA Associated disorders
Type 1 (distal) Hemolytic anemia
Early hearing loss
Normal hearing; delayed hearing loss
Type 2 (proximal), isolated Ocular abnormalities (band keratopathy, cataracts, glaucoma); defective
dental enamel; intellectual impairment; basal ganglia calcification
Type 2, Fanconi syndrome Dent disease
Cystinosis
Tyrosinemia type 1
Fanconi-Bickel syndrome
Wilson disease
Galactosemia
Hereditary fructose intolerance
Lowe syndrome
Glycogen storage disease type I
Mitochondrial disorders
Type 3 (combined) Osteopetrosis; blindness, deafness
Type 4 (hyperkalemic) Congenital adrenal hyperplasia
Pseudohypoaldosteronism (PHA)
PHA type 2, Gordon syndrome
494 I Essential Pediatrics
NEPHROLITHIASIS AND NEPHROCALCINOSIS should include renal function tests, blood levels of cal
cium, phosphorus, uric acid, pH and bicarbonate. Detec
Renal calculi are uncommon in children and occur usually
tion of specific crystals in the urine may suggest an
in the setting of an underlying metabolic abnormality.
etiology (Fig. 17.22). High (>5.5) urine pH in first morning
Symptoms include dysuria, hypogastric pain, hematuria
sample suggests defective tubular acidification.
and occasionally urinary infections. Nephrocalcinosis
Quantitation of calcium, oxalate and uric acid in timed
refers to formation of crystalline deposits within the renal
urine collections evaluates excretion of solutes as com
parenchyma, presenting as enhanced renal echogenicity,
pared to normal individuals. Alternatively, solute excre
which may be cortical, medullary or diffuse. Table 17.24
tion is expressed as a ratio to urinary creatinine in spot
lists common underlying metabolic causes. Urinary tract
samples. Patients with hypercalciuria require evaluation
infection, particularly with urease producing organisms
for hypercalcemia (intact PTH, 25-hydroxyvitamin D) and
like Proteus, favors precipitation of magnesium ammonium
for association with incomplete distal renal tubular
phosphate and calcium phosphate (struvite stones).
acidosis, hypomagnesemia, hypophosphatemic rickets
Progressive renal impairment may occur in patients with
and abnormalities of the thyroid hormone. Where
nephrocalcinosis, untreated obstruction or recurrent UTI.
available, stone analysis is performed using X-ray diffrac
Evaluation tion or infrared spectroscopy.
Ultrasonography detects most radiopaque and radiolucent Idiopathic Hypercalciuria
calculi and nephrocalcinosis. High resolution computerized
tomography detects even minute calculi. Plain radio This is the most common underlying cause in patients with
graphs and intravenous pyelography are rarely required; nephrolithiasis, but may alternatively present with
the latter is useful only if suspecting radiolucent or low microscopic and gross hematuria. A family history of
density stones (uric acid, xathine), duplex system or hematuria or nephrolithiasis is often present. Urinary
obstruction, particularly in a young child where perfor calcium to creatinine ratio in the early morning 'spot' urine
ming CT would necessitate sedation. However, high serves as a screening test. The upper limit of normal in
resolution ultrasonography may overdiagnose nephro children over 2 years is 0.2 (mg/mg). The diagnosis is
confirmed by an accurate measurement of 24 hours
�alcinosis, particularly in newborns where physiologically
mcreased echogenicity or deposition of Tamm-Horsfall urinary calcium; values greater than 4 mg/kg/day are
protein is mistaken for medullary nephrocalcinosis. abnormal. Blood levels of calcium and magnesium are normal.
Investigations aiming at detecting abnormalities show Idiopathic hypercalciuria should be distinguished from
a metabolic cause in 50% patients. Initial investigations hypercalciuria secondary to persistent hypercalcemia (e.g.
hyperparathyroidism, vitamin D toxicity) or associated
Table 17.24: Underlying metabolic abnormalities in children with renal tubular acidosis. A high fluid intake and diet
with nephrolithiasis or nephrocalcinosis low in animal protein and salt is advised. Therapy with
thiazide diuretics, which reduces urinary calcium
Hypercalciuria with hypercalcemia
excretion, may be required.
Vitamin D overdose
Primary hyperparathyroidism Endemic Vesical Calculi
Production of PTH related peptide (malignancy, sarcoidosis)
Vesical calculi are usually single stones, detected in young
Hypercalciuria with normal serum calcium
boys ( <5-year-old) in some regions of the country, e.g.
Idiopathic hypercalciuria Rajasthan, Andhra Pradesh and North-Eastern states and
Familial hypophosphatemia with hypercalciuria in neighboring countries, e.g. Pakistan and Afghani�tan.
Distal renal tubular acidosis These stones are composed of ammonium acid urate and
Dent disease calcium oxalate. Risk factors include consumption of a
Bartter syndrome with/without sensorineural deafness predominantly cereal (wheat or jowar) based diet, which
Autosomal dominant hypocalcemia with hypercalciuria has low amounts of calcium and phosphate and high
Familial hypomagnesemia, hypercalciuria and nephro oxalate content. Recurrent diarrheal episodes contribute
calcinosis by causing dehydration and an acidic, concentrated urine.
Lowe syndrome A high intake of dairy products and animal proteins has
Frusemide use led to a decline in the prevalence of these stones. Treatment
Miscellaneous causes requires suprapubic cystolithotomy; these stones rarely
Primary hyperoxaluria (type I, type II) recur.
Cystinuria
Abnormal purine, pyrimidine metabolism: Lesch-Nyhan Primary Hyperoxaluria
syndrome, glycogenosis type 1, xanthinuria
Primary hyperoxaluria type 1 is an autosomal recessive
Melamine toxicity
disorder of glyoxylate metabolism with deficient activity
498 Essential Pediatrics
..
C
Fig. 17 .22: Morphology of urine crystals may suggest etiology of renal stones. (a) Envelope-shaped oxalate dihydrate crystals;
(b) Florets of calcium phosphate; (c) Coffin lid-shaped triple phosphate; (d) Hexagonal cystine crystals
of the liver-specific enzyme, alanine glyoxylate amino disulfide bonds of cystine to form the more soluble
transferase causing overproduction of endogenous homodimer, cysteine.
oxalate, which manifests as renal stones and/ or
nephrocalcinosis. Precipitation of oxalate also affects the Management of Renal Calculi
eyes, heart, bones and bone marrow. The diagnosis is Stones less than 5-7 mm in size may pass spontaneously.
suggested by elevated oxalate in plasma and/ or urine, Extracorporeal shock wave lithotripsy (ESWL) may
and confirmed by deficient activity of the enzyme on liver suffice for small stones. Percutaneous nephrolithotomy
biopsy and sequencing of the affected gene, AGXT. may be appropriate in patients with relative contra
Treatment is supportive; some patients with partial indication for ESWL or with stones too large for
deficiency benefit from pyridoxine supplementation. lithotripsy. Ureteroscopy is useful for distal and mid
Patients presenting in childhood progress to end-stage ureteric calculi. Open surgery is necessary for stones
renal disease by adolescence and require combined liver more than 3 cm in size or those with associated
kidney transplantation. pelviureteric junction obstruction.
UTI should be treated and an adequate fluid intake
Cystinuria ensured. Patients with idiopathic hypercalciuria may
This autosomal recessive disorder is characterized by benefit from a low salt intake; dietary calcium restriction
impaired proximal tubular reabsorption of cystine and is not necessary. Persistent hypercalciuria is treated with
dibasic amino acids (ornithine, lysine and arginine). oral potassium citrate, an inhibitor of crystallization.
Supersaturation of urine with cystine crystals may lead Thiazide diuretics reduce urine calcium excretion; their
to formation of recurrent radiopaque calculi and account long-term use is, however, restricted due to side effects.
for 10% of cases presenting in childhood. The diagnosis is Prolonged alkali supplementation is necessary in patients
suggested by presence of hexagonal crystals in urine, with distal RTA.
urinary excretion of specific amino acids (as above) and
positive urine nitroprusside cyanide test. Confirmation Suggested Reading
requires quantification of urinary cystine excretion (24 hr • Copelovitch L. Urolithiasis in children: medical approach. Pediatr
or cystine:creatinine ratio), stone analysis or genetic Clin North Am 2012;59:881-96.
testing. A high fluid intake and urinary alkalization help, • Rumsby G. Genetic defects underlying renal stone disease. lnj J
Surg. 2016;36(Pt D): 590-595.
since cystine is poorly soluble at normal urinary pH but • Tasic V, Gucev Z. Nephrolithiasis and nephrocalcinosis in
dissolves well at pH >8.0. Agents such as penicillamine children-metabolic and genetic factors. Pediatr Endocrinol Rev
and tiopronin prevent formation of calculi by cleaving 2015;13:468-76.
Disorders of Kidney and Urinary Tract 1499-
postvoid residual urine or dysfunctional voiding. Cardiac Multicystic dysplastic kidney: A multicystic dysplastic
arrhythmias are a rare but serious adverse event effect of kidney (MCDK) is an enlarged nonfunctioning kidney
tricyclic antidepressants, which are, therefore, not with cysts of varying sizes resulting from abnormal
recommended. Anticholinergic drugs reduce uninhibited differentiation of the metanephros. Affecting 1 in 2400 to
bladder contractions and are useful in children who have 4300 live births, it is the most common cystic renal
significant daytime urge incontinence besides nocturnal malformation in children. Ultrasonography shows
enuresis. The usual dose is 5 mg for oxybutynin or 2 mg characteristic findings, including multiple thin-walled
for tolterodine at bedtime, given above 6 years of age. noncommunicating cysts of varying size, in an enlarged
Desmopressin (DDA VP, 0.2-0.4 mg orally; oral melt kidney without identifiable parenchyma or renal pelvis
120-240 µg) works by reducing the volume of urine. Its (Fig. 17.23).
rapid onset of action makes it a satisfactory choice for Most patients with MCDK have a normal contralateral
special occasions like staying out for the night. Relapse kidney showing compensatory hypertrophy. However,
rates are high after stopping the medication. 20-40% cases may show associated abnormalities of the
contralateral genitourinary tract, such as vesicoureteric
Suggested Reading reflux or pelviureteric junction obstruction. A DMSA scan
• Thurber S. Childhood enuresis: Current diagnostic formulations, confirms that the affected kidney is nonfunctional and
salient findigns, and effective treatment modalities. Arch Psychiatr rules out reflux-associated scarring of the contralateral
Nurs 2017;31:319-23. kidney. Children with MCDK require regular monitoring
• Van Herzeele C, Walle JV, Dhondt K, Juul KV. Recent advances in
managing and understanding enuresis. FlOOORes. 2017;6;1881. by ultrasound to ensure compensatory hypertrophy of the
normal kidney and progressive involution of the affected
CONGENITAL ABNORMALITIES OF kidney, which is undetectable by 5-7 years of age in most
KIDNEY AND URINARY TRACT cases. Progressive renal impairment is seen, only if other
abnormalities are associated. The risk of malignant
Congenital abnormalities of kidney and urinary tract transformation (Wilms' tumor) and hypertension is
(CAKUT) are common and account for about 25% cases negligible. Nephrectomy is not indicated except in
of CKD in children. presence of severe hypertension, suspected malignancy,
or a large kidney that fails to involute.
Single Kidney
In unilateral renal agenesis, one kidney fails to form while Obstructive Uropathy
the other is normal in size, position and function. Agenesis Obstructive anomalies of the urinary tract are an important
may occur due to primary failure of formation of the cause of irreversible renal damage in childhood. The
ureteric bud or its inability to engage with the renal common lesions include pelviureteric junction obstruction,
mesenchyme. The condition may occur sporadically or as vesicoureteric junction obstruction and posterior urethral
part of syndromes such as brachio-otorenal, DiGeorge, valves. Diagnosis is suspected on antenatal ultrasono
Fanconi anemia, Fraser or nail-patella syndromes. Renal graphy or following presentations with dribbling of urine,
agenesis is asymptomatic, usually detected incidentally on poor urinary stream, fever and/ or urinary tract infections.
ultrasonography. Usually, there is compensatory Chronic obstruction results in dysfunction of distal tubules
hypertrophy of the normal kidney. A DMSA scan helps in with impaired urinary concentration and acidification,
ruling out scarring due to associated vesicoureteric reflux
or an ectopic kidney. Children with single kidney should
avoid contact sports. While affected patients are expected
to maintain glomerular function, they require annual
monitoring for hypertension and proteinuria.
Fetuses with bilateral renal agenesis or hypoplasia
rarely survive to term. Lack of fetal urine production leads
to oligohydramnios and limb anomalies. Neonates show
low set ears, flat nose, prominent epicanthic folds and
small chin (Potter fades). Pulmonary hypoplasia is the
usual cause of death.
Renal Dysplasia
Renal dysplasia implies abnormal development of renal
parenchyma. Primitive ducts surrounded by connective
tissue, metaplastic cartilage, poorly differentiated Fig. 17 .23: Multicystic dysplastic kidney. Multiple, thin-walled
glomeruli and dilated tubules are present. Bilateral total and noncommunicating cysts involve the left kidney on
renal dysplasia is fatal in the neonatal period. postnatal ultrasound at one month age
Disorders of Kidney and Urinary Tract lso1-
leading to polyuria, polydipsia, failure to thrive, refractory are commonly associated with duplex systems, particularly
rickets and systemic acidosis. in girls. Endoscopic deroofing is the treatment of choice.
Pelviureteric junction (PUT) obstruction: Stenosis of the
PUJ may be unilateral or bilateral. Obstruction is more Miscellaneous
common in boys and in presence of ectopic, malrotated Renal ectopia, renal fusion: An ectopic kidney may lie in
or horseshoe kidney. It may present as an asymptomatic the pelvis or the iliac fossa. It may be structurally normal
flank mass, or with upper abdominal pain, UTI or or hypoplastic. The patient may be asymptomatic, or have
hematuria. Ultrasonography shows a dilated renal pelvis abdominal discomfort or dysuria. A horseshoe kidney
without ureteric dilatation. Radionuclide (DTPA) renal results from fusion of identical poles of both kidneys.
scan shows impaired drainage of the affected kidney Patients with horseshoe kidney show vesicoureteric reflux
which does not improve despite administration of a in 30% cases.
diuretic. Where scintigraphy is not available, intravenous
pyelography shows renal pelvis dilatation with an abrupt Renal duplication: A duplex (duplicated) system is a
cut-off at the PUJ. Mild cases are followed up with kidney with two pyelocalyceal systems. In patients with
ultrasound. Surgical treatment by pyeloplasty is indicated partial or incomplete duplication, either a single or bifid
if the relative function of the affected kidney is impaired. ureter is present; in those with complete duplication, two
Nephrectomy may be required for a kidney with ureters from the affected side empty separately into the
extremely poor function that does not improve despite bladder. Evaluation consists of imaging of the upper tract
temporary nephrostomy, severe hypertension or recurrent (ultrasonography, DTPA renal scan, intravenous pyelo
urinary infections. graphy) to evaluate for obstruction and lower tract (MCU)
for vesicoureteric reflux.
Posterior urethral valves: These are an important cause
of distal urinary tract obstruction in boys. The usual ANTENATAL HYDRONEPHROSIS
presenting features are dribbling, abnormal urinary
stream, palpable bladder and recurrent UTI. The presence Extensive use of antenatal ultrasonography has lead to
of severe obstruction in utero may lead to renal dysplasia, increasing detection of CAKUT. On antenatal ultrasound,
with mild to moderate renal dysfunction at birth. hydronephrosis is identified in 4-5% pregnancies.
Antenatal ultrasound shows bilateral hydrouretero However, the majority of cases of antenatal hydro
nephrosis with or without a thick-walled bladder and nephrosis resolve without sequelae, representing transient
oligohydramnios. The diagnosis is confirmed on MCU, physiological obstruction or stasis. Patients require
which shows dilated posterior urethra and valves at its monitoring by ultrasound during the antenatal period for
junction with the anterior urethra. The bladder is enlarged progressive worsening and association with oligo
and may show diverticuli and trabeculations; secondary hydramnios, which suggests severe lower urinary tract
vesicoureteric reflux is common. obstruction. A postnatal ultrasound is recommended
Endoscopic fulguration of the valves is performed as during the first week of life and on day 1 in severe cases.
early as possible. Alternatively, temporary urinary diver Neonates with posterior urethral valves, solitary kidney
sion by vesicostomy or bilateral ureterostomies is or bilateral hydronephrosis and impaired renal function
necessary. Long-term follow-up is necessary since a require prompt management. Neonates showing signi
significant proportion of patients show progressive kidney ficant unilateral or bilateral dilatation should undergo a
disease. Bladder dysfunction is common, with delayed MCU at 4-6 weeks of life to detect vesicoureteric reflux; if
continence or incontinence, poor bladder sensation and a reflux is ruled out, a diuretic renal dynamic (DTPA) scan
poorly compliant low capacity bladder. If pharmacotherapy may be required done to detect significant PUJ or VUJ
fails, patients may require clean intermittent catheterization obstruction and evaluate differential renal function. Most
and occasionally bladder augmentation. cases with mild to moderate hydronephrosis require only
ultrasound monitoring and show spontaneous resolution
Phimosis: Up to the age of 2 years, the prepuce cannot
by 2-5 years of age. Surgery is indicated in presence of
be fully retracted because of congenital adhesions with
obstructive drainage pattern associated with low
the glans. The diagnosis of phimosis should thus be made
differential function, and/ or recurrent UTI. Infants with
with caution in young children. Indications for therapy
vesicoureteric reflux should receive continuous antibiotic
include recurrent balanoposthitis, forceful/ difficult
prophylaxis.
urination, paraphimosis or recurrent urinary tract
infections. Figure 17.24 shows a proposed algorithm for postnatal
evaluation and management of antenatally detected
Ureterocele: This is a congenital condition in which the hydronephrosis. Parents of infants with antenatal
terminal part of the ureter distends within the bladder to hydronephrosis should be counseled regarding increased
form a sac-like pouch. Symptoms include recurrent urinary risk of urinary tract infections and their prompt manage
infections, abdominal pain and urolithiasis. Ureteroceles ment.
502 Essential Pediatrics
Postnatal ultrasound
Initial scan in first week; repeat at 4-6 weeks
..
APO <7 mm SFU grade 1-2; APO 7-10 mm Mild hydronephrosis with ureteric dilatation
l
obstruction
mu,.Uc ""og,aphy
l
���-�
Not obstructed Obstructed pattern Antibiotic Refer for surgery
I prophylaxis I
Ultrasound q 3-6 months until Surgery if obstructed pattern with differential function <40%
resolution* or decline on follow-up
Monitor by ultrasound until resolution*
*Parents of infants with hydronephrosis should be counseled regarding the risk of urinary tract infections
Fig. 17.24: Postnatal evaluation in patients with antenatal hydronephrosis. A postnatal ultrasound is recommended at 3-7 days
except in suspected lower urinary tract obstruction, where it is done earlier. Postnatal hydronephrosis is classified using Society for
Fetal Urology (SFU) grade or renal pelvic anteroposterior diameter (APD). Infants with normal findings should undergo a repeat
study at 4-6 weeks. Patients with isolated mild hydronephrosis (unilateral or bilateral) should be followed with sequential ultrasounds,
at 3 and 6 months, followed by 6-1 2 monthly until resolution; those with worsening hydronephrosis require closer evaluation.
Patients with higher grades of hydronephrosis or dilated ureter(s) are screened for underlying obstruction or vesicoureteric reflux.
Diuretic renography is useful in detecting pelviureteric junction or vesicoureteric junction obstruction and determining the need for
surgery.
Fig. 17 .25: Findings on ultrasonography in polycystic kidney disease. (a) Note bulky enlarged kidney with increased echogenicity,
loss of corticomedullary differentiation and occasional visible cyst (arrow) in a child with autosomal recessive polycystic kidney disease;
(b) Renal architecture is disorganized by multiple irregular cysts of varying sizes in autosomal dominant polycystic kidney disease;
also note the foci of calcification
grandparents should be screened; rare cases are due to de cytosolic proteins called nephrocystins. Patients with
novo mutations. Therapy with angiotensin-converting nephronophthisis present during the first decade of life
enzyme inhibitors helps control hypertension and limits with polydipsia, polyuria or enuresis, growth retardation
hyperfiltration and proteinuria. The role of inhibitors of and renal insufficiency, acidosis and anemia. Extrarenal
the mTOR pathway (sirolimus and everolimus) and V2 features may include retinitis pigmentosa; ocular motor
receptor antagonists (tolvaptan) is being explored. apraxia, hypotonia and cerebellar or midbrain
abnormalities (Joubert syndrome); skeletal chondro
Glomerulocystic Kidney Disease dysplasia (Jeune syndrome); and hepatic fibrosis with
The predominant finding in glomerulocystic kidney pancreatic dysplasia.
disease (GCKD) is cysts involving glomeruli, diagnosed The diagnosis of nephronophthisis is supported by the
most definitely on renal biopsy. Ultrasonography shows ultrasound or CT finding of small kidneys with corti
small subcortical cysts with increased kidney echogenicity comedullary cysts and poor corticomedullary differ
and loss of cortical medullary differentiation. The entiation. Renal histology shows cysts involving the
condition may occur sporadically, with autosomal collecting ducts, tubular dilatation with atrophy and
dominant inheritance, as a part of known syndromes interstitial fibrosis. While medullary cystic kidney disease
(tuberous sclerosis, trisomy 13) or in association with other is histologically indistinguishable from nephronophthisis,
renal diseases such as dysplasia, ADPKD or ARPKD. the disease is inherited in an autosomal dominant manner,
Mutations in the hepatocyte nuclear factor 13 gene lead to and presentation is delayed to adulthood.
the renal cysts and diabetes syndrome, characterized by
GCKD, maturity onset diabetes and genitourinary Suggested Reading
abnormalities.
• Avni FE, Hall M. Renal cystic diseases in children: new concepts.
Pediatr Radio! 2010;40:939-46
Nephronophthisis-Medullary
Cystic Disease Complex • Emma F, Salviati L. Mitochondrial cytopathies and the kidney.
Nephrol Ther. 2017;13 Suppl 1:S23-S28.
This group includes recessively inherited cystic disorders • Kwatra S, Krishnappa V, Mhanna C, et al. Cystic diseases of
caused by mutations in genes, named NPHP 1-9, encoding childhood: A review. Urology. 2017;110:184-191.
Chapter
18
Endocrine and
Metabolic Disorders
PSN Menon • Anurag Bajpai
GENERAL PRINCIPLES
Endocrine glands play a crucial role in the maintenance ,-------------------- R --------------------------------\
,
of body physiology and homeostasis. The hypothalamic
pituitary axis regulates most endocrine organs including
thyroid, adrenals and gonads, and processes like growth,
puberty, and regulation of salt and water homeostasis.
Adenylate cyclase
Evaluation
History: Perinatal history, birth weight and length should
be recorded. History of birth asphyxia, breech presentation,
neonatal hypoglycemia, micropenis and prolonged
jaundice should alert the pediatrician for the possibility
of GHD. Features of chronic infections, cardiopulmonary Fig. 18.4: Achondroplasia: Note the abnormal body proportions
disorders, malabsorption and raised intracranial tension and the characteristic facies.
Endocrine and Metabolic Disorders lso1-
Table 18.2: Pointers to the etiology of short stature electrolytes, liver and renal function tests and venous
Pointer Etiology blood gases (renal tubular acidosis). Estimation of skeletal
maturation (bone age) forms an important aspect of
Midline defects, Growth hormone deficiency
evaluation of short stature.
micropenis
Step 2: The next step in evaluation involves evaluation for
Rickets Renal failure, malabsorption, renal
hypothyroidism (free T4 and TSH), celiac disease (tissue
tubular acidosis
transglutaminase antibody) and Turner syndrome
Pallor Renal failure, malabsorption, (karyotype in all girls).
nutritional anemia
Step 3: Evaluation for GH-IGF (insulin-like growth factor)
Malnutrition Protein energy malnutrition,
axis is performed after common causes of growth
malabsorption, celiac disease, cystic
retardation are excluded. This is important as systemic
fibrosis
illness and hypothyroidism influence the GH-IGF axis.
Obesity Hypothyroidism, Cushing syndrome, Random or fasting blood GH level measurements do not
Prader-Willi syndrome, pseudohypo confirm the diagnosis of GHD, as GH hormone secretion
parathyroidism
is pulsatile. The diagnosis of GHD requires pharmacologic
Metacarpal Turner syndrome, pseudohypo stimulation tests. GHD is suspected when the peak level
shortening parathyroidism of GH is less than 10 ng/mL following stimulation. The
Cardiac murmur Turner syndrome, congenital heart common provocative agents used are insulin, glucagon,
disease clonidine or GHRH. Levels of IGF-1 and IGF binding
Mental retardation Hypothyroidism, Down syndrome, protein-3 (IGFBP-3) are helpful to diagnose GHD and
Turner syndrome, pseudohypo Laron syndrome. GHD may be associated with other
parathyroidism pituitary hormone deficiencies and appropriate
investigations should be carried out to detect deficiency
of these hormones, if GHD is present. CT or MRI scans of
Corrected height SOS hypothalamic and pituitary regions are essential to rule
out developmental or acquired neurological lesions.
>-2 sos <-2 sos
Management
+ +
I No evaluation I Growth velocity General measures: Management of short stature involves
correction of the underlying cause and provision of
adequate nutrition intake. Patients should be advised diet
>1 sos <-1 sos
rich in protein and calorie content. They should be
Physiological encouraged to increase their physical activity. Iron and
variant vitamin deficiencies should be corrected, if present. Zinc
supplementation (10 mg/day for 3-6 months) may help in
• Normal phenotype
improving growth in patients with idiopathic short stature.
Abnormal
Specific therapy: Initiation of specific treatment is effective
Genetic syndrome Hemogram, LFT, RFT, bone age, chest X-ray, in restoring growth in hypothyroidism (thyroxine), celiac
Skeletal dysplasia malabsorption studies, blood gas
disease (gluten-free diet) and renal tubular acidosis
..
Normal
T hyroid profile,
(bicarbonate supplements). A short course of testosterone
helps boys with constitutional delay of growth and
puberty. Treatment of genetic syndromes and skeletal
celiac serology, karyotype in girls dysplasias is extremely difficult. Some of them do respond
Normal to GH therapy. Surgical techniques for bone lengthening
(e.g. Ilizarov procedure) have been used with variable
IGF-1, IGFBP-3 success in selected forms of skeletal dysplasia.
GH provocation tests
Growth hormone: GH is highly effective patients with
..
Abnormal GHD. GH therapy may result in increase in final height
by 20-30 cm from pretreatment levels. The treatment is
GH deficiency given as daily night-time injections (25-50 µg/kg/day)
Laron syndrome till epiphyses close. GH therapy is monitored by
Fig. 18.5: Approach to a child with short stature. GH growth assessment of physical growth and bone age measurements.
hormone; IGF-1 insulin-like growth factor-1; IGFBP-3 IGF binding Lab parameters are often not helpful to monitor GH
protein-3; LFT liver function tests ; RFT renal function tests; therapy, even though IGF-1 levels have been tried. The
SDS standard deviation score treatment is expensive and all efforts should be made to
sos I Essential Pediatrics
DI. Neurological infections including tuberculosis may Document urine output No further evaluation
manifest with central DI later.
2
Urine output >2 L/m /day
Nephrogenic DI: This results from inherited or acquired Urine osmolality
resistance to vasopressin. Congenital nephrogenic DI due
to mutation in vasopressin receptor (V2) presents in
<300 mOsm/kg >300 mOsm/kg
infancy with failure to thrive, recurrent fever and
dehydration. Polyuria is often absent in this setting. i i
Hypokalemia and hypercalcemia are important causes of Creatinine, blood gas Osmotic diuresis
nephrogenic DI. Exclude DM
Inefficient aldosterone action: These include adrenal Investigations: Initial investigations should include
insufficiency, isolated aldosterone deficiency or testing for urine sugar and early morning specific gravity
aldosterone resistance. They present with hyp onatremia, or osmolality. Blood gases, urea, electrolytes, calcium and
hyperkalemia and dehydration. The condition may be creatinine should be estimated. High plasma osmolality
lethal. Failure to thrive is common. Pigmentation is (>300 mOsm/kg or sodium >146 mEq/L) with low urine
characteristic of adrenal insufficiency. Polyuria and salt osmolality ( <300 mOsm/kg and urine specific gravity
wasting in the neonatal period should prompt evaluation <l.005) suggest the diagnosis of DI, which needs further
for congenital adrenal hyperplasia (CAH). Genital classification on the basis of response to AVP. Patients
ambiguity in girls is a clue to the diagnosis of CAH. with normal plasma osmolality and low urine osmolality
Excessive water drinking (psychogenic polydipsia): The Table 18.5: Pointers to diagnosis of polyuria
condition is rare and a diagnosis of exclusion.
Feature Diagnosis
Evaluation Cleft lip, cleft palate Hypopituitarism
Metabolic bone Renal tubular acidosis (RTA), renal
Subjective estimates of urine output and nocturia may
disease failure
suggest polyuria; however, these cannot substitute for
measurement of 24-hour urine output and fluid intake. Growth failure Nephrogenic diabetes insipidus, RTA,
congenital adrenal hyperplasia,
Urine output in excess of 2 L/m2/day or 5 mL/kg/hr
Bartter syndrome
confirms polyuria (Fig. 18.6).
Rash, ear discharge Histiocytosis
Clinical: Diabetes mellitus is suggested by polyphagia, Pigmentation Adrenal insufficiency
recurrent infections and failure to thrive. Renal tubular
Genital ambiguity Congenital adrenal hyperplasia
acidosis should be suspected when acidotic breathing,
510 Essential Pediatrics
( <300 mOsm/kg) should undergo water deprivation test. reduces urine output by 50-70%. This should be combined
Urinary osmolality >300 mOsm/kg (specific gravity with salt restriction and reduction in solute load.
>1.010) excludes the possibility of complete DI.
MRI of the hypothalamic-pituitary region and anterior Suggested Reading
pituitary hormone evaluation should be done in central • Allen DB, Backeljauw P, Bidlingmaier M, et al. GH safety workshop
DI. Evaluation of nephrogenic DI includes renal imaging position paper: a critical appraisal of recombinant human GH
therapy in children and adults. European J Endocrinol 2016;174:Pl-
and serum electrolytes. 9.
Water deprivation test: This test is indicated in children • Fenske W, Allolio B. Clinical review: Current state and future
perspectives in the diagnosis of diabetes insipidus: a clinical review.
with polyuria with low urinary osmolality and normal J Clin Endocrinol Metab 2012;97:3426---37.
plasma osmolality. The aim is to increase plasma • Godbole T, Menon PSN. Polyuria, Diabetes Insipidus and
osmolality above 300 mOsm/kg (or serum sodium above Syndrome of Inappropriate Secretion of ADH. In: Gupta P, Menon
146 mEq/L) to allow the opportunity for maximal renal PSN, Ramji S, Lodha R, Eds. PG Textbook of Pediatrics, Second
concentration. Renal failure and RTA should be excluded Ed. New Delhi: Jaypee Brothers Medical Publishers (P) Ltd; 2018.
pp 2669-76.
before the test. Water deprivation test is not required in
• Growth Hormone Research Society. Consensus guidelines for the
the presence of hypematremia. It should be done on an diagnosis and treatment of growth hormone (GH) deficiency in
inpatient basis due to the risk for dehydration. childhood and adolescence: Summary statement of the GH
Water deprivation is started early in the morning. The Research Society. J Clin Endocrinol Metab 2000;85(11) 3990-3.
child is weighed and target weight loss calculated (5% • Muglia IJ, Majoub JA. Disorders of Posterior Pituitary. In: Sperling
MA. Pediatric Endocrinology. 3rd ed. Philadelphia: Saunders; 2008.
of total body weight). Body weight, urine output and pp. 195-227.
urine and blood osmolality are monitored hourly. The test • Rosenbloom AL. Growth hormone insensitivity. In: Radovick S,
is stopped when urine osmolality increases above Macgillivray MH. Pediatric Endocrinology: A Practical Clinical
750 mOsm/kg or specific gravity is more than 1.010 Guide. 2nd Ed. New York: Springer Science; 2013. pp. 29-53.
excluding DI. The test is also discontinued when serum • Vyas A, Menon RK. Growth hormone deficiency and resistance.
sodium is above 146 mEq/L (target achieved) or weight In: Gupta P, Menon PSN, Ramji S, Lodha R, Eds. PG Textbook of
Pediatrics, Second Ed. New Delhi: Jaypee Brothers Medical
loss is more than 5% (risk of dehydration). Urine osmolality Publishers Pvt Ltd; 2018. pp 2676---80.
below 300 mOsm/kg in the presence of plasma osmolality
above 300 mOsm/kg confirms DI and needs evaluation DISORDERS OF THYROID GLAND
by a formal vasopressin test. Partial forms of DI may have
urine osmolality between 300 and 750 mOsm/kg and also Physiology
require to be evaluated. Biosynthesis of thyroid hormones involves interaction of
Vasopressin response test: This test is performed to differen iodine, tyrosine, thyroglobulin and the enzyme, thyroid
tiate central DI from nephrogenic DI. Urine osmolality peroxidase. Thyroid peroxidase is the rate-limiting
is measured one and four hours after vasopressin enzyme in thyroid hormone synthesis. This process is
injection (0.1 unit/kg). An increase in urine osmolality regulated by TSH (Fig. 18.7). TSH secretion is, in turn,
by more than 50% of baseline level is diagnostic of central under the direct control of the thyrotropin-releasing
DI while a smaller increase suggests nephrogenic DI. hormone (TRH) released from the hypothalamus and
feedback control of thyroxine. Thyroid hormones bind to
intracellular receptors and activate transcription factors.
Management Most triiodothyronine (T3) in the circulation is produced
Management of polyuria is guided by the underlying by peripheral conversion of thyroxine (T4) by the enzyme
cause. Treatment of underlying diabetes mellitus (insulin), monodeiodinase. This process is stimulated in thyroid
adrenal insufficiency (hydrocortisone) and renal tubular hormone-depleted states as a protective mechanism to
acidosis (bicarbonate supplementation) is effective in produce more T3 . Thus T3 levels are the last to fall in
reducing urine output. Behavioral therapy is recommended hypothyroidism, and are not a reliable indicator of the
for psychological polydipsia. disease.
Central DI: Central DI is managed with vasopressin Thyroid hormones play an active role in the regulation
analogs. Desmopressin (DDAVP), a vasopressin analog of somatic and intellectual growth, intermediary
has high potency and prolonged duration of action. It can metabolism and thermoregulation. There is a critical phase
be given by intranasal (2.5-10 µg 12 hourly), or sublingual in the early neonatal period for the effect of thyroid
or oral (50-200 µg 12 hourly) route. Patients with idiopathic hormone on mental development. This underscores the
DI should be followed for evolving brain tumors. need for early diagnosis and appropriate management of
congenital hypothyroidism. TSH levels increase
Nephrogenic DI: Hydrochlorothiazide and amiloride immediately after birth, resulting in increase in T3 and T4
combination (1-2 mg/kg/day of thiazide) reduces urine levels, and reach their maximum by 24 hours. Their levels
output by 40%. Addition of indomethacin to this regimen fall to normal in the next few weeks. TSH levels should
Endocrine and Metabolic Disorders ls11-
Thyroid function is assessed by serum TSH and free and/ complete agenesis, partial agenesis to ectopic thyroid.
or total T4 and T3 • TSH is the most sensitive indicator of
Increased incidence of thyroid dysgenesis is noted in
primary (thyroidal) hypothyroidism, but is not as helpful Down syndrome. Biosynthetic defects include disorders
in the diagnosis of central (pituitary or hypothalamic)
affecting iodine transport, peroxidation, thyroglobulin
hyp othyroidism. Serum T4 level is a better indicator of
synthesis and deiodination. Pendred syndrome, a disorder
thyroid status than serum T3 due to increased conversion
of the pendrin gene, is associated with decreased
of T4 to T3 during thyroid-depleted states. Considering intracellular transport of iodine and deafness. Nongoitrous
the variability in the levels of circulating thyroxine-binding
congenital hypothyroidism is known to be associated with
globulin (TBG), estimation of free thyroid hormones is genes TSHR, PAXB and TSHB. Transient congenital
superior to total hormone levels in the diagnosis of hypothyroidism may occur following transplacental
hyp othyroidism. Low free T4 (FT4) and low TSH levels
passage of TSH receptor blocking antibodies, iodine
suggest central hypothyroidism, while low FT4 levels with
exposure and treatment with antithyroid drugs (e.g.
high TSH levels indicate primary hypothyroidism. amiodarone).
Persistent elevation of TSH in the presence of normal FT4
suggests subclinical hypothyroidism. Elevated FT4 and Clinical features: Features of congenital hypothyroidism
undetectable TSH levels imply a hyperthyroid state. are nonspecific and often difficult to identify in the
neonatal period. They become prominent with increasing
Hypothyroidism age. However, the window period for neurological
Hypothyroidism is caused by defects in the hypothalamic intervention would have elapsed in most children by that
pituitary axis (central hypothyroidism), thyroid gland time. This underscores the need for neonatal screening
(primary hyp othyroidism) or the peripheral sensitivity to for congenital hypothyroidism. Clinical manifestations
thyroxine (Table 18.6). include hoarse cry, facial puffiness, umbilical hernia,
hypotonia, mottling of skin and lethargy (Fig. 18.8).
Congenital Hypothyroidism Prolonged jaundice, constipation and unexplained
Congenital hypothyroidism is the most common hypothermia may also indicate hypothyroidism. Open
preventable cause of mental retardation. Congenital posterior fontanel is an important indicator of congenital
hypothyroidism is more commonly reported in India (1 hypothyroidism (Table 18.7).
in 1000 newborns) compared to western countries (1 in
4000). Evaluation: History of maternal thyroid disease or
ingestion of antithyroid medications should be probed.
Etiology: With wider coverage of iodine supplementation Family history of hypothyroidism suggests dyshormono
program, the incidence of iodine deficiency has declined genesis, while recurrent transient hypothyroidism
and thyroid dysgenesis has emerged as the most common indicates a disease related to maternal TSH receptor
cause of congenital hypothyroidism in India (75% of all antibody. Residence in iodine deficient area may suggest
cases). The disorder encompasses a spectrum ranging from the diagnosis of iodine deficiency. Presence of goiter
512 Essential Pediatrics
I Thyroid scan I
+
No uptake
I
Ectopic uptake
+
Increased uptake
.
Thyroid agenesis Antibodies binding to TSH receptor
�Maternal
-----'-· antibodies
Negative Positive
Endemic cretinism: This is a disorder associated with Table 18.13: Etiology of hyperthyroidism
endemic goiter and severe iodine deficiency with Infancy
characteristic clinical features, which include deaf-mutism,
squint, mental retardation and characteristic spastic or Transplacental passage of thyroid antibodies
rigid neuromotor disorder. Two types of endemic TSH receptor activating mutation
cretinism are described. Neurological cretinism is After infancy
characterized by deaf-mutism, squint, proximal spasticity Graves disease (TSH receptor stimulating antibody)
and rigidity (more in the lower extremities), disorders of Release of preformed thyroid hormone: Subacute thyroiditis
stance and gait with preservation of vegetative functions, Toxic thyroid nodule, toxic multinodular goiter
occasional signs of cerebellar or oculomotor disturbance Iatrogenic
and severe mental deficiency. Retarded psychomotor Pituitary resistance to T 3
development, severe short stature, coarse facial features
and myxedema without deaf-mutism characterize common. Examination reveals firm homogeneous goiter.
myxedematous cretinism. Iodine deficiency is also Eye signs are relatively uncommon compared to adults
associated with poor school performance in children and and are related to sympathetic over-activity (lid lag,
recurrent pregnancy loss in women. ophthalmoplegia, absence of wrinkling) or autoimmune
infiltration (chemosis, proptosis). Tachycardia, cardiac
Prevention and control: Iodine deficiency disorders are arrhythmia and high output cardiac failure may occur.
best prevented as treatment is usually ineffective.
Iodinated salt or iodized oil are highly efficacious in Diagnosis: The diagnosis is confirmed by the demonstra
preventing iodine deficiency. Treatment of endemic tion of elevated serum free T4 and T3 levels. The presence
cretinism may eliminate signs of hypothyroidism but of goiter, infiltrative eye signs and hyp erthyroidism are
neuromotor and intellectual deficiency are irreversible. suggestive of Graves disease. Absence of goiter should
Surgical removal of large goiters is indicated only to raise the possibility of transient hyperthyroidism as part
relieve airway obstruction or for cosmetic reasons. of autoimmune thyroiditis. Differentiating thyrotoxicosis
The National Goiter Control Programme of the Ministry from thyroiditis is important, as antithyroid drugs are not
of Health and Family Welfare in India began in 1962 with required in children with thyroiditis who may progress
establishment of salt iodination plants. The program is to hypothyroidism. Diffusely increased radiotracer uptake
directed towards control of iodine deficiency disorders is suggestive of Graves disease while reduced uptake is
and ensuring that only iodized salt is used in India. The characteristic of thyroiditis.
recommended daily intake of iodine is 40-120 µg for
children up to the age of 10, 150 µg for older children and
Management: Antithyroid drugs are ineffective in the
acute phase due to lag period in their onset of action.
adults and an additional 25 µg and 50 µg during
Propylthiouracil is contraindicated in children due to
pregnancy and lactation, respectively. Based on an
hepatotoxicity. Treatment should be started with
assumption of a mean intake of salt of 5 g/day, the
methimazole (0.5-1.0 mg/kg/day) in 3-4 divided doses.
recommended level of iodination is one part of iodine in
Beta-blockers (propranolol 2 mg/kg/day in two divided
25,000 to 50,000 parts of salt.
doses) are effective in ameliorating of sympathetic
Hyperthyroidism symptoms. Iodinated contrast (idopate 0.001 µg/kg/day)
and Lugol iodine (5% iodine and 10% potassium iodide;
Hyperthyroidism is relatively uncommon in children. It
126 mg/mL iodine, 1 drop 8 hourly) are effective in
is most commonly seen in young girls, caused by Graves
reversing of features of hyperthyroidism. Prednisolone (1-
disease (Table 18.13).
2 mg/kg/day) inhibits peripheral conversion of T4 to T3
Clinical features: The condition should be suspected in and is useful in treatment of hyp erthyroid storm. Cardiac
children with weight loss with increased appetite, tremors, failure refractory to these measures requires treatment
diarrhea, warm extremities, increased sweating and with digitalis.
anxiety. Inability to concentrate, personality changes, Surgery and radioiodine ablation should be considered
mood instability and poor school performance are in patients with failure of medical management. Patients
516 Essential Pediatrics
with large or toxic nodular goiter require partial or total PTH increases serum calcium by stimulating bone
thyroidectomy. Radioiodine (131 1) is now increasingly used resorption (osteoblast), calcitriol production (proximal
in the management of childhood Graves disease. tubule) and renal calcium resorption (distal tubule).
Calcitriol is the only hormone that regulates intestinal
Neonatal Hyperthyroidism calcium absorption. Calcitriol is formed by activation of
One percent of babies born to mothers with Graves disease vitamin Din the liver (25-hydroxylation) and kidney (la
show fetal thyrotoxicosis and cardiac failure. Management hydroxylation). Sunlight is the major source of vitamin D
includes maternal antithyroid drugs and digitalization. with minor contribution from dietary sources. la
This usually occurs within the first week of life but may hydroxylase enzyme in the kidneys is the rate-limiting step
be delayed, if mother is on antithyroid medications or has of calcitriol synthesis. Calcitonin, secreted by the
concomitant TSH receptor blocking antibody. Treatment parafollicular cells of thyroid in response to elevated
should include antithyroid drugs, propranolol and calcium levels, lowers serum calcium levels by decreasing
corticosteroids. The condition is self-limiting and resolves bone resorption and increasing urinary calcium excretion.
over 3-6 months. It has a minor role on calcium homeostasis.
Table 18.14: Etiology of hypocalcemia calcitriol resistance (vitamin D-dependent rickets type
Deficiency of ionic calcium (chelation) 11) are associated with hypocalcemia. Phosphate levels
Phosphate load are low due to secondary hyperparathyroidism. Vitamin
Tumor lysis D deficiency is the most common cause of hypocalcemia
Rhabdomyolyis in children. Rickets may be absent. Maternal vitamin D
deficiency is common in India and results in reduced
Top feeds
calcium and vitamin D stores in children. These infants
Total calcium deficiency develop hypocalcemia during periods of rapid bone
PTH deficiency (hypoparathyroidism) growth (4-8 weeks of life). Vitamin D-dependent rickets
Aplasia: DiGeorge syndrome presents with early onset severe hypocalcemia and
Autoimmune: Polyglandular endocrinopathy types I and II rickets.
Infiltration: Wilson disease, hemochromatosis, thalassemia
Increased chelation: Increased calcium binding results in
Transient: Hypomagnesemia, maternal hyperparathyroidism,
post-surgery reduction of ionic calcium and features of hypocalcemia.
PTH resistance (pseudohypoparathyroidism) This is most commonly related to high phosphate levels
Vitamin D deficiency (renal failure or release of intracellular phosphate due to
Nutritional hemolysis, tumor lysis or rhabdomyolysis). Increased
1 a-hydroxylase deficiency: Renal failure, VDDR type I phosphate levels in cow milk and commercial formula is
Calcitriol resistance: VDDR type II an important cause of neonatal hypocalcemia. Metabolic
Increased inactivation: Phenytoin, phenobarbitone or respiratory alkalosis increases albumin binding of
calcium resulting in hypocalcemia.
PTH: Parathyroid hormone; VDDR: Vitamin D-dependent rickets
Evaluation
action of PTH characterize these disorders. Hypopara
thyroidism may occur as part of congenital malformation Evaluation is directed towards identification of etiology
or acquired destruction of the parathyroid glands. and assessment of the severity of illness.
Autoimmune hypoparathyroidism is the most common Clinical: Detailed history of the age of onset, presenting
form in older children and frequently associated with features, frequency of episodes of hypocalcemia and
autoimmune polyendocrinopathy type 1. family history should be obtained. Neonates should be
DiGeorge syndrome characterized by abnormal screened for prematurity, birth asphyxia, maternal
development of third and fourth pharyngeal pouches is hyperparathyroidism and initiation of top feeds.
caused by deletion of part of chromosome 22q. This results Congestive cardiac failure, recurrent infections and
in maldevelopment of thymus (resulting in T cell abnormal fades are suggestive of DiGeorge syndrome.
immunodeficiency), parathyroid glands (resulting in
hypoparathyroidism), heart (resulting in conotruncal Investigations: Initial evaluation should include serum
defects) and face (abnormal fades). Activating mutation phosphate levels, renal and liver function tests and serum
of calcium-sensing receptor is associated with low PTH alkaline phosphatase (Table 18.15 and Fig. 18.11).
and calcium levels with paradoxically increased urinary Phosphate regulation is dependent on PTH and inefficient
calcium excretion (familial hypercalciuric hypocalcemia). PTH action results in hyperphosphatemia. Hypocalcemia
due to decreased vitamin D action is associated with
Hypomagnesemia is an important cause of transient secondary hyperparathyroidism and low phosphate
hypoparathyroidism and should be excluded in children levels. Thus hypocalcemia with hyperphosphatemia in the
with refractory hypocalcemia. absence of phosphate load (exogenous or tissue lysis) and
normal renal function suggests parathyroid insufficiency.
PTH resistance (pseudohypoparathyroidism, PHP): This Hypomagnesemia should be considered in patients with
is caused by an inactivating mutation in the gene encoding refractory hypocalcemia and normal or low phosphate
for stimulatory subunit of G protein (Gsa). This presents levels. 25-hydroxyvitamin D levels should be measured
with clinical features of hypoparathyroidism in the wake in children with rickets to identify vitamin D deficiency.
of elevated PTH levels. PHP may be associated with the
phenotype of Albright hereditary osteodystrophy such as Management
round fades, brachydactyly, short stature, obesity, short
fourth and fifth metacarpals (brachymetacarpia), In children with severe hypocalcemia (ionic calcium
osteodystrophy and heterotopic ossification. <0.8 mmol/L), parenteral calcium should be administered
(2 mL/kg intravenously over 5-10 min) after obtaining
Vitamin D related: Vitamin D deficiency (nutritional, blood sample for calcium. Calcium gluconate (10%, 9 mg
malabsorption), decreased la-hydroxylase action (renal calcium per mL) is the preparation of choice. Care should
failure, vitamin D-dependent rickets type I), increased be taken to administer the drug slowly (to avoid cardiac
inactivation of vitamin D (antiepileptic drugs) and effects) and avoid extravasation (to prevent skin necrosis).
518 Essential Pediatrics
+ I
+
elevated levels of PTH.
Management: Treatment of acute hypercalcemia involves
Low or normal High
+
high fluid intake followed by diuresis (furosemide 1 mg/
kg). Bisphosphonates and antiresorptive agents are
Renal failure
Phosphate load indicated, if there is no response to these measures.
No rickets Hypoparathyroidism Hemodialysis may be required in refractory cases. Surgical
Pseudohypoparathyroidism exploration is indicated in all cases of hyperpara
Vitamin D deficiency thyroidism. Short course of glucocorticoids (prednisolone
Vitamin D dependent 2 mg/kg/day for 3 weeks) is indicated in children with
rickets Hypomagnesemia iatrogenic vitamin D excess or increased la-hydroxylase
action (fat necrosis or sarcoidosis).
Fig. 18.11 : Evaluation of a child with hypocalcemia
Parenteral calcium should be started at a dose of 80 mg/ Suggested Reading
kg/day and should be gradually tapered over two days. • Davies JH, Shaw NJ. Investigation and management of
hypercalcaemia in children. Arch Dis Child 2012;97:533-8.
The management of nutritional and refractory rickets is
• Desai MP, Menon PSN, Bhatia V. Pediatric Endocrine Disorders,
given in Chapter 8. 3rd edn. Hyderabad: Universities Press (India) 2014. pp 1395-431.
• Hallick MF. Vitamin D deficiency. New Engl J Med 2007; 357: 266-81.
Hypercalcemia • Hollick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation,
Hypercalcemia (serum calcium > 11 mg/dL) is rare in treatment and prevention of vitamin D deficiency: Endocrine
Society Clinical Practice Guidelines. J Clin Endocrinol Metab 2011;
children. Its causes include increased bone resorption 96: 1911-30.
(hyperparathyroidism, malignancy and immobilization) • Lee JY, So T, Thackray J. A review on vitamin D deficiency
or excessive vitamin D action (iatrogenic excess and treatment in pediatric patients. J Pediatr Pharmacol Ther
increased la-hydroxylase activity). 2013;18:277-91.
• Tiosano D, Hochberg Z. Hypophosphatemia: The common
Etiology: Hyperparathyroidism is the commonest cause denominator of all rickets. J Bone Miner Metab 2009; 27: 392-401.
of chronic hypercalcemia in children. Homozygous • Zhou P, Markowitz M. Hypocalcemia in infants and children.
Pediatr Rev 2009;30:190-2.
inactivating mutations of the calcium-sensing receptor
present with severe neonatal hyperparathyroidism and DISORDERS OF ADRENAL GLANDS
hypocalciuria. Parathyroid adenoma is rare before the age
of 10 years. Rarely, hypercalcemia may be associated with Physiology
other conditions, e.g. Williams syndrome (supravalvular Adrenal cortex produces three important groups of
aortic stenosis, abnormal fades) or hypophosphatasia hormones-glucocorticoids, mineralocorticoids and
(inactivating mutation of alkaline phosphatase). Vitamin androgens. The process of steroidogenesis involves
D-related hypercalcemia occurs in children receiving conversion of cholesterol to steroid hormones through a
parental vitamin D or inadvertently high doses of oral series of enzymatic processes. Cholesterol is transferred
vitamin D. Increased la-hydroxylase activity may occur into the mitochondria in a process mediated by the
in patients with granulomatous diseases (tuberculosis, steroidogenic acute regulatory protein (StAR), an ACTH
sarcoidosis) or fat necrosis. dependent protein. The most clinically relevant step in
Clinical features: They are often nonspecific, including steroidogenesis is 21-hydroxylation mediated by the
muscular weakness,anorexia,nausea,vomiting,constipation, enzyme 21-hydroxylase (P450c21). This step is crucial for
polydipsia and polyuria. Ectopic calcification in the kidney, the production of cortisol and aldosterone (Fig. 18.12).
basal ganglia and skin are common. Bony deformities and Cortisol, the major glucocorticoid hormone has an
pathological fractures may be present. Infants present with important role in intermediary metabolism causing
failure to thrive,poor feeding,hypotonia and seizures. Serum increased blood glucose levels and enhanced catabolism
total and ionized calcium levels are elevated with low levels of proteins and lipids.
Endocrine and Metabolic Disorders ls19-
Cholesterol
SIAR
Mitochondrial transport
Cholesterol DH EAS
CYP11A1
POR POR
Pregnenolone >-----._17 _ -0
_ H_ p
_ re
_ g n_ en _ n_ _e_;----•1,_D_ H_ EA
_ _olo _ _�____, HSD17 Androstenediol
'----��-----'CYP17A1, � CYP17A1,
HSD3B2 17a-Hydroxylase HSD3B2 17, 20-lyase HSD3B2 HSD3B2
Corticosterone CORTISOL
CYP11B2
18-Hydroxylase
18-0H-Corticosterone
CYP11B2
18-oxidase
ALDOSTERONE
Fig. 18.12: Pathways of steroid biosynthesis. The key enzymes mediating synthesis of principal steroids are named according to
their site of action and the nomenclature of cytochrome P450 enzymes. StAR steroidogenic acute regulatory protein;
DOC deoxycorticosterone; DHEA dehydroepiandrosterone; DHEAS DHEA sulfate; DHT dihydrotestosterone. The enzyme nomenclature: CYPl lAl:
P450 side chain cleavage enzyme, P450scc or 20,22-desmolase; HSD3B2: 3j3 -hydroxysteroid dehydrogenase type 2; CYPl7A1: l7a-hydroxylase
orl7 ,20 lyase; CYP21A2: 21-hydroxylase; CYPl 1 Bl: l l j3-hydroxylase; CYPl 1 B2: This has 3 actions-l 1 j3-hydroxylase, 18-hydroxylase and 18-oxidase;
POR: P450 oxidoreductase, CYPl 9A1: Aromatase, HSD178: 1713-hydroxysteroid dehydrogenase, SRD5A2: Sa-reductase type 2
Aldosterone acts on distal renal tubules and collecting hypercortisolism caused by an ACTH-producing pituitary
ducts of kidneys to promote sodium and fluid tumor. Classic features of Cushing syndrome such as
reabsorption. Aldosterone deficiency causes urinary salt central obesity, striae, moon fades and buffalo hump are
wasting resulting in salt-wasting crisis (hyponatremia, rare in children (Fig. 18.13). Growth failure and obesity
hyp erkalemia and metabolic acidosis). are common; other features include hypertension,
Adrenal androgens are necessary for the development of hirsutism, delayed puberty, behavioral problems, bone
pubic and axillary hair in girls. pain and muscle weakness.
Adrenocorticotropic hormone (ACTH), a polypeptide Etiology: Cushing syndrome may be caused by increased
secreted by the anterior pituitary, is the major regulator endogenous production or exogenous administration
of glucocorticoid and androgen synthesis. Intravascular (Table 18.16). Prolonged steroid treatment is the
volume, serum potassium levels and renin-angiotensin commonest cause of childhood Cushing syndrome.
system are the chief regulators of aldosterone synthesis. Increased adrenal glucocorticoid production may be
ACTH has only a minor role in aldosterone regulation. related to increased ACTH levels or represent autonomous
ACTH deficiency as in secondary adrenal insufficiency adrenal hyperfunction. Adrenal pathology is more likely
is, therefore, not associated with salt-wasting. ACTH in young children, while pituitary causes are common
secretion is stimulated by hypothalamic corticotropin after puberty. Ectopic ACTH production is rare in
releasing hormone (CRH) and suppressed by cortisol as children.
part of a feedback loop.
Evaluation: Investigations are directed towards
Adrenocortical Hyperfunction-Cushing Syndrome confirming the diagnosis of Cushing syndrome and
The most common disorder of adrenocortical hyperfunction finding the etiology. Commonly used screening tests
is Cushing syndrome. The term Cushing disease refers to include assessment of diurnal cortisol rhythm, overnight
s20 I Essential Pediatrics
Ultrasound, CT scan, MRI scan and 123 I metaiodo hyp erpigmented such as areola and genitalia. Pigmenta
benzylguanidine (MIBG) scintigraphy are used for tion is absent in children with secondary adrenal
localization. Often the tumors are multiple. insufficiency.
Management: Surgery is the treatment of choice. Evaluation: All patients suspected to have adrenal
Transabdominal exploration of all the sites with removal insufficiency should undergo urgent testing for serum
of tumors is advocated. Preoperative alpha blockade is electrolytes and blood sugar. Basal levels of cortisol are
needed using phenoxybenzamine and prazosin. Recently, low but can be in the normal range. Elevated plasma renin
calcium channel blocking agents have been used activity indicates mineralocorticoid deficiency. ACTH
successfully. stimulation test (cortisol estimation 60 minutes after
0.25 mg of intramuscular or intravenous ACTH injection)
Adrenal Insufficiency is the best test for adrenocortical reserve. Serum cortisol
Adrenal insufficiency may be related to adrenal defects levels lower than 18 µg/dL are suggestive of adrenal
(primary adrenal insufficiency; autoimmune destruction, insufficiency.
infection, steroidogenic defect, hemorrhage), decreased The next step in evaluation of adrenal insufficiency is
ACTH production (secondary adrenal insufficiency) or estimation of ACTH levels. Elevated ACTH levels suggest
ACTH resistance. primary adrenal pathology while low levels points
towards pituitary defect. Further evaluation of primary
Etiology: Autoimmune adrenal dysfunction is the adrenal insufficiency includes abdominal CT scan and
commonest cause of primary adrenal failure (Addison workup for tuberculosis.
disease) beyond infancy. Autoimmune adrenal failure is
often associated with autoimmune polyendocrinopathy Management: The initial management of salt-wasting
type 1 and 2. Infections due to tuberculosis and human crisis includes correction of shock by fluid boluses. Hydro
immunodeficiency virus (HIV) are known to result in cortisone is given immediately at a dose of 50 mg/m2,
primary adrenal failure. Adrenal hemorrhage in the followed by 100 mg/m2 /day in four divided doses.
setting of meningococcal and other bacterial infections Frequent monitoring of hemodynamic parameters, urine
(Waterhouse-Friderichsen syndrome) is an important output and serum electrolytes are required. Once the child
cause of adrenal insufficiency. Congenital adrenal is hemodynamically stable, hydrocortisone is tapered to
hyp erplasia (CAH) due to deficiency of 21-hydroxylase the physiological dose (10 mg/m2 / day). Fludrocortisone
or 313-hydroxysteroid dehydrogenase and deficient acetate (0.1 mg/day) is added once hydrocortisone dose
steroidogenesis due to defective steroidogenic acute is <50 mg/m2/day.
regulatory protein (StAR; causing lipoid CAH) are the Long-term management of adrenal insufficiency
chief causes in the neonatal period. requires lifelong replacement of glucocorticoids and
Secondary adrenal insufficiency is caused by congenital mineralocorticoids. Parents should be educated about the
malformations (holoprosencephaly, midline defects), need for increasing dose during periods of stress. The dose
genetic defects or acquired insults (neurosurgery, tumor, of glucocorticoid should be increased 2-3 times in
radiation). This is usually associated with other anterior conditions of minor stress (fever and mild infection) and
pituitary hormone deficiencies as well. In secondary 4-5 times in severe stress (severe infection or surgery).
adrenal insufficiency, mineralocorticoid function is These doses should continue throughout the period of
preserved, as ACTH does not regulate aldosterone stress. Patients with secondary adrenal insufficiency
secretion. Thus, salt-wasting is not observed. Prolonged require lower dose of glucocorticoids (6-10 mg/m2 / day);
steroid treatment is associated with suppression of the mineralocorticoid replacement is not necessary.
hypothalamic-pituitary axis resulting in adrenal
insufficiency after discontinuation of medications. Again, Congenital Adrenal Hyperplasia
mineralocorticoid activity is preserved in these patients.
Congenital adrenal hyperplasia (CAH), a group of
Clinical features: Adrenal insufficiency presents with autosomal recessive defects in steroid synthesis, is
slowly progressive lethargy, vomiting, salt craving, characterized by deficiency of adrenocortical hormones
fatigue, postural hypotension, hypoglycemia and episodes on one hand and excess of steroid precursors on the other
of shock during severe illness. The concomitant presence (Fig. 18.12). CAH is the commonest adrenal disorder in
of shock, hyponatremia, hyperkalemia and hemoconcen childhood.
tration is characteristic of acute adrenal insufficiency and
warrants immediate steroid replacement. Primary adrenal 21-hydroxy/ase Deficiency
insufficiency is characterized by hyperpigmentation due 21-hydroxylase deficiency is the commonest form of CAH
to elevated levels of melanocyte-stimulating hormone. accounting for over 90% of all cases. This disorder is
Hyperpigmentation is present in sun-exposed areas such associated with diminished synthesis of the cortisol and
as elbows and palmar creases and areas that are normally aldosterone. Low cortisol levels stimulate ACTH
Endocrine and Metabolic Disorders ls2a-
synthesis. Elevated ACTH level causes accumulation of Table 18.20: Comparison of commonly used steroid preparations
steroid precursors (e.g. dehydroepiandrosterone,
Preparation Potency (compared Biological
androstenedione and 17-hydroxyprogesterone). Depending to hydrocortisone) half-life
on the severity of enzyme deficiency, the disease forms a
spectrum of presentation as highlighted below. Gluco- Mineralo- Growth
corticoid corticoid inhibitory
Salt-wasting form: These patients are the most severely Hydrocortisone 1 1 1 6 hours
affected and present in the neonatal period with
virilization and salt-wasting. Abnormal genital appearance Cortisone 0.8 1.25 1.25 5 hours
should prompt the diagnosis in girls. Diagnosis is often Prednisolone 4 0.25 8 8 hours
missed in boys as they lack specific clinical features. They Dexamethasone 20 0 40 12 hours
present after second week of life with failure to thrive, Fludrocortisone 0.1 100 0.1 12 hours
polyuria, hyp erpigmentation and shock. Early diagnosis
is mandatory to prevent mortality. 21-hydroxylase
in those with simple virilizing and non-classic forms. The
deficiency should be suspected in neonates with
best method of diagnosing these patients is the estimation
ambiguous genitalia, polyuria, shock, recurrent vomiting
of 17-0HP levels before and 60 minutes after an
and features of sepsis with negative septic screen. The
intramuscular injection of ACTH (0.25 mg).
diagnosis is confirmed by measurement of blood levels
of 17-hydroxyprogesterone (17-0HP). If these tests are not Management: These patients require lifelong steroid
available, the child should be managed empirically in the replacement therapy. Patients with salt-wasting and
lines of adrenal insufficiency. virilizing forms are treated with hydrocortisone (10-15
Simple virilizing form: A subset of patients with 21- mg/m2/day) and fludrocortisone (0.1 mg/day). After
hydroxylase deficiency (25%) synthesizes enough completion of growth and pubertal development,
aldosterone to prevent adrenal crisis. These patients have synthetic glucocorticoid preparations (dexamethasone,
features of androgen excess in the form of virilization in prednisolone) can be used (Table 18.20).
girls and peripheral precocious puberty in boys (Fig. 18.15).
Other Variants
Non-classic form: This disorder is associated with partial
21-hydroxylase deficiency. Clinical manifestations are Enzyme deficiencies other than 21-hydroxylase deficiency
related to mild hyperandrogenism that presents with account for less than 10% of cases of CAH (Table 18.21).
hirsutism, acne and menstrual irregularity in adolescents. Patients with 11-hydroxylase deficiency and 17-
hydroxylase deficiency present with hyp ertension and are
Diag nosis: Diagnosis of the salt-wasting form is managed with hydrocortisone alone. Deficiencies of StAR
established by demonstration of extreme elevation of 17- and 3-hydroxysteroid dehydrogenase manifest as salt
0HP levels (10000-20000 ng/dL, normal <90 ng/dL) in wasting crisis and require therapy with mineralocorticoid.
presence of clinical and laboratory features of adrenal
insufficiency. 17-0HP levels are elevated to a lesser extent Suggested Reading
• Bajpai A, Menon PSN. Congenital adrenal hyperplasia. In: Gupta
P, Menon PSN, Ramji S, Lodha R, Eds. PG Textbook of Pediatrics,
second Ed. New Delhi; Jaypee Brothers, 2018; pp 2712-7.
• Brandao Neto RA, de Carvalho JF. Diagnosis and classification of
Addison disease. Autoimmune Rev 2014; 13: 408--11.
• Desai MP, Menon PSN, Bhatia V. Pediatric Endocrine Disorders,
3rd edn. Hyderabad: Universities Press, 2014; pp 221-267.
• Greaves RF, Jevalikar G, Hewitt JK, Zacharin MR. A guide to
understanding the steroid pathway: new insights and diagnostic
implications. Clin Biochem 2014; 47: 5-15.
• Shulman DI, Palmert MR, Kemp SF for the Lawson Wilkins Drug
and Therapeutics Committee. Adrenal insufficiency: Still a cause
of morbidity and death in childhood. Pediatrics 2007; 119: e484-94.
• Speiser PW, Azziz R, Baskin LS, et al. Congenital adrenal
hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine
Society clinical practice guideline. J Clin Endocrinol Metab 2010;
95: 4133-60.
• Storr HL, Chan LF, Grossman AB, Savage MO. Pediatric Cushing
Fig. 18.15: Congenital adrenal hyperplasia secondary to 21- syndrome: epidemiology, investigation and therapeutic advances.
hydroxyl ase deficiency. Note the clitoral hypertro p hy, Trends Endocrinol Metab 2007; 18: 167-74.
hyperpigmentation and increased rugosity of the labial folds • Savage MO, Storr HL. Pediatric Cushing's disease: management
giving a male ap pearance to the female genitalia issues. Indian J Endocrinol Metab 2012; 16: 5171-5.
524 I Essential Pediatrics
OBESITY Weight for height: This compares the child's weight to the
expected weight for his/her height and is useful in
The incidence of childhood obesity has increased rapidly
children below 2 years of age (see Chapter 2). Weight for
in the last decade. The prevalence of overweight and/or
height more than 120% is diagnosed as obesity.
obesity in Indian children is around 20% posing significant
risk of lifestyle diseases in future. Skin/old thickness: Skinfold thickness measured over the
subscapular, triceps or biceps regions is an indicator for
Criteria for Diagnosis of Obesity subcutaneous fat. Age specific percentile cut-offs should
Obesity implies excessive fat and not merely excess weight. be used with values more than 85th percentile being
As methods of measuring body fat are cumbersome and abnormal.
expensive, several clinical and anthropometric parameters W aist circumference and waist h ip r atio: Waist
are used as markers of obesity. circumference is measured at the minimum circumference
Body mass index: Body mass index (BMI) is the most widely between the iliac crest and the rib cage. Hip circumference
used parameter to define obesity. It takes into account is measured at the maximum protuberance of the buttocks,
weight as well as the height. It is calculated by the formula: and the waist hip ratio (WHR) may be calculated from
these values. Waist circumference itself is a satisfactory
BMI = Weight (kg)-;- height (m2)
marker of abdominal adiposity, a risk factor for metabolic
Children with BMI more than 85th percentile for age and cardiovascular effects of obesity. Waist circumference
are considered overweight while those with more than greater than 75% is a risk factor for metabolic
95th percentile for age are obese. BMI is a good indicator complications. WHR is probably a more refined method
of body fat but is unreliable in short muscular individuals. but is not age-independent; norms for Indian children are
BMI greater than 99th percentile (120% of 95th percentile) not available.
implicate severe obesity. The cutoffs for obesity should
take into consideration the local population. As the aim Etiology
of assessing BMI is to identify individuals at risk for In most children with obesity, environmental and the
metabolic complications, lower BMI cutoffs have been hereditary factors play the major role. Underlying etiology
recommended for Indian adults (23 kg/m2 for overweight is identified in a few cases ( <1%). The causes of childhood
and 27 kg/m2 for obesity). Thus the use of CDC charts obesity are classified in Table 18.22.
would underestimate the problem of obesity in Indian
children and IAP 2015 growth charts should preferably Constitutional obesity: Most children with obesity do not
be used for defining obesity. have an organic cause. This is caused by imbalance in
Endocrine and Metabolic Disorders ls2s-
Table 18.22: Etiology of obesity risperidone), antidepressants (paroxetine) and anti
Constitutional epileptics (valproic acid, lamotrigine).
Environmental factors (95% cases) Evaluation
Pathological
Initial evaluation is guided to differentiate constitutional
Endocrine: Cushing syndrome, deficiency of growth hormone, from pathological obesity (Table 18.23). Normal growth,
hypothyroidism, pseudohypoparathyroidism generalized pattern and lack of developmental delay or
Hypothalamic: Head injury, infection, brain tumor, radiation, dysmorphism imply constitutional obesity, which does
after neurosurgery not need extensive investigations.
Drugs: Antiepileptic drugs, steroids, estrogen
History: Family history of obesity and its complications
Genetic syndromes: Prader-Willi, Laurence-Moon-Bardet
should be recorded. Detailed history of physical activity,
Biedl, Beckwith-Wiedemann, Carpenter syndromes
dietary recall and periods of inactivity should be assessed.
Monogenic disord ers: Leptin deficiency, or resistance, Increased appetite in a child with recent onset obesity may
abnormalities of melanocortin-4 receptor and proconvertase
indicate the possibility of a hypothalamic lesion. Features
of raised intracranial tension along with history of
energy intake and expenditure. These children are tall for neurologic infection, head trauma or neurosurgery
age, a factor that differentiates them from pathological suggest the prospect of an underlying neurologic cause
obesity. They have proportional obesity and normal for obesity. Intake of drugs linked with development of
development. It is important to identify this subgroup of obesity such as steroids and antiepileptics should be
children to avoid unnecessary investigations. probed.
Endocrine causes: Growth failure, developmental delay Examination: Look for features of endocrinopathies,
and dysmorphism in an obese child denote an endocrine dysmorphic syndromes and complications such as
etiology. Cushing syndrome is characterized by central hypertension and acanthosis nigricans (Fig. 18.16). Special
obesity, hypertension, and striae with retarded skeletal emphasis should be given to sexual maturity and ocular
maturation. Hypothyroidism is an extremely rare cause examination. Hypogonadism is an important feature of
of isolated obesity and other features such as develop obese children with Laurence-Moon-Bardet-Biedl and
mental delay and coarse skin are always present. In GH Prader-Willi syndromes (Figs 18.17, 18.18 and Tables 18.24,
deficiency and pseudohypoparathyroidism, growth 18.25). Parents of obese girls are often concerned about
retardation and hypocalcemia are dominant clinical
features and obesity is a less prominent sign.
Table 18.23: Differentiating features of constitutional and
Genetic syndromes: Several genetic syndromes have pathological obesity
obesity as their major clinical feature. Many of these Feature Constitutional Pathological
syndromes are associated with hypogonadism or Pattern Generalized Central
hypotonia (Prader-Willi, Carpenter and Laurence-Moon Growth rate Accelerated Retarded
Bardet-Biedl syndromes).
Skeletal maturation Advanced Retarded
Hypothalamic obesity: CNS insults due to surgery, Dysmorphic features Absent May be present
radiation, tumors and trauma result in rapid onset obesity. Endocrine features Absent May be present
These disorders are associated with excessive appetite,
signs and symptoms of CNS involvement and other
hypothalamic-pituitary defects.
Monogenic obesity: Monogenic obesity represents a very
small proportion of children with obesity. They are more
likely when the obesity is morbid, has an early onset of
obesity and strong family history. Leptin deficiency was
the first monogenic cause of obesity identified. Inefficient
leptin action (deficiency or resistance) results in
uncontrolled appetite and obesity. Abnormalities in
mineralocorticoid receptor and proconvertase are
associated with obesity. Melanocortin-4 receptor (MC4-
R) defects are the commonest monogenic form of obesity
and are associated with growth acceleration.
Drugs: Commonly used drugs associated with obesity Fig. 18.16: Acanthosis nigricans on the back of neck in a girl
include corticosteroids, anti psychotics (olanzapine, with obesity
s26 I Essential Pediatrics
Table 18.26: Complications of obesity Respiratory system: Obese children are at risk of
respiratory distress and bronchial asthma. Obesity
Category Complications
predisposes to the development of obstructive sleep apnea
Metabolic Insulin resistance, type 2 diabetes, metabolic and hyp oventilation syndrome.
syndrome, hyperandrogenism
Cardiovascular Hypertension, dyslipidemia, atherosclerosis Gastrointestinal system: Obesity is associated with
Gastrointestinal Non-alcoholic fatty liver disease, gall gastroesophageal reflux disease and non-alcoholic fatty
stones, gastroesophageal reflux liver disease. Fatty liver is present in 40% of children with
Skeletal Blount's disease, slipped capital femoral obesity but elevated serum transaminases occur only in
epiphysis, fractures 25% of these children. Gallstones are noted in 2% children
Respiratory Obstructive sleep apnea, hypoventilation
with obesity. Rapid weight fluctuations are associated
syndrome with the gallstone disease. Gallstone should be suspected
in an obese child with recurrent abdominal pain, jaundice,
Neurological Benign intracranial hypertension
nausea and intolerance to fatty foods.
Endocrine system: Endocrine complications are the most Psychological issues: Obesity is associated with increased
important adverse effects of childhood obesity. Central prevalence of mood disorders. This represents intrinsic
to this is the development of insulin resistance caused by effects of obesity and psychological effects of bullying.
overspill of fat and its deposition in liver and skeletal
muscle. Insulin resistance predisposes to development of Assessment of Complications
type 2 diabetes, polycystic ovarian disease, metabolic The high incidence of complications in obese children calls
syndrome and non-alcoholic fatty liver disease. Hyp er for regular follow-up screening. Investigations should
androgenism is a common feature in obese girls. Obesity include a baseline oral glucose tolerance test using blood
has also been associated with accelerated growth, skeletal sugar levels fasting and 2 hours after 1.75 g/kg glucose
maturation and early puberty in girls. (maximum 75 g), lipid profile and liver function tests. Age
Cardiovascular system: Obese children have a higher pre appropriate cutoffs should be used for these investigations
valence of dyslipidemia, hypertension and atherosclerosis. (Table 18.27). These tests should be repeated every 3 years,
Importantly hypertension may be masked, requiring if normal. Fasting insulin has limited role and is not
repeat blood pressure measurements. Childhood obesity routinely required. Mildly elevated liver transaminases
is associated with increased risk of adult coronary disease. are common in obese children; persistent elevation beyond
twice the upper limit indicates non-alcoholic steato
Central nervous system: Benign intracranial hyp ertension hepatitis. Children with elevated transaminases should
is common in children with obesity and presents with undergo ultrasound abdomen and work-up for other
headache and vomiting. causes of hepatic dysfunction (hepatitis B and C, Wilson
Orthopedics: Obese children have a higher risk of flat foot, disease and autoimmune hepatitis). Sleep studies may be
Blount disease (tibia vara), fractures, genu valgum and required in the presence of snoring, daytime somnolence
osteoarthritis. The most debilitating complication is or lethargy.
slipped capital femoral epiphysis. This presents with dull
aching pain in knee, hip or groin with abnormal gait. Management
Blount disease presents with progressive bowing of legs Management of childhood obesity is challenging with
and knee pain. X-ray of knee and hip should be done in major impetus on lifestyle measures (Fig. 18.19). Specific
obese children with recurrent pain in hip or knee or management is available for only a few situations. Diet,
abnormal gait. activity and behavioral measures are the cornerstone of
Table 18.27: Pediatric cutoffs for investigations for assessment of obesity complications
Investigation Normal Borderline Abnormal
Blood glucose (fasting) <100 mg/dl 100-125 mg/dl >126 mg/dl
Blood glucose (2 hours after glucose) <140 mg/dl 140-199 mg/dl >200 mg/dl
Total cholesterol <170 mg/dl 170-199 mg/dl >200 mg/dl
LDL-cholesterol <110 mg/dl 110-129 mg/dl >130 mg/dl
Triglyceride <90 mg/dl 90-129 mg/dl >139 mg/dl
H DL-cholesterol >45 mg/dl 40-45 mg/dl <40 mg/dl
Serum aspartate aminotransferase <40 IU/L 40-80 IU/L >80 IU/L
(AST or SGOT)
528 Essential Pediatrics
Body mass index I like dancing, sports and running should made to ensure
I a minimum of 30 minutes daily. Weight bearing exercises
+ + and over-regimented schedule should be avoided.
2-3.5 sos >3.5 sos
Assess for complications
+
Complications or
Specific Management
Specific treatment should be initiated in children with
Insulin resistance hypothyroidism, GH deficiency and Cushing syndrome.
Children with mildly elevated TSH level do not need
Lifestyle modification Lifestyle modification/ treatment. Obese children with Prader-Willi syndrome
Diet, physical activity Add metformin/
statin, if indicated and growth failure may benefit from GH therapy.
Octreotide is effective in hypothalamic obesity while the
No improvement use of leptin is reserved for leptin deficiency.
Nutritional therapy: The child should be advised to stick Bariatric surgery is considered in severe obesity when
to regular meals. Skipping breakfast and snacking in other measures fail. The intervention is preferred after
between meals should be discouraged. The caloric intake achieving final height to avoid potential adverse growth
should be reduced by 20%. Overzealous restriction and effects. Bariatric surgery is a major surgical undertaking,
fad diets are not recommended. Food pyramid and 'traffic and should be viewed as a potentially life-saving and not
light' approach for diet may be used to highlight healthy just a cosmetic procedure. Patients need to adhere to strict
eating pattern. Special emphasis is laid on fixed portion dietary restriction for life. Laparoscopic adjustable
size, decreased junk food consumption, avoiding banding is the recommended procedure in children.
television viewing while eating, and increased fruit Malabsorptive procedures and gastric sleeve are not
consumption. recommended for children.
• Barlow SE, Expert Committee. Expert committee recommendations In boys, puberty starts with testicular enlargement at
regarding the prevention, assessment, and treatment of child and 11.5 years (range 9 to 14 years). This is followed by penile
adolescent overweight and obesity: summary report. Pediatrics
2007; 120 Suppl 4:Sl64.
enlargement and pubarche; spermarche occurs by 14 years.
• Mathai S, Derraik JG, Cutfield WS, et al. Increased adiposity in Peak growth velocity in boys correlates to testicular
adults born preterm and their children. PLoS One 2013;8:e81840. volume of 10 mL.
• Speiser PW, Rudolf MCJ, Anhalt H, et al on behalf of Obesity
Consensus Working Group. Consensus statement: Childhood Assessment of Puberty
obesity. J Clin Endocrinol Metab 2005; 90: 1871-1887.
The stage of pubertal assessment is assessed using Tanner
DISORDERS OF THE GONADAL HORMONES staging system (Figs 5.1, 5.2). Breast development beyond
Tanner II in girls and testicular volume greater than 4 mL
Puberty indicates the onset of puberty. Maximum growth spurt
Puberty is the phase of life when secondary sexual charac occurs during early puberty in girls (Tanner II-ill) compared
teristics appear and mature, and capability of reproduction to boys where it occurs later (Tanner III-IV) (Table 18.28).
is attained. Deviations from the normal pattern of puberty Menstrual periods are irregular in the first few years before
have major diagnostic and therapeutic implications. attainment of regular ovulatory cycles. It is important to
differentiate adrenarche (pilosebaceous development
Physiology related to increase in adrenal steroids) from gonadarche
Puberty involves development of primary (testicular and (genital development related to increase in GnRH) in girls.
penile growth in boys and breast, ovarian and uterine
growth in girls) and secondary sexual characteristics Precocious Puberty
(pubic and axillary hair growth, change of voice in boys, Pubertal onset before the age of 8 years in girls and 9.5 years
acne and axillary odor). Sex hormones (estrogen in girls in boys is suggestive of precocious puberty. Precocious
and testosterone in boys) play an important role in the puberty may be due to stimulation of the hypothalamic
development of primary sexual characteristics, while pituitary axis (gonadotropin-dependent precocious
adrenal androgens are involved in the development of puberty) or autonomous sex hormone production
secondary sexual characteristics in girls. (gonadotropin-independent).
Kisspeptin, a hypothalamic peptide, is the key regulator
of puberty. Acting as the 'on-off switch' of puberty, Precocious Puberty in Girls
kisspeptin initiates GnRH pulses. Initially, GnRH pulses Precocious puberty is common in girls and may represent
occur only during nights followed by secretion during a normal variation in the age at onset of puberty. In most
both day and night. This leads to increase in the levels of cases, puberty is slowly progressive with no long-term
gonadotropins, and thereby, sex hormones. LH is a better adverse effect. Endocrine workup should be restricted to
indicator of pubertal status compared to FSH. Pulsatile girls with progressive forms of puberty.
secretion of GnRH makes basal gonadotropin levels an
unreliable indicator of pubertal status. The hypothalamic Gonadotropin-dependent precocious puberty (central
pituitary-gonadal axis is under feedback control. Thus precocious puberty) is much more common than
secretion of LH is inhibited by testosterone and estrogen gonadotropin-independent precocious puberty (Table 18.29).
produced by the Leydig cells and theca cells, respectively. In more than 90% cases, no underlying cause is identified.
Inhibin produced by the Sertoli and granulosa cells inhibits It may be caused by a variety of pathologies of the central
FSH production. nervous system. Hyp othalamic hamartoma, a neuronal
migration defect, is the commonest cause of organic central
Patterns of Pubertal Development precocious puberty. The disorder presents with early onset
The pattern of pubertal development is different in girls and rapid progression of puberty, seizures and uncontrolled
and boys. Puberty starts at around the age of 10 years in laughter episodes (gelastic epilepsy).
girls (range 8-12 years) and is completed over 5 years.
Breast enlargement (thelarche) is the first event followed Table 18.28: Comparison of pattern of pubertal development
by the development of pubic hair (pubarche) and onset of in boys and girls
menstrual cycles (menarche). Breast development may be Girls Boys
asymmetrical in the initial phase. Menarche usually occurs Onset 10-12 years 12-14 years
2 years after thelarche usually during stage III and IV.
First sign Breast Testicular enlargement
Pubertal development is closely linked to remaining development
growth potential of the child. Thus a girl is expected to
Growth spurt Tanner II Tanner Ill and IV
gain around 20 cm from breast stage II development and
and Ill
5-8 cm after achieving menarche. Discordant pubertal
Sexual Menarche Spermarche 14-15 years
development (menarche within one year of thelarche)
maturity 14 years
suggests a hyperestrogenic state with withdrawal bleeding.
530 Essential Pediatrics
Table 18.29: Etiology of precocious puberty in girls which presents with a constellation of cutaneous (multiple
Gonadotropin-dependent or central precocious puberty
cafe au lait spots), skeletal (multiple fibrous dysplasia) and
endocrine abnormalities (hyperthyroidism, rickets and
Idiopathic
GH excess). Precocious puberty occurs at an early age and
Tumors: Hamartoma, pituitary adenoma, craniopharyngioma,
is rapidly progressive. Prolonged untreated primary
glioma
hypothyroidism may induce early puberty due to action
Infections: Neurotuberculosis, meningitis
of TSH on FSH receptor. Delayed bone age and growth
Injury: Head trauma, neurosurgery, cranial irradiation
are characteristics.
Malformation: Arachnoid cyst, hydrocephalus, septo-optic
dysplasia
Evaluation
Gonadotropin- independent or peripheral precocious
puberty
Aims of evaluation include confirmation of diagnosis,
identification of underlying etiology and determination
Hypothyroidism
of prognosis and treatment (Fig. 18.20).
Ovarian estrogen: McCune-Albright syndrome, cyst, tumor,
aromatase excess Clinical: History should include the onset, progression
Adrenal estrogen: Estrogenic adrenal adenoma and extent of puberty. Exposure to steroids, estrogens and
Exogenous estrogen exposure androgens should be enquired. Family history of
Incomplete variants precocious puberty and early menarche points towards
idiopathic central precocious puberty. Features of
Isolated thelarche
hypothyroidism should be assessed. Advanced growth is
Isolated pubarche (adrenarche)
characteristic of precocious puberty; growth retardation
Isolated menarche
indicates hypothyroidism or concomitant GH deficiency.
Gonadotropin-independent precocious puberty (peri Examination of vaginal mucosa for estrogen effect
pheral precocious puberty) is rare and usually caused by provides clues regarding the pubertal status of the patient.
estrogenic ovarian cysts. Fluctuating pubertal development Red, glistening vaginal mucosa suggests lack of estrogens
and early vaginal bleeding (due to hyperestrogenic state) while pink mucosa with mucus is indicative of estrogen
is common. The condition is usually self-resolving and effect. Abdominal examination for adrenal or ovarian mass
there is no need for treatment. Recurrent ovarian cysts should be done. Features of McCune-Albright syndrome
should raise the possibility of McCune-Albright syndrome, include cafe au lait spots, polyostotic fibrous dysplasia,
a somatic activating mutation of stimulatory G protein, bony deformities and polyendocrinopathy.
•
Retarded
[ Exclude hypothyroidism [
•
Normal
+ +
Low LH
•
GnRH stimulation test
Elevated LH
+I
Prepubertal LH response
+
Pubertal LH response
+
Gonadotropin-independent PP Gonadotropin-dependent PP
Ultrasound adrenal and ovary MRI brain
Bone scans for fibrous dysplasia
Fig. 18.20: Approach to precocious puberty in girls. DHEA/S dehydroepiandrosterone sulfate; FSH follicle-stimulating hormone;
GnRH gonadotropin-releasing hormone; LH luteinizing hormone; MRI magnetic resonance imaging
Endocrine and Metabolic Disorders 1sa1-
Investigations: Assessment of pubertal status is based on Incomplete Variants of Precocious Puberty
basal or stimulated gonadotropin levels. Pooled These disorders represent normal variants and do not
gonadotropin levels are preferred due to their pulsatile require specific treatment. Their identification helps in
secretion. LH is a better indicator compared to FSH, since restricting the extent of diagnostic workup and counseling.
the former increase significantly during puberty. LH levels
in the pubertal range (>0.6 mU/L with LH/FSH ratio > 1) Isolated thelarche: Isolated breast development may
is suggestive of development of puberty. represent isolated thelarche or first manifestation of central
Bone age helps in assessing the height compromise and precocious puberty. Bone age, gonadotropin levels and
in predicting final height. Advanced bone age (more than pelvic ultrasound help in differentiating the two
two years ahead of chronological age) suggests progressive conditions. Normal growth, prepubertal LH, age
precocious puberty, while normal bone age indicates appropriate bone age and small uterine size suggest
slowly progressive puberty. Retarded growth and skeletal isolated thelarche. These children usually present around
maturation is diagnostic of hypothyroidism. Thyroid the age of 1-2 years and show gradual regression of
function should be assessed to rule out hypothyroidism thelarche by 5 years of age.
in these girls. Isolated adrenarche: Premature adrenarche refers to
MRI of brain should be done in girls with onset of development of pubic hair and acne in the absence of
puberty <6 years of age, rapid progression and associated breast development or menarche. Most cases are
neurological features. Ultrasound of abdomen and pelvis physiological variants. Rarely, androgen excess due to
helps in diagnosing follicular cysts and ovarian and adrenal (21-hydroxylase deficiency, 11/3-hydroxylase
adrenal mass. Girls with prepubertal LH levels should deficiency, adrenal tumor) or ovarian (tumor, polycystic
undergo ultrasound of ovary and adrenals (for ovarian ovarian disease) causes may be identified. Normal bone
cyst and adrenal tumor) and skeletal survey (fibrous age and absence of virilization suggest premature
dysplasia). adrenarche and no treatment.
Management Isolated menarche: Vaginal bleeding in the absence of
Aims of management include treatment of underlying thelarche is against the diagnosis of gonadotropin
cause, management of associations, puberty suppression dependent precocious puberty. Vaginal bleeding occurs
and achievement of target height potential. The significant early in course of estrogen excess states like ovarian cysts,
long-term consequence of precocious puberty is short hypothyroidism and McCune-Albright syndrome.
stature. Growth is accelerated at presentation. This is Vaginal bleeding without breast development requires
associated with disproportionately advanced bone age evaluation of local causes (infection, foreign body, sexual
resulting in premature epiphyseal fusion culminating in abuse or tumors).
compromised final height. Precocious Puberty in Boys
Gonadotropin-dependent precocious puberty: Drugs used Precocious puberty is less common in boys, but when
for pubertal suppression include medroxyp rogesterone present is usually associated with significant pathology.
acetate (MPA), cyproterone and GnRH analogs. MPA does This mandates prompt evaluation and treatment of all
not improve height outcome and is considered in girls with boys with precocious puberty.
intellectual disability where final height is not important.
Long-acting GnRH analogs are the only agents effective Etiology
in improving height outcome. They cause sustained Gonadotropin-dependent and independent precocious
stimulation and desensitization of pituitary leading to puberty accounts for similar number of cases (Table 18.30).
reversal of pubertal changes. GnRH analogs should be
considered in girls with early onset (before 6 years of age) Gonadotropin-dependent precocious puberty: The etiology
rapidly progressive puberty and height compromise (bone is similar to girls, except that organic causes are common.
age to chronological age difference more than two years). Hypothalamic hamartoma, craniopharyngioma,
The treatment is discontinued at the chronological age of hydrocephalus and tubercular meningitis are important
11 years and bone age of 12.5 years. causes (Figs 18.21 and 18.22). These disorders are
associated with increase in testicular volume and elevated
Gonadotropin-independent precocious puberty: Thyroxine basal and GnRH-stimulated LH.
replacement reverses the pubertal changes of hypo
thyroidism. Treatment for McCune-Albright syndrome is Gonadotropin-independent precocious puberty: This is
directed towards inhibiting estrogen production caused by increased androgen production by testis and
(aromatase inhibitors: anastrazole, letrozole) or estrogen adrenals, with prepubertal LH levels. Adrenal over
action (tamoxifen, estrogen receptor antagonist: production due to CAH is the chief cause of peripheral
fulvestrant). Size and morphological features guide precocious puberty in boys; adrenal tumors are rare.
treatment of ovarian cysts. Human chorionic gonadotropin (hCG) secreting tumors
532 Essential Pediatrics
Management
Management of central precocious puberty includes
treatment of underlying pathology and GnRH analog
therapy. GnRH analog should be continued till the age of
12 years. CAH is managed with hydrocortisone and
fludrocortisone. Surgery is the treatment of choice for
adrenal and testicular tumors, while radiotherapy is
effective in hCG-secreting tumors. Aromatase inhibitors
and antiandrogens are indicated in testotoxicosis.
Delayed Puberty
Fig. 18.21: Central p recocious puberty secondary to Delayed puberty is more common in boys than in girls.
hypothalamic hamartoma Most children with delayed puberty have constitutional
Endocrine and Metabolic Disorders 1533-
Prepubertal LH levels
GnRH stimulation test
I Pubertal LH levels I Systemic disorders: Renal failure, liver disease, celiac disease,
renal tubular acidosis, cystic fibrosis
Nutritional disorders: Malnutrition, anorexia nervosa
Endocrine disorders: Hypothyroidism, hyperprolactinemia, type
1 diabetes
Prepubertal LH response Pubertal LH response Permanent
Adrenal imaging
Isolated hypogonadotropic hypogonadism
Genetic: KAL 1, GnRH receptor, LH, FSH, DAX1 mutations
Dysmorphic syndromes: CHARGE, Prader-Willi, Laurence
Normal imaging Mass lesion Moon-Bardet-Biedl
i I MRI brain Multiple pituitary hormone deficiencies
ACTH stimulation test Adrenal tumor I Malformations: Holoprosencephaly, septo-optic dysplasia,
midline defects
Genetic disorders: PROP1, LH gene deletions
Brain tumors: Craniopharyngioma, germinoma, glioma
+
Normal 17-0HP levels High 17-0HP
Brain injury: Surgery, infection, radiation, trauma
Check hCG levels
I
@b Infiltrative disorders: Histiocytosis, autoimmune disorders
+ + Hypergonadotropic hypogonadism
.. ..
Gonadal dysgenesis: Turner syndrome, SRY deletion, trisomy
Normal High
18, 13, 21
LH receptor study hCG-secreting tumor Steroidogenic defects: StAR, 17a-hydroxylase, 17P-hydroxy
CT brain, chest and abdomen steroid dehydrogenase or aromatase deficiency
Ovarian insults: Surgery, radiation, alkylating agents, infections
Fig. 18.23: Approach to precocious puberty in boys. ACTH Autoimmune ovarian failure: Autoimmune polyendocrinopathy
adrenocorticotropic hormone; CAH congenital adrenal Gonadotropin resistance: LH and FSH receptor mutations
hyperplasia; CT computed tomography; FSH follicle-stimulating Isolated amenorrhea
hormone; GnRH gonadotropin-releasing hormone; hCG human
chorionic gonadotropin; LH luteinizing hormone; MRI magnetic Structural malformations: MOllerian agenesis, vaginal septum,
imperforate hymen
resonance imaging; 1 7-0HP 1 7-hydroxyprogesterone
Inefficient androgen action: Complete androgen insensitivity
syndrome
delay emphasizing the need for watchful monitoring and DAX1: Dosage sensitive sex reversal; FSH: Follicle-stimulating hormone;
conservative approach. GnRH: Gonadotropin-releasing hormone; LH: Luteinizing hormone;
KAL 1: Kallman syndrome gene 1; StAR: Steroidogenic acute regulatory
protein; SRY: Sex determining region on Y chromosome
Delayed Puberty in Girls
Delayed puberty in girls is defined as lack of secondary by ovaries and elevated gonadotropin levels. Causes
sexual characteristics by the age of 13 years. Absence of include Turner syndrome, ovarian failure and enzymatic
menarche by the age of 16 years, or 5 years after onset of defects in estrogen synthesis.
puberty indicates pubertal delay.
Evaluation
Etiology Goals of evaluation include identification of constitutional
Delayed puberty may be caused by defects in the delay, organic etiology requiring neuroimaging and
hypothalamic-pituitary axis, ovaries or genital tract decision regarding treatment.
(Table 18.31). Defects in the hypothalamic-pituitary
Clinical: Family history of delayed puberty provides a
axis are associated with low gonadotropin levels
clue to constitutional delay in puberty. Patients are
(hypogonadotropic hyp ogonadism). This may be related
screened for chronic systemic or neurological diseases,
to reversible causes such as systemic diseases,
Turner syndrome or hypothyroidism, and poor olfactory
malnutrition, eating disorders, hyperprolactinemia and
sensation. Amenorrhea with normal secondary sexual
hypothyroidism. Irreversible defects include destruction
characteristics indicates anatomical defects.
of the hyp othalamic-pituitary axis by infection, surgery,
radiation or tumor. Defective smell sensation, low GnRH Investigations: Workup is directed towards screening for
levels and hypogonadotropic hypogonadism characterize systemic disorders (liver, renal or gastrointestinal disease),
Kallmann syndrome, a neuronal migration defect due to followed by estimation of FSH levels and karyotype.
mutation of KALl gene. Hypergonadotropic hypo Steroidogenic defects are likely, if karyotype and pelvic
gonadism is associated with defective estrogen production ultrasound are normal. In patients with low/ normal FSH
sa4 I Essential Pediatrics
I I
Constitutional delay of puberty and growth
Low FSH High FSH Systemic disorders: Renal failure, liver disease, celiac disease,
Prolactin levels Exclude ovarian insult
renal tubular acidosis, cystic fibrosis
I Karyotype
t
Nutritional disorders: Malnutrition, anorexia nervosa, bulimia
+
High HH
+ nervosa
Endocrine disorders: Hypothyroidism, hyperprolactinemia, type
Normal
Hyperprolactinemia Smell sensation Ultrasound pelvis 1 diabetes mellitus
Thyroid profile CNS imaging Autoimmune evaluation
CNS imaging Pituitary functions Steroidogenic precursors Permanent
Isolated hypogonadotropic hypogonadism
Fig. 18.24: Approach to delayed puberty in girls. CNS central
Genetic disorders: KAL1, GnRH receptor, LH, FSH, DAX1
nervous system; HH hypogonadotropic hypogonadism; FSH
mutations
follicle-stimulating hormone
Dysmorphic syndromes: CHARGE, Prader-Willi, Laurence
Moon-Bardet-Biedl, Robinow
levels, prolactin and thyroid profile is measured to exclude Multiple pituitary hormone deficiencies
reversible causes (Fig. 18.24). Neuroimaging and pituitary Malformations: Holoprosencephaly, septo-optic dysplasia,
function tests should be done, if these levels are normal. midline defects
Genetic disorders : PROP1, LH gene deletions
Management Brain tumors: Craniopharyngioma, germinoma, glioma
All patients with hyp ergonadotropic hypogonadism and CNS insults: Surgery, infection, radiation, trauma
irreversible hypogonadotropic hypogonadism need Infiltrative disorders: Histiocytosis, sarcoidosis, hemo
hormone replacement. Hormone replacement should be chromatosis
deferred till the bone age of 12 years to avoid deleterious Hypergonadotropic hypogonadism
effects on height. The goal of treatment is to initiate and
Chromosomal abnormalities: Klinefelter syndrome, gonadal
maintain sexual characteristics and to prevent
dysgenesis
osteoporosis. Treatment should be started with low dose Steroidogenic defects: StAR, 17a-hydroxylase, 17[3-hydroxy
estrogens (2 µg ethinylestradiol, 0.3 mg conjugated steroid dehydrogenase deficiency, Smith-Lemli-Opitz syndrome
estrogen or 0.1 mg estradiol valerate every day) and Testicular insults: Radiotherapy, chemotherapy, trauma, torsion,
gradually increased every 3 months till adult doses infections
(20 µg of ethinylestradiol, 1.25 mg of conjugated estrogen Malformations: Vanishing testis syndrome, cryptorchidism
or 1 mg estradiol valerate daily by 2 years) are reached. Inefficient testosterone action: 5a-reductase deficiency
Medroxyprogesterone acetate (5-10 mg from day 11 to Resistance to testosterone action: Androgen insensitivity
21) should be added two years after initiation of treatment syndrome
or when withdrawal bleeding occurs. DAX1 dosage sensitive sex reversal; FSH follicle-stimulating hormone;
GnRH gonadotropin-releasing hormone; LH luteinizing hormone; KAL 1
Delayed Puberty in Boys Kallman syndrome gene 1, SIAR steroidogenic acute regulatory protein
Delayed puberty is more common in boys than girls and
is usually due to a constitutional delay. Lack of pubertal Delayed puberty is common in Prader-Willi, Laurence
changes by the age of 14 years is suggestive of delayed Moon-Bardet-Biedl, Noonan and Robinow syndromes.
puberty in boys.
Hypergonadotropic hypogonad ism (testicular failure) may
Etiology be due to chromosome abnormalities (e.g. Klinefelter
syndrome), partial gonadal dysgenesis, steroidogenic
Constitutional delay in growth and p uberty is the defects and acquired testicular injury (infection, radiation,
commonest cause of delayed puberty in boys (Table 18.32). or chemotherapy) (Fig. 18.25).
They have growth retardation and delayed bone age.
Family history of delayed puberty is present. Gonado Evaluation
tropin levels are prepubertal similar to hypogonadotropic
hypogonadism. Clinical: Family history of delayed puberty suggests
constitutional delay in puberty. History of delayed growth
Hypogonadotropic hypogonadism: This may be reversible spurt with continued growth in adult years and late onset
due to systemic illnesses or permanent due to neurological of shaving in father and brothers is common. Patients are
insult (e.g. infection, surgery, radiation or tumor). Kallmann examined for features of systemic disease(s); history of head
syndrome is an important cause of isolated gonadotropin injury, neurosurgery and intracranial space occupying
deficiency and presents with impaired smell sensation. lesions suggest a defect in the hypothalamic-pituitary axis.
Endocrine and Metabolic Disorders lsas-
Delayed puberty
Screening investigations
Gonadotropin
Low High
Clinical follow-up Exclude testicular insult
GnRH/hCG test Karyotype
Response No response
CDPG Permanent HH
MRI head
Low
hCG test
Testicular biopsy
Low High/normal
5a-reductase defect partial AIS
Investigations: Initial step includes estimation of LH, FSH mosaic forms like 45X/ 46XX and 45X/ 46XY are also
and testosterone levels. Elevated gonadotropin levels observed. Premature atresia of ovarian follicles and
(hypergonadotropic hypogonadism) should be followed bilateral streak gonads may be present.
by karyotype (Klinefelter syndrome) and evaluation for
biosynthetic defects. Boys with low LH and FSH levels Clinical Features
may have constitutional delay in puberty or hypo Short stature is a frequent finding. Turner syndrome is
gonadotropic hypogonadism. They may be distinguished identified at birth by presence of lymphedema, cystic
by hCG stimulation test or GnRH stimulation test hygroma and left-sided obstructive cardiac lesions. Features
(Fig. 18.26). However, these tests are nondiscriminatory in childhood include cubitus valgus (wide carrying angle),
in most cases and follow-up after a course of testosterone shield chest with widely spaced nipples, web neck and short
is the best strategy. Patients with hypogonadotropic fourth metacarpal (Table 18.33). Cardiac associations such
hypogonadism should undergo evaluation of hypo as coarctation of aorta, mitral valve prolapse and aortic
thalamic-pituitary axis and neuroimaging. stenosis are common. Renal malformations such as
Management horseshoe kidney, duplication of renal pelvis and agenesis
may be present. Endocrine associations include hypo
Testosterone treatment should be deferred till the age of thyroidism and diabetes mellitus.
14 years and bone age of 13.5 years. Boys with suspected
constitutional delay in puberty should receive three
monthly injections of testosterone enanthate (100 mg). This Table 18.33: Pointers to the diagnosis of Turner syndrome
should be repeated, if adequate response is not achieved. Age group Features
Serum testosterone levels should be estimated three
Intrauterine period Increased neck translucency, cystic
months after the last dose of the drug. Low testosterone hygroma
levels indicate hypogonadotropic hyp ogonadism and the
Infancy Cystic hygroma, lymphedema,
need for continued treatment.
coarctation of aorta, partial
Turner Syndrome anomalous pulmonary venous
return (PAPVR)
Turner syndrome is the most important cause of Childhood and Growth failure, hearing defect,
hypergonadotropic hypogonadism in girls. The disorder adolescence delayed puberty, skeletal abnor
affects 1 in 2500 newborn phenotypic females. These girls malities
present with short stature, classical phenotype and Adulthood Secondary amenorrhea, infertility
delayed puberty. While most common karyotype is 45X,
536 Essential Pediatrics
Gonadal differentiation: Germ cells arise from the Table 18.35: Karyotype based classification of disorders of
coelomic epithelium of hindgut and migrate to the gonadal sex differentiation (DSD)
ridge at 4-6 weeks of gestation. These cells combine with 46,XX DSD
somatic cells to give rise to the bipotential gonad. A Androgen excesss
transcriptional factor present on the Y chromosome called Congenital adrenal hyperplasia
the sex-determining region of the Y chromosome (SRY) is
21-hydroxylase deficiency
one of the most important regulators of sexual
11 !3-hydroxylase deficiency
differentiation. SRY acts in conjunction with other genes
313-HSD deficiency
like Wilms tumor gene 1 (WT1), S0X9 (a transcription
POR deficiency
factor on X chromosome) and dosage-sensitive sex reversal
(DAX1) gene to induce testicular development. In the Placental aromatase deficiency
absence of SRY, the bipotential gonad develops into ovary. Maternal virilizing tumors
Maternal ingestion of androgenic drugs,
Genital differentiation: Following development of testis, Abnormal gonadal developments
antimiillerian hormone secreted by Sertoli cells induces Ovotesticular DSDs
regression of Miillerian ducts. Testosterone produced by 46,XX testicular DSD (SRY+, S0X9 duplication)
Leydig cells is responsible for sustenance of Wolffian ducts. 46,XY DSD
Dihydrotestosterone (DHT), produced by action of Sa
Disorders of androgen synthesis or actions
reductase on testosterone, is responsible for male external
LH receptor mutationss
genital development (scrotal fusion and development of
Congenital adrenal hyperplasia
corpus spongiosum and penile corpus cavernosa).
StAR deficiency
Feminization is the default process of sexual
313-HSD deficiency
development. In the absence of antimiillerian hormone
and testosterone, Miillerian ducts differentiate into 17-hydroxylase/17,20-lyase deficiency
fallopian tubes, uterus and the upper two-thirds of the POR deficiency
vagina. Labioscrotal swellings and urethral folds do not 1713-HSD deficiency
fuse and give rise to labia majora and minora, respectively. 5a-reductase deficiency: Types I and II
The genital tubercles form the clitoris while canalization Androgen insensitivity syndrome (AIS): Complete or partial
of the vaginal plate creates the lower portion of the vagina. Smith-Lemli-Opitz syndrome
Prenatal exposure to androgens may lead to labioscrotal Abnormal gonadal development
fusion, while exposure thereafter usually causes Gonadal dysgenesis: Complete or partial
clitoromegaly alone and no labial fusion. Gonadal regression
Ovotesticular DSD
Classification Other conditions
DSD may be caused by defects in gonadal differentiation Persistent MOllerian duct syndrome
(gonadal dysgenesis), androgen production (increased in Sex chromosome DSD
females and reduced in males) or action (androgen 45,X (Turner syndrome and variants)
insensitivity syndrome) (Table 18.35). 47,XXY (Klinefelter syndrome and variants)
Increased androgen production in girls: Excess androgen 45,X/ 46,XY (mixed gonadal dysgenesis, ovotesticular DSD)
production during the critical period of fetal development 46,XX/46,XY (chimeric, ovotesticular DSD)
may result in masculinization of a female. These disorders HSD: Hydroxysteroid dehydrogenase; POR: P450 oxidoreductase;
are the commonest form of DSD. Congenital adrenal StAR: Steroidogenic acute regulatory protein
hyp erplasia should be excluded in all children with DSD.
21-hydroxylase deficiency is characterized by deficiency
of glucocorticoids and mineralocorticoids with elevated Inefficient androgen action in boys: These disorders result
androgen levels. Delay in diagnosis could be fatal, from decreased production, activation or action of
underscoring the importance of early diagnosis. 11� androgens. Androgen insensitivity syndrome (AIS)
hydroxylase deficiency, 313-hydroxysteroid dehydrogenase previously referred to as testicular feminization syndrome,
deficiency and P450 oxidoreductase deficiency are the an X-linked disorder of androgen action, is the commonest
other forms of CAH that present with virilization. cause and is characterized by resistance to androgens. AIS
Transplacental androgen exposure due to maternal forms a spectrum ranging from a normal female to a boy
medications or hyperandrogenism may lead to virilization with hypospadias, to a male with infertility. Complete
in newborns. These disorders are readily identifiable by androgen insensitivity presents in the neonatal period as
history of virilization in mother. Rarely aromatase a girl with inguinal mass and primary amenorrhea in older
deficiency may be associated with virilization of mother girls. Pubic and axillary hair is sparse or absent. Milllerian
during pregnancy and DSD in the newborn. structures are absent. High DHT levels are diagnostic. Sa-
saa I Essential Pediatrics
reductase deficiency is associated with reduced DHT Table 18.36: Clinical pointers to etiology of disorders of
production. These children virilize during puberty due sexual differentiation (DSD)
to increased testosterone levels. High testosterone and low Pointer Likely diagnosis
DHT levels are diagnostic. Testosterone biosynthetic
defects include deficiency of StAR, 3[3-hydroxysteroid Pigmentation Congenial adrenal hyperplasia, SF1
defect, StAR defect
dehydrogenase, 17a-hydroxylase and 17[3-hydroxysteroid
Polydactyly Smith-Lemeli-Optiz syndrome
dehydrogenase enzymes. Diagnosis requires estimation
Skeletal dysplasia S0X9 defect
of testosterone precursors and basal and hCG-stimulated
Genital asymmetry Mixed gonadal dysgenesis,
testosterone and androstenedione levels. ovotesticular DSD
Disorders of gonadal differentiation: These disorders are Hypertension 11 P-or 17 a-hydroxylase defect
associated with abnormal gonadal development. The Hemihypertrophy WT1 mutation
gonad is usually streak (no functional gonadal tissue). Renal failure Denys-Drash syndrome
Combinations of partially functional testis or ovary or
ovotestis may be observed. SRY gene deletion results in Genital examination: The most important step is
normal female phenotype with 46,XY karyotype. identification of gonads. Bilaterally rounded structures
Mutations in genes involved in the testicular differentiation below the inguinal canal are most likely testis. Unilateral
(WT1, SOX9, steroidogenic factor 1 and DAX1) are other gonads are suggestive of mixed gonadal dysgenesis. The
causes of 46,XY gonadal dysgenesis. These disorders are labioscrotal region should be evaluated for the extent of
associated with renal (WT1 mutation), skeletal (SOX9) and fusion (Fig. 18.28). Miillerian structures may be confirmed
adrenal abnormalities (DAX1). 46,XY gonadal dysgenesis by rectal examination. The length of phallus and number
is associated with risk of development of gonadoblastoma. of openings in the urogenital region should be recorded.
Asymmetric gonadal location may result in asymmetric Asymmetrical labioscrotal region is suggestive of gonadal
genital appearance. 46,XX gonadal dysgenesis is usually dysgenesis or ovotesticular DSD. The genitalia should be
caused by SRY translocation and presents as normal staged according to the classification proposed by Prader
appearing male. Ovotesticular DSD, the new term for true from grades I to V, with grade I representing female with
hermaphroditism, is characterized by the presence of both clitoromegaly and V male with cryptorchidism.
ovarian and testicular tissue in the same individual. Investigations: Initial investigations should include
karyotyping, estimation of blood levels of electrolytes and
Evaluation 17-0HP and pelvic ultrasound. Fluorescent in situ
Detailed workup for DSD is indicated in the infants with hybridization (FISH) can be used to confirm the presence
genital ambiguity, girls with inguinal masses (probable of Y chromosome. Identification of Miillerian structures
AIS), boys with cryptorchidism (probable 21-hydroxylase is an important part of evaluation of ambiguous genitalia.
deficiency) and penoscrotal hypospadias (probable
undervirilization disorder) and adolescent girls with
amenorrhea (probable AIS). 21-hydroxylase deficiency
should be excluded by estimating blood electrolytes and
levels of 17-0HP.
Clinical: Family history of genital ambiguity is suggestive
of genetic disorders such as 21-hydroxylase deficiency or
androgen insensitivity syndrome. CAH is likely, if there
is a history of fetal losses and sibling deaths and family
history of consanguinity. On the other hand, history of
similar disorder in healthy male relatives (brothers and
maternal uncles) is suggestive of AIS. Gonads in complete
AIS may be mistaken for inguinal hernia and operated.
Intake of progestational drugs during first trimester and
features of virilization in mother should be searched.
Failure to thrive, polyuria and lethargy indicate 21-
hydroxylase deficiency (Table 18.36). Virilization during
puberty is suggestive of Sa-reductase deficiency, while
feminization indicates AIS. General examination should
include assessment for facial dysmorphism and Fig. 18.28 46,XY DSD due to partial androgen insensitivity
hyperpigmentation. Maternal examination for features of syndrome. Note the nearly female appearance of the external
hyperandrogenism like hirsutism, acne and change in genitalia with an underdeveloped buried penis and poorly
voice should be done. developed scrotum and testes
Endocrine and Metabolic Disorders 1539
-
Genitogram is helpful in determination of level of fusion, complete AIS should also be reared as females. Decision
which is of surgical importance. Further investigations are of gender of rearing is difficult in disorders of inefficient
guided by clinical and laboratory evaluation. androgen action. This should depend on genital appea
Presence of Milllerian structures with clitoromegaly rance, surgical feasibility and psychological evaluation.
and no palpable gonads in a child with 46,XX karyotype
Surgery: There has been a trend of performing early
indicate androgen excess state and need for estimation of
surgeries before gender identity is established. Most
serum 17-0HP to rule out CAH. Similarly absence of
centers perform clitoroplasty at the age of 1 year with
Milllerian structures in a child with 46,XY karyotype is
vaginoplasty reserved during puberty for girls with
suggestive of inefficient testosterone action and should
vaginal stenosis. Gonadectomy should be done in gonadal
be evaluated with estimation of testosterone and DHT.
dysgenesis or ovotesticular DSD, if a Y cell line is present.
The presence of both Milllerian structures and palpable
gonads indicates gonadal dysgenesis or ovotesticular Cryptorchidism (Undescended Testes)
DSD. Absent gonads and Milllerian structures may be
caused by vanishing testis syndrome or dysfunctional Cryptorchidism is present in about 3% of full-term infants
intra-abdominal testis. Estimation of levels of anti and 20% of premature infants. In most of these cases testes
Milllerian hormone (AMH) and hCG stimulation test are descend spontaneously by the age of one year with a
helpful in differentiating the two conditions. Children with decrease in the prevalence to 1%. Spontaneous testicular
vanishing testis will have low levels of AMH and descent is unlikely after the age of one year and the
inappropriate response to hCG stimulation. prevalence in adult population is 0.8%.
Management Etiology
Management involves parental counseling, decision about Most children with undescended testis do not have an
sex of rearing, timing of surgical correction and identifiable underlying cause. Endocrine causes, account
gonadectomy. for only a small proportion of boys with undescended
testis. The possibility of salt-wasting 21-hydroxylase
Parental counseling: Birth of a child with DSD generates deficiency presenting with sex reversal should be
significant parental anxiety and stress. The most important considered in newborns with bilateral cryptorchidism.
aspect of counseling is reassurance of parents that the child Undescended testis may be associated with hypo
is healthy and the condition is amenable to surgical and/ pituitarism, dysmorphic syndromes and disorders of
or medical treatment. Gender specific connotation (his or androgen production and action.
her, testis, ovary) should be avoided and neutral terms like
gonads and phallus be used. Future implications regarding Evaluation
sexual and fertility prospects should be discussed. It is important to differentiate true undescended testis
Decision about gender of rearing: Gender assignment from retractile or ectopic testis due to therapeutic and
should depend on the potential for future sexual and prognostic implications (Fig. 18.29). Poorly developed
reproductive function, anatomical status, feasibility of scrotum and inability to bring down the testis to the scrotal
reconstructive surgery and social acceptance and norms. sack suggests true undescended testis. Retractile testis is
Girls with virilization disorders usually have potential for an otherwise fully descended testis that has an active
fertility and should be reared as females. Individuals with cremasteric reflex, which retracts it into the groin.
Undescended testis
Present Absent
Assess scrotal development hCG test
•
Normal
•
Absent
Undescended testis
Positive
Undescended testis
Negative
I Ano�chia I
I hCG trial I
No treatment
+ I
+ I Surgery I
Descended No response
Follow up Orchidopexy
Penoscrotal hypospadias and genital ambiguity are and not to induce puberty. Boys with micropenis should
suggestive of disorders of androgen production or action. be reared as males as normal sexual function is usually
The hCG stimulation test should be done in boys with attainable with early intervention.
bilateral nonpalpable testis to differentiate abdominal
testis from anorchia. Suggested Reading
• Ahmed SF, Achermann JC, Arlt W, et al. UK guidance on the initial
Management evaluation of an infant or an adolescent with a suspected disorder
of sex development. Clin Endocrinol 2011;75:12-26.
Undescended testis is associated with significant • Desai MP, Menon PSN, Bhatia V. Pediatric Endocrine Disorders,
complications like torsion, trauma, inguinal hernia, 3rd ed. Hyderabad: Universities Press (India) Private Ltd; 2014.
testicular dysfunction and development of malignancy. pp 269-297.
These children should be treated early because of the • Houk CP, Hughes IA, Ahmed SF, Lee PA. Summary of consensus
increased risk for malignancy and infertility in later life. statement on intersex disorders and their management.
International Intersex Consensus Conference. Pediatrics
The optimal time of therapy is before the age of one year. 2006;118:753-7.
The commonly used medical treatment is human chorionic • Mongan NP, Tadokoro-Cuccaro R, Bunch T, Hughes IA. Androgen
gonadotropin (hCG) 250 units below 1 year, 500 units insensitivity syndrome. Best Pract Res Clin Endocrinol Metab
between 1 and 5 years and 1,000 units above 5 years 2015;29:569-80.
administered twice a week for 5--6 weeks. Good response • Rey RA, Grinspon RP. Normal male sexual differentiation and
etiology of disorders of sex development. Best Pract Res Clin
occurs within a month. Retraction rate of testes after Endocrinol Metab 2011;25:221-38.
cessation of therapy is high. If the response to hCG is poor, • Penson D, Krishnaswarni S, Jules A, McPheeters ML. Effectiveness
patient should be treated early with orchiopexy. of hormonal and surgical therapies for cryptorchidism; a systematic
review. Pediatrics 2013;131:e1897-907.
Micropenis
DIABETES MELLITUS
A penis whose length in stretched position is less than 2 SD
below the mean for the age is termed micropenis. Most often Diabetes mellitus is a metabolic disorder characterized by
it is the result of primary or secondary testicular failure. hyp erglycemia and glycosuria. The factors that contribute
to hyp erglycemia include decreased insulin secretion and
Etiology its action and increased glucose production. Hyperglycemia
Micropenis results from decreased androgen action during resulting from diabetes mellitus causes damage to several
fetal life. It may be due to hypogonadotropic hypogonadism organs and body systems, including the kidneys, eyes and
as in Kallmann syndrome, Prader-Willi syndrome, septo cardiovascular system. There is substantial change in the
optic dysplasia, or Klinefelter syndrome. It may also be a epidemiology of diabetes in children in recent years. While
manifestation of partial androgen insensitivity syndrome type 1 diabetes caused by insulin deficiency remains the
or testosterone biosynthetic defects. predominant form in children, type 2 diabetes is emerging
as an important entity in obese adolescents.
Evaluation
Diagnostic Criteria
Penile length should be measured in a fully stretched state
by grasping the glans between thumb and forefinger. A The definition of diabetes in children is similar to adults.
firm ruler or caliper should be pressed against the pubic Fasting blood glucose more than 126 mg/dL (7 mmol/L),
ramus to depress the suprapubic fat pad. The measurement postprandial blood glucose two hours after an oral glucose
should be made along the dorsum to the tip of the glans load of 75 g of more than 200 mg/dL (11.1 mmol/L) or
penis excluding the length of foreskin. Penile size is often random blood glucose greater than 200 mg/ dL with
underestimated in boys with obesity (due to the supra classical symptoms is diagnostic of diabetes mellitus
pubic fat) and hypospadias (due to chordee). Investigations (Table 18.37).
should include estimation of gonadotropin and Glycated hemoglobin or hemoglobin Ale (HbAlc) is
testosterone levels. Low gonadotropin and testosterone now accepted as a diagnostic criterion for diabetes in
levels indicate hypogonadotropic hypogonadism.
Elevated gonadotropin levels (hypergonadotropic Table 18.37: Diagnostic criteria of diabetes mellitus (American
hyp ogonadism) should prompt evaluation for testicular Diabetes Association, 2016)
dysgenesis, steroidogenic defects or AIS. Parameter Levels
Fasting plasma glucose �126 mg/dl (7.0 mmol/L)
Management
2 hours after 1.75 g/kg glucose �200 mg/dl (11.1 mmol/L)
All boys with micropenis are treated with a course of low
Random blood glucose �200 mg/dl (11.1 mmol/L)
dose testosterone (25 mg testosterone enanthate or
with symptoms
cypionate monthly for three doses). The aim of this short
course of testosterone treatment is to increase penile length HbA1c �6.5% (48 mmol/mol)
Endocrine and Metabolic Disorders 541-
adults with levels greater than 6.5% indicating diabetes. Table 18.38: Classification of diabetes mellitus
The validity of HbAlc as diagnostic criteria in children is (American Diabetes Association 2014)
still disputed. Most children with type 1 diabetes have I. Type 1 diabetes
blood glucose level substantially higher than 200 mg/dL
Absolute insulin deficiency due to beta cell destruction:
and do not need a glucose tolerance test. Tolerance testing Up to 95% of all pediatric diabetes
is restricted to children with obesity and suspected type 2
diabetes. The test is performed after adequate 1. IA (autoimmune)
carbohydrate intake for three days (150 g/m2/day) and 2.18 (non-autoimmune)
overnight fast. The child is given glucose (1.75 g/kg, II. Type 2 diabetes
maximum 75 g) as a chilled liquid with blood glucose Insulin resistance with relative insulin deficiency: 10-50%
measurements done at O and 120 minutes. of diabetes in adolescents depending on ethnicity served.
Classification Ill. Other specific types of diabetes
Reduced levels of action of insulin cause diabetes. Most 1. Genetic defects of beta cell function: Maturity onset
children with diabetes have type 1 diabetes caused by diabetes of the young (MODY), neonatal diabetes,
mitochondrial disorders
damage to beta cells of pancreas (Table 18.38). Type 2
diabetes is an important cause in obese adolescents. Other 2. Genetic defects in insulin action: Insulin receptor defects,
forms of childhood diabetes include genetic forms of lipodystrophy, type A insulin resistance, Rabson
Mendenhall syndrome
diabetes (monogenic diabetes of young, MODY) and
neonatal diabetes. 3. Diseases of exocrine pancreas: Pancreatitis, trauma/
pancreatectomy, cystic fibrosis, fibrocalcific pancreatic
In most situations, the type of diabetes is evident on disease, hemochromatosis
clinical presentation and extensive diagnostic workup is
4. Genetic syndromes: Turner, Klinefelter, Down, Prader
not required. Investigations for classification of diabetes
Willi, Wolfram, Laurence-Moon-Bardet-Biedl syndromes
are reserved for children with onset after puberty (likely
to be type 2 diabetes or MODY), no ketoacidosis at 5. Endocrinopathies: Growth hormone excess, Cushing
syndrome, hyperthyroidism
diagnosis (likely to be type 2 diabetes or MODY), those
with obesity and acanthosis nigricans (likely to be type 2 6. Drug or chemical induced: Steroids, L-asparaginase,
diabetes) or in the presence of abdominal pain and cyclosporine, tacrolimus, interferon, pentamidine,
steatorrhea (exocrine pancreatic disorder). thiazides, diazoxide, phenytoin
Investigations for classification for diabetes include 7. Infections: Congenital rubella, cytomegalovirus
ultrasound abdomen (for pancreatic calcification), levels 8. Uncommon forms: Stiff-man syndrome, anti-insulin
of C-peptide (a marker of beta cell function), GAD and receptor antibodies
insulin autoantibodies (indicators of autoimmune nature IV. Gestational diabetes
of type 1 diabetes) and genetic analysis for MODY Diabetes diagnosed in the second and third trimesters of
(Table 18.39). The disease classification is often challenging pregnancy that is clearly not overt diabetes
as C-peptide levels may be low due to glucotoxicity in
the initial stage of type 2 diabetes and autoantibodies are (ICA). These antibodies usually predate the clinical
positive in only 60% of Indian children with type 1 presentation of insulin-dependent diabetes mellitus by a
diabetes. few months or years. This suggests that they play a major
role during the initial pathogenesis of the disease. The
Type l Diabetes Mellitus prevalence of antibodies in newly diagnosed Indian
Type 1 diabetes is the commonest form of childhood children with type 1 diabetes is substantially lower.
diabetes characterized by insulin deficiency due to
damage to beta cells of pancreas. The disorder requires Clinical Features
lifelong insulin replacement. Children and adolescents usually present with symptoms
of diabetes that are ongoing for a month or two prior to
Epidemiology seeking physician's contact, with an acute increase in
There is a significant geographic variation in the incidence symptoms over the previous week. Symptoms of type 1
of type 1 diabetes. Scandinavia has the highest incidence, diabetes include polyuria, nocturia, enuresis, polydipsia,
with Finland having the incidence of 35/100,000/year. recent weight loss, polyphagia and fatigue. Recent acute
Indian data suggest an incidence of 10.5/100,000/year. infection is often noted at presentation. Unfortunately,
Type 1 diabetes can occur at any age but has two these symptoms are often ignored resulting in delayed
discernible age peaks of higher incidence. The first peak diagnosis.
occurs around 5 to 7 years is related to exposure to viral
infections, while the second peak around puberty is linked Course of Illness
to increase in GH and sex steroids. Most children respond to insulin therapy. Once insulin is
initiated, blood sugars gradually decline. Often, after
Pathogenesis around a week of insulin therapy, the need for exogenous
Children born to parents with type 1 diabetes have a insulin declines, due to a transient recovery of insulin
higher risk of developing the disease. The risk is higher, secretion. This phase is called the "honeymoon phase of
if the affected parent is father (7% compared to 4%, if diabetes". Some children may be completely insulin-free
mother is affected). If a sibling is affected, the risk is 6% during this time. This phase lasts from a few days to a
when the onset is before 10 years of age and 3% thereafter. month, and rarely to one year. The need for insulin
The role of heredity is less significant in type 1 diabetes gradually increases till such time when the pancreas can
compared to type 2. In studies on identical twins, no longer secrete insulin. At this point, the daily insulin
concordance rates of only 30-40% have been reported for requirement plateaus at around 0.8-1 unit/kg/day.
type 1 diabetes suggesting that factors other than heredity
play an important role in the pathogenesis of the disease. Ambulatory Care
The most important genetic focus for type 1 diabetes Day-to-day management of type 1 diabetes involves
lies in chromosome 6 and is linked with expression of HLA medical management of glycemic control, and avoidance
antigens. HLA-DR3 and DR4 have emerged as important of acute complications and prevention of chronic
determinants of developing type 1 diabetes. Other genes complications on one hand and achieving social, scholastic
implicated in pathogenesis include insulin gene and and psychological goals of the child on the other.
cytotoxic T lymphocyte antigen 4 (CTLA4). Together these Comprehensive education and ongoing involvement with
genes can explain around 60% heritability of type 1 the family is mandatory. Teamwork approach with
diabetes. Protection against the disease is provided by the pediatrician/endocrinologists, diabetic nurse educator,
HLA-DR2 haplotype. social worker and nutritionist is essential.
Infections predisposing to type 1 diabetes include
mumps, coxsackievirus, cytomegalovirus and rubella Insulin
(congenital rubella syndrome). Rodenticides have been Insulin is the cornerstone of type 1 diabetes management.
implicated in the development of diabetic ketoacidosis in The body secretes insulin at a basal rate with intermittent
Korea. There is increasing evidence that early introduction secretion with meals. The aim of management is to mimic
of cow's milk protein may be an important factor in the this pattern as best as possible.
subsequent development of diabetes in genetically
susceptible infants. This has led to delayed introduction Dose: Insulin dose is guided by pubertal status with lower
of cow's milk in infants. dose for prepubertal children (0.6 unit/kg/day) compared
to pubertal (1.0-1.2 unit/kg/ day) and post-pubertal
There is substantial evidence for autoimmunity in type children (1.0 unit/kg/day). In the post-ketoacidosis phase,
1 diabetes. Lymphocytic infiltration around the beta cells the dose may be as high as 2-2.5 unit/kg/day.
is found on autopsy of individuals of type 1 diabetes who
die due to incidental causes. At diagnosis, 70-80% of white Preparations: Chemical modifications of insulin alter their
children with type 1 diabetes have islet cell antibodies action profile providing flexibility in tailor made insulin
Endocrine and Metabolic Disorders 1543-
regimen. Currently all available forms of insulin are multiple daily injections is preferred in most children with
derived by recombinant DNA technology (Table 18.40). the exception in a resource-poor setting where a
conventional regimen is more practical.
Short-acting (regular) insulin: Regular insulin that is
structurally the same as natural insulin, is the agent of Basal bolus regimen: Basal bolus regimen mimics
choice for IV infusion while managing diabetic physiological insulin secretion with the use of a long-acting
ketoacidosis (DKA). On subcutaneous administration, the basal insulin (detemir or glargine, 40-50% of total daily
medication forms hexamers in the skin, delaying onset of dose) and mealtime rapid-acting analog (aspart, glulisine
action by 30-60 minutes. Regular insulin should hence be or lispro, 50-60% of total daily dose, Fig. 18.30). The
given 30 minutes before a meal, which may be a problem mealtime dose is distributed over 3-5 times a day
in young children and toddlers with unpredictable eating depending on the diet pattern of the child. This regimen
patterns. The longer duration of action is helpful, if there offers flexibility, as changes in mealtimes do not cause
is a substantial gap between meals especially in school significant fluctuations in glycemic control. The risk of
going children who have early breakfast and late lunch. hypoglycemia is also lower compared to mixed split
regimen.
Rapid-acting insulins (lispro, aspart and glulisine): These
insulins do not form hexamers after injection and have Mixed split regimen (two or three injections per day,
immediate onset of action. They are ideal for toddlers with Fig. 18.31): This involves the combination of short- and
irregular eating patterns and can be given even after a intermediate-acting insulin mixed at the time of injection.
meal. They provide better post-meal glycemic control The injections are given before breakfast (two-thirds of
compared to regular insulin and reduce the risk of daily dose) and before dinner (one-third of daily dose).
hypoglycemia. Insulin analogs are, however, expensive The ratio of short- to intermediate-acting insulin is 1 to 2.
and provide inadequate lunchtime cover on a two This regimen has the advantage of less frequent injections
injection regime.
Intennediate-acting insulin (NPH): NPH is a chemically
-1, Short-acting
modified insulin (protamine) with prolonged duration of
action of 12-18 hours. It is traditionally used with short
acting insulin for mixed split regime, but has significant
intra-individual variability in absorption resulting in Long-acting
fluctuating glycemic control. -1,
t t tt
18-36 hours. They are useful as basal insulin in basal bolus
regimen.
Insulin Regimen Fig. 18.30: Basal bolus regimen. Intermediate- (NPH) or long
acting insulin (glargine or detemir) is given before dinner or at
The decision about the choice of insulin regimen is bedtime (40-50% of total daily dose; black arrow). Rapid- or
dependent on age, socioeconomic status and level of short-acting insulin (aspart or lispro) is given before each meal
glucose control of a child. A physiological regimen with (50-60% of total daily dose; blue arrows)
s44 I Essential Pediatrics
Diabetes Education
1- Short-acting
Structured diabetes education is mandatory for the
management of diabetes in children. Key areas to be
covered in the program include pathophysiology of
diabetes, insulin use, sick day management, hypoglycemia,
nutrition, physical activity and social issues (Table 18.41).
Nutritional Management
Breakfast Lunch Dinner Bedtime The key to successful nutritional management in type 1
tt tt diabetes is flexibility. Overzealous control is associated
with rebellious behavior and dietary indiscretion. There
Fig. 18.31: Mixed split regimen. Insulin is given before breakfast is no 'diabetic diet' for children and they should be
(two-thirds of daily dose) and dinner (one-third of daily dose). encouraged to have a normal healthy diet. Importance
Each injection is a combination of intermediate- or long-acting should be given to consistency of mealtimings. Dietary
(NPH or detemir; two-thirds of the total dose; black arrows) and exchanges and a 'nutritional pyramid approach' are useful
short- (regular) or rapid-acting insulin (lispro or aspart, one-third in providing variety for children. Occasional treats during
of the total dose; blue arrows). Regular meal pattern is required
to prevent hypoglycemia
special occasions and eating out are allowed, if covered
appropriately with insulin (Table 18.42).
Monitoring
1- Short-acting
Self-monitoring of blood glucose (SMBG): SMBG is critical
for management of type 1 diabetes. It should ideally be
done before each meal and at bedtime. Post-meal and
midnight blood sugars are measured as required, adjusted
according to the patient age (Table 18.43). In children with
significant glycemic variability, continuous glucose
Breakfast Lunch Dinner Bedtime monitoring system (CGMS) provides information about
tt tt glycemic control every 5 minutes over a 72-hour period
to help decide about insulin adjustment.
Fig. 18.32: Modified mixed split regimen. The night-time Hemoglobin Ale: HbAlc is a marker of glycemic control
intermediate-acting insulin has been shifted from before dinner over previous 3 months and is the best predictor of long
to bedtime. This is indicated in the presence of nocturnal term complications. Target levels for HbAlc are less than
hypoglycemia and high pre-breakfast blood glucose levels. 7.5% in children and adolescents. These levels may be
Delayed peak of intermediate-acting insulin reduces the risk of falsely low in children with sickle cell disease, iron
nocturnal hypoglycemia on one hand while providing deficiency and increased red cell turnover as in hemolytic
reasonable cover for morning hyperglycemia anemia. Falsely elevated HbAlc levels are seen with
uremia and high dose aspirin treatment.
and lower cost. The regimen requires rigid dietary control
and strict lifestyle with regular mealtimes and snacks. In Follow-Up
a variation of the regimen, the intermediate-acting insulin
is shifted to bedtime to prevent nocturnal hyp oglycemia Children with diabetes should be followed every three
and morning hyperglycemia (Fig. 18.32). months or more frequently as needed. Clinical assessment
should include assessment of growth, puberty, blood
Continuous subcutaneous insulin infusion (insulin pump): glucose levels, and examination of injection sites and care
Insulin pump is an external device that infuses insulin at of feet. Children with persistent hypoglycemia should be
a predetermined rate with additional boluses given at evaluated for adrenal insufficiency, hypothyroidism,
mealtime. The basal dose can be adjusted for different celiac disease and diabetic nephropathy with decreased
times of the day and boluses tailored to different amount insulin excretion. Puberty is associated with an increase
and types of meals to provide good glycemic control with in insulin requirement due to the effect of sex hormones
limited glycemic variability. Insulin pump is superior to and GH. The requirement further increases in adolescents
basal bolus regimen in terms of insulin requirement, with obesity.
glycemic variability and weight gain. Closed loop systems
and insulin pumps with capability to detect blood sugar Sick Day Care
levels and infusing desired amount of insulin, are expected Key aspects of sick day management include frequent
to be available soon and provide physiological glycemic blood glucose monitoring, regular fluid intake and
control. treatment of the intercurrent illnesses. Insulin requirement
Endocrine and Metabolic Disorders 1545-
usually increases during a febrile illness but may decrease between 80 and 270 mg/dL. Blood ketones should be
with vomiting and diarrhea. Basal insulin should never measured, if blood glucose is more than 270 mg/dL.
be omitted in sick children with type 1 diabetes. In children Children with moderate ketosis (blood ketones between
with blood glucose less than 80 mg/ dL, rapid-acting 1 and 1.5 mmol/L) should be given extra regular insulin
insulin should be withheld and the dose of intermediate (10% of total daily dose). Impending OKA (blood ketone
acting insulin is reduced by 20-30%. No extra insulin is >1.5 mmol/L) is managed with extra doses of regular
required in children with febrile illness and blood glucose insulin (15-20% of total daily) and hourly blood glucose
546 Essential Pediatrics
+ + Fatty acids I
Less than 80 mg/dl 80-270 mg/dl More than
Encourage fluids, 270 mg/dl
Oral correction of
hypoglycemia rest Check blood or
Omit short-acting insulin Blood glucose urine ketone
Decrease basal insulin 4 hourly
by 20-50%
Blood glucose after
one hour Ketosis Acidosis Osmotic diuresis
... ... ... Fruity odor Abdominal pain
Rapid breathing
Dehydration
Loss of Na', K', PO;
Blood <1 mmol/L Blood 1-1.5 mmol/L Blood >1.5 mmol/L
Urine-negative Urine-trace or small Urine-moderate or large
Fig. 18.34: Pathophysiology of diabetic ketoacidosis. GH growth
Extra insulin 5% of Extra insulin 10%
TDD ofTDD
Extra insulin 20% ofTDD hormone; K + potassium; Na + sodium; PO� phosphate
Hourly glucose, ketone
Blood glucose Blood glucose Consider hospitalization
after 2 hours after 1 hour fatty acid production. Oxidation of fatty acids in liver
generates �-hydroxybutyrate and acetoacetic acid
Fig. 18.33: Guidelines for sick day management in children (ketones). Accumulation of ketoacids produces acidosis
with type 1 diabetes mellitus. TDD total daily dose resulting in Kussmaul breathing (acidosis), abdominal
pain (acidosis) and fruity odor of breath (acetone).
monitoring (Fig. 18.33). The child should be hospitalized, Hyperglycemia results in increased urinary water losses
if recurrent vomiting, poor oral intake and persistent due to osmotic diuresis and dehydration. Acidosis causes
hyper- or hypoglycemia are present. shift of intracellular ions, most importantly potassium and
Hypoglycemia phosphate, to the extracellular compartment. However,
serum levels of potassium are variable, depending on the
Hypoglycemia is common in children with diabetes and stage of DKA. Initially, serum potassium levels are high;
is an impediment to glycemic control. It should be as therapy with insulin is initiated, the patient becomes
considered in presence of autonomic (e.g. sweating, hypokalemic. Hyperglycemia also falsely lowers serum
palpitations, tremor, hunger) or neuroglycopenic sodium resulting in pseudohyponatremia; each 100 mg/dL
symptoms (e.g. headache, confusion, drowsiness, seizures). elevation in blood sugar lowers sodium by 1.6 mEq/dL.
Children with hypoglycemia should immediately receive
15-20 g of rapidly absorbed glucose, followed by long When to Suspect
acting carbohydrate. Severe hypoglycemia is a medical
There is need for high index of suspicion for DKA and it
emergency and should be treated with injectable glucagon
should be considered in the differential diagnosis of the
(150 g/kg) or intravenous dextrose.
following:
Diabetic Ketoacidosis • Encephalopathy: CNS infections, severe malaria,
DKA is the most severe acute complication of diabetes poisoning
mellitus. Previously believed to be limited to subjects with • Acute abdomen: Pancreatitis, appendicitis
type 1 diabetes, DKA is increasingly observed in type 2 • Dehydration: Gastroenteritis
diabetes and MODY. Early identification and management • Tachypnea: Bronchial asthma, pneumonia
are essential to limit the extent of mortality and morbidity • Hyperglycemia with acidosis without ketosis: Renal failure,
associated with DKA. Thirty to forty percent of freshly septicemia
diagnosed children with type 1 diabetes present with • Ketoacidosis without hyperglycemia: Starvation, salicylate
DKA. Although epidemiological data from India is poisoning, organic acidemia
lacking, the figure is higher than the developed countries.
Criteria for Diagnosis
Pathophysiology DKA should be diagnosed in presence of all of the
DKA is the end result of absolute or relative insulin following: (i) hyperglycemia (glucose >200 mg/dL);
deficiency combined with excess of counter-regulatory (ii) metabolic acidosis (pH <7.3, bicarbonate <15 mEq/L);
hormones such as glucagon, catecholamines, cortisol and and (iii) ketosis (blood ketone > 1.5 mmol/L, or urine
GH (Fig. 18.34). DKA is usually precipitated by infection, ketone >2+).
stress and trauma, and conditions associated with
increased insulin requirement and higher level of counter Management
regulatory hormones. These hormonal alterations result DKA is a life-threatening condition and should be
in hyperglycemia and lipolysis resulting in increased free managed in a hospital equipped with facilities for
Endocrine and Metabolic Disorders 1547-
intravenous infusion and measurement of blood gas and Assess airway, breathing and circulation
electrolytes. Children younger than 2 years of age and Oxygen, fluid bolus (10 ml/kg)
those with severe DKA should be managed in an ICU.
Fluid: Maintenance and deficit over 48 hours
Evaluation 0.45% saline with KCI 40 mmol/L
Insulin infusion 0.1 IU/kg/hour
Clinical: Initial evaluation should be guided towards
assessment of adequacy of airway, breathing and
circulation. Level of dehydration is ascertained along with Blood glucose
hemodynamic status. Careful neurological evaluation
including assessment of level of consciousness, pupils +
More than 270 mg/dl
I
+
Less than 270 mg/dl
(dilated fixed in presence of cerebral herniation), cranial
nerves (sixth nerve palsy suggests cerebral edema) and Increase infusion by 10% till 0.2 IU/kg/hr Acidosis
deep tendon reflexes (brisk if raised intracranial tension)
is mandatory.
Persistent Resolved
Add dextrose in fluid SC insulin, stop infusion
Investigations
Serum sodium: There is usually a significant sodium deficit Fig. 18.35: Management of diabetic ket oacidosis. KCI
potassium chloride; SC subcutaneous
(4-6 mEq/kg). The sodium levels are falsely reduced in
hyperglycemia mandating the need to use corrected
osmolality). In most children the fluid deficit is 5-10%.
sodium. Rapid decline in serum sodium is a risk factor
Fluid requirement is usually around 3-3.5 L/m2/day
for cerebral edema.
(Table 18.44). Care is taken to avoid fluid administration
Serum potassium: There is substantial intracellular of more than 4 L/m2/day due to risk of cerebral edema.
potassium deficit(� mEq/kg). Serum levels are, however, The amount of fluids given at other centers prior to referral
normal or high due to extrusion of intracellular potassium should also be considered while calculating fluid
due to acidosis and insulin deficiency. Treatment of DKA requirements.
is associated with the risk of hypokalemia due to its
intracellular shift following reversal of metabolic acidosis Insulin: Insulin should be administered after initial
and correction of insulin deficiency. hydration as blood glucose levels fall rapidly even without
insulin. Early insulin treatment is associated with drastic
Serum phosphate: Usually there is significant phosphate fall in plasma osmolality, hypokalemia and increased risk
deficit. of cerebral edema.
Infection screening: Transient leukocytosis is common; Continuous intravenous infusion is the preferred route.
infection should be considered in presence of persistent The intravenous tubing should be flushed with insulin as
leukocytosis and fever. insulin binds to plastic tube. There is no role of initial
Renal function tests: High blood urea usually indicates insulin bolus. Insulin infusion should be started at
severe DKA. 0.1 unit/kg/hr. In infants and mild DKA, the infusion rate
should be kept at 0.05 unit/kg/hr. The dose should be
Electrocardiography: This is often done to screen for hypo increased if fall in glucose is less than 50 mg/dL/hr. The
or hyp erkalemia. dose is increased in quantum of 0.02 IU/kg/hr. The insulin
infusion rate should be reduced only after resolution of
Management acidosis.
Initial stabilization: The child should be assessed for If facility for intravenous insulin is not available,
adequacy of airway, breathing and circulation. Initial intramuscular regular insulin may be used. The first dose
fluid bolus of 10 mL/kg normal saline over 1-hour should is 0.3 unit/kg followed by 0.1 unit/kg hourly. Recurrent
be given in children with dehydration (Fig. 18.35). intravenous boluses of insulin should be avoided due to
Oxygen and respiratory support should be provided if the risk for cerebral edema. Subcutaneous insulin is not
required. The child should be kept nil by mouth with recommended due to decreased absorption in the setting
insertion of nasogastric tube and urinary catheter, if of poor perfusion.
unconscious.
Serum sodium: Most patients have significant sodium
Fluid therapy: Fluid therapy is the mainstay of treatment deficits(4-6 mEq/kg). Slow rise in sodium in patients with
for DKA. However, rapid and excessive fluid intake is a rapid fall in glucose is a risk factor for cerebral edema.
risk factor for developing cerebral edema. The aim is to Normal saline (154 mEq/L) should be used in the first
provide maintenance requirement and deficit evenly over 6 hours of therapy; thereafter the sodium content should
48 hours (7 2 hours for children with high plasma be between 77 and 154 mEq/L.
548 I Essential Pediatrics
Serum potassium: Although there is deficit in total body four-hourly blood ketone, pH, bicarbonate and electrolytes
potassium, extracellular potassium levels may initially be (Table 18.45).
high due to acidosis and insulin deficiency. There is a risk
of life-threatening hypokalemia following correction of Discontinuation of acute treatment: Subcutaneous insulin
insulin deficiency and resolution of metabolic acidosis. In should be considered once the patient is conscious, ready
patients with initial potassium levels less than 3.5 mEq/ to accept orally and has resolution of acidosis. Regular or
L, potassium replacement should precede administration rapid acting insulin (0.25 unit/kg) should be given
of insulin. In other situations potassium replacement is 30 minutes before eating. Alternatively the child may be
begun, at a concentration of 40 mEq/L, after initial started on a basal bolus or mixed split regime. Insulin
hydration at the time of initiation of insulin infusion. infusion should be stopped only 30 minutes after insulin
Potassium should not be administered if the level is to provide overlap, and avoid recurrence of hyperglycemia.
>6 mEq/L, the patient is anuric or ECG changes of Complications of OKA
hyp erkalemia are present.
OKA is a life-threatening condition with potential for
Dextrose: Hyperglycemia resolves prior to correction of significant long-term morbidity. Timely identification and
acidosis. Decreasing insulin infusion rate with lowering treatment of these complications are essential (Table 18.46).
of blood glucose is not recommended since that would
prolong the duration of acidosis. Dextrose (5%) is therefore Cerebral edema: Cerebral edema is the most serious
added to intravenous fluids once blood glucose levels fall complication of OKA and the most common cause of
below <270 mg/dL. death. The incidence of clinical cerebral edema is 0.5-1.0%
in developed countries, but is higher in India. Risk factors
Acid-base management: Alkali treatment should be include age less than 5 years, severe acidosis, insulin bolus,
avoided as it poses risks for cerebral edema, lactic acidosis excessive hydration and alkali treatment. Cerebral edema
and hypokalemia. It is considered only if pH is less than usually presents at 4-12 hours following treatment, but
6.9 with hemodynamic compromise or if there is severe may be present at diagnosis. The condition is suspected
hyp erkalemia (serum potassium >6.5 mEq/L with ECG in presence of persistent hemodynamic instability or
changes). worsening in clinical condition after initial improvement.
Early pointers include headache, vomiting, drowsiness,
Monitoring irritability, and hypertension with bradycardia. Severe
Careful clinical and laboratory monitoring is necessary. cerebral edema is indicated by unconsciousness, focal
This should include hourly monitoring of neurological neurological deficits, papilledema and fixed dilated
status, heart rate, blood pressure and fluid input/output. pupils. The diagnosis is clinical and there is no need for
Laboratory monitoring includes hourly blood glucose and confirmation by imaging. Children with suspected
Endocrine and Metabolic Disorders 1549-
Table 18.46: Complications of OKA Growth failure occurs in children whose diabetes is not
well controlled. Mauriac syndrome occurs with poor
Acute Chronic
control of diabetes and is characterized by hepatomegaly,
Cerebral edema Growth hormone deficiency pale skin and extreme short stature.
Infections: Bacterial, fungal Mental retardation
Hypoglycemia Diabetes insipidus Delayed puberty is associated with inadequate control of
Hypokalemia diabetes and delayed bone age.
Acute respiratory distress
syndrome Hypoglycemic unawarene ss is caused by frequent
Venous thrombosis hypoglycemia associated with tight metabolic control of
diabetes. It is due to impaired counter-regulatory response
cerebral edema should be immediately treated with to hypoglycemia. Raising blood sugar targets and
intravenous mannitol (5 mL/kg) followed by fluid prevention of hypoglycemia usually causes reversal of
restriction and head end elevation. hypoglycemic unawareness.
Infections: Bacterial and fungal infections are common. Retinopathy is characterized by microaneurysms and
Indicators include persistent fever, leukocytosis, black proliferative disease. Earlier 80-90% individuals developed
nasal discharge (rhinocerebral mucormycosis) and eye disease by 15 years of diabetes. With intensive
hemoptysis (pulmonary aspergillosis). management of diabetes this complication is delayed to
Hyperosmolar Non-Ketotic State beyond childhood. Ophthalmologic examination should
be conducted once the child is more than 10-year-old and
This condition is characterized by severe hyp erglycemia has had diabetes for 3-5 years. Annual follow-up is
(usually >600 mg/dL), hyperosmolality (>350 mOsm/kg), suggested.
low plasma ketones (negative or positive at <1:2 dilution)
and severe dehydration. Although chiefly a complication Peripheral ne uropa thy is unusual in children and
of type 2 mellitus, it can occur in type I diabetes if insulin adolescents. This results in decreased nerve conduction
is present to prevent ketoacidosis, but is insufficient to velocity and sensory changes. An abnormality in vibration
control the blood sugar. Management is similar to DKA perception may be the first finding.
with a need for slower dehydration correction, more fluids
and lower insulin requirement. Nephropathy is defined by presence of albumin in the
urine. Annual screening for microalbuminuria is initiated
Long-term Complications of Type 1 Diabetes once the child is 10 years of age or has had diabetes for
Regular screening for long-term complications is essential 5 years. If screening shows elevated ratio of spot urine
for their early identification, prevention and appropriate microalbumin to creatinine, 24 hours urine microalbumin
treatment (Table 18.47). Screening for complications should is estimated. Patients with significant microalbuminuria
be started after 5 years of diagnosis if the onset of diabetes should receive ACE inhibitors to delay the progression of
is before puberty, and 2 years if diagnosed in puberty. nephropathy.
Lipoatrophy is fat atrophy at the injection site. This can Dyslipidemia: Fasting lipid profile is performed on all
be prevented by rotation of injection sites. children more than 2-year-old at time of diagnosis (after
Limited joint mobility, due to flexion contractures of glucose control is achieved), or if there is family history
metacarpophalangeal and proximal interphalangeal joints, of high cholesterol (>240 mg/dL) and/or a cardiovascular
is typically noted in the hands. event before 55 years. If there are no concerns of hyp er-
550 I Essential Pediatrics
Table 18.47: Screening for complications in children with type 1 diabetes mellitus
Complications Indications Procedures Management
Retinopathy First eye examination after Initial examination of dilated Improvement in diabetes control
3 months of diagnosis; fundus Laser treatment for visual loss
screening after 11 years
Prepubertal Duration of diabetes >5 years
from onset
Pubertal Duration of diabetes >2 years
from diagnosis
Nephropathy Annual screening after 11 years Annual screening for micro Improvement in diabetes control
Prepubertal Duration of diabetes >5 years albuminuria: Albumin excretion Control of blood pressure
from onset rate (AER) 20-200 µg/min or ACE inhibitors to reduce proteinuria
Pubertal Duration of diabetes >2 years AER 30-300 mg/day
from diagnosis
Hypothyroidism At diagnosis; thereafter every Serum TSH and FT4 estimation Thyroxine therapy
2 years Thyroid autoantibodies
Hyperlipidemia Annual screening after 12 years Serum lipid profile Strict diet control
Prepubertal At diagnosis; thereafter every 5 years Statins
Pubertal At diagnosis; thereafter every 2 years
lipidemia in the family, screening is performed after onset Type 2 Diabetes Mellitus
of puberty (>12 years). For pubertal children (>12-year Type 2 diabetes in children and adolescents is increasing
old), a fasting lipid profile is performed at diagnosis after rapidly with the advent of childhood obesity epidemic.
glucose control is achieved. If LDL is <100 mg/ dL, lipid The disorder presents with milder symptoms than type 1
profile is repeated every 5 years. If lipids are abnormal, diabetes though OKA can develop occasionally. Diagnosis
annual monitoring is recommended in both age groups. is established based on presence of obesity, acanthosis
Intervention is needed if fasting LDL >100 mg/ dL, initially nigricans, elevated insulin levels, normal C-peptide, and
by dietary modification with decrease in saturated fat in lack of glutamic acid decarboxylase (GAD) antibodies.
diet. A pharmacologic agent is added for LDL >160 mg/ Lifestyle measures and metformin are the mainstay of
dL, and in patients at risk of cardiovascular disease and treatment. Adolescent type 2 diabetes, however, has an
LDL values 130-159 mg/ dL after initiation of dietary aggressive course compared to adult type 2 diabetes, with
changes and lifestyle intervention. The goal of therapy is faster loss of cell function. Children who present with
LDL level <100 mg/ dL. ketosis are treated with insulin initially and transitioned
to oral hypoglycemic agents once endogenous glucose
Hope for Future secretion recovers. These children and adolescents should
Given the need for lifelong treatment in type 1 diabetes, be evaluated for hyperlipidemia, diabetic retinopathy and
it is only expected that most patients seek permanent nephropathy at diagnosis. It is recommended that children
cure from the malady. Unfortunately no such cure is at risk of type 2 diabetes be regularly screened for diabetes.
available at the moment. The efforts at developing cure
for type 1 diabetes are directed towards reversing the
Monogenic Diabetes of Young (MODY)
autoimmune process or restoration of 13-cell mass. MODY represents a group of inherited conditions
Immunosuppressive agents (steroids, cyclosporine A, characterized by impaired cell function. The disorder
azathioprine, anti-thymocyte globulin and anti-CD3 presents with relatively mild, non-ketotic diabetes in a lean
antibody) have resulted in only partial and transient individual with strong family history of diabetes affecting
response. These strategies are limited by the fact that over three generations. The condition responds to lifestyle
95% of 13-cell mass is destroyed by the time of diagnosis measures and low doses of sulfonylurea.
of the disease. The other, more appealing approach for
cure for type 1 diabetes mellitus, involves restoration of Neonatal Diabetes Mellitus
13-cell mass using pancreatic, islet cell or stem cell Onset of diabetes before three months of life suggests
transplantation. Pancreatic transplant is a major neonatal diabetes. It is a challenging condition requiring
endeavor requiring long-term immunosuppression and meticulous monitoring and treatment. The disease
is not recommended in adolescents with type 1 diabetes. represents transient cell dysfunction (transient neonatal
Studies have failed to show long-term remission with diabetes), permanent insulin secretion defect (permanent
islet cell or stem cell transplantation. neonatal diabetes) or congenital insulin resistance
Endocrine and Metabolic Disorders 1ss1-
syn drome. The most common cause of permanent • American Diabetes Association position statement: Standards of
neonatal diabetes is activating KATP channel, the on-off medical care in diabetes 2016. Diabetes Care 2016, Sl:112
button for insulin secretion. These disorders are amenable • Atkinson MA, Eisenbarth GS, Michel AW. Type 1 diabetes. Lancet
2014; 383: 69-82.
to treatment with sulfonylurea. • Dunger DB, Sperling MA, Acerini CL, et al. ESPE/LWPES
consensus statement on diabetic ketoacidosis in children and
Suggested Reading adolescents. Arch Dis Child 2004;89:188-203.
• Acerini C, Craig ME, de Beaufort C, et al. Introduction to ISPAD • International Society for Pediatric and Adolescent Diabetes. ISPAD
Clinical Practice Consensus Guidelines 2014 Compendium. Clinical Practice Consensus Guidelines 2014. Pediatric Diabetes
Pediatric Diabetes 2014;15:l-3. 2014;Supp 20:1-290.
• American Diabetes Association. Clinical practice guidelines 2014. • Melendez-Ramirez LY, Richards RJ, Cefalu WT. Complications of
Diabetes Care 2014;37:S14-85. type 1 diabetes. Endocrinol Metab Clin North Am. 2010;39:625-40.
Chapter
19 Diseases of
Central Nervous System
Rashmi Kumar
j
Maintain airway, breathing, circulation respiratory tract infection, gastroenteritis, viral exanthem,
Administer oxygen
bacterial infection, malaria or immunization. Febrile
Blood electrolytes; glucose; seizures must be differentiated from acute symptomatic
calcium; magnesium; seizures due to intracranial infection and those triggered
liver and kidney function tests;
blood counts; by fever in children with underlying epilepsy.
toxicology (if indicated)
Types
IV lorazepam (0.1 mg/kg) or midazolam (0.1 mg/kg);
up to 2 doses, 5 minutes apart A simple febrile seizure is a generalized seizure (without
Correct metabolic abnormality (e.g. IV glucose, if hypoglycemia) focal features) that lasts less than 15 minutes and occurs
only once within a 24 hours period of fever in a neuro
If seizure continues, logically normal child. About 15-20% cases are complex
administer sequentially febrile seizure, diagnosed in presence of any of the following:
(i) focal signs or symptoms; (ii) duration > 15 minutes; or
IV phenytoin or fosphenytoin 20 mg/kg infusion
Repeat, if needed, at 10 mg/kg
(iii) recurrent seizures within the same febrile illness.
Recurrent febrile seizures may be noted in children with:
(i) age <18 months; (ii) family history; (iii) multiple
IV sodium valproate 20-40 mg/kg infusion seizures; (iv) first seizure at low temperature (<40 ° C).
Outcome
IV levetiracetam 20-60 mg/kg infusion
at 5 mg/kg/min After an initial febrile seizure, 3-12% children develop
epilepsy by adolescence. The risk of epilepsy is 1.5-2.4%
for simple febrile seizures and increases in children with:
IV phenobarbitone 20 mg/kg infusion
Repeat, if needed, up to twice, at 10 mg/kg (i) pre-existing neurodevelopmental abnormality; (ii)
complex febrile seizure; and (iii) family history of epilepsy.
It was suggested that a prolonged febrile seizure in infancy
IV midazolam at 1-15 µg/kg/min infusion can cause hippocampal injury and mesial temporal
sclerosis, leading to temporal lobe epilepsy. Subsequent
Coma induced by phenobarbitone
�Ol studies demonstrate that a hippocampus that has already
(J
(or thiopentone and propofol) infusion a, been damaged either by a perinatal insult or genetic pre
>
'jjj disposition may cause prolonged febrile seizure in infancy.
C:
/ Consider / a,
Management
IV ketamine and oral topiramate ..!:
An acute episode of seizure is terminated by intravenous
lmmunotherapy Dietary therapy lorazepam or midazolam. In case the patient presents in
Vagal nerve stimulation Epilepsy surgery status, standard protocol for management of status
epilepticus is followed.
Fig. 19.1 : Sequential drug therapy in the management of status
epilepticus In first episode of febrile seizure, lumbar puncture is
indicated in clinically suspected meningitis or if Hib/
seizures. The condition can cause multi.organ dysfunction, pneumococcal immunization status is not known.
neurodevelopmental sequelae, and, in 10% cases, death. Prophylaxis
Figure 19. 1 summarizes the management of status
epilepticus. The term refractory status epilepticus is used for In children with risk factors for recurrence or those with
seizures that persist despite the use of benzodiazepine and frequent recurrences (2?:3 in 6 months or 2?:4 in one year),
one anticonvulsant in appropriate doses. Seizures that do intermittent prophylaxis reduces recurrences by 80%. Oral
not respond despite 24 hours of anesthesia are termed super benzodiazepines (diazepam O. 6-0. 8 mg/ kg/day in
refractory. 3 divided doses or clobazam 0.8-1 mg/kg/day in 2 divided
doses) should be started at the first sign of any febrile
Febrile Seizures illness and continued for first 3 days of febrile illness.
Febrile seizures refer to seizures associated with high
grade fever (>38 ° C) occuring in neurologically healthy Acute Symptomatic Seizures
children between 6 months and 5 years of age, without A seizure occurring within a week of acute neurological
underlying intracranial infection and without history of injury, such as stroke, trauma, anoxia, active inflammation
Diseases of Central Nervous System lsss-
and infection, and within 24 hours of acute metabolic of the affected limb of up to 24 hours may result, and is
derangements, requires evaluation with serum electrolytes, known as Todd's palsy. Focal or partial seizures may spread
lumbar puncture and neuroimaging if indicated clinically. to involve the whole body (secondary generalization).
Antiepileptic therapy is initiated and discontinued after Complex partial seizures are associated with
3-6 months if awake and sleep EEG records are normal. automatisms or loss of consciousness. Complex partial
seizures arising from the temporal lobe are also called
EPILEPSY psychomotor epilepsy. Patients may have a 'deja vu'
Epilepsy is defined as occurrence of two unprovoked feeling, visual, olfactory or visceral aura and peculiar
seizures over a day apart beyond the neonatal period. posturing or automatisms which are usually repetitive.
Patients with one unprovoked seizure and a high There is no memory for the event.
probability of further seizures in the next decade, similar
Etiology
to the recurrence risk ( over 60%) following two
unprovoked seizures, are also termed having epilepsy. Epilepsy may have genetic, structural, metabolic and
The International League Against Epilepsy (ILAE) 2017 unknown etiology.
classification categorizes epilepsy using semiological
phenomena at onset, as follows. Differential Diagnosis
Various paroxysmal events mimic epilepsy. Entities seen
Generalized Onset Epilepsy commonly in children are discussed.
Tonic-clonic Benign, neonatal sleep myoclonus: A well infant presents
A tonic phase lasting at least 30 seconds and associated with bursts of myoclonic or clonic movements only during
with uprolling of eyeballs, frothing from mouth, tongue sleep in the first week of life. The movements abort as
bite, perioral cyanosis and/or incontinence of stool and soon as the child awakens. The conditions lasts for a few
urine, is followed by clonic movement of all limbs. weeks to months. Only reassurance is required.
Myoclonic Breath holding spells: This behavioral problem usually
affects boys between 6 months and 3 years of age. The
Sudden, jerky shock-like violent contractions involve axial sequence of events is typical. The child first has a long
and appendicular muscles. cry, usually after being denied some demand. Then the
child holds his breath and turns blue and limp. This may
Atonic
be followed by tonic and a few clonic movements. Parents
Sudden loss of tone involving axial and appendicular must be reassured and advised about consistent parenting
muscles. practices. They should refrain from giving into the child's
demand or giving him undue attention just after the
Spasm episode. Iron deficiency should be treated.
Well-sustained, sudden inward and/or outward Syncope: This usually occurs in the upright position. Patient
movements of head, neck, trunk and extremities occur in may have been standing immobile for sometime or have
cluster or in isolation. suffered sudden fear or emotion. The fall to the ground is
Absence usually not as sudden as in a convulsion. The patient is
pale and pulse is slow. The attack is aborted by lying flat or
Brief periods of behavioral arrest, lasting 30-60 seconds, with legs elevated as this improves the cerebral blood flow.
occur without associated motor phenomenon.
Psychogenic seizures: These occur more commonly in
Tonic older girls. The patient subconsciously tends to gain
Only tonic phase, as described in tonic-clonic seizure, something. There are bizarre body movements with eyes
occurring without the clonic component. tightly shut and pelvic thrusts. Very often the child does
it when there is an audience around.
Focal Onset Epilepsy
Epileptic Encephalopathies
These may be motor, sensory or autonomic. They account
for 60% of epilepsies in childhood. They more often have Conditions in which epileptiform abnormalities them
a structural cause. Important causes are atrophic lesions, selves contribute to progressive cognitive decline form a
scars, inflammatory granulomas, strokes and vascular part of one of two common syndromes.
insults, head trauma, abscess and neoplasms. In our country,
neurocysticercus granulomas are a common cause, which West Syndrome
classically produce a ring or disc like enhancing lesions This is the most common epileptic encephalopathy in
on neuroimaging. A simple focal or partial seizure is not infancy, and is characterized by the triad of epileptic
associated with loss of consciousness. A transient paralysis spasms, hypsarrhythmic EEG and psychomotor
556 I Essential Pediatrics
a
Fig. 19.2: Neural tube defects. (a) Tuft of hair overlying spina bifida occulta; (b} Dorsolumbar meningomyelocele; (c) Occipital
encephalocele
55a I Essential Pediatrics
Fig. 19.3: Findings in tuberous sclerosis include: (a) Subependymal nodule on non-contrast CT of brain; (b) Cortical tubers on axial
FLAIR magnetic resonance imaging; (c) Hypopigmented ash leaf macule; and (d) Hyperpigmented maculopapular facial rash
(adenoma sebaceum)
Diseases of Central Nervous System lssg-
Suggested Reading
• Little H, Kamat D, Siva swamy L . Common neuro cutaneous
syndromes._Pediatr Ann 2015; 44: 496-504.
• Vezina G. Neuroimaging of phakomato ses: overview and
advances. Pediatr Radio! 2015; 45 Suppl 3: 5433-42.
Encephalopathies
Acute disseminated encephalomyelitis
Postinfectious: Typhoid, shigella, Reye syndrome
Hypoxic encephalopathy, heat hyperpyrexia
Metabolic: Diabetic acidosis, uremic coma, hepatic coma,
neonatal hyperbilirubinemia, lactic acidosis, mitochondrial
disorders, inborn errors of metabolism
Fluid and electrolyte disturbances.
Hypernatremia, hyponatremia, alkalosis, acidosis
Toxic: Heavy metals (lead, mercury, arsenic), insecticides,
Cannabis indica, carbon monoxide
Fig. 19.5: Bulbar conjunctiva! telangiectasia in a child wit h ataxia Post-vaccination
telangiectasia
sso I Essential Pediatrics
polymorphonuclear cells. Protein is mildly increased and lasting 7-10 days. In severe cases, signs of raised
sugar is normal. Etiology is determined in only a small intracranial tension and hyperventilation are followed by
proportion. Viral detection by CSF polymerase chain shock and rapid death. Others recover gradually over
reaction (PCR) or specific antibodies are necessary but weeks to months, but majority of survivors have
have low diagnostic yield. prominent extrapyramidal sequelae.
Sick patients require careful monitoring in an intensive
care unit, targeting maintenance of vital functions and Diagnosis
ensuring asepsis, adequate nutrition, good nursing care CSF shows nil to moderate pleocytosis with elevated
and appropriate physiotherapy. Symptomatic management protein and normal sugar. MRI shows characteristic
includes administering antipyretics and anticonvulsants changes in bilateral thalami, basal ganglia and midbrain
and measures to reduce intracranial tension. (Fig. 19.6a). JE virus specific IgM can be detected by ELISA
in CSF and serum and has 95% sensitivity and specificity
Japanese Encephalitis (JE) when performed in CSF by 10 days of illness; earlier
JE virus is the leading cause of viral encephalitis in India samples may be negative. Viral isolation and detection
and worldwide, with the majority of cases occuring in by PCR in CSF or brain during early illness has low yield.
Asia. In India, most cases are reported from southern and
eastern states with outbreaks during and after monsoons. Management
Management is essentially supportive, as outlined above.
Etiology and Transmission
JE virus is a single stranded neurotropic RNA virus Prevention
belonging to family Flaviviridae. The chief vector across JE can be controlled by reducing contact with mosquitoes
Asia is Culex tritaenirrhynchus, a zoophilic mosquito that (using insecticide spray, larvicides, bed nets and
breeds in rice fields. The infection is zoonotic, with pigs repellants), vaccination of pigs and location of pigsties
and Ardeid birds as the chief hosts that harbor, amplify away from human dwelling, and, most usefully, by
and transmit the infection without developing illness, vaccinating susceptible humans. However, human
despite signifincat viremia. Man is an incidental dead-end vaccination does not interrupt the natural cycle of JE virus
host in whom the brief viremia deters further transmission. and does not provide herd immunity. JE vaccination is
now part of the National Immunization Program in
Clinical Features endemic states (see Chapter 10).
JE tends to occur in epidemics and outbreaks, chiefly Mouse brain killed vaccine: This was the earliest vaccine
affecting children between 5 and 15 years of age or young to be manufactured against JE but is no longer in use.
adults. A prodrome of fever, headache, vomiting and Live-attenuated SA-14-14-2 strain vaccine: This is the only
diarrhea, lasting a few hours to days, is followed by an live-attenuated JE vaccine currently available. It is
acute encephalitic stage with persistent fever, seizures, produced by Chengdu Biologicals and is being used in
coma, focal deficits and signs of raised intracranial tension the public sector in China since 1998, Nepal (since 1999)
Fig. 19.6: Magnetic resonance imaging in acute encephalitis. (a) Axial FLAIR images showing bilateral thalamic involvement in
Japanese B encephalitis; (b) Coronal T2-weighted images showing right temporal involvement in herpes encephalitis; and (c)
Axial FLAIR images showing bilateral subcortical and periventricular patchy asymmetrical white matter signal changes in acute
disseminated encephalomyelitis
Diseases of Central Nervous System 1ss1-
and India (since 2006). Studies conducted in Nepal kg every 8 hour for 14-21 days. However, despite early
reported efficacy of 99.3% in the same year, 98.5% after therapy, less than 40% patients survive without disability
one year and 96.2% after 5 years. An Indian study found and 5% may relapse.
vaccine efficacy to be 94.5% after 6 months. Dose is 0.5 ml
given subcutaneous. Acute Bacterial Meningitis
IC51 Vaccine-Ixiaro: This is a new generation formalin This is a relatively common and potentially fatal condition.
inactivated vaccine manufactured by Intercell (Austria) A high index of suspicion is essential to enable timely
and distributed by Novartis Vaccines. It is prepared diagnosis and treatment.
from the SA-14-14-2 strain grown in Vero cells. This is the
only JE vaccine to have received US Food and Drug Risk Factors and Pathogenesis
Administration (FDA) approval for use in adults and Infections are most common in the first 5 years of life. Risk
children beyond 2 months of age. This vaccine produced factors include bacterial colonization of nasopharynx,
with Austrian collaboration is available in India as JEEV overcrowding, poverty and male sex. Anatomic defects
(Biological E Ltd). Schedule is 2 doses 28 days apart such as fracture base of skull, pilonidal sinus and
followed by a booster after one year. Dose is 0.25 ml below immunodeficiencies predispose to meningitis. Bacteremia
3 years and 0.5 ml beyond. is followed by lodging of bacteria in choroid plexus and
Indian Strain vaccine: Another Vero cell-derived purified the meninges. An intense inflammation leads to meningeal
inactivatedJE vaccine is developed from an Indian strain exudates, ventriculitis, perivascular inflammatory
of the virus (821564 XZ) isolated in Kolar, Karnataka, exudates, venous occlusion, infarction, necrosis and/ or
during the early 1980s and characterised by the National raised intracranial pressure.
Institute of Virology, Pune. This vaccine was developed
through public-private partnership between the Indian Etiology
Council of Medical Research and Bharat Biotech Ltd. It The causative organisms vary with age. In the first 2
has received manufacturing and marketing approval from months of life, the most common pathogens include Gram
the Drug Controller General of India and is being negative bacteria, followed by Staphylococcus aureus, group
marketed by the name,JENVAC. B streptococci and Listeria monocytogenes. Between 2-24
Chimeric vaccine: AnotherJE vaccine under development months, Hemophilus influenzae type b infections are most
is the live attenuated YFV-17D/ JEV vaccine (Acambis, common, followed by Streptococcus pneumoniae and
UK). The premembrane and envelop (prME) genes of an meningococcus. Beyond 2 years of age, pneumococcus and
attenuated human vaccine strain (SA-14-14-2) ofJE virus meningococcus are the most common organisms, followed
are inserted between core and nonstructural genes of a by Hemophilus influenzae type b.
yellow fever 17D infectious clone, resulting in a live
chimeric vaccine. Recruitment for phase 3 studies is Clinical Features
ongoing in Thailand. Clinical features vary with age. Newborn and young
infants present with lethargy, poor feeding, shrill cry and
Herpes Simplex Virus (HSV) Encephalitis seizures. Older infants present with fever, poor feeding,
This is the leading cause of sporadic encephalitis and has irritability and photophobia. A tense bulging anterior
a severe fulminant presentation with high rates of fontanelle in a febrile infant suggests meningitis. Older
mortality and disabling sequelae. A non-specific prodrome children present with abrupt onset of high fever, severe
of headache, malaise, fever and vomiting is followed by unrelenting headache, anorexia, myalgia, photophobia
altered consciousness, focal or generalised seizures and and meningeal signs, and may develop convulsions and
focal neurologic deficits. Presence of focal signs is coma.
considered characteristic of HSY encephalitis. Presentations Meningeal signs are lacking till 2 years of age. Signs of
include movement disorders, stroke, behavioral raised intracranial pressure include hypertension,
disturbances, hallucinations and memory loss. bradycardia, bulging fontanelle, third or sixth cranial
Examination of the CSF reveals pleocytosis, mild nerve palsy, posturing or breathing abnormalities.
protein elevation and occasionally, red blood cells. EEG Papilledema is unusual, especially in infants. A search
may show a characteristic picture of periodic lateralised should be made for septic foci elsewhere. Purpuric rash
epileptiform discharges. Neuroimaging shows suggests meningococcemia.
characteristic temporal lobe signal changes, with MRI
being more sensitive than CT (Fig 19.6b). PCR for HSVl Differential Diagnosis
in the CSF has 75% sensitivity and 100% specificity and is Viral and tuberculous meningoencephalitis are the chief
considered the gold standard for diagnosis. differential diagnoses. The latter is particularly
Management includes supportive care and specific considered when faced with partially treated bacterial
antiviral treatment with intravenous acyclovir at 20 mg/ meningitis.
562 Essential Pediatrics
Fig. 19.7: Computed tomography in acute encephalitis. Contrast enhanced images showing: (a) Bilateral subdural effusion in a
child with acute bacterial meningitis; (bl Communicating hydrocephalus with basal meningeal enhancement in a child with
tubercular meningitis; (c) Ring enhancing lesion with eccentric dot in left parietal lobe suggestive of neurocysticercosis;
and (d) Non-contrast image shows multiple calcified neurocysticeri lesions, described as 'starry sky'
Diseases of Central Nervous System 1563-
radiographic evidence of tuberculosis and findings on CSF Clinical Features and Diagnosis
examination and neuroimaging. The diagnosis is Patients are usually older than 3 years and present with
confirmed if CSF culture or PCR is positive for recent onset of focal or generalised epilepsy. Neuro
Mycobacterium tuberculosis or acid-fast bacilli are present. imaging reveals one or multiple ring-enhancing lesions
Gene Xpert is a quick cartridge based test for M. tuber with perifocal edema (Fig. 19.7c) with or without an
culosis genome and drug resistance to rifampicin. asymmetric scolex within the ring. Patients may
occasionally present with encephalitis and raised
Treatment intracranial pressure with or without seizures.
Antitubercular treatment includes two months of four Neuroimaging in these cases reveals cerebral edema in a
drug (intensive) therapy and 10 months of two drug brain studded with cysts in various stages, including
(maintenance) therapy (Chapter 11). Intravenous is enhancing and nonenhancing cysticerci, termed a 'starry
dexamethasone is followed by oral administered for 8-12 sky' appearance (Fig. 19.7d).
weeks to prevent sequelae. Patients with obstructive The combination of clinical and radiological findings
hydrocephalus require CSF diversion by shunt or third is usually diagnostic. Radiological differential diagnoses
ventriculostomy. include tubercular and Toxoplasma granulomas. Serology
by enzyme linked immunoelectrotransfer blot assay has
Prognosis high sensitivity (100%) and specificity (83-100%) for
Prognosis is related to patient age and stage of disease at multiple and extraparenchymal neurocysticercosis, but
has poor diagnostic utility for one to few cysticerci and
diagnosis. Early treatment (stage 1) results in complete
calcified lesions.
cure. While 80% of patients treated in stage 2 of disease
survive, 50% show sequelae. Only 50% of patients treated
Management
in stage 3 survive and 80% show sequelae. Complications
include hydrocephalus, optic neuritis, infarction and Symptomatic treatment of seizures is essential. Anti
spinal block due to arachnoiditis. Sequelae include focal epileptic therapy is continued for at least 6 months and
neurological deficits, epilepsy, intellectual disability, until the lesions disappear. Definitive antihelminthic
blindness and occasionally, endocrinopathies. therapy is recommended for up to 5 lesions. Albendazole
is the preferred agent and is administered at 15-20 mg/
Neurocysticercosis kg/ day in two divided doses for a week. Cysticidal
therapy is contraindicated in ocular neurocysticercosis and
Parasitic infestation of the brain by the encysted larvae of cysticercal encephalitis since degenerating cysts may
pork tapeworm Taenia solium is a public health problem evoke intense inflammatory response. All patients should
in many developing regions including Southeast Asia, first receive oral prednisolone at 1-2 mg/kg/day for 5-7
Latin America and sub-Saharan Africa. The condition days, beginning prior 2-3 days to antihelminthic therapy.
affects 9% people across ages and 13% of children.
Neurocysticerci account for up to 35% patients presenting Acute Disseminated Encephalomyelitis
with seizures in rural regions, with active or degenerating
Immune-mediated cerebral inflammation may follow viral
neurocysticerci being more common than calcified
exanthem or vaccination. While measles is the most
granulomas. Humans acquire the infection by consuming
common cause, causative infections include rubella,
undercooked pork containing cysticerci or by eating food
mumps, varicella zoster, influenza A and B, Rickettsia and
contaminated with feces containing tapeworm eggs. The
Mycoplasma pneumonia. Vaccines that may precipate the
eggs form larvae that cross into the bloodstream to seed
syndrome are rabies, vaccinia, measles and yellow fever.
the brain.
Patients present with altered consciousness, convulsions
and multifocal neurological signs affecting cerebellum,
Pathogenesis optic nerves, long tracts and spinal cord. Fever may be
Parenchymal or cerebral infection is more common than absent at onset. CSF may reveal mild pleocytosis. MRI
extraparenchymal neurocysticercosis, manifesting as shows characteristic scattered lesions in the white matter,
intraventricular, spinal or ocular cysts or arachnoiditis. at times affecting the deep grey matter and other areas
Cysts may be single or multiple, and usually form at the (Fig. 19.6c). Treatment options include pulse corticosteroids,
gray-white matter interface. Four stages are recognised, intravenous immunoglobulin and plasmapheresis.
namely the vescicular, colloidal, granular-nodular and
nodular-calcified lesions. The first two or active stages Autoimmune Encephalitis
carry low risk of seizures and do not enhance on Neurological syndromes presenting with neuropsychiatric
neuroimaging. Cysticerci usually cause seizures in the features, mutism, movement disorders, seizures and
degenerating or granular-nodular stage, and are detected cognitive decline may be caused by serum and/or CSF
as enhancing lesions on MRI. antibodies against ion channels, receptors and associated
564 Essential Pediatrics
proteins. Anti-NMDA receptor antibody encephalitis, Table 19.6: Etiology of cerebral palsy
voltage-gated potassium channel antibody-associated Genetic or prenatal
encephalitis and limbic encephalitis are well described in
Structural malformations of nervous system
adults, often occurring as paraneoplastic syndrome.
Congenital or intrauterine infections
However, 23-40% of patients present in childhood.
Maternal or obstetric complications
Treatment options include pulse methylpredisolone,
Teratogens
intravenous immunoglobulin, plasma exchanges and
intravenous rituximab. Perinatal
Birth asphyxia
Encephalopathies Prematurity; low birth weight
The term encephalopathy is used for diffuse cerebral Birth trauma; intracranial hemorrhage
dysfunction due to a non-inflammatory pathology, as Hyperbilirubinemia; hypoglycemia
against encephalitis which is characterized by Central nervous system (CNS) infection
inflammation. However, the two are often difficult to Postnatal
distinguish clinically. Fever cannot discriminate between CNS infection
the two entities as encephalopathy may be precipitated Hypoxia
by systemic infection, and fever may have an alternative Trauma; toxins
cause.
Dengue Encephalopathy affecting 2-3 infants per 1000 live births. While perinatal
asphyxia was considered the most common cause, it
Neurological manifestations, including encephalopathy,
accounts for less than 10% of cases. Various causes are
are common with dengue infections and may be caused
listed in Table 19.6.
by vasculitis, cerebral edema, hypoperfusion or
hyponatremia. However, virus invasion of the brain Clinical Features
producing encephalitis has also been documented.
The most common presentation is with developmental
Reye Syndrome delay. Physical findings are persistence of neonatal
reflexes, increased tone, fisting with cortical thumb,
This acute encephalopathy may follow a viral upper
scissoring of legs, toe-walking, abnormal posture and gait,
respiratory tract infection (90% cases) or varicella (5-7%).
abnormal movements and/ or hyperreflexia. Common
History of salicylate ingestion is common. The onset is
comorbidities include intellectual disability, microcephaly,
abrupt with protracted vomiting followed by delirium,
seizures, behavioral problems, difficulty in speech,
combative behavior and stupor. While most children have
language, swallowing or feeding, blindness, deafness,
a mild course, there may be rapid worsening with seizures,
squint, malnutrition, sleep disturbances and excessive
coma and death. Common findings include mild
drooling. Contractures may develop that are initially
hepatomegaly, hypoglycemia and elevated serum
dynamic and later fixed.
transaminases (>3-fold) and ammonia and coagulopathy
with normal levels of serum bilirubin. Liver biopsy reveals Classification
diffuse microvesicular fatty infiltration without any
inflammation or necrosis. Cerebral palsy is classified topographically as
quadriplegic, hemiplegic, monoplegic or diplegic, and
Suggested Reading physiologically as spastic, dyskinetic, ataxic or mixed.
Spastic palsy may be quadriplegic, diplegic or hemiplegic,
• Kumar R, Tripathi P. Japanese encephalitis. In: PG Textbook for
Postgraduates. eds: Gupta P, Menon PSN, Ramji S, Lodha R. Jaypee while dyskinetic palsy may be choreoathetoid or dystonic.
Brothers Medical Publications, New Delhi. 2015. pp 2144-2150. Spastic quadriplegia is the most common type of cerebral
• Lehman RK, Schor NF. CNS Infections. In: Nelson Textbook of palsy in India. It is often caused by perinatal asphyxia or
Pediatrics.eds: Kleigrnan RM, Stanton BF, St Geme JW, Behrman neonatal illness. Common comorbidities are intellectual
RE 19th edn. Elsevier Philadelphia, 2011, pp 1998.
disability, seizures, pseudobulbar palsy, microcephaly,
• Kumar R. Viral encephalitis and encephalopathies. In: Medical
Emergencies in Children. Eds: Meharban Singh. 5th edn. Sagar squint or visual disturbances, speech abnormalities and
Publications. New Delhi. 2012; pp 324-32. deformities. Neuroimaging may show cystic encephalo
malacia.
CEREBRAL PALSY Spastic diplegia is the second most common type, and is
Cerebral palsy refers to permanent, nonprogressive and linked to prematurity. Intellect is often preserved.
occasionally evolving, disorders of tone, movement or Neuroimaging shows periventricular leucomalacia.
posture, caused by an insult to the developing brain. It is Spastic hemiplegic palsy usually results from a vascular
the most common chronic motor disability in childhood, insult or perinatal stroke. Early hand preference is a clue.
Diseases of Central Nervous System lsss-
Neuroimaging usually reveals focal changes or a deficiency. Static disorders such as cerebral palsy may
porencephalic cyst. These children are usually mobile. appear to regress due to formation of contractures,
They may have preserved or impaired intellect. epilepsy, movement disorders or emotional problems.
Dyskinetic or extrapyramidal palsy may result from Epileptic encephalopathies also cause neuroregression.
asphyxia or kernicterus. Rigidity, dystonia, dyskinesia and Acute deterioration following illness, trauma or brain
drooling are prominent while intellect is relatively infections after which the child remains static or improves
preserved. Radiology may indicate abnormalities in basal need to be differentiated. The neurocutaneous disorders
ganglia or thalamus. also have progressive neurologic deterioration. Diseases
like lupus erythematosis and multiple sclerosis can also
Ataxic palsy is caused by cerebellar malformations and appear like a progressive degeneration.
is associated with other cerebellar signs.
Mixed CP refers to a presentation including both spastic Evaluation
and extrapyramidal features. A detailed history should elicit the age at onset, course
and evolution of illness, history of consanguinity and
Evaluation family history. Progressive deterioration may be difficult
A detailed history is taken to detect various manifestations to detect in patients with infantile onset. Other features
and antecedent events. Physical and neurologic include feeding difficulties, vomiting, failure to thrive,
examination should include detailed assessment of lethargy, irritability and lack of visual fixation and social
development and evaluation for dysmorphism and interaction. Small molecule disorders (aminoacidopathies;
neurocutaneous markers. Spasticity is classified using urea cycle disorders; organic acidemias and fatty acid
tools such as Gross Motor Function Classification System oxidation defects) typically have a relapsing and remitting
and Modified Ashworth Scale. course with progressive deterioration, while large
molecule storage diseases (lysosomal storage disorders;
Management glycogen storage disorders and mucopolysaccharidoses)
Management requires multidisciplinary inputs from the have chronic progressive course. Physical examination
pediatrician, occupational therapist, physiotherapist, should focus on appearance (Fig. 19.8), detailed
clinical psychologist, orthopedic surgeon, speech neurological examination including fundoscopy, hepato
therapist, ophthalmologist, ENT specialist, social worker splenomegaly, and specific findings in eye, skin and
and special educator. Generalised spasticity is managed
by physiotherapy and drugs such as diazepam, baclofen,
tinazidine or dantrolene. Localized spasticity can be
effectively treated with injection of botulinum A toxin.
Some patients may require tendon release or tendon
lengthening. Dystonia is managed with trihexiphenidyl,
botulinum or levodopa.
Suggested Reading
• Evaluation of a child with cerebral palsy. Aneja S. Indian J Pediatr.
2004 Jul; 71(7):627-34.
• Fenichel GM. Hemiplegia, paraplegia and quadriplegia. In: Clinical
Pediatric Neurology. 7th edn. Saunders, Philadelphia. 2013.
Chapter 10, 11.p 236-70.
• Gulati S, Sondhi V. Cerebral palsy: An overview. Indian J Pediatr.
2017 Nov 20 [In Press].
• Stavsky M, Mor 0, Mastrolia SA, Greenbaum S, Than NG, Erez 0.
Cerebral Palsy-Trends in Epidemiology and Recent Development
in Prenatal Mechanisms of Disease, Treatment, and Prevention.
Frontiers in Pediatrics. 2017; 5:21. doi:10.3389/fped.2017.00021.
NEUROLOGICAL REGRESSION
Various disorders present with progressive deterioration
in mental and motor functions, causing loss of acquired
milestones. Inherited metabolic storage disorders are the
most common etiology; other causes include sequelae of
infections (e.g. HIV encephalopathy, subacute sclerosing Fig. 19.8: Coarse facial features with psychomotor retardation
panencephalitis and progressive rubella panencephalitis), in a child with (a) Mucopolysaccharid osis t ype 2; and
hydrocephalus, hypothyroidism and vitamin B 12 (b) Cretinism (congenital endemic hypothyroidism)
s66 I Essential Pediatrics
Treatment
The first priority is to evaluate for and manage conditions
for which specific therapy is available, such as
hypothyroidism, hydrocephalus, vitamin B12 deficiency,
lead poisoning, Wilson disease, adrenoleukodystrophy,
and biotinidase deficiency. Specific diets are useful in
conditions such as galactosemia, fructose intolerance and
phenylketonuria. Enzyme replacement therapy is
available for Gaucher disease, milder variant of
mucopolysaccharidosis type 1, glycogen storage disease
Fig. 19.9: Characteristic predominantly posterior white matter
type 2 (Pompe disease) and Fabry disease. Transplantation
involvement in a patient with adrenoleukodystrophy
of the bone marrow and liver may be useful in patients
skeleton that may indicate the underlying etiology. with Hurler disease and glycogen storage disease,
Table 19.7 lists disorders based on age of onset; specific respectively. Several disorders are already screened for
clinical and diagnostic features are discussed in as part of newborn screening programs in many countries.
Chapter 24. While most conditions have a poor outcome, specific
Biochemical tests are targeted towards detecting the diagnosis enables prenatal counseling and antenatal
suspected defect and include serum ammonia, arterial diagnosis in subsequent pregnancies.
Diseases of Central Nervous System 1567-
illnesses like hypo- or hypertonia, weakness and ataxia. months. Patients should receive prophylaxis against group
This chapter will focus on involuntary abnormal A streptococcal infection. Pimozide, valproate,
movements, i.e. excessive movements that are not under haloperidol, benzodiazepines or phenothiazines may be
the patient's control. They usually occur as a result of used to control abnormal movements.
disorders of the basal ganglia. Chorea and other abnormal movements may be seen
Abnormal movements have been classified into during recovery from tubercular or viral (especially JE)
5-6 types but there is such a rich variety of movements meningoencephalitis. Movements usually last several
that all cannot be classified or even described. They require weeks to months and may be incapacitating.
visualization.
Abnormal movements need to be differentiated from Athetosis
convulsions. Unlike convulsions that are usually These are slow, writhing, distal movements of the limbs.
paroxysmal, occur during sleep or wakefulness and are It may occur alone, usually after perinatal brain injury
associated with altered consciousness and abnormal EEG, (perinatal asphyxia, kernicterus), or along with chorea,
abnormal movements are usually non-paroxysmal, tend as choreoathetosis.
to occur in awake state and disappear during sleep, and
are unlikely to be associated with loss of consciousness or Dystonia
EEG abnormality. Important types are discussed below. This refers to abnormal posture due to sustained muscle
contraction. Focal dystonias, such as blepharospasm,
Chorea orofacial or hemifacial spasm and writer's cramp are rare
This is a rapid, random, non-rhythmic, non-stereotyped in childhood. However, generalized dystonias in children
and quasipurposive movement, often superimposed on a may begin as focal dystonia.
voluntary movement. Chorea may move from limb to limb
or one side of body to another, giving the impression of Torticollis
restlessness. Describing chorea is tough as the movement Sustained turning of the head to one side may be caused
is not stereotyped. 'Jack in the box 'movements may be by dystonia, benign paroxysmal torticollis, cervico
seen. The movements are often elicitable by asking the medullary malformations or syringomyelia, diplopia,
patient to raise both arms above the head or stretched out juvenile rheumatoid arthritis, posterior fossa or cervical
in front. The examiner may feel alternating 'milkmaid' cord tumors and stemocleidomastoid injury or tumor.
movements upon holding the patient's hand. The most
common conditions presenting with chorea in India are Benign Paroxysmal Tort/col/is
Sydenham chorea, Wilson disease and sequelae of
Benign paroxysmal torticollis is believed to be a migraine
meningoencephalitis (Table 19.10).
variant. Episodes of head tilting and rotation to one or
Sydenham Chorea (rheumatic chorea) other side begin in the first year. Pallor, irritability, malaise
and vomiting may be associated. Attacks last 1-3 days,
This is an immune-mediated late manifestation of remit spontaneously and recur 3-6 times per year.
rheumatic fever. Onset is insidious, often with unilateral
chorea. Hypotonia, dysarthria and emotional !ability may Dopa Responsive Oyston/a
be present. The condition improves gradually over 3-4
Dopa responsive dystonia or Segawa disease is inherited
Table 19.10: Causes of chorea in an autosomal dominant or recessive manner. Children
Chorea as predominant symptom present between 4 and 8 years of age with gait disturbance,
toe walking and/ or posturing of arms. A diurnal pattern
Inherited defects: Glutaric aciduria, benign familial chorea,
Wilson disease, Fahr disease, abetalipoproteinemia,
is observed in more than half, with symptoms worsening
Huntington chorea, ataxia telangiectasia, Lesch-Nyhan by the evening. Small doses of levodopa provide
syndrome immediate and complete relief. Untreated patients may
Systemic disorders: Sydenham chorea, hyperthyroidism, progress to parkinsonism with cogwheel rigidity and
systemic lupus erythematosus bradykinesia.
CNS infections
Tumors Idiopathic Torsion Oyston/a
Drugs: Anticonvulsants, oral contraceptives, antiemetics, Idiopathic torsion dystonia is an autosomal dominant
theophylline condition with variable penetrance, occurring most
Chorea as one of the symptoms commonly in Ashkenazi Jews. Presentation peaks
bimodally at 9 years and 45 years. Dystonia begins in the
Perinatal brain insult
legs to become generalized. Dysarthria, dysphagia,
Postinfectious
orofacial movements, postural tremor and blepharospasm
Vascular disease: Stroke, Moyamoya disease
may be present. Botulinum toxin helps in focal problems.
570 Essential Pediatrics
Trihexiphenidyl, baclofen, carbamazepine, benzodia generalized myoclonus that occurs chiefly during action
zepines or levodopa may be useful. Outcomes vary from or stress, involves the face, trunk or proximal muscles,
complete disability to functional independence. has onset in first or second decade of life, and is associated
with normal EEG and neuroimaging. Therapy with
Wilson Disease nitrazepam or clonazepam may be useful.
Wilson disease, an autosomal recessive disorder
characterized by copper accumulation in liver, brain and Tics
cornea, presents variably at 3-50 years. Children usually These are sudden, brief, purposeless, complex stereotyped
present with acute or chronic hepatitis or hepatic failure. movements or utterances, which are exacerbated by stress,
Neurological symptoms predominate in the second are suppressible and disappear during sleep. Examples
decade, and include disturbance of speech or gait, often include clearing the throat, eye blinking, grimacing, lip
unchanged for years, followed by dysarthria, dystonia, smacking and shrugging of shoulders.
rigidity, abnormalities of gait and posture, tremor and Tourette syndrome is characterized by motor and verbal
drooling. Dementia and psychiatric symptoms may also tics and attention deficit. Verbal tics include snorting,
occur. Almost all cases with neurological involvement sniffing, grunting or hissing. Disease course waxes and
show golden-brown pericorneal discoloration, termed wanes over prolonged period. The condition is perhaps
Kayser-Fleischer rings. Diagnosis is suggested by reduced caused by streptococcal infection in genetically predisposed
serum ceruloplasmin levels ( <20 mg/ dl), increased individuals. Pimozide, haloperidol or fluphenazine may
urinary copper excretion and increased hepatic copper be used if the tics are bothersome.
content on biopsy. Patients require lifelong chelation with
oral 0-penicillamine or trientine, titrated to maintain Tremor
urinary copper excretion at 5-10 times normal. Pyridoxine,
zinc and vitamin E is given. Patients slowly recover over These are involuntary oscillating, rhythmic and usually
months. However, some patients progress to liver failure distal movements of low amplitude on both sides of an
despite therapy, necessitating liver transplantation. axis. Tremors may be physiological, precipiatated by
anxiety, fatigue, stress or drugs such as xanthines,
Pantothenate Kinase associated Neurodegeneration adrenergic agonists, nicotine, thyroid hormone and
amphetamines. Tremors may be secondary to injury to
Pantothenate kinase associated neurodegeneration is an
basal ganglia following meningoencephalitis and
autosomal recessive disorder associated with iron deposi
neurodegenerative diseases.
tion in basal ganglia. Patients present with progressive
dystonia, initially affecting feet, leading to equinovarus Infantile Tremor Syndrome
deformity, followed by rigidity in hands. Two-thirds
patients have retinitis pigmentosa while one-fourth Infantile tremor syndrome was described in exclusively
develop seizures. MRI is characterized by 'eye of tiger' breastfed Indian infants, presenting at 8-18 months of age
appearance of the basal ganglia on T2-weighted images. with listlessness, developmental delay and regression,
Management is symptomatic. pallor, depigmented sparse hair and hyperpigmented
knuckles. Subsequent symptoms include progressive limb
Symptomatic Genera/zed Dystonia tremors, bleating cry, and arms positioned like a 'bird
Symptomatic generalized dystonia may follow various about to take flight'. The condition is linked to cobalamin
types of brain injury. Progressively severe dystonia is deficiency and responds to therapy with cobalamin and
observed beginning 2-3 years after kernicterus or perinatal propranolol.
asphyxia. Patients with stroke, head trauma, tumor of
basal ganglia, antiphospholipid syndrome and neuronal Suggested Reading
storage disease may show hemidystonia. • Fenichel GM. Movement disorders. In: Clinical Pediatric
Neurology. 7th edn. Saunders, Philadelphia. 2013; pp 277-294.
Myoclonus • Kruer MC. Pediatric movement disorders. Pediatr Rev 2015; 36:
104-116.
These are sudden, brief, jerky, involuntary movements • Schlaggar BL, Mink JW. Movement disorders in children. Pediatr
that are focal, multifocal or generalized. Generalized Review 2003; 24:39-50.
myoclonus is not stereotyped. Myoclonus is more • Silveira-Moriyama L, Kovac S, et al. Phenotypes, genotypes, and
common when awake but may not disappear completely the management of paroxysmal movement disorders. Dev. Med
Child Neurol. 2018 (In press).
during sleep. It may occur in isolation, as part of myoclonic
epilepsy, where EEG shows epileptiform discharges, or
STROKE
as part of systemic or CNS disorders. Myoclonus cannot
be voluntarily suppressed. A very wide variety of systemic Neurological weakness of one-half of the body (upper and
and central nervous system disorders can cause lower limb), termed hemiplegia, is caused most commonly
myoclonus. Essential myoclonus refers to focal or by a stroke, defined as rapidly developing focal or global
Diseases of Central Nervous System ls11-
disturbance of brain function lasting more than 24 hours most common (90%) presentation is with hemiparesis,
with no obvious nonvascular cause. Other causes of hemisensory signs, aphasia and/ or visual field defects.
hemiplegia include transient ischemic attack, Todd palsy, Cortical strokes may cause convulsions, contralateral
granuloma, tumor, abscess, encephalitis, demyelinating hemiparesis, cortical sensory loss and aphasia. Internal
disorders, congenital brain malformation, neurocutaneous capsule infarction may cause contralateral dense
disorders and migraine. hemiplegia, upper motor neuron type of facial palsy,
Stroke may be broadly classified as ischemic or hemianesthesia and homonymous hemianopia. Altered
hemorrhagic variants that account for 55% and 45% of all sensorium may occur with posterior fossa stroke.
cases in childhood, respectively. Ischemic stroke may be Brainstem infarction causes crossed paralyses of cranial
caused by arterial thrombi or embolism or due to cerebral nerve ipsilaterally and contralateral limb palsy.
venous sinus thrombosis. Weakness due to stroke is Initial stabilisation includes attention to airway,
typically sudden, worst at the onset and improves breathing and circulation, supportive treatment for
gradually over days to months. Almost 20% of childhood hypoxemia, hypoglycemia, dehydration, seizures and fever.
stroke is recurrent. Thrombolysis with tissue plasminogen activator (tPA),
adminstered intravenously within 3 hours and intra
Acute lschemic Stroke arterial within 6 hours of the event, are recommended in
One or more risk factors for acute ischemic stroke, listed adults; however, no clear guidelines are available for
in Table 19.11, are present in two-thirds of patients. In the children. Pending investigations for cause, ultra
others, no cause for stroke can be found despite extensive fractionated or low molecular weight heparin may be
evaluation. Patients with arterial thrombi may have administered.
prodromal symptoms, stuttering course and history of Suggested evaluation is listed in Table 19.12. Neuro
transient ischemic attacks, while those with embolism imaging should be done as soon as possible. Ultrasound
usually present with sudden loss of function. The precise is useful if fontanelle is open. Transcranial Doppler shows
neurological deficit depends on the site of infarction. The changes in cerebral blood flow velocity in moderate to
Table 19.12: Investigation for stroke Table 19.13: Causes of intracranial hemorrhage
Complete blood count with erythrocyte sedimentation rate Arteriovenous malformation: Sporadic; hereditary hemorrhagic
Hemoglobin electrophoresis telangiectasia
Complete lipid profile Capillary telangiectasis
Imaging: Carotid Doppler; computed tomography if hemorrhage Cavernous malformations
suspected; MR imaging, arteriography and venography; carotid Aneurysms
angiography, if indicated Bleeding and clotting diathesis
Echocardiography and electrocardiography Vasculitis
Evaluation for procoagulant state Hypertension
• During acute phase: Serum homocysteine levels; genetic Trauma
testing for mutations (factor V Leiden, prothrombin gene);
activated protein C resistance; lupus anticoagulant,
anticardiolipin and p2 glycoprotein-1 antibody lntracranial Hemorrhage
• After 8-12 weeks: Levels of protein C, S and antithrombin Ill Clinical presentation is more dramatic than with ischemic
Antinuclear and anti-neutrophil cytoplasmic antibody; stroke, with severe headache and vomiting due to raised
rheumatoid factor intracranial pressure, and meningeal signs due to leaking
of blood into the CSF. Causes of intracranial hemorrhage
are listed in Table 19.13. A thorough evaluation is
warranted as a potential cause is found in about 90% cases.
It must be noted that cerebral venous sinus thrombosis
also can result in ICH because of back pressure.
CT scan is preferred to MRI in diagnosis of hemorrhage.
MR, CT or 4-vessel carotid angiography is required to
delineate arteriovenous malformations and aneurysms.
Complete blood counts, including platelet count, clotting
factor assays like von Willebrand factor antigen, factor
VIII and factor XII and liver function tests are required.
Management consists of resuscitation and supportive
care. Identification of the cause may be followed by defini
tive treatment, in addition to rehabilitative measures.
severe ischemia. CT is preferred in unstable patients or Table 19.14: Risk factors for cerebral venous sinus thrombosis
when intracranial hemorrhage is suspected. It may be Dehydration, hypoxia
normal in early ischemic stroke for up to 72 hours after Cardiac disease: Congenital, postoperative, post-catheterization
onset, after which there is edema in the affected area
Anemias: Sickle cell disease, iron deficiency anemia,
(Fig. 19.10). MRI can identify ischemia within hours and
thalassemia
diffusion weighted imaging within 45 minutes. While four
vessel carotid angiogram is most accurate for distal Head and neck infections
arteries, lesions of internal carotid artery, moyamoya Metabolic: Homocystinuria; prothrombotic disorders
disease, arteriovenous malformations and aneurysms, MR Nephrotic syndrome
angiography is a satisfactory alternative. Malignancy: Leukemia, lymphoma
Appropriate rehabilitation should be planned. Long Systemic diseases: Systemic lupus erythematosus, Beh9et
term low dose aspirin is administered to prevent disease, inflammatory bowel disease
recurrence. Treatment of the underlying cause is important Drugs: L-asparaginase, oral contraceptives, steroids
to prevent recurrence. Conditions with a high risk of
Other structural conditions: Head injury, brain tumor,
recurrence (e.g. cardiac or prothrombotic disorders) hydrocephalus, Sturge-Weber syndrome
require long-term oral anticoagulants.
Diseases of Central Nervous System 1573-
empty delta sign. CT or MR venography is more definitive. Table 19.15: Causes of paraplegia or quadriplegia
Diffusion and perfusion MRI and digital subtraction Spastic
angiography are needed in equivocal cases. A detailed
evaluation for prothrombotic states is essential. Compressive
Tuberculosis of spine with or without paraspinal abscess
Initial treatment is supportive. Antibiotics are given if
bacterial infection is suspected. Ultrafractionated heparin Extradural: Metastasis from neuroblastoma, leukemia,
or low molecular weight heparin followed by warfarin lymphoma; inflammatory process, such as epidural abscess
(usually posterior to the spinal cord), bony abnormalities such
for 3-6 months is the treatment of choice. Thrombolytic
as achondroplasia, Morquio disease, hemivertebrae and
treatment is recommended only in selected cases. occipitalization of atlas vertebra, atlantoaxial dislocation
lntradural: Neurofibroma, dermoid cyst
Suggested Reading
lntramedullary: Glioma, ependymoma, hemato- or hydro
• AHA Scientific statement management of stroke in infants and myelia
children. Stroke 2008; 39: 2644-2691.
Noncompressive myelopathies
• Crawford LB, Golomb MR. Childhood stroke and vision: A review
of the literature. Pediatr Neurol. 2017; doi: 10.1016/ Vascular anomalies of the spinal cord: Arteriovenous
j.pediatrneurol.2017.11.007. malformations, hemangiomas and telengiectasia
• Rosa M, De Lucia S, Rinaldi VE, et al. Paediatric arterial ischemic Trauma or transaction of cord
stroke: acute management, recent advances and remaining issues.
Transverse myelitis/myelopathy: Viral, neuromyelitis optica,
Ital J Pediatr 2015; 41:95-107.
segmental necrosis due to vascular occlusion, e.g. of anterior
• Tsze DS, Valente JH. Pediatric stroke: A review. Emergency
Medicine International 2011; 2011:734506. spinal artery
Familial spastic paraplegia
PARAPLEGIA AND QUADRIPLEGIA Lathyrism
Degenerative spinal cord disease
Paraplegia refers to weakness of trunk and both lower
limbs, while quadriplegia denotes weakness of all four Supra-cord lesions
limbs. Paraplegia or quadriplegia may occur due to Cerebral palsy
disorders of cerebrum, spinal cord, peripheral nerves, Hydrocephalus
neuromuscular junction or muscles (Table 19.15). While Bilateral cortical disease
cerebral disorders are upper motor neuron type, spinal Bilateral white matter disease
cord lesions may cause either upper or lower motor Flaccid weakness
neuron involvement and the other three types of lesions Spinal shock in the initial stages of spinal cord damage, e.g.
show lower motor neuron involvement. after trauma, vascular, inflammatory, neoplastic lesions, or
transverse myelopathy
Cerebral Disorders Guillain-Barre syndrome
Acute poliomyelitis
Lesions involving parasaggital and periventricular areas,
Spinal muscular atrophies
in particular, cause paraplegia or quadriplegia. Common
Peripheral neuropathies
causes include perinatal asphyxia, structural malformations
Botulism, Riley-Day syndrome
and sequalae of CNS infections.
Pseudoparalysis
Spinal Cord Disorders Surgery, osteomyelitis, fractures, myositis, metabolic myopathy
These may cause acute or chronic progressive paraplegia
or quadriplegia. Cervical cord lesions present as in isolation or as part of Down syndrome, mucopoly
quadriplegia, whereas lower lesions present as paraplegia. saccharidosis (e.g. Morquio syndrome) or Klippel-Feil
Lower motor neuron signs are present at the level of the syndrome (decreased number and abnormal fusion of
cord lesion and upper motor neuron signs are noted below cervical vertebrae). These are later replaced by upper
the lesion. Acute transverse lesions of the cord may cause motor neurone signs within a few days to weeks.
spinal shock with loss of all motor, sensory, autonomic
and reflex functions below the level of lesion. Patients with Transverse Myelitis
chronic spinal cord lesions present with clumsy gait, foot Transverse myelitis is an acute demyelinating condition
deformity and/ or stunted limb growth. Malformations of the cord characterized by sudden onset of often symme
like meningocele and meningomyelocele are obvious at trical leg weakness with loss of reflexes, movements and
birth. The skin overlying spinal dysraphism may show sensation below a certain level with bladder and bowel
abnormalities like pigmentation, tuft of hair, lipoma or dysfunction over 1-2 days. Longitudinally extensive
sinus. Congenital atlanto-axial dislocation may cause acute transverse myelitis may occur with optic neuritis sequen
or slowly progressive quadriplegia at any age, and is tially or together, termed Devic disease (neuromyelitis
usually caused by odontoid hypoplasia, occurring either optica). Diagnosis is enabled by contrast enhanced
574 Essential Pediatrics
Table 19.18: Management of raised intracranial pressure pediatric posterior fossa tumors. Boys are affected
2-4 times as often than girls. These rapidly growing,
Raise head end by 30 degrees; keep head in midline
malignant tumors present with cerebellar signs and
Hyperventilate to maintain PC02 at 30-35 mm Hg features of raised intracranial pressure. Neuroimaging
Administer mannitol at 0.25-1 g/kg (1.25-5 mUkg of 20% reveals a midline mass arising from the vermis, effacing
solution) as intravenous (IV) bolus; repeat every 8 hours for the fourth ventricle and basal cisterns, causing obstructive
48-72 hours
hydrocephalus (Fig. 19.lla). The tumors are usually
Administer hypertonic (3%) saline at 0.1-1 mUkg/hr to maintain hyperdense with prominent enhancement (90%) and
serum sodium at 145-155 mEq/L associated with cysts or necrosis (40-50%) or calcification
Administer IV furosemide at 1-2 mg/kg/dose (10-20%). Forty percent of patients have evidence of CSF
Switch to oral acetazolamide or glycerol when stable seeding at diagnosis. The prognosis is poor.
Consider corticosteroids (oral or IV) for vasogenic edema Cerebellar astrocytoma: These arise from either cerebellar
Consider decompressive craniectomy hemispheres, and present with ataxia, incoordination and
nystagmus. Most tumors are low-grade and slow-growing
Medulloblastoma: These midline cerebellar tumors and carry a satisfactory prognosis as they can usually be
usually affect young children, accounting for 30-40% of excised completely.
Fig. 19.11: Contrast enhanced tomography in the setting of raised intracranial tension showing (a) Enhancing heterogenous mass
arising from vermis suggesting medulloblastoma; (bl Left parietal enhancing lesion with midline shift in a case of brain abscess;
and (c) Multiple basal ring enhancing lesions and meningeal enhancement in a patient with tubercular meningitis
Diseases of Central Nervous System lsn-
Brainstem glioma: These usually present between 5 and surrounding edema. Large lesions show mass effect,
10 years of age with lower cranial nerve palsies, long tract distortion of surrounding structures and midline shift
signs, cerebellar signs and signs of raised intracranial (Fig. 19.llb). CSP may show mild pleocytosis due to
pressure. While both focal brainstem gliomas and diffuse meningeal reaction; however, lumbar puncture is usually
intrinsic pontine glioma carry grave prognosis, the latter contraindicated because of risk of herniation. Management
have worse outcomes. includes administration of intravenous antibiotics with
Ependymoma of the fourth ventricle: These arise from cells good penetration into the CSP for 4-8 weeks. Anaerobic
lining the ventricle. Tumors arising from the floor of the coverage must be ensured. A third-generation cephalo
fourth ventricle present with torticollis and ataxia, while sporin with vancomycin and metronidazole provides
those arising from the side of the ventricle affect cranial satisfactory empiric coverage. Drainage of the abscess
nerves, presenting with impaired hearing, dysphagia and must be done through burr hole, craniectomy, craniotomy
clumsiness. or by stereotactic aspiration.
Craniopharyngioma: These are cystic benign supratentorial Subdural Collections
tumors arising from the squamous epithelial rest cells of
Subdural collections usually occur as a complication of
the Rathke pouch. Clinical features include growth failure,
bacterial meningitis, chiefly in infancy. Subdural
visual field defects (bitemporal hemianopsia or unilateral
effusions are usually sterile and resolves spontaneously;
or asymmetric field defects), signs of raised intracranial
drainage is only necessary if associated with pressure
pressure and endocrine abnormalities like diabetes
effect. They may, however, be associated with prolonged
insipidus and delayed puberty. X-ray skull may reveal
fever. Subdural empyemas are collections of pus in
calcifications. Treatment includes cyst aspiration and
subdural spaces and are detected on imaging by an
radiotherapy.
enhancing capsule. They usually require drainage but may
Glioma of cerebral hemispheres: These usually present refill. Subdural hematomas are usually traumatic and
with seizures and hemiparesis; features of raised present with features of chronically raised intracranial
intracranial pressure are usually delayed. Histologically, pressure. A vascular membrane forms around the
these may be astrocytoma, oligodendroglioma or hematoma. As blood cells get absorbed, the fluid's protein
glioblastoma. content increases, thus increasing oncotic pressure that
Glioma of optic nerve: These relatively uncommon tumors draws fluid into the hematoma. The collection grows,
usually occur in a setting of NFl and present with tearing small bridging veins within the hematoma, further
decreased vision, and later with proptosis, symptoms of increasing bleeding. The sequence of bleeding, increased
raised intracranial pressure, focal neurological deficits and pressure and growth repeats itself. The skull may show
hydrocephalus. Hypothalamic involvement may result in positive transillumination. Imaging reveals a biconvex
polyuria and polydipsia. Imaging indicates an enlarged collection, as compared to the crescent shape seen with
optic nerve. epidural collections.
Hydrocephalus Management
This term refers to abnormal accumulation of CSF in the Untreated hydrocephalus before sutural fusion results in
brain, leading to increased pressure and increased grossly increased head size and cortical thinning. After
ventricular size, and if occurring before sutural fusion, in sutural fusion, untreated cases usually succumb to raised
increased head size. intracranial pressure. While medical measures may
temporarily reduce intracranial pressure, CSF diversion,
Pathophysiology most commonly by a shunt, is more useful. Usually valved
CSF is produced by the ventricular choroid plexus by tubing is placed between the ventricle and peritoneal
ultrafiltration and active secretion at a rate of 20 mL/hr cavity. The ventriculoperitoneal shunt usually requires
and passes through the ventricular system to be absorbed multiple revisions as the child grows older. Shunt surgery
by arachnoid granulations into venous sinuses. may be complicated by infection leading to meningitis,
Hydrocephalus is termed obstructive when there is shunt displacement, block or kinking leading to chronic
obstruction to flow of CSF in the ventricular system and shunt dysfunction, and abdominal complications such as
communicating when there is increased production or peritonitis or abscess. Another option for obstructive
defective absorption of CSF due to non-obstructive causes. hydrocephalus is endoscopic third ventriculostomy that
Chief causes are listed in Table 19.19. allows CSF to pass directly into the basal cisterns.
Prognosis
Clinical Features
A large head may cause difficulty in delivery, making Outcomes of hydrocephalus are guarded. Almost two
Cesarean section necessary. Infants present with large thirds of children have variable mental and motor
tense anterior fontanelle or an abnormally rapid growth disabilities, even with appropriate treatment.
in head size, manifest as increase in head circumference Idiopathic lntracranial Hypertension
by more than 1 cm every fortnight, separation of sutures
by more than 0.5 cm after the first 2 weeks and persistent Previously termed benign intracranial hypertension or
widening of the squamoparietal sutures. After sutural pseudotumor cerebri, the condition is characterised by
fusion, children usually present with symptoms of raised normal or reduced ventricular size and normal CSF
intracranial pressure. A positive Macewen or crack pot chemistry. Idiopathic intracranial hypertension usually
sound on skull percussion suggests sutural separation. affects adults or adolescents, chiefly female, and is
The setting sun sign indicates upward gaze palsy due to associated with obesity. Its pathophysiology remains
pressure on the quadrigeminal plate. unclear. Suggested mechanisms include increased CSF
Differential diagnosis of a large head include rickets, production, decreased CSF absorption or increased
hemolytic anemia, achondroplasia, familial macrocephaly, cerebral venous pressure, in a setting of endocrinopathy,
megalencephaly and neurometabolic disorders (muco anemia or use of vitamin A derivatives, tetracyclines,
polysaccharidoses, Tay-Sachs, Canavan and Alexander steroids or hormonal contraceptives.
diseases). Where fontanelle is open, cranial ultrasound Patients present with symptoms of increased intracranial
reveals increased ventricular size. CT scan and MRI pressure, such as headache, diplopia or blurred vision. Sixth
provide details on severity and etiology. Mildly enlarged cranial nerve palsy may occur as a false localizing sign. If
ventricles may be seen in cerebral atrophy and should not present, papilledema and visual deficits require prompt
be confused with hydrocephalus. evaluation and treatment. Options in management include
oral acetazolamide, glycerol or corticosteroids, repeated
lumbar puncture and surgical decompression (optic nerve
Table 19.19: Causes of hydrocephalus sheath decompression and shunt surgery).
Congenital
Suggested Reading
Aqueductal stenosis (X-linked)
Dandy-Walker malformation • Aylward, Shawn C. et al. Pediatric intracranial hypertension.
Pediatric Neurology 2017; 66:32-43.
Arnold-Chiari malformation • Fenichel GM. Management of increased intracranial pressure. In:
Vein of Galen malformation Clinical Pediatric Neurology. 7th edn. Saunders, Philadelphia. 2013.
Intrauterine infections (toxoplasmosis, rubella, cytomegalo pp 89-112.
virus) • Kumar R. Approach and management of children with raised
Arteriovenous malformation intracranial pressure. J Pediatr Crit Care 2015; 2:13.
Acquired
COMA
lntraventricular hemorrhage
CNS infections Definition and Pathophysiology
Tumors and space occupying lesions, especially of posterior The word coma, derived from the Greek word 'koma' or
fossa
deep sleep, represents a state of sustained severe alteration
Diseases of Central Nervous System 1579
-
of consciousness. Normal consciousness is maintained by apneustic and ataxic breathing patterns suggest
integrity of cerebral cortex, thalamus and brainstem and progressive brainstem compression. Clues to etiology on
regulated by the ascending reticular activating system, examination include evidence of injury and tongue bite
located in upper pons, midbrain and diencephalon. (trauma); jaundice and fetor hepaticus (liver disease);
Altered consciousness or coma results from diffuse lesions petechiae (coagulopathy); ketotic breath odor (metabolic
of bilateral cerebral cortex or focal lesions of the ascending disease); dry flushed skin (belladonna poisoning) and
reticular activating system (Table 19.20). The most moist skin with increased salivation (organophosphorus
common causes of coma are trauma and CNS infections. poisoning).
Raised intracranial pressure causes herniation of brain
structures, compressing the brainstem (Table 19.17). Neurological Examination
The severity of coma is assessed by Glasgow Coma Scale
Evaluation modified for use in children (Table 19.21). Alternatively,
General Physical Examination the alert, response to verbal, response to pain,
unresponsive (AVPU) scale is administered, using a deep
Patients with raised intracranial pressure show painful stimulus by a strong pinch or pressure on the
bradycardia and hypertension. The respiratory pattern nailbed or supraorbital area. Meningeal signs, tone and
may indicate the level of the lesion. Cheyne Stokes posturing are looked for. Decerebrate posturing suggests
breathing is observed in diencephalic involvement, while injury to upper pons, while decorticate posturing indicates
Table 19.20: Causes of coma bilateral cortical lesion with preserved brainstem function.
Causes without focal neurological signs Flaccid areflexia indicates loss of all cortical and brainstem
Cerebrospinal fluid is normal functions up to the pontomedullary junction.
Poisonings, narcotic agents, toxins Fundoscopy may indicate papilledema, hemorrhage or
Metabolic disorders, e.g. hypoglycemia, diabetic acidosis, signs of hypertension. Pupils are pinpoint in pontine
uremia, inborn metabolic errors, Reye syndrome, hepatic lesions and morphine poisoning and small, equal and
encephalopathy reactive in coma due to metabolic or toxic causes. Bilateral
Head injury, concussion fixed dilated pupils are seen preterminally, in severe
Septicemia, cerebral malaria, dengue ischemia or with atropine or belladonna poisoning.
Postictal Unilateral unreactive pupil indicates impending
Hyperpyrexia, febrile encephalopathy transtentorial herniation. Sixth cranial nerve palsy is often
Water intoxication
a false localizing sign.
Cerebrospinal fluid is abnormal
Focal neurological deficits suggest a structural lesion.
Meningitis
Papilledema, hypertension, bradycardia, abnormal
Encephalitis
Subarachnoid hemorrhage breathing pattern, posturing and third and sixth cranial
Cerebral vein thrombosis nerve palsies suggest raised intracranial pressure.
Midline cerebral tumors Brainstem reflexes including doll's eye, oculovestibular
and corneal reflexes provide information on the integrity
Causes associated with focal neurological signs
of the brainstem.
Demyelinating disorders
Postictal coma Investigations
lntracerebral bleed, vascular malformation
Tumors, infarcts, strokes Complete blood counts, blood glucose, electrolytes,
Infections: Brain abscess, subdural empyema, encephalitis kidney and liver fiunction tests, venous blood gas, serum
Head injury, intracranial hemorrhage ammonia and lactate should be ordered. Where indicated,
Miscellaneous screening for toxins should be performed. Blood and CSF
cultures should be obtained if suspecting an infection.
Systemic illnesses, hypertension, shock
Neuroimaging helps assess for structural brain injury.
Table 19.21: Glasgow Coma Scale modified for children below 2 years of age
Score Best motor response Best verbal response Eye opening
1 None None None
2 Extension to pain Moaning to pain To pain
3 Flexion to pain Crying to pain To call
4 Withdrawal to pain Irritable cry Spontaneous
5 Localises Cooing and babbling
6 Moves on command
580 Essential Pediatrics
including the brainstem. Criteria for brain death are listed Cerebral angiography
in Table 19.22. The proximate cause of brain death should
Electroencephalography
be known and the condition should be irreversible, with
Transcranial Doppler ultrasonography
potentially reversible causes excluded, including use of
Cerebral scintigraphy
CNS depressants, hypothermia, shock, and metabolic and
endocrine disturbances. All brainstem reflexes should be *Adapted from American Academy of Pediatrics, Task Force on Brain
absent with apnea. Since brains of young infants have Death in Children 2011, and the American Academy of Neurology,
Practice Parameters for the Clinical Diagnosis of Brain Death; and
increased resistance to damage, longer observation consistent with the Indian Transplant of Human Organs (THO) Act, 2014
periods and ancillary tests are recommended in this group. '35 ° C according to the THO act
Two independent physicians must conduct a full MTwo tests 6 hours apart at all ages according to the THO Act
examination twice at the recommended time interval. The
apnea test should be performed by disconnecting the Suggested Reading
patient from the ventilator after achieving normal blood
• Act and Rules under Transplant of Human Organs Act (THOA)
gas, allowing arterial carbon dioxide to rise to 60 mm Hg
Transplantation of Human Organs and Tissues Rules, 2014;
or 20 mm Hg above baseline; absence of respiratory effort available at notto.nic.in/ act-end-rules-of-thoa.htm.
(positive apnea test) is consistent with brain death. • Nakagawa et al. Guidelines for the determination of brain death
It is possible to sustain life on life support systems in infants and children: An update of the 1987 Task Force
sometimes indefinitely even after brain death but the indi recommendations. Critical Care Medicine. 2011; 39: 2139-55.
vidual can never return to a functional state. The diagnosis • Taylor DA, Ashwal S. Impairment of consciousness and coma. In:
Swaiman KF, Ashwal S, Ferriero DM. eds. Pediatric neurology:
of brain death is important in deciding to discontinue the
principles and practice.5th ed. Philadelphia: Elsevier Publications;
life support systems and also for organ transplantation. 2006. p. 1379-1400.
Different countries have their own laws and criteria for • SharmaS, Kochar GS,Sankhyan N, GulatiS. Approach to the child
diagnosis of brain death. with coma. Indian J Pediatr.2010; 77:1279-87.
Chapter
20
Neuromuscular Disorders
Sheffali Gulati
A motor unit comprises one anterior horn cell and all the Inflammatory disorders such as dermatomyositis are
muscle fibers that it innervates. Neuromuscular disorders associated with waxing and waning course and pain.
may be due to lesions anywhere along the motor unit. Cardiac disease often accompanies Duchenne muscular
These include neuronopathies (disorders of anterior horn dystrophy, Pompes disease and myotonic dystrophy. Skin
cell), neuropathies (disorders of axon or its myelin), rash is seen in dermatomyositis; eyes are involved in
neuromuscular junction disorders and myopathies myotonic dystrophy, congenital muscle dystrophies and
(disorders of muscle). mitochondrial diseases. Liver involvement may be seen
with mitochondrial disorders, acid maltase deficiency and
APPROACH TO EVALUATION carnitine deficiency.
581
582 Essential Pediatrics
Central Hypotonia
Peripheral Hypotonia
mother suggest a neuromuscular junction disorder. • McDonald CM. Clinical approach to the diagnostic evaluation of
Predominantly proximal muscle weakness, normal or hereditrary and acquired neuromuscular diseases. Physical
medicine and rehabilitation clinics of North America. 2012;
depressed tendon reflexes and static or improving course 23(3):495-563.
indicate a muscle disease. Deep tendon reflexes are
preserved in muscle disease or, if reduced, are in Muscle Weakness in Older Children
proportion to the degree of muscle wasting and weakness. Distal weakness is predominantly seen in neuropathies
Atrophy is less prominent in muscle disorders. and some muscle disorders like myotonic dystrophy.
Central hypotonia is characterized by preserved muscle Proximal weakness has broad differential diagnosis
power and normal or brisk deep tendon reflexes. (Fig. 20.2). The child may complain of difficulty in rising
Sometimes patients may display features of both central from the chair, going up and down the stairs or reaching
and peripheral hypotonias; common causes of mixed with their arms. Some disorders such as chronic
hypotonia include hypothyroidism, motor unit disorders inflammatory demyelinating polyneuropathy (CIDP) and
with superimposed hypoxia, acid maltase deficiency, certain muscle dystrophies show both proximal and distal
mitochondrial disorders and infantile neuronal weaknesses.
degeneration.
DISORDERS AFFECTING ANTERIOR HORN CELLS
Mixed hypotonia: Features of both central and peripheral
hypotonias as in lysosomal storage disorders, Spinal muscular atrophy and poliomyelitis are the two
mitochondrial disorders and peroxisomal disorders. most common anterior horn cell disorders in children.
Besides these, other enteroviruses (e.g. coxsackievirus and
Suggested Reading echovirus), juvenile form of amyotrophic lateral sclerosis,
• Ahmed MI, Iqbal M, Hussain N. A structured approach to the and neurometabolic disorders like Tay-Sach disease,
assessment of a floppy neonate. Journal of Pediatric Neurosciences. neuronal ceroid lipofuscinosis and Pompe disease, may
2016;11(1):2-6. also involve anterior horn cells.
• Jan M. The hyp otonic infant: Clinical approach. Journal of Pediatric
Neurology 5 (2007) 181-187. Spinal Muscular Atrophy
• Darras BT, Jones HR Jr, Ryan MM, et al., 2015. Neuromuscular
disorders of Infancy, Childhood and Aldolesence:A clinician This is an autosomal recessive disease caused by a
Approach 2nd ed.Elsevier, London. mutation in the SMNl gene at chromosome 5ql3.2 region.
Neuromuscular Disorders Issa-
Proximal muscle weakness
This region also carries SMN2 gene, the copy number of present later in childhood (>18 months) and are usually
which acts as a main modifier of the various clinical able to walk. These children are often misdiagnosed as limb
phenotypes encoding the SMN protein of anterior motor girdle muscular dystrophy or myopathy. Global areflexia,
horn cells. Four clinical types are recognized. Type 0: It is fasciculations, polyminimyoclonus and tremors give a clue
the most severe form and presents in the fetal life. Most towards underlying anterior horn cell pathology.
children do not survive. Patients with type 1 disease Treatment is supportive and includes respiratory care,
(Werdnig-Hoffmann disease) present with profound management of problems in feeding and swallowing,
hypotonia, flaccid weakness and global areflexia ensuring adequate nutrition, treatment for gastro
(Fig. 20.3). Respiratory weakness, poor swallowing and esophageal reflux, orthopedic care and rehabilitation,
tongue fasciculations are common. These children usually appropriate immunization and family education and
never learn to sit. Aspiration pneumonia is an important counseling. Newer genetic based therapies have been
cause of morbidity and mortality. Patients with type 2 developed for SMA like SMNl gene replacement
disease (Dubowitz disease) have onset of illness at 6--18 therapy and SMN2 upregulation/ modification. Spinraza
months of age and are usually able to sit unaided. They (Nusinersen) is an antisense oligonucleotide and is the first
may develop kyphoscoliosis, tremors (polyminimyo disease modifying therapy approved for SMA. It has
clonus), poor swallowing and respiratory insufficiency. shown significant benefits in these patients, but needs
Patients with type 3 disease (Kugelberg Welander disease) repeated intrathecal administrations.
Suggested Reading
• Darras BT, Markowitz JA, Monani UR, et al. Spinal muscular
atrophied: A clinical approach, second ed. Academic Press, San
Diego 2015: 117-145.
• Faravelli I, Nizzardo M, Comi PG, Corti S. Spinal muscular
atrophy-recent therapeutic advances for an old challenge. Nat
Rev Neurol 2015; 11: 351-359.
• Mercuri E, Bertini E, Iannaccone ST. Childhood spinal muscular
atrophy: controversies and challenges. Lancet Neural 2012; 11:
443-52.
• Patient Education Leaflets on SMA; available at http://aiims.edu/
aiims/departments/pediatrics/ped_neuro/patientedu.htm
• Scoto M, Finkel RS, Mercuri E, Muntoni F. Therapeutic approaches
for spinal muscular atrophy (SMA). Gene Ther. 2017 Sep; 24(9):
514 -9.
PERIPHERAL NEUROPATHIES
Fig. 20.3: A 5-month-old boy with motor delay and repeated Most neuropathies are chronic. Guillain-Barre syndrome
chest infections, shows generalized hypotonia, absent deep
is the most common cause of acute neuropathy. Clinical
tendon reflexes, poor muscle power and tongue fasciculations.
Note the 'frog-like' posture and subcostal retractions due to features, presentation, electrophysiological characteristics
respiratory muscle weakness. A diagnosis of spinal muscular and laboratory studies help in evaluating the diagnosis
atrophy type 1 was made (Fig. 20.4).
584 Essential Pediatrics
1
Diphtheria disease 1 and 3 Mononeuritis multiplex*
Toxic, e.g. arsenic Metachromatic
leukodystrophy
Krabbe disease
' i
Trauma Vasculitis Guillain-Barre syndrome
Adrenoleukodystrophy
Focal compression Leprosy Charcot-Marie-Tooth disease
Entrapment Leukemia, lymphoma Human immunodeficiency virus
Porphyria Deficiency of vitamin B 12 or E
Cryoglobulinemia Induced by chemotherapy
Porphyria
Diabetes
*Mononeuritis multiplex refers to the involvement of multiple separate non-contiguous peripheral nerves, either simultaneously or serially.
Fig. 20.4: Approach to peripheral neuropathies in childhood. AIDP acute inflammatory demyelinating polyneuropathy; CIDP
chronic inflammatory demyelinating polyneuropathy.
Table 20.2: Diagnostic criteria for Guillain-Barre syndrome Initiative, AFP is defined as any case of AFP in children
Features required for diagnosis <15-year-old, or any paralytic illness at any age when polio
is suspected. Common causes of AFP include Guillain
Progressive weakness in more than 1 limb (usually starts in
legs)
Barre syndrome, poliomyelitis, transverse myelitis,
traumatic neuritis, postdiphtheric neuropathy and
Areflexia (or decreased tendon reflexes) in weak limbs
nonpolio enteroviral illnesses. The differential diagnosis
Features that strongly support diagnosis varies with age (Table 20.3); distinguishing features are
Progression of symptoms over days to 4 weeks summarized in Table 20.4.
Relative symmetry of symptoms Major immunization initiatives have resulted in sharp
Mild sensory symptoms or signs decline in poliomyelitis across the world. The last case of
Autonomic dysfunction confirmed wild poliovirus (Pl type) in India was reported
Cranial nerve involvement, most common bilateral weakness
from West Bengal in January 2011. On 27 March 2014, the
of facial muscles. WHO declared India a polio-free country, since no cases
Absence of fever at the onset of neurological symptom
of wild polio were reported in three years.
Typical electrophysiological findings Acute Flaccid Paralysis (AFP) Surveillance
Abnormal or absent F wave and H reflex
AFP surveillance underpins the polio eradication initiative
Reduced motor with or without sensory nerve action potentials
(axonal variant: AMAN)
and is the chief strategy to screen for circulating wild polio
virus in the post-polio eradication era. All patients with
Prolonged distal latencies, reduced conduction velocities,
presence of conduction block or increased temporal dispersion
AFP within the last 6 months should be reported to
(demyelinating variant: AIDP) Surveillance Medical Officer of the World Health
Albuminocytologic dissociation: High concentration of protein
Organization. Other conditions that require notification
in CSF; mononuclear cell counts <50/mm3 include: (i) isolated facial palsy; (ii) isolated bulbar palsy;
(iii) unproven hypokalemia; (iv) neck flop; (v) floppy baby;
Features that raise doubt about the diagnosis (vi) flaccid hemiplegia; (vii) encephalitis; (viii) postictal
Bladder or bowel dysfunction at onset and/or persistent bladder weakness; and (ix) post-diphtheric polyneuritis.
or bowel dysfunction Surveillance is done in major four steps: (i) finding and
Fever at onset reporting children with AFP, (ii) transporting stool
Sharp sensory level samples for analysis, (iii) isolating and identifying
Marked persistent asymmetry of weakness poliovirus in laboratory, and (iv) mapping the virus to
Severe pulmonary dysfunction with limited limb weakness at determine its origin.
onset These cases are immediately investigated, within
Severe sensory signs with limited weakness at onset 48 hours of notification, by a trained medical officer. After
CSF showing increased number of mononuclear cells (>50 confirming the case as AFP, the investigator takes medical
cells/mm3) or polymorphonuclear cells history and conducts examination, and proceeds with
AMAN: Acute motor axonal polyneuropathy, AIDP: Acute inflammatory other aspects of case investigation including collection and
demyelinating polyneuropathy
Table 20.3: Differential diagnoses of acute flaccid paralysis
Suggested Reading Muscle disorders Inflammatory myopathy
Periodic paralysis
• Hughes RA. Give or take? Intravenous imrnunoglobulin or plasma
Hypokalemia
exchange for Guillain-Barre syndrome. Crit Care 2011; 15:174.
• Joint Task Force of the EFNS and the PNS. European Federation of Infections
Neurological Societies/Peripheral Nerve Society Guideline on Neuromuscular Myasthenia gravis
management of chronic inflammatory demyelinating polyradiculo junction disorders Botulism
neuropathy. Eur J Neurol 2010; 17: 356-363. Eaton-Lambert syndrome
• Yuki N, Hartung HP, Guillain-Barre syndrome N Eng J Med
2012;366:2294-2304. Neuropathies Guillain-Barre syndrome
• Wilmshurst JM, Ouvrier R. Hereditary peripheral neuropathies of Traumatic neuritis
childhood: a brief overview for clinicians. Neuromuscul Disord Postdiphtheric neuropathy
2011; 21:763-7. Porphyria
Vasculitis
ACUTE FLACCID PARALYSIS
Anterior horn Poliomyelitis
Acute flaccid paralysis (AFP) is a clinical syndrome cell disorders Nonpolio enteroviruses
characterized by rapid onset of weakness, progressing to Spinal cord disease Transverse myelitis
maximum severity within several days to weeks. The term Spinal cord compression
'flaccid' refers to the absence of spasticity or other upper Trauma
motor neuron signs. In the Global Polio Eradication
Neuromuscular Disorders 1sa1-
Table 20.4: Differentiating among common causes of acute flaccid paralysis
Poliomyelitis Gui/lain-Barre syndrome Transverse myelitis Traumatic neuritis
Fever Present; may be May have a prodromal May have a Absent
biphasic illness prodromal illness
Symmetry Asymmetric Symmetrical Symmetrical Asymmetric
Sensations Intact; may have Variable Impaired below the May be impaired in distribu-
diffuse myalgias level of the lesion tion of the affected nerve
Respiratory May be present May be present May be present Absent
insufficiency
Cranial Affected in bulbar Usually affected Absent Absent
nerves and bulbospinal
variants
Radicular signs May be present Present Absent Absent
Bladder, Absent Transient; due to Present Absent
bowel complaints autonomic dysfunction
Nerve May be abnormal Abnormal Normal Abnormal
conduction
Cerebrospinal Lymphocytic Albumino-cytologic Variable Normal
fluid pleocytosis; dissociation
normal or
increased protein
MRI spine Usually normal Usually normal Characteristic* Normal
* Local enlargement of the spinal cord and increased signal intensity over several spinal segments
transportation of stool specimens for laboratory testing, A case is classified as polio, if wild poliovirus is isolated
search for additional cases and outbreak investigation in from the stool specimen. Cases with inadequate stool
the affected community, 60 days follow-up examination, specimens and having residual weakness who have died
analysis of laboratory results and case classification. or are lost to follow up undergo additional investigation
Collection of stool specimens from every patient is an and are presented for review by the National Expert
important aspect of the eradication strategy. From every Review Committee. This committee classifies the case as
case of AFP, two stool specimens are collected, ideally compatible with polio or discarded as non-polio AFP.
within 14 days of onset of paralysis and at least 24 hours Experience indicates that at least 1 case of non-polio AFP
apart. While the optimal period for detection of poliovirus occurs for every 100 000 children aged <15 years per year
in the stool is within 14 days of onset of paralysis, specimens (background AFP rate). As per National Polio Surveillance
may be collected from any late-reported case up to 60 days Project, the non polio AFP rate, which is an indicator of
from the onset of paralysis. Beyond 60 days after paralysis, surveillance sensitivity should be equal or to more than
the likelihood of detecting poliovirus is very low. Voided 1:100, 000.
stool sample, is preferred. In cases where it is not possible,
Suggested Reading
other methods include digital extraction (when child is
constipated or dies), postmortem stool collection (contents • Chatterjee A, Vidyants, Dhole TN. Polio cardication in India.
Vaccine 2013;18:1268-75.
of large intestine) and use of rectal tube. Enema or
• Surveillance of acute flaccid paralysis, 3rd edn. New Delhi: Ministry
purgatives are not recommended. Each specimen should of Health & Family Welfare, Government of India; 2005
be 8 g each (about the size of one adult thumb), collected in
a clean, dry, screw-capped container. The specimens are NEUROMUSCULAR JUNCTION DISORDERS
collected, labeled and then transported in the 'cold chain'.
Two types of cell lines are used for poliovirus isolation. Disorders affecting the neuromuscular junction can be
The human rhabdomyosarcoma (RD) cell lines favor acquired or inherited (Table 20.5). They are usually pure
growth of all enteroviruses, and L20B cell lines favor the motor syndromes affecting proximal, bulbar or extraocular
growth of only polioviruses. If cytopathic effects appear muscles.
in L20B cell line, the isolate then goes for neutralization
test to determine the serotype (type 1, 2 or 3) using Myasthenia Gravis
appropriate antisera. Intratypic differentiation is done to About 20% patients with myasthenia have onset in
determine, if the isolate is wild or vaccine poliovirus; the childhood or adolescence. Fatigable weakness is the
former isolates undergo genetic sequencing. hallmark. Most patients have ptosis or ophthalmoplegia
s88 I Essential Pediatrics
which may be asymmetric and variable over time. of the clinical sign (ptosis, ophthalmoplegia, dysarthria)
Pupillary reactions are normal. Children may develop under observation. Edrophonium is not recommended for
diplopia on sustained gaze or continuous activity like use in infants due to high risk of arrhythmias and short
reading. On attempting to tightly close the eyes, after a duration of action which precludes objective assessment.
few minutes, the cornea may get exposed due to inability Neostigmine may also be used as a diagnostic test. The dose
to sustain contraction of orbicularis oculi (peep sign). used is 0.125 mg/kg in an infant and 0.04 mg/kg IM in an
About half of the children with ocular findings may older child. It is slower in action, with anticipated response
develop bulbar or limb girdle weakness within 2 years. in 10-15 min and maximum in 30 min (Fig. 20.6). If the
Bulbar weakness may manifest in form of difficulty in result is equivocal or negative, the dose may be repeated
swallowing and chewing and nasal and slurred speech. in 4 hours.
Limb weakness is usually symmetric and proximal. Deep
Repetitive nerve stimulation studies are abnormal in
tendon reflexes are either normal or reduced in proportion
50-70% cases with generalized myasthenia gravis. A
to the degree of muscle weakness. Respiratory muscles
decrement of >10% is characteristic. Electromyography
may also get involved and may lead to myasthenic crises.
may be normal or may show unstable or myopathic
Myasthenia gravis may be associated with thyroid dis
muscle unit action potentials. Single fiber electromyo
orders, systemic lupus erythematosus, diabetes mellitus
graphy is more sensitive and may show increased jitter
and rheumatoid arthritis. Thymomas are found chiefly in
or blocking.
adolescent onset myasthenia gravis and are rare (<5%) in
early childhood. Acetylcholine receptor (AChR) antibodies may be positive
in children with myasthenia gravis; the rates are lower in
Transitory neonatal myasthenia occurs in about 15% of
peri- and prepubertal children (50-60%). Antibodies to
babies born to myasthenic mothers. Symptoms start within
muscle-specific kinase (Anti-MuSK) are seen in 40%
a few hours after birth but may be delayed till the third
seronegative patients. X-ray chest or CT of anterior
day. These include difficulty in feeding, weak cry,
mediastinum may show thymoma or thymic hyperplasia.
hypotonia, lack of facial expression and respiratory
insufficiency. Supportive care suffices in most cases. Oral Congenital Myasthenia Syndromes
or intramuscular pyridostigmine, usually for 4-6 weeks,
The congenital myasthenia syndromes are exceptionally
may be warranted in severe cases. rare. They should be suspected in seronegative myasthenia
Edrophonium testing is usually the first test performed in gravis, floppy infant with underdeveloped muscles and
a suspected case of myasthenia gravis. The dose used is in adults with childhood history of difficulties affecting
0.1-0.2 mg/kg; may be repeated every minute to a total cranial, respiratory, truncal or limb muscles. Common
dose of 5 mg (weight <34 kg) or 10 mg (weight >34 kg). features include hypotonia, limb weakness, feeding and
Effects are seen within 10 seconds and persist till 120 respiratory difficulties, arthrogryposis, ptosis, ophthalmo
seconds. A positive result consists of transient resolution paresis, dysphagia and dysarthria. They do not respond
to steroids and other immunosuppressants. Conditions
Table 20.5: Neuromuscular junction disorders in children like endplate acetylcholinesterase deficiency and slow
channel congenital myasthenia may worsen with
Immune mediated Metabolic causes
pyridostigmine.
Myasthenia gravis Botulism
Lambert-Eaton myasthenic Organophosphate Treatment
syndrome poisoning
Snake envenomation
Cholinesterase inhibitors are the initial treatment for
Congenital myasthenic myasthenia gravis. Pyridostigmine is commonly used at
syndromes T ick paralysis
Hypermagnesemia doses of 1-7 mg/kg/day in 4 divided doses. Prednisolone,
Choline acetyltransferase at low doses (0.5 mg/kg/d), may be used in a nonacute
deficiency Drugs
setting. Azathioprine, cyclosporine, cyclophosphamide
Paucity of synaptic vesicles Aminoglycosides and mycophenolate mofetil are used as steroid sparing
Endplate acetyl Erythromycin drugs or for refractory cases. Drugs that interfere with
cholinesterase deficiency Tetracycline neuromuscular transmission (Table 20.4) should be used
Acetylcholine receptor Fluoroquinolones with caution. Thymectomy is beneficial in seropositive
defects Neuromuscular blocking
Mutations in rapsyn or patients.
agents A myasthenic crisis necessitates cardiorespiratory
plectin
Phenytoin monitoring and support. It should be differentiated from
Dok-7 deficiency D-penicillamine cholinergic crises due to overdosage of acetylcholin
Lithium esterase inhibitors. Antecedent events, predominance of
Interferon a
cholinergic symptoms, ice pack test and edrophonium
Neuromuscular Disorders I sag-
Fig. 20.6: Juvenile myasthenia gravis: A 9-year-old boy presented with drooping of eyelids, more in the evening than morning, and
restricted eye movements. Examination revealed asymmetric ptosis, external ophthalmoplegia, normal pupils and normal motor
examination. Note the improved ptosis (a) before and (b) after administration of neostigmine
challenge test help differentiate the two entities. IVIG or Suggested Reading
plasmapheresis may be required in patients with • North NK, Wang HC, Clarke N, et al. Approach to the diagnosis
myasthenic crisis. of congenital myopathies. Neuromuscular Dis 2014; 24:97-116.
• Wang HC, Dowling JM, North K, et al. Consensus statement on
Suggested Reading standard of care for congenital myopathies. J Child Neurol 2012;
• Castro D, Derisavifard, S, Anderson, M, et al. Juvenile myaesthenia 27:363.
gravis: a twenty year experience. J Clin Neuromuscular. Dis 2013;
14, 95-102. Muscle Dystrophies
• Sanders DB, Wolfe GI, Benatar M, et al. International consensus
guidelines for management of myasthenia gravis. Neurology 2016; The muscular dystrophies are diseases of muscle membrane
87:419-25. or supporting proteins characterized by pathological
evidence of ongoing muscle degeneration and regenera
MUSCLE DISORDERS
tion. Diagnosis of these disorders is based on clinical presen
Congenital Myopathies tation, genetic testing, muscle biopsy and muscle imaging.
The congenital myopathies are a diverse group of muscle
Dystrophinopathies
disorders caused by genetic defects in the contractile
apparatus of the muscle and defined by distinctive Dystrophinopathies are a group of disorders resulting
histochemical or ultrastructural changes on muscle biopsy. from mutations in the dystrophin gene (located on short
Majority of these disorders present as 'floppy infant' arm of X chromosome, Xp21). Duchenne muscular
syndrome. The common presenting features include dystrophy is the most common dystrophinopathy with
hypotonia, static or non-progressive muscle weakness and an incidence of 1 in 3500 live male births. Its allelic variant,
normal or decreased deep tendon reflexes. Respiratory Becker muscular dystrophy, differs by a later onset
insufficiency, feeding difficulties, contractures and skeletal (usually >6 years old), and slower progression (wheel
deformities may be present. They may also present in late chair confinement >15 years), a higher incidence of
childhood or adulthood (Table 20.6). myalgias, occasional rhabdomyolysis following exercise
Serum creatine kinase is either normal or mildly raised. and early cardiomyopathy.
Electromyography reveals a myopathic pattern. The Over 4700 mutations are reported in the Leiden
disorders are clinically indistinguishable; distinction is Duchenne dystrophy database. 65% of the pathogenic
possible by characteristic features on skeletal muscle biopsy changes are large partial deletions. Mutations in the
incorporating new immunohistochemical techniques and dystrophin gene can cause Duchenne muscular dystrophy
electron microscopy. Advances in molecular genetics have or Becker muscular dystrophy. The phenotypic variation
improved our understanding of congenital myopathies. is explained by the reading frame hypothesis. In >90% of
sgo I Essential Pediatrics
cases, mutations that disrupt the reading frame (frame probe amplification (MLPA) are used for detection of
shift) lead to dystrophin deficiency and cause Duchenne mutations. Muscle biopsy may be required in mutation
dystrophy. In Becker dystrophy, mutations maintain the negative cases and to differentiate between Duchenne and
reading frame (inframe mutations) and result in abnormal Becker dystrophy. Biopsy shows necrosis and attempted
but partly functional dystrophin. regeneration of individual muscle fibers, variable muscle
Children with Duchenne dystrophy become fiber diameter with both hypertrophic and small fibers,
symptomatic before age of 5 years and may have history and central nuclei. Later, almost the entire muscle is
of delayed walking. Gait disturbances become apparent replaced by fibrofatty tissue. On immunohistochemistry,
at 3-4 years of age. Waddling gait, Gower sign and calf absence of dystrophin (1, 2, 3) staining is seen in Duchenne
muscle pseudohypertrophy (Fig. 20.7) are classical dystrophy; dystrophin staining is reduced and patchy in
findings. Weakness of neck flexors is early. Other muscles Becker dystrophy.
that show hypertrophy include vastus lateralis, Management: Patients with Duchenne dystrophy requires
infraspinatus, deltoid, gluteus maximus, triceps and multidisciplinary management, aiming for maintenance of
masseter. The progression of weakness may plateau muscle strength and range of motion of joints by exercise,
between 3 and 6 years of age, followed by increasing gait physiotherapy and avoidance of prolonged immobility.
difficulty, development of contractures and lumbar Corticosteroids (prednisone, deflazacort) are the only
lordosis. The age at loss of independent ambulation in therapies proven to improve strength and prolong
untreated patients is between 8.8 and 10.5 years. After loss ambulation in children with the disease. Low dose
of ambulation, there is worsening kyphoscoliosis, prednisolone may be started with aim of preserving upper
increasing upper limb weakness and bulbar dysfunction. limb strength, reducing progression of scoliosis and
Weakness of intercostal and diaphragmatic muscles delaying decline in respiratory and cardiac functions.
with spinal deformity affects respiratory function. Supportive management also includes pulmonary and
Dropping of vital capacity <20% of normal leads to cardiac care, nutrition, calcium homeostasis, appropriate
nocturnal hypoventilation. Cardiomyopathy and immunization and orthopedic care (Table 20.7). Newer
arrhythmias are major cardiac manifestations. Children therapies include exon skipping using antisense
with deletion of exons 48 to 53 are especially prone to oligonucleotides. Phase 3 trials have shown significant
cardiac complications. The cause of death is a combination clinical benefits and Eteplirsen has been FDA approved,
of respiratory insufficiency and cardiomyopathy. Other although more clinical data is required to prove its efficacy.
features include variable degree of intellectual disability
and impaired gastric motility. Myotonic Dystrophy Type 1
Around 10% of female carriers show variable degree It is the most common muscular dystrophy seen in adults.
of weakness with elevated levels of creatine kinase, calf This disorder transmitted in an autosomal dominant
hypertrophy, myalgias and cramps and increased risk of manner, is caused by an abnormal expansion (>80) of
dilated cardiomyopathy. Rarely, the full Duchenne trinucleotide [CTG] repeats in the DMPK gene on
phenotype is present in girls with complete inactivation chromosome 19. The classic form presents in childhood with
of normal X chromosome. myotonia, facial weakness, distal limb weakness, cataracts
Serum creatine kinase levels are highly elevated (>10 (iridescent spoke-like posterior capsular cataract), frontal
times upper limit of normal), but do not correlate with baldness, endocrinopathies (testicular atrophy,
severity of the disease or response to treatment. Multiplex hyperinsulinism, adrenal atrophy and growth hormone
PCR and the more sensitive multiplex ligation dependent disturbances), cardiac arrhythmias and disturbed
Neuromuscular Disorders 1591-
Fig. 20.7: (a) Duchenne muscular dystrophy. The child presented with progressive gait difficulties and lurching. Examination shows
proximal muscle weakness, more in the lower limbs, calf hypertrophy and positive Gower sign. (b) Examination in another child
shows hypertrophy of deltoid and infraspinatus with wasting of posterior axillary fold muscles (Valley sign)
Table 20.7: Management of Duchenne muscular dystrophy diplegia, clubfoot and gastroparesis. Myotonia is absent in
Corticosteroids neonates and infants. There may be a history of decreased
fetal movements and polyhydramnios in the mother. EMG
Indication: Children >2 years with static or declining function
shows a myopathic pattern and myotonia ('revving engine'
Dose: Prednisolone 0.3-0. 75 mg/kg/day
sound). Genetic testing is confirmatory.
(initially 0.3----0.5 mg/kg/day, if non-ambulatory)
Medications that block sodium channels (procainamide,
Deflazacort, 0.9 mg/kg/day (preferred in children with
disopyramide, phenytoin, quinine, mexiletine); tricyclic
excessive weight gain or behavioral problems)
antidepressants (clomipramine, imipramine); diuretics
Ensure immunization against pneumococcus, influenza and
varicella before starting steroids (acetazolamide, thiazides) and other agents (taurine,
nifedipine, diazepam, carbamazepine, prednisone and
Monitoring albuterol) have been used for treatment, with variable results.
Pulmonary function tests: Every 6 months if non-ambulatory;
annually in ambulatory patients Facioscapulohumeral Muscular Dystrophy
Echocardiography. Once in 2 yr for <10 yr of age; annually if The clinical spectrum of this autosomal dominant disorder
>10 years ranges from asymptomatic children to wheelchair bound
Serum calcium, phosphate, 25(0H) vitamin D3 (biannually) patients. The age at onset is variable. The disease may start
DEXA scan annually with asymmetric facial weakness followed, sequentially,
Physical therapy by scapular fixator, humeral, truncal and lower limb
weakness. Biceps and triceps are typically involved with
Effective stretching and appropriate positioning at various sparing of deltoid and forearm muscles resulting in the
joints, assistive devices to prevent contractures, avoid high
"Popeye" arm appearance. Lower abdominal muscles are
resistance strength training
weaker than upper abdominal muscles resulting in Beevor
Surgery: For fixed contractures and spinal deformities
sign. Side-to-side asymmetry of muscle weakness is typical
Other components (Fig. 20.8). Other features include high frequency hearing
Respiratory and cardiac care loss, Coats disease (retinal telangiectasia, exudation and
Management of gastrointestinal problems detachment), atrial arrhythmias and restrictive respiratory
Psychosocial management disease. The diagnosis is confirmed by demonstrating the
Family education and genetic counseling shortening of the macrosatellite repeat D4Z4 which is
normally in one allele of 4q35. Treatment is supportive.
Newer therapies
Exon skipping, gene therapy, cell therapy, pharmacological Limb Girdle Muscular Dystrophy
approaches (utrophin upregulation, read through Limb girdle muscular dystrophy is a group of clinically
compounds, myostatin inhibitors) heterogeneous syndromes with autosomal dominant or
recessive inheritance. Most childhood onset limb girdle
gastrointestinal motility. The congenital form may present dystrophies are associated with predominant lower
with respiratory failure, poor feeding, hypotonia, facial extremity weakness. Cardiac or other systemic involvement
-592 Essential Pediatrics
Fig. 20.8: Facioscapulohumeral dystrophy: (a) Note the facial weakness and inability to completely close the eyes;
(b) Asymmetric scapular winging
is variable. Serum creatine kinase is modestly elevated immune system. Dermatomyositis is the most common
but can be high in the sarcoglycanopathies, dysferlino pediatric inflammatory myopathy, which typically affects
pathy and caveolinopathy. Autosomal recessive limb skin and muscle but may involve joints, gut, lung, heart
girdle dystrophies have early onset, rapid progression and and other internal organs (see Chapter 22).
higher creatine kinase values. Treatment is symptomatic.
Metabolic Myopathies
Congenital Muscular Dystrophy The metabolic myopathies are a group of muscle disorders
These patients usually present at birth or in first year of resulting from failed energy production related to defects
life. Infants show hypotonia, weakness, arthrogryposis, in glycogen, lipid or mitochondrial metabolism. The
bulbar dysfunction or respiratory insufficiency. Weakness symptoms arise due to a mismatch between the rate of
is static or slowly progressive. Diagnosis is supported by ATP utilization and the capacity of muscle metabolic
dystrophic myopathic features on muscle biopsy, elevated pathways to regenerate ATP. Affected children and adults
creatine kinase levels and exclusion of common present with exercise intolerance, weakness and
myopathies of newborn. myoglobinuria; newborns and infants present with severe
multisystem disorders. Most metabolic myopathies have
Suggested Reading intermittent rather than static findings. Some children
• Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, present with progressive proximal muscle weakness
Brumbaugh D, et al. Diagnosis and management of Duchenne mimicking a dystrophy or an inflammatory myopathy.
muscular dystrophy, part 1: diagnosis, and neuromuscular, In patients with glycolytic or glycogenolytic defects,
rehabilitation, endocrine, and gastrointestinal and nutritional
management. Lancet Neurol. 2018 Mar;17(3):251-67. symptoms are induced by either brief isometric exercise,
• Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Colvin such as lifting heavy weights, or by less intense but
MK, et al. Diagnosis and management of Duchenne muscular sustained dynamic exercise. In disorders of lipid
dystrophy, part 3: primary care, emergency management, metabolism, the abnormalities are induced by prolonged
psychosocial care, and transitions of care across the lifespan. Lancet exercise and fasting. Investigations include serum creatine
Neurol. 2018 Feb 1; pii: 51474-4422(18)30026-7.
• Bonneman CG, et al. Diagnostic approach to the congenital kinase and ammonia, urine myoglobulin, tandem mass
muscular dystrophies. Neuromuscul Disord. 2014;24(4),289-311. spectroscopy, gas chromatography mass spectrometry,
• Gloss D, Moxley RT, Ashwal S, Oskoui M. Practice guideline update electrophysiological studies, forearm ischemia exercise
summary: Corticosteroid treatment of Duchenne muscle test, muscle biopsy and molecular studies.
dystrophy. Neurol 2016;86:465-72.
• Patient education leaflets is available at http://aiims.edu/aiims/ Suggested Reading
departments/pediatrics/ped_neuro/patientedu.htm
• Thornton CA, Myotonic dystrophy. Neurol. Clin. 2014;32(3):705-719. • Berardo A, DiMauro S, Hirano M. A diagnostic algorithm for
metabolic myopathies. Curr Neural neuroscience Rep. 2010
Inflammatory Myopathies Mar;10(2):118-26.
• Lilleker JB, Keh YS, Roncaroli F, Sharma R, Roberts M. Metabolic
The inflammatory myopathies are a diverse group of myopathies: a practical approach. Practical Neurology. 2017 Dec
disorders in which muscle appears to be injured by the 8; practneurol-2017-001708.
Chapter
21
Childhood Malignancies
Rachna Seth
Leukemias, the most common cancer in children, are function and marrow failure. They are classified as
malignant neoplasms arising from clonal proliferation of lymphoid or myeloid depending on the lineage of the
abnormal hematopoietic cells, disruption of normal marrow progenitor stem cell involved and as acute or chronic
depending on their natural history. Acute lymphoblastic Acute Myeloid Leukemia (AML)
leukemia (ALL) and acute myeloid leukemia (AML) are Acute myeloid leukemia (AML) also termed as acute non
common; a small proportion has chronic myeloid leukemia lymphoblastic leukemia, the second most common type
(CML) and juvenile myelomonocytic leukemia (JMML).
of leukemia in children, accounts for 15-20% of leukemia
Acute Lymphoblastic Leukemia (ALL) in children. AML is much more complex and resistant
disease than ALL and results from clonal proliferation of
ALL is the most common childhood malignancy accounting
hematopoeitic precursors of myeloid, erythroid and
for one-fourth of all childhood cancers and three-fourths of
megakaryocytic lineage. Intensive myelosuppressive
all newly diagnosed patients with acute leukemia. Its
induction and post-remission therapy result in long-term
incidence is approximately 3-4 cases per 100,000 children
below 15 years of age. Boys have higher rates than girls, survival in 40-50% patients.
especially in adolescents with T-cell ALL. There is a peak in
incidence of childhood ALL between2 and 5 years due to ALL Etiopathogenesis
associated with a pre-B lineage (common ALL). Significant The etiology of acute leukemia is unknown in the majority.
progress in treatment of ALL in last two decades has lead to Several genetic syndromes are associated with an
cure rates of over 80% in most developed countries. increased risk of leukemia (Table 21.3).
Childhood Malignancies 1595-
Table 21.3: Genetic and environmental risk factors for childhood leukemia
Genetic Environmental
Down syndrome Ionizing radiation
Fanconi anemia Alkylating agents: Cyclophosphamide, ifosfamide, carboplatin, procarbazine
Shwachman-Diamond syndrome Epipodophyllotoxins: Etoposide, tenoposide
Bloom syndrome Nitrosourea: Nitrogen mustard
Ataxia telangiectasia Benzene
Diamond-Blackfan anemia
Kostmann syndrome
Li-Fraumeni syndrome
Severe combined immune deficiency
Paroxysmal nocturnal hemoglobinuria
Neurofibromatosis type I
Fig. 21.2: (a) Bone marrow from a child with acute lymphoblastic leukemia shows reduced normal marrow elements which are
replaced by lymphoblasts. The neoplastic lymphoblasts are slightly larger than lymphocytes and have round or convoluted nuclei,
fine chromatin, often with a smudged appearance, inconspicuous nucleoli and scant basophilic cytoplasm. (b) Peripheral smear
of a 6-year-old child diagnosed with acute myeloid leukemia (AML-M2 ) showing a myeloblast containing an Auer rod (pink-colored
aggregated lysosome)
Fig. 21.3: (a) An 8-year-old child presented with acute lymphoblastic leukemia, prolonged fever and generalized lymphadenopathy;
(bl A 6-year-old child with acute myelold leukemia showing bilateral subconjunctlval bleeds. (c) A 9-year-old child with acute
myeloid leukemia showing gum hypertrophy; (d) A 10-year-old girl with acute myeloid leukemia presenting with proptosis (chloroma
orbit)
(superior mediastinal syndrome). A large mediastinal thrombocytopenic purpura (ITP), aplastic anemia and
mass may cause superior vena cava syndrome with facial viral infections (e.g., cytomegalovirus) that might result
edema and plethora, throbbing headache, conjunctiva in leukemoid reactions and pancytopenia. ITP is the most
congestion and dilated neck veins. common cause of acute onset petechiae and purpura in
Patients with high tumor burden may present with very children. There is no evidence of anemia and have normal
high total white cell (TLC) count (hyperleukocytosis, TLC TLC and differential count. Bone marrow smear reveals
>100 000 I mm3) or tumor lysis syndrome. normal hematopoiesis and normal or increased number
A few patients (5-10%) have central nervous system of megakaryocytes. Aplastic anemia may present with
involvement at diagnosis; they present with cranial nerve pancytopenia, or juvenile rheumatoid arthritis with fever,
palsies, seizures and occasionally raised intracranial joint symptoms (limp, arthralgia or arthritis), pallor,
pressure (headache, vomiting, irritability, papilledema). splenomegaly and leukocytosis. ALL should be
The diagnosis of CNS leukemia is made on examination distinguished from other malignancies (neuroblastoma,
of the cerebrospinal fluid. Overt testicular leukemia is seen non-Hodgkin lymphoma, rhabdomyosarcoma, Ewing
in -1 % boys, when it presents with firm, painless, sarcoma and retinoblastoma) that present with bone
unilateral or bilateral swelling of the testes; the diagnosis marrow involvement.
is confirmed on biopsy. Rare sites of extramedullary
Laboratory Features and Diagnosis
involvement include heart, lungs, kidneys, ovaries, skin,
eye or the gastrointestinal tract. Clinical presentation, peripheral blood counts and
The clinical presentation of AML is similar to ALL but morphology are indicative of the diagnosis of ALL
more likely to have high TLC and incidence of infections (Table 21.8). Children may present with pancytopenia or
(Fig. 21.3b). Unlike ALL, lymphadenopathy and massive
Table 21.8: Evaluation of a child with suspected leukemia
hepatosplenomegaly is not very common. However, infants
and toddlers with M4 and M5 AML subtypes have more • History and physical examination
organomegaly, high leukocyte counts and CNS disease at • Complete blood count and differential count
diagnosis. Gum hyp ertrophy a common feature of the M4 • Peripheral smear examination (cell morphology), leukocyte
subtype (Fig. 21.3c). Disseminated intravascular platelet count, immune phenotype
coagulation may occur with any subgroup, but is common • Chest X-ray (include lateral view, if mediastinal mass is present)
in acute promyelocytic leukemia (M3). Chloromas are • Blood electrolytes, urea, creatinine, uric acid, lactate
localized collections of leukemic cells that which may occur dehydrogenase, calcium, phosphate, bilirubin, and
at any site including CNS, neck, bones (typically orbit) and oxaloacetate and pyruvate transaminases
skin (Fig. 21.3d). Patients with high TLC may present with • Prothrombin time, coagulation profile
signs of leukostasis such as pulmonary infiltrates causing • Bone marrow aspirate: Morphology, immunophenotype,
respiratory distress or stroke. Central nervous system cytogenetics, FISH/PCR for specific translocations
involvement may occur in up to 15% patients. • Bone marrow biopsy
• Serology: HIV antibody, hepatitis B surface antigen and
Differential Diagnosis antibody, hepatitis C antibody
The clinical profile of ALL may mimic infectious • CSF cytology (give first dose of methotrexate with diagnostic
tap)
mononucleosis, acute infectious lymphocytosis, idiopathic
sga I Essential Pediatrics
and presence of minimal residual disease at end of show better outcomes than AML in those without trisomy
induction by PCR assay or by flow cytometry (Table 21.9). 21. Children with trisomy 21 are also at higher risk for
-15-20% patients with ALL relapse, most commonly ALL. However, these patients do not show a preleukemic
in the bone marrow followed by CNS and testis. The phase and their outcome is inferior to those without Down
prognosis for patients who relapse depends on the site syndrome and ALL.
and time of relapse. Early bone marrow relapse before
completing maintenance therapy has the worst prognosis; Suggested Reading
late relapses after cessation of maintenance therapy show • Arora RS, Arora B. Acute leukemia in children: A review of the
better (30-40%) survival. Relapse at extramedullary sites, current Indian data. South Asian J Cancer. 2016; 5(3):155-160.
particularly testis, is more favorable in terms of survival. • Seth R, Singh A. Leukemias in children. Indian J Pediatr 2015; 82(9):
Late isolated CNS relapse (> 18 months) can be effectively 817-24.
• Taga T, Tomizawa D, Takahashi H, Adachi S. Acute myeloid
cured with cranial irradiation and systemic chemotherapy. leukemia in children: Current status and future directions. Pediatr
Therapy for relapse is more aggressive than first line Int 2016; 58: 71-80.
therapy. • Pui CH, Carroll WL, Meshinchi S, Arced R. Biology, risk
Adverse prognostic factors in AML include: Older age, stratification and therapy of pediatric acute leukemias: an update.
obesity, MO and M7 subtype, and CNS disease at J Clin Oncol 2011; 29:551-65.
diagnosis. Lack of minimal residual disease, M3 subtype, • Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, et
al. Childhood acute lymphoblastic leukemia: Progress through
AML associated with Down syndrome and presence of collaboration. J Clin Oncol. 2015;33:2938-48.
favorable cytogenetics [Invl6, t(8;21), t(15;17)] are
associated with favorable outcome. CHRONIC MVELOID LEUKEMIA
Late Effects of Treatment Chronic leukemias constitute 3% of leukemias in
Long-term effects of treatment are of concern.Patients who childhood. Chronic myeloid leukemia (CML) is a clonal
have received cranial irradiation at a young age are at risk disorder that originates in a pluripotent hematopoietic
for cognitive and intellectual impairment and development stem cell and is characterized by myeloid hyperplasia of
of CNS neoplasms. There is a risk of secondary AML after the bone marrow, extramedullary hematopoiesis,
intensive use of epipodophyllotoxins (etoposide, elevation of white blood cell count (with appearance of
teniposide). Endocrine dysfunction leads to short stature, the complete range of granulocyte precursors in the
obesity, precocious puberty, osteoporosis, thyroid peripheral blood). CML bears a specific cytogenetic
dysfunction and growth hormone deficiency. Patients marker that is known as the Philadelphia (Ph)
with prior therapy with an anthracycline are at risk of chromosome. Ionizing radiation is implicated in the
cardiac toxicity. pathogenesis of CML. Two main forms of well differen
tiated myelogenous leukemia are recognized.
Down Syndrome and Acute Leukemia
Adult CML: The condition is clinically and hematologically
Children with Down syndrome (trisomy 21) have a 15-20 comparable to the adult form of chronic myelogenous
fold higher risk of acute leukemia, compared to the general leukemia and occurs in children above the age of 4 years
population with a cumulative risk of -2.1%. The ratio of (Fig. 21.5a).
ALL to AML in Down syndrome is similar to that in other
children. One-half to two-thirds patients of acute leukemia Juvenile CML: This form presents in infancy and early
in children with Down syndrome are ALL, the exception childhood, usually below the age of 4 years, and has a
being the first 3 years of life when AML predominates more rapid course (Fig. 21.5b).
and exhibits a distinctive biology. Approximately 10%
children with Down syndrome develop a preleukemic Adult Variety of CML
clone, transient myeloproliferative disorder with somatic Though the adult variety of CML is a common leukemia
mutations in hematopoeitic transcription factor GATAl. in adults, it is rare in children accounting for 3-5% cases.
These children present with high leukocyte count, CML patients show a triphasic course: The usual phase at
circulating blasts in peripheral blood, hepatospleno diagnosis (-85% patients) is the chronic phase, which may
megaly, effusions, anemia and thrombocytopenia in the progress to the accelerated phase and blast crisis
neonatal period, which resolves by 3 months. About 20% resembling acute leukemia in which myeloid or lymphoid
patients with the transient myeloproliferative disorder blasts proliferate in an uncontrolled manner.
develop AML. AML in children with Down syndrome Children present in the chronic phase with fatigue,
generally develops before 5 years of age, has low leukocyte malaise, weight loss, excessive sweating, abdominal
count and does not have CNS involvement; two-thirds fullness, and bleeding due to platelet dysfunction;
show acute megakaryocytic leukemia (FAB M7). Since splenomegaly is usually massive. Symptoms of leukostasis
blast cells in these patients have high sensitivity to such as headache, dizziness and visual disturbances may
medications, they require less intense chemotherapy and occur rarely. Symptoms in the accelerated phase or blast
Childhood Malignancies lso1-
count shows all forms of myeloid cells from promyelocytes,
myelocytes and metamyelocytes to polymorphonuclear
leukocytes; basophilia is common. Genetic testing for the
Philadelphia (Ph) chromosome in conjunction with
marrow morphology allows confirmation of the diagnosis.
Treatment
The aim of treatment is to control increasing white cell
counts. First and second-generation oral tyrosine kinase
inhibitors (TKI) are the treatment of choice. Majority of
patients achieve complete hematologic and cytogenetic
response following imatinib therapy and the rate of
progression to accelerated or blast crisis is reduced. The
starting dose of imatinib is 340 mg/m2/day.Bone marrow
cytogenetics is monitored every 6 months until a complete
cytogenetic response is obtained. Survival after
development of accelerated phase is usually less than a
year and after blast transformation only a few months.
Allogeneic stem cell transplantation is recommended for
patients who do not respond to TKI.
most common type in developed countries, whereas in lymphocyte depletion), bulky mediastinal disease,
developing countries including India, the mixed cellularity extensive splenic involvement and more than 5 nodal sites
type accounts for -60% cases. On immunophenotyping, in stage III. Bone involvement by classical HL may cause
the classic subtypes are positive for CD15 and CD30 and pain. Bone marrow involvement rarely results in
may be positive for CD20, whereas NLPHL is negative cytopenias and has been associated with a variety of
for CD15 and CD30 but positive for CD20 and CD45. paraneoplastic syndromes.
Fig. 21.6: (a) This l 0-year-old boy presented with fever and significant bilateral cervical lymphadenopathy. Lymph node biopsy
showed features of Hodgkin lymphoma; (bl A l 0-year-old boy with fever, significant right cervical lymphadenopathy was diagnosed
as Burkitt lymphoma; (c) Chest X-ray of a 7-year-old boy with mediastinal mass and left-sided pleural effusion. He was diagnosed
as T lymphoblastic lymphoma on lymph node biopsy
604 Essential Pediatrics
Table 21.13: Diagnostic evaluation for children with Hodgkin approach is elimination of radiation-associated adverse
lymphoma effects like myocardial dysfunction, musculoskeletal
Physical examination; measure size and number of lymph growth deficits and second malignancy.
nodes Treatment for patients with favorable clinical
Complete blood counts, ESR, CRP, liver and renal functions, presentation (localized node involvement: Stage I, II, IIIA;
alkaline phosphatase, LDH absence of B symptoms; no evidence of bulky disease)
Biopsy of lymph node or involved extranodal site consists of 2-4 cycles of chemotherapy (ABVD/others) and
low dose involved field radiation. Unfavorable clinical
Chest X-ray posteroanterior and lateral views; measure
mediastinal mass thoracic cavity ratio
presentation (B symptoms; bulky mediastinal/peripheral
lymphadenopathy; extranodal extension of disease;
CT scan: Neck, chest and abdomen
advanced disease: Stage IDB-IV) are treated with 4--6 cycles
Bone marrow biopsy (all children except stages IA, IIA) of ABVD with/without radiotherapy. The role of
Bone scan (recommended in children with bone pains or raised additional radiotherapy in stage III and IV lymphoma is
alkaline phosphatase) controversial. Hematopoietic stem cell transplantation
CT scan brain, cerebrospinal fluid examination (if indicated (HSCT) is offered to patients who relapse or for those who
clinically) are refractory to primary therapy.
Gallium scan, positron emission tomography (PET ) (identifies
more sites than conventional imaging; accurate for residual Prognostic Factors
mass) Factors affecting outcome include pretreatment factors
PET-CT identifies more sites of initial disease than conventional (advanced stage, presence of 'B' symptoms, bulky disease,
imaging and is accurate in detecting tumor tissue in post extranodal extension, male sex and elevated ESR) and
therapy masses. Rapid early response (significant reduction treatment related factors (rapidity of response to initial
in disease volume and PET negativity within 1-2 chemotherapy cycles of chemotherapy). Hodgkin lymphoma is one of
cycles) has favorable outcome. PET-CT is advised �3 weeks
the most curable cancers of childhood, especially if
following completion of chemotherapy, and 8-12 weeks
postradiation
detected in early stages. Appropriate staging, availability
of advanced techniques of investigation and use of risk
Surgical staging with lymph node sampling and lymph
adapted treatment protocols have resulted in excellent
angiography (in selected cases)
overall survival.
therapy ranges between 15 and 25 Gy with modifications Suggested Reading
based on patient age, response to chemotherapy and
• Metzger M, Krasin MJ, Hudson MMz Onciu M. Hodgkin
presence of bulky/residual tumor. Several studies have lymphoma. In: Principles and Practice of Oncology. Eds. Pizzo PA,
demonstrated that chemotherapy alone is effective therapy Poplack DG. Lippincott Williams Wilkins, Philadelphia, 2011; pp
for pediatric Hodgkin lymphoma. The advantage of this 638-62.
Table 21.16: St. Jude staging system for childhood non-Hodgkin lymphoma
Low risk (localized)
I Single tumor (extranodal), single anatomic area (nodal) excluding mediastinum or abdomen
II Single tumor (extranodal) with regional node involvement
Primary gastrointestinal tumor (completely resected with or without involvement of mesenteric nodes
Two/more tumors/nodal areas on one side of the diaphragm
High risk (advanced)
Ill All primary intrathoracic (mediastinal , pleural and thymic) tumors
All extensive primary intra-abdominal disease
All paraspinal or epidural tumors regardless of other tumor sites
Two/more nodal or extranodal areas on both sides of diaphragm
IV Any of the above with central nervous system and/or bone marrow involvement
Fig. 21.7: Retinoblastoma: (a) Familial retinoblastoma in two siblings; (b) A 3-year-old boy showing leukocoria; (c) A 3-year-old boy
with phthisis bulbi
sos I Essential Pediatrics
Diagnosis Treatment
The diagnosis is based on history, clinical examination and The aim of treatment is survival with eradication of
imaging. Ocular examination of both eyes should be done disease; maintenance of vision and preservation of globe
under anesthesia. Imaging studies such as ultrasound, and vision are secondary goals. Treatment depends on
CT /MRI (preferred) scans are used to assess the orbital, size, location, extent of the tumor and whether it is
optic nerve and for intracranial extension. Rarely children hereditary or sporadic. Retinoblastoma is curable when
with hereditary retinoblastoma show a pineal tumor the disease is intraocular.
(trilateral retinoblastoma) that is detected on imaging. CSF Laser therapy: Argon or diode laser is the primary
and bone marrow examination are done only if indicated treatment for smaller tumors, but is also sometimes used
on clinical examination or imaging. Biopsy or aspiration after chemoreduction.
cytology is not routinely required unless the diagnosis is
in doubt. Occasionally an adjacent lymph node needs to Cryotherapy: A special probe applied through the sclera
be aspirated for metastasis. Screening for RB1 mutations to produce low temperatures (--60 to -80 ° C) is suitable for
on peripheral blood or tumor tissue, helps differentiate tumors smaller than 4 disc diameters close to the retina.
somatic from germline mutations. Chemotherapy: Chemotherapy enables salvaging the
affected eye, avoiding enucleation or external beam
Staging radiotherapy and risk of second malignancies. Systemic
Retinoblastoma may be intraocular or extraocular. chemotherapy most often comprises a combination of
Intraocular retinoblastoma denotes that the disease is vincristine, carboplatin and etoposide. Chemotherapy may
limited to the eye, and is confined to the retina or extends also be used for chemoreduction, as an adjunct modality
to the choroid, ciliary body, anterior chamber and optic or for therapy of metastasis. Newer routes of drug
nerve head (Tables 21.18 and 21.19). Extraocular (melphalan, carboplatin) administration by periocular,
retinoblastoma refers to extension of the illness beyond intravitreal and intraophthalmic artery injection have
the eye, including tissues around the eye (orbital improved outcomes in intraocular retinoblastoma.
retinoblastoma) or spread to the central nervous system, Enucleation: In cases of unilateral disease with large
bone marrow or lymph nodes (metastatic retino tumors where no useful vision can be preserved,
blastoma). enucleation is performed early. In children with bilateral
Childhood Malignancies 1609-
disease systemic chemotherapy is used initially, followed kidney tissue called nephrogenic rests. WTl is the best
by local treatment with laser photocoagulation or characterized Wilms tumor gene, with mutations of this
cryotherapy in order to preserve vision. The eye with the gene observed in approximately 20% of Wilms tumors,
no useful vision should be enucleated in these cases. occasionally in association with mutations in CTNNBl
Radiotherapy: External beam radiotherapy is considered, (catenin beta l; 3p22.l) and WTX (gene on X-chromosome).
if chemotherapy and focal therapy fail. Radiotherapy may The WTl gene is located on chromosome llp13 and
encodes for a transcription factor that is critical for normal
lead to orbital deformity, sicca syndrome, cataracts,
radiation retinopathy, neovascular glaucoma and risk of development of kidneys and gonads. WT2 is localized to
a second malignancy. a cluster of genes at llpl5. Patients with WTl mutations
have higher risk of recurrence and bilateral disease.
Hematopoietic stem cell transplantation: Patients with Children with some genetic syndromes are predisposed
extraocular disease have poor prognosis with respect to to Wilms tumor. These include WAGR (Wilms tumor,
survival. Those with regional extraocular disease aniridia, genitourinary abnormalities and mental
(involving orbit, optic nerve or preauricular region) may retardation, WTl delllp13), Denys-Drash syndrome
be treated with a combination of conventional (renal failure, mesangial sclerosis, male hermaphroditism,
chemotherapy and external beam radiotherapy. Patients WTl missense mutation) and Beckwith-Wiedemann
with distant metastasis require high dose chemotherapy, syndrome (hemihypertrophy, macroglossia, omphalocele,
external beam radiotherapy and hematopoietic stem cell organomegaly, WT2 delllp15.5). Loss of heterozygosity
transplantation. of lp and/or 16q and high expression of telomerase are
associated with poorer outcome in Wilms tumor.
Prognosis
Most tumors that are confined to the eye are cured. Focal Pathology
therapy or enucleation is curative in more than 95% of The histopathology may be favorable (differentiated
patients with unilateral disease. Cures are infrequent when blastemal, stromal and epithelial cells) or unfavorable
extensive orbital or optic nerve extension has occurred or (diffuse or focal anaplasia, clear cell sarcoma, rhabdoid
the patient has distant metastasis. tumor). Most tumors are unicentric; 11% are multicentric.
Genetic counseling is an important component of
management. All first degree relatives of children with Diagnosis
known or suspected hereditary retinoblastoma should Most patients present with an asymptomatic abdominal
have regular examination for evidence of malignancy until mass detected by their parents or physician during routine
7 years of age. examination. Features at diagnosis include: hematuria
(10-25%), hypertension (25%), abdominal pain (30%),
Suggested Reading fever (20%), anorexia and vomiting. Wilms tumor should
• Bhavna Chawla, Rachna Seth, Laxmi Moksha. Chemotherapy for be considered in any child with abdominal mass. Tumor
Ocular Cancers. Trimurthy Velpandian. Pharmacology of Ocular
thrombus extending into the inferior vena cava is found
Therapeutics. Adis Springer. 2016:333-58.
• Canturk S, Qaddoumi I, Khetan V, et al. Survival of retinoblastoma in 4-10%. Other features at presentation include anemia,
in less developed countries, impact of socioeconomic and health thrombocytosis, acquired deficiency of von Willebrand
related indicators. Br J Ophthalmol 2010; 94; 1432-36. factor and factor VII, and polycythemia. Differential
• Chawla B, Hasan F, Azad R, et al. Clinical presentation and survival
of retinoblastoma in Indian children. Ophthlmol 2016;100:172-78.
• Dimara H, Kimani K, Dimba EAO, et al. Retinoblastoma. Lancet Table 21.20: Evaluation of Wilms tumor
2012; 379:1436-46.
Investigation Purpose
WILMS TUMOR Abdominal ultrasound Organ of origin, identify
contralateral kidney
Wilms tumor or nephroblastoma is the commonest Location of tumor thrombus in
malignant neoplasm of the kidney and second vena cava
most common abdominal malignancy in children. CT scan Localization of tumor and
Approximately 6% of all childhood cancer is Wilms tumor extent of spread
with a peak incidence at 2-3 years of age. Individuals with Chest X-ray Pulmonary metastasis
horseshoe kidney have a higher risk of Wilms tumor.
Bone scan, skeletal survey Bone metastasis, especially in
Genetics clear cell sarcoma
Brain imaging (MRI, CT scan) Brain metastasis in rhabdoid
While a vast majority of Wilms tumors are sporadic, tumor and clear cell sarcoma
1-2% may be familial. Familial tumors occur at an earlier
Fine needle aspiration cytology Cytological confirmation of
age and have a high propensity for being bilateral. The
tumor prior to chemotherapy
tumor is thought to develop in the foci of embryonal
610 Essential Pediatrics
Table 21.21: Staging for Wilms tumor (National Wilms Tumor Study Group)
Stage I Tumor confined to the kidney and completely resected
Renal capsule and sinus vessels not involved beyond 2 mm
Regional lymph nodes dissected and negative
Stage II Tumor extends beyond the kidney but is completely resected with negative margins and lymph nodes
At least one of the following: (i) Penetration of renal capsule; (ii) invasion of renal sinus vessels
Stage Ill Residual tumor abdomen following surgery confined to abdomen
Lymph nodes (renal hilum, para-aortic chain, beyond) show tumor
Diffuse peritoneal contamination by tumor
Implants on peritoneal surface
Tumor extends beyond surgical margins (microscopy, gross examination)
Tumor not completely resected because of infiltration of vital structures
Stage IV Hematogenous metastasis, metastasis to distant lymph nodes
Stage V Bilateral renal involvement at time of initial diagnosis
diagnosis includes neuroblastoma and other flank masses • Fernandez C, Geller JI, Ehrlich PF, Hill AD, Kalapurakal JA, Grundy
including hydronephrosis, multicystic kidney, and PE, Dome JS. Renal tumors.In: Principles and Practice of Pediatric
Oncology. Eds. Pizzo PA, Poplack DG, Lippincott Williams and
rarely abdominal lymphoma and retroperitoneal
Wilkins, Philadelphia, 2011; 861-85.
rhabdomyosarcoma. Features of associated syndromes
• Perlman EJ, Grundy PE, Anderson JR et,al. WTl mutation and
may be present in 10-20%. Evaluation and staging of llp15 loss of heterozygosity predict relapse in very low risk
Wilms' tumor are discussed in Tables 21.20 and 21.21. Wilms tumor treated with surgery alone. J Clin Oncol 2011;
29:698-703.
Treatment • Prasad M, Vora T, Agarwala S, et al. Management of Wilms Tumor:
The approach to treatment differs across the world. While CMR Conseesus document. Indian J Pediatr 2017;84:437-45.
the Childrens Oncology Group recommends upfront
resection of the tumor, the International Society of NEUROBLASTOMA
Pediatric Oncology (SIOP) recommends preoperative
Neuroblastoma, derived from the neural crest, is the most
chemotherapy without biopsy. The outcome with both
approaches is similar. Upfront surgery provides accurate common intra-abdominal and extracranial solid tumor in
diagnosis prior to starting chemotherapy while children, accounting for 7-8% of all cancers. This is a
preoperative chemotherapy shrinks the tumors making disease of early childhood with approximately 90%
surgery easier and decreasing the risk of spillage and patients presenting before 5 years of age and almost 50%
rupture. Radiation has limited role in the management. within the first 2 years of life. The etiology is not known
Patients <2-year-old with tumors <550 g with favorable but familial cases occur, and there is association with
histology are at low risk and may be treated with neurofibromatosis, Hirschsprung disease, heterochromia,
nephrectomy alone followed by close observation. Chemo fetal hydantoin and fetal alcohol syndromes and
therapy for other stages I or II patients includes vincristine Friedreich ataxia. Rearrangement or deletion of the short
and actinomycin for 18 weeks. Doxorubicin and arm of chromosome 1 is present in 80% patients.
abdominal radiation are additional therapies for stage ill Neuroblastoma is one of the few cancers that may undergo
illness. Cyclophosphamide, carboplatin and etoposide are spontaneous regression.
used for anaplasia and metastatic disease. Pulmonary
The pathology varies from extremely undifferentiated
radiation is used for pulmonary metastasis.
small round blue cell tumor (neuroblastoma) to tumors
Overall -90% of children with Wilms' tumor are long
with mature Schwannian stroma with ganglion cells
term survivors. Young age, low stage and low weight
(ganglioneuroblastoma and ganglioneuroma). The
( <550 g) are favorable prognostic factors. Presence of
characteristic histopathologic feature is the Homer-Wright
anaplasia and loss of heterozygosity of lp or 16q increase
pseudorosettes which are circular groupings of dark
the risk of recurrence. Survivors of Wilms' tumor have
tumor cells surrounding pale neurofibrils. Neuro
relatively few late effects. Cardiotoxicity, renal failure,
blastomas can resemble other small round blue cell tumors
second malignancy and pulmonary toxicity is reported in
survivors of advanced stage disease who receive intensive such as rhabdomyosarcoma, Ewing sarcoma and non
chemotherapy and radiation. Hodgkin lymphoma, but are differentiated by
characteristic immune histochemistry. The pathology is
Suggested Reading closely correlated with prognosis, and tumors that show
• Buckley KS. Pediatric genitourinary tumors. Curr Opin Oncol 2012; better differentiation, more Schwannian stroma and low
24:291-96. mitosis-karyorrhexis index have favorable outcome.
Childhood Malignancies ls11-
Fig. 21.8: Neuroblastoma. (a) 'Raccoon's eye' (left eyelid) in a child with metastatic disease; (bl CT abdomen showing a suprarenal
mass suggestive of neuroblastoma
Quantitation of serum neuron-specific enolase and children from infancy to 5 years of age. These may present
ferritin, amplification of Myc-N gene, tumor cell ploidy as an asymptomatic abdominal mass; as disease progresses
and age-based histologic classification are of prognostic patients have abdominal pain, weight loss, vomiting and
value. Patients with neuroblastoma can be divided into anorexia. Serum a fetoprotein (AFP) is a useful diagnostic
those with favorable and unfavorable features. The former, marker for disease assessment during and after completion
characterized by young age (<1.5 years), favorable stage of therapy. Tumor thrombi may extend into hepatic veins
(I, II and IV-S) (Table 21.22), normal levels of ferritin and and inferior vena cava. Liver may become involved due to
favorable histology, has a survival expectancy of 90% or metastasis from cancers which include lymphoma
more. Older patients with stage III or IV disease, serum (Hodgkin and non-Hodgkin lymphoma) neuroblastoma,
ferritin >150 ng/mL and tumors of unfavorable histology Wilms tumor and desmoplastic small cell tumor. Benign
have survival rates of 20% or less. neoplasms of liver include mesenchymal hamartoma,
hemangioma, hemangioendothelioma, adenoma and
Treatment teratoma.
Treatment modalities include chemotherapy, surgery and Diagnostic imaging includes CT or MRI of the abdomen
radiation therapy. Localized neuroblastoma can be treated along with the CT of the chest for evaluation of metastatic
by surgery alone and does not require chemotherapy disease. Complete resection of the tumor either by partial
(Table 21.23). Patients with stage IV-S just require careful hepatectomy or by liver transplantation is critical for
observation. Chemotherapy is the chief of treatment for successful treatment.
advanced neuroblastoma. The regimens used include Hepatocellular carcinoma is an aggressive hepatic
OPEC (vincristine, cyclophosphamide, cisplatin, teniposide neoplasm affecting older children or adolescents. Children
(VM-26), CADO (vincristine, cyclophosphamide, with biliary atresia, infantile cholestasis, glycogen storage
doxorubicin) and PECADO (vincristine, cyclophosphamide, disease and wide array of cirrhotic diseases are
doxorubicin, cisplatin, tenoposide). Other modalities predisposed to developing hepatocellular carcinoma.
include surgery, radiotherapy and autologous bone
marrow transplantation. Addition of cis-retinoic acid to SOFT TISSUE SARCOMA
autologous stem cell transplantation has been shown to
improve survival in patients with high risk neuro Pediatric soft tissue sarcomas are a group of malignant
blastoma. In all treatments good remissions are often tumors that originate from primitive mesenchymal tissue
reached, but the recurrence rate is high. and account for 6-7% of all childhood tumors.
Rhabdomyosarcomas account for more than half of all
Suggested Reading cases of soft tissue sarcoma in children. Other soft tissue
sarcomas include fibrosarcoma, synovial sarcoma and
• Bansal D, Totadris, chinnaswamy G, et al. Management of
neuroblastoma: ICHR Consensus Document Indian J Pediatr 2017; malignant peripheral nerve sheath tumors.
84:446-55. Soft tissue sarcomas may arise in any part of the body,
• Simon T, Hero B, Schulte JH, et al. 2017 GPOH guidelines for most common by the trunk and the extremities. These
diagnosis and treatment for patients with neuroblastic tumors. Klin neoplasms can present initially as an asymptomatic solid
Pediatr 2017;229:147-67.
mass, or may be symptomatic because of local invasion to
adjacent organs. Approximately 15-30% patients have
MALIGNANT TUMORS OF THE LIVER
metastatic disease at presentation, chiefly affecting the
Primary tumors of the liver are rare; over two-thirds of these lung. Other sites for metastases include the skin, bone,
tumors are malignant. Over 80% of malignant liver tumors liver, and lymph nodes. Treatment modalities include
in children are hepatoblastomas.The disease usually affects surgery, radiation and chemotherapy.
Childhood Malignancies 1613-
Osteogenic Sarcoma
Its peak incidence is during adolescence, correlating with
rapid bone growth. The distal femur and proximal tibia
are the most frequent sites followed by proximal
humerus and middle and proximal femur. Flat bones,
e.g. vertebrae, pelvic bones and mandible are rarely
affected. Patients present with a localized painful
swelling that may be attributed to traumatic or infective
conditions, delaying the diagnosis by months. Metastasis
occurs early to the lungs and other bones. Germline
mutations of tumor suppressor genes, including the
retinoblastoma (RB1) gene are associated with increased
incidence. Li-Fraumeni syndrome, associated with
germline mutations of the tumor suppressor p53 gene,
is characterized by increased incidence of breast cancer,
soft tissue sarcoma, osteosarcoma, adrenocortical
carcinoma and leukemia in first degree relatives. High
dose radiation therapy, such as that for Ewing sarcoma
or brain tumors, predisposes to development of
osteosarcoma, either in or at sites distant from the
Fig. 21.9: Ewing sarcoma. Radiograph showing permeative lytic
radiation field. Benign bone lesions such as Paget disease, lesion with a prominent soft-tissue mass extending from the
multiple hereditary exostoses, fibrous dysplasia and bone. Periosteal reaction is seen. The onion-skin (sunburst
enchondromatosis may occasionally undergo malignant pattern) indicates an aggressive process suggesting Ewing
transformation to osteosarcoma. sarcoma
-614 Essential Pediatrics
Fig. 21.11: Langerhans cell histiocytosis. (a) Radiograph of skull showing lytic lesions; (b) The seborrhea, skin lesions and jaundice
Langerhans Cell Histiocytosis (LCH) of teeth. Other manifestations include seborrheic skin
LCH is a rare non-malignant disease with unknown rash (Fig. 21.llb) in scalp area and back (60%),
etiology characterized by a clonal proliferation of lymphadenopathy (33%), hepatosplenomegaly (20%)
pathologic cells with the characteristics of Langerhans tachypnea, air leaks, parenchymal lung infiltrates (15%),
cells in single/multiple sites and an unpredictable jaundice, abdominal distension, neurodegenerative
course. The clinical presentation is heterogeneous symptoms and features of malabsorption. Pituitary
ranging from single system involvement to a dysfunction may result in growth retardation and
multisystem life threatening disease (Table 21.26). The diabetes insipidus. Severe disease is characterized by
hallmark of LCH is the presence of Birbeck granules fever, weight loss, malaise, failure to thrive and liver
(BG) on electron microscopy and positivity for S-100 dysfunction. Liver involvement may result in sclerosing
protein and CDla positivity. The number of Langerhans cholangitis and cirrhosis. Bone marrow involvement may
cells with BG can vary in different lesions. Langerin lead to anemia and thrombocytopenia.
(CD207) is a type II transmembrane protein associated
with BG and is presumed to be more sensitive and Diagnosis
specific than CDla. The classical histopathologic feature of LCH is the
The spectrum of LCH (eosinophilic granuloma, Hand presence of lesional histiocytes of LC phenotype, with
Schuller-Christain disease, Letterer-Siwe disease) reflects varying proportion of macrophages, T lymphocytes,
varying extents of the disease. The course of disease is eosinophils and multinucleated giant cells. The cells show
unpredictable, varying from rapid progression and death, positivity to S-100, CDla, and langerin (CD 207); BG are
to repeated recurrence and recrudescence with chronic seen on electron microscopy. Diagnostic work up should
sequelae, to spontaneous regression and resolution. include biopsy from most appropriate site, complete blood
Patients with disease that is localized (skin or bone) have count, liver function tests, coagulation studies, skeletal
a good prognosis and are felt to need minimum or even survey, chest X-ray and urine specific gravity. These
no treatment. In contrast, multiple organ involvement, include ultrasound abdomen, CT chest and or abdomen
particularly in young children (under 2-year-old), carries and MRI brain. Bone marrow biopsies are required to
relatively poor prognosis. exclude infiltration.
The most common involvement is of the skeleton Treatment for localized disease or single bony lesion
(80%). Bone lesions can be single or multiple affecting varies from observation, curettage, indomethacin,
skull bones, long bones, vertebrae, mastoid and bisphosphonates, low dose radiation to systemic
mandible. The lesions may be painless or present with chemotherapy. Multisystem disease is treated with
pain and local swelling; X-rays show sharp lytic lesions chemotherapy, combining vinblastine, prednisone and
(Fig. 21.lla). Clinical manifestation includes vertebral 6-mercaptopurine. Childhood LCH may have long-term
collapse and spinal compression, pathological fractures sequelae some of which occur many years after completion
in long bones, chronic draining ears and early eruption of treatment.
Childhood Malignancies 1617-
Table 21.27: Diagnostic criteria for HLH attributed to defects in function of natural killer and
HLH diagnosis established, if one of the two is fulfilled
cytotoxic cells, leading to pathological activation of T cells
and macrophages and production of proinflammatory
A molecular diagnosis of HLH (e.g. PERF, SAP, MUNCmutations)
cytokines (interferon gamma, tumor necrosis factor alpha
OR
and interleukins). Young children with HLH and known
5 of the following 8 criteria are fulfilled gene mutations, or a family history of HLH are described
• Fever as having primary HLH. Older children with HLH or
• Splenomegaly children without identifiable mutations are described to
• Cytopenias in at least two cell lines have secondary or acquired HLH, secondary HLH to
Hemoglobin <90 g/L infection or other stimuli (e.g. juvenile rheumatoid arthritis,
Platelets <100 x 109/L SLE). Diagnostic criteria of HLH is shown in Table 21.27.
Neutrophils <1 x 109/L
• Hypertriglyceridemia and/or hypofibrinogenemia ONCOLOGIC EMERGENCIES
Fasting triglycerides >3 mmol/L (>265 mg/dl) Oncologic emergencies may present at diagnosis of the
Fibrinogen <1.5 g/L malignancy, during course of the disease or as a consequence
• Hemophagocytosis in bone marrow, spleen or lymph nodes of therapy. A solid tumor may invade or compress vital
• Low or absent activity of natural killer cells organs like trachea, esophagus or superior vena cava.
• Ferritin >500 µg/L Effusions into the pleural space or pericardium may
• Soluble cD25 (soluble interleukin-2 receptor) >2400 units /ml compromise functions of lung and heart. Metastasis into the
brain may lead to cerebral edema and features of raised
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSES (HLH) intracranial tension. Spinal cord tumor involvement may lead
to cord compression. Bone marrow involvement results in
HLH is an aggressive and potentially fatal syndrome which anemia, bleeding due to thrombocytopenia or coagulation
results from an inappropriate prolonged activation of abnormalities (disease/chemotherapy), leukostasis,
lymphocytes and macrophages (Table 21.27). HLH is thrombosis, cerebrovascular episodes and infections.
Hormonal problems can occur because of paraneoplastic long-term effects of cancer treatment, integrate them
secretions (Table 21.28). Metabolic complications may occur appropriately into society, provide referrals to specialists
prior to/at onset of chemotherapy following lysis of tumor as needed, offer psychological counseling and transition of
cells. Therapy related complications include myocardial patients to adult care when ready. The term long-term
dysfunction (anthracyclines), extravasation of drugs survivor refers to patients who are disease free for a
(anthracyclines, vinca alkaloids), hemorrhagic cystitis minimum period of 5 years. 92% children who were disease
(cyclophosphamide), cerebrovascular accidents (methotrexate, free up to 5 years, were alive at 15 years after diagnosis.
1-asparaginase) and pancreatitis (1-asparaginase,
corticosteroids). Early diagnosis and urgent management of Late Effects Associated with Childhood Cancer
these conditions will save lives and allow for treatment of The common late effects of pediatric cancer comprise
the underlying malignancy. deficits in growth and development, organ function,
reproductive capacity and health of offspring and
Suggested Reading
development of subsequent neoplasms.
• Seth R, Bhat AS. Management of common oncologic emergencies.
i. Growth and development: The components affected
Indian J Pediatr 2011; 78(6):709-17.
• Seth R, Singh P, Puri K, Arora A, Rathore AS. Morbidity profile include linear growth, sexual maturation,
and outcome of hyp erleukocytosis in childhood acute leukemia: musculoskeletal development, skeletal maturation,
experience from a tertiary center. Int J Hematol Res. 2015; 26:90-4. intellectual function, emotional and social
maturation (Table 21.29).
LATE EFFECTS AND SURVIVORSHIP ii. Organ function: Exposure to higher cumulative
With refinements in diagnostics and advances in chemotherapy and radiation doses required for more
therapeutics and supportive care the overall survival of biologically aggressive refractory disease increases
childhood malignancy has increased significantly over the the risk of both vital and nonvital organs toxicity.
past few decades. Over 80% children and adolescents with These include anthracycline related cardiotoxicity,
cancer survive 5 or more years from diagnosis in many pulmonary function abnormalities and, chronic liver
centers and are effectively cured of the disease. This is disease.
however at the cost of increased morbidity in the form of iii. Reproductive capacity and pregnancy outcomes:
various late effects of cancer treatment. It is estimated that Reproductive functioning may be affected by various
a third to half of childhood cancer survivors will anticancer modalities (surgery, chemotherapy and
experience a late term effect of cancer therapy; of which radiation). Alkylating chemotherapy is toxic to the
up to half may be life threatening. gonads. They produce a dose related gonadal germ
The main goals of the Cancer Survivorship Program are cell injury. In boys, alkylators damage germ cells
to improve the health and well-being of childhood cancer leading to infertility. Compared to boys, girls
survivors by promoting adherence to a schedule of follow maintain an ovarian function at higher cumulative
up appointments and routine screening tests, educate doses of alkylating agents and if dysfunction occurs
patients, parents and healthcare professionals about the it is often reversible.
Table 21.29: Late effects of pediatric cancer therapy on growth and development
Domain Specific effect Predisposing therapy Modifying host factors
Linear growth Delayed/accelerated growth Radiation of hypothalamic Younger age poses higher risk
Short stature; growth failure pituitary axis
Sexual maturation Delayed puberty; hypogonadism Alkylating agents; radiation of Boys at higher risk for gonadal injury
Precocious puberty hypothalamic-pituitary axis Girls at higher risk for precocious
puberty
Musculoskeletal Hypoplasia, fibrosis Radiation impacting bones Younger age at irradiation
development Uneven/reduced skeletal growth and soft tissues
Skeletal maturation Osteopenia Corticosteroids Younger age at irradiation
Osteoporosis Methotrexate
Osteonecrosis Radiation >40 Gy; corticosteroids Older age (> 1 O yr)
Intellectual function Neurocognitive deficits; reduced High dose methotrexate, Younger age at irradiation
IQ; behavioral problems cytarabine, cranial irradiation
Emotional and social Mental health disorders Any cancer experience Girls and CNS tumor survivors at
maturation Educational problems increased risk
Vocational issues; unemployment
Psychosocial issues
Childhood Malignancies 1619-
Sperm production is reduced in a dose dependent Autologous HSCT involves the removal and storage of
manner following radiation. Reversible azoospermia patient's own stem cells, which subsequent re-infusion
is seen at doses of 1-3 Gy but is irreversible at higher following high dose myeloablative therapy. Higher doses
doses (>3 Gy). Prepubertal status does not protect of myeloablative chemotherapy can be administered than
from germ cell injury. Abdominal, pelvic or spinal is otherwise possible. There is no risk of graft rejection or
radiation also contributes to germ cell depletion in GvHD. This approach was initially restricted to solid
girls. Ovaries of younger girls are more resistant to tumors (neuroblastoma, germ cell tumors, retinoblastoma,
radiation damage as compared to ovaries of older medulloblastoma) where bone marrow was free of disease,
women. Radiation doses >20 Gy cause irreversible but is now being used for hematological malignancies and
ovarian failure and doses between 20 and 30 Gy lymphomas.
delay pubertal development.
iv. Second malignant neoplasm (SMN): Pediatric cancer Peripheral HSCT: CD34 positive cells are mobilized from
survivors are at an increased risk for development marrow into circulation in sufficient numbers for clinical
of second cancers; host factors (genetics, immune use by use of recombinant human hematopoietic growth
function, and hormonal status), primary cancer factors. These cells can establish durable marrow
therapy, environmental exposure and lifestyle engraftment.
factors play a role in the occurrence of secondary
neoplasms. Common malignancies that occur as Umbilical cord transplantation: Cord blood banks are
second neoplasms include acute myeloid leukemia another source of stem cells. The graft composition and
(AML) including myelodysplastic syndrome and biological properties of umbilical cord stem cells are
solid tumors. Secondary AML commonly develops different from adults. Cord blood transplantation is
in association with use of alkylating agents or associated with enhanced engraftment and reduced
topoisomerase II inhibitor therapy. Radiation incidence of GvHD.
therapy is also implicated in the occurrence of SMNs
like acute leukemia and solid tumors involving the Uses of BMT
breast, thyroid, CNS, bones, and soft tissues. The
Allogenic BMT is indicated in all patients of acute myeloid
latency for occurrence of SMN varies from 2-3 years
leukemia after the first remession, except these with
to as long as 10 years. Breast cancer is the most
favorable cytogentics and good risk group which includes
frequently reported secondary solid tumor in
acute promyelocytic leukemia with translocation t(l5;17),
childhood cancer survivors with incidence varying
from 10 to 20% by 20 years from radiation. t (8;21) and inversion (16) or low levels of minimal residual
disease.
BONE MARROW TRANSPLANTATION (BMT) BMT is indicated in patients with acute lymphoblastic
leukemia during their first remission and a risk factor
BMT is the established therapy for congenital or acquired including hypodiploidy, t(4;11) biophenotypic leukemia
disorders of the hematopoietic system and hematologic and high minimal residual disease after induction.
malignancies. Transplantation is also indicated after second and
Allogenic hematopoietic stem cell transplantation (HSCT) subseqent remissions.
occurs between a donor and a recipient who are BMT may also be considered for various non-malignant
immunologically identical. It can lead to graft vs host disorders, e.g. severe combined immunodeficiency,
disease (GvHD), where immune cells from the donor react Wiskott-Aldrich syndrome, severe aplastic anemia and
against antigens on host cells and graft rejection where storage disorders.
immune competent host cells destroy donor stem cells
before the graft is established. The risk of relapse of Suggested Reading
malignant disease is lower following allogenic HSCT • Guilcher GMT. Hematopoietic stem cell transplantation in children
because of immune effects of the graft on malignant cells. and adolescents. Pediatr Rev 2016;37:135-44.
Chapter
22
Rheumatological Disorders
Surjit Singh
A small proportion of children with acute lymphocytic of one or more joints with onset below 16 years of age and
leukemia show bone and joint pains. Bone pain, that is persisting for at least 6 weeks. It has the following subtypes:
more marked at night, is the predominant complaint in i. Systemic
affected children. Hemogram shows lymphocytic ii. Oligoarthritis: (a) persistent (b) or extended
predominance and thrombocytopenia, in contrast to a iii. Polyarthritis: Rheumatoid factor negative
polymorphonuclear predominance and thrombocytosis
iv. Polyarthritis: Rheumatoid factor positive
characteristic of juvenile idiopathic arthritis. A bone
v. Psoriatic arthritis
marrow examination is required to confirm the diagnosis.
vi. Enthesitis-related arthritis
X-linked agammaglobulinemia (Bruton disease) may
sometimes present as an unusual 'aseptic'arthritis (due vii. Undifferentiated arthritis: that (a) fits no other
to Mycoplasma infection), but accompanying respiratory category; or (b) fits more than one category
infection is usually present. JIA is not rare; its estimated prevalence ranges from
Arthritis can, at times, be the presenting complaint of 0.4 to 1.3 per 1000 children below 16 years of age. It is the
hemophilia or human immunodeficiency virus infection. commonest rheumatological disorder of childhood and
one of the most common causes of disability, chronic
Legg-Calve-Perthes Disease morbidity and school absenteeism. While Western studies
suggest that JIA is more common in girls, in India, female
This is characterized by an avascular necrosis of the
predominance is not marked.
femoral head, occurring usually in boys 5-10 years of age.
Systemic JIA (sJIA) is now considered to be a separate
It may be a manifestation of an underlying hyper
disease altogether. It is classified as an auto-inflammatory
coagulable state (hypofibrinolysis or deficiency of protein
disorder in which the innate immune system is primarily
C or S). Familial occurrence is commmon and the condition
affected unlike other types of JIA which represent defects
is bilateral in 10% patients. Affected children present with
of acquired immunity. The ILAR definition for sJIA
a painful limp. Initial X-rays may be normal. Isotope bone
requires that fever be present for at least 2 weeks and
scans and magnetic resonance imaging are required to
should be accompanied by one or more of the following:
confirm the diagnosis. Subsequent X-rays show a
Evanescent rash, generalized lymphadenopathy, hepato
characteristic sequential progression: (i) Widening of joint
splenomegaly or serositis.
space, (ii) fragmentation of epiphysis with patchy areas
of increased lucency or density, (iii) abnormalities of shape
of femoral head and neck, and (iv) deformed head. Etiology
Treatment options include femoral varus osteotomies or The immune system is intimately involved in the evolution
containment splints. of JIA. HLA DRS and DRS are linked to early onset
oligoarthritis (seen more often in girls), B27 to late onset
Juvenile Idiopathic Arthritis oligoarthritis (seen more commonly in boys) and DR4,
The term juvenile idiopathic arthritis (JIA) was proposed Dw4 and DRl to rheumatoid factor positive polyarthritis.
by the Pediatric Standing Committee of the International JIA is not a homogeneous disease and the different
League of Associations for Rheumatology (ILAR). It refers subtypes may represent separate clinical conditions.
to a group of conditions characterized by chronic The etiopathogenesis of JIA remains an enigma. Several
inflammatory changes of the joints. It is defined as arthritis environmental triggers (e.g. infection with rubella virus,
622 Essential Pediatrics
parvovirus B19, M. tuberculosis, Mycoplasma pneumoniae Polyarthritis: Polyarthritis occurs in 25-30% of patients
and enteric organisms, physical trauma or psychological and is more common in girls. Joint pain, out of proportion
stress) are linked to the onset of JIA, but their exact role is to the degree of joint swelling, is the usual complaint. Fever
not clear. Cytokines like tumor necrosis factor-a (TNF-a), and malaise can be significant. Two subtypes are known:
IL-6 and IL-1 have to have an important role to play in
Rheumatoid factor negative: This subtype may occur at any
the pathogenesis of the disease. A number of auto
age in childhood. Knees, wrists and hips are the joints
antibodies (for instance, antinuclear antibody) may be seen
usually affected. Small joints of hands and feet are less
in the sera of children with JIA. The classical IgM
commonly involved and rheumatoid nodules are not seen.
rheumatoid factor is almost never detectable in preschool
Joint disease in this subtype of JIA is far less severe than
children with JIA. Older girls with polyarticular small joint
that seen in patients who are rheumatoid factor positive.
disease of the hands (especially involving the
metacarpophalangeal and proximal interphalangeal Rheumatoid factor positive: Age at onset is late childhood
joints) may, however, be RF positive. or early adolescence. The arthritis is symmetrical, additive,
severe and deforming and typically involves small joints
Clinical Subtypes of hands, especially the metacarpophalangeal and the
Three major types of onset are described according to the proximal interphalangeal. Cervical spine and temporo
presentation during the first 6 months of disease, namely mandibular joints can also be affected. This subtype is the
systemic JIA (with fever and rash), oligoarthritis (4 or only category of JIA which is somewhat similar pheno
fewer joints involved) and polyarthritis (more than 4 joints typically to adult onset rheumatoid arthritis. Rheumatoid
involved). nodules are present in some patients and they usually
indicate severe disease.
Systemic ]IA (s]IA): About 5-15% of patients withJIA may
have acute onset disease with prominent systemic Psoriatic arthritis: Psoriatic arthritis is said to be present
features. These systemic features may sometimes precede when there is arthritis in association with psoriasis or any
joint manifestations by weeks or months. This condition 2 of the following features-dactylitis, nail pitting and
should, therefore, be considered in differential diagnosis psoriasis in a first degree relative. Arthritis may precede,
of any child with prolonged fever. The illness can occur accompany or follow occurrence of psoriasis in children.
at any age and is more common in boys. Clinical features suggestive of psoriatic arthritis include
It usually begins as an intermittent fever with a simultaneous occurrence of small and large joint arthritis
characteristic twice daily peak. Fever is generally more or involvement of distal interphalangeal joints.
prominent in evening. It is accompanied by an evanescent Enthesitis-related arthritis: This condition is more
maculopapular truncal rash. The rash may be difficult to common in boys, typically older than 8 years. Asymmetric
recognize in individuals with dark skin. Affected children large joint (e.g., knee, ankle, hip) involvement of lower
show marked irritability that decreases with subsidence extremity is characteristic. Many children are HLA B27
of fever. Serosal involvement (in the form of pericarditis positive, and a proportion of these may go on to develop
or pleuritis) may be prominent. Hepatosplenomegaly and ankylosing spondylitis later as adults. However,
lymphadenopathy are common at presentation and sacroiliitis and spondylitis are usually not significant till
can lead to diagnostic confusion. There is moderate late adolescence. Self-limiting acute symptomatic iritis
neutrophilic leukocytosis and an elevated erythrocyte may occur in some patients but it does not progress onto
sedimentation rate along with thrombocytosis. the chronic iridocyclitis seen in oligoarthritis of young
Rheumatoid factor is negative. girls. A family history of ankylosing spondylitis, psoriasis,
Oligoarthritis: Oligoarthritis is the most frequent type of Reiter disease and low back pain may be obtained in these
JIA accounting for approximately 60-70% of patients. Four children.
or fewer joints (usually large) are affected during the first
6 months of disease. Joint swelling, rather than joint pain, Laboratory Investigations
is the usual complaint. Two subtypes are described: The The clinician should recognize the differing patterns of
term persistent (if number of affected joints continues to joint involvement in various types of JIA. This 'pattern
be 4 or less) and extended (if number of affected joints recognition' is often the most important diagnostic clue.
exceeds 4 during the disease course). Laboratory investigations may be of a little or no help in
Oligoarthritis is more common in young girls, typically arriving at a diagnosis.
3-5 years of age. Asymmetric involvement of knee or ankle Synovial fluid aspiration for microscopy and culture is
is characteristic. Small joints of hands and feet are not indicated in children with monoarthritis because septic
involved. Asymptomatic, and potentially blinding, arthritis may need to be excluded (Table 21.2). Complete
iridocylitis can be seen in 25% patients with early onset blood counts should be requested along with an
oligoarthritis, and is especially common in girls with erythrocyte sedimentation rate. Acute lymphocytic
antinuclear antibody (ANA) positivity. leukemia can sometimes have an arthritic presentation,
Rheumatological Disorders 1623-
and such children may be mistakenly diagnosed as having rofecoxib, valdecoxib) have lower gastrointestinal adverse
JIA. Bone marrow aspiration is therefore necessary if use effects, but are not recommended for use in children.
of glucocorticoids is being contemplated for treatment of Although the mechanism of action of all NSAIDs is the
JIA. same, idiosyncratic responses are well known and a given
C-reactive protein measurement is a surrogate marker patient may respond to one NSAID and not to the other.
of disease activity and is helpful on follow-up. Plain Response to therapy is usually slow and this fact must be
radiographs of affected joints are obtained at time of initial explained to the parents. Treatment must continue for at
diagnosis and may be repeated for assessment of erosive least 4-6 weeks before a decision to switch over to another
disease. It should be noted that screening for rheumatoid NSAID is made.
factor is not a useful test for diagnosis of arthritis in young Disease modifying anti-rheumatic drugs (DMARDs)
children, but it is an important prognostic factor in need to be started in almost all children with polyarthritis.
situations where it is positive. Weekly methotrexate (15-25 mg/m 2/week given
subcutaneously or orally) has simplified management of
Treatment severe forms of JIA. Children seem to tolerate
Management of JIA is multidisciplinary. Physiotherapy methotrexate better than adults and have fewer adverse
and occupational therapy should be tailored to specific effects. Once the child is in stable remission (usually
needs of an individual child, in order to prevent defor achieved after several months), the drug can be tapered
mities and facilitate 'mainstreaming' and rehabilitation. to the minimum effective dose and then stopped.
Physical therapy helps in relieving pain, maintenance of Methotrexate should always be given under close medical
posture and joint mobility, improves muscle strength and supervision. Periodic testing of liver functions is
prevents fixed flexion deformities. All patients with JIA mandatory. Development of hepatic fibrosis, a dreaded
need to be assessed by an ophthalmologist so that uveitis adverse effect, is uncommon. Hydroxychloroquine is a
can be detected early and treated appropriately. Children useful adjunct and is often used along with methotrexate.
with oligoarthritis need regular ophthalmological follow Leflunomide, an inhibitor of pyrimidine synthesis, has
up as uveitis can develop later. been used in adults with rheumatoid arthritis.
Medical therapy: NSAIDs are the mainstay of symptomatic Intra-articular injections of glucocorticoids (usually
management. The conventional NSAIDs inhibit both triamcinolone) are the preferred therapy for children with
isoforms of the enzyme cyclo-oxygenase, i.e. COX-1 oligoarthritis who do not respond to an initial trial of
(constitutive; mediates physiologic prostaglandin NSAIDs. Systemic glucocorticoids (usually prednisolone
production necessary for gastrointestinal mucosal integrity 1-2 mg/kg/day; occasionally methylprednisolone
and adequacy of renal blood flow) and COX-2 (inducible; 10-30 mg/kg) are necessary for severe unremitting
mediates pathologic prostaglandin production, especially arthritis, systemic manifestations (e.g. pericarditis,
at sites of inflammation). NSAIDs commonly used in myocarditis, vasculitis) and rapidly progressive disease.
children are naproxen and ibuprofen. Indomethacin is Prednisolone, when used in this manner, is usually given
believed to be of particular use in enthesitis related arthritis. as bridge therapy for a few weeks while awaiting the
Doses of commonly used NSAIDs are given in Table 22.3. clinical response of methotrexate.
Development of Reye syndrome is a distinct possibility Iridocyclitis warrants therapy with local steroid
while a child is receiving NSAIDs, especially if there is an instillation and mydriatic eye drops. Weekly methotrexate
intercurrent viral illness. All children with NSAIDs must therapy is required for patients with severe uveitis.
be monitored for gastrointestinal adverse effects. The Newer modalities of treatment include recently
recently introduced selective COX-2 inhibitors (e.g. introduced biological agents like anakinra (IL-1 receptor
antagonist); canakinumab (monoclonal antibody to IL-1);
tocilizumab (monoclonal antibody to IL 6 receptor);
Table 22.3: Doses of commonly used NSAIDs
infliximab, golimumab and adalimumab (monoclonal
Dose, Maximum dose, Frequency of antibodies to TNF-a); etanercept (recombinant soluble
mg/kg/day mg/day administration TNF receptor p75 fusion protein) and abatacept (inhibitor
Naproxen 15-20 750 Twice daily of T cell activation). Etanercept and infliximab are
Ibuprofen 35-45 2400 Four times powerful biological agents against TNF-a. While
daily etanercept has been used in children with polyarthritis
1-2
not responding to methotrexate, infliximab has been more
lndomethacin 150 Three times
daily commonly used in adults with spondyloarthropathy.
Tocilizumab and anakinra have found favour in children
Diclofenac 2-3 150 Four times
daily
with severe forms of sJIA. While these biologics are
now being increasingly used as first line therapy in children
Piroxicam 0.3-0.6 20 Once daily
with JIA, long-term safety of these products remains
The analgesic dose is usually half the anti-inflammatory dose unclear.
s24 I Essential Pediatrics
Course severe and has a poorer prognosis than adult SLE. The
Oligoarthritis usually has a good prognosis but localized hallmark of SLE is the presence of antinuclear antibodies
deformities can develop due to asymmetric growth of (ANA). Marked female predominance characteristic of
limbs. Children with enthesitis related arthritis can adult SLE is usually not apparent in young children.
develop spondylitis and sacroiliitis later, especially if they
Diagnosis
are HLA B27 positive.
Children with rheumatoid factor positive polyarthritis Diagnosis of SLE is facilitated by Systemic Lupus
have a disease pattern similar to adults and show erosive International Collaborating Clinics (SL ICC) criteria
and deforming arthritis. Prognosis is better for (Table 22.4). However, SLE is always a clinical diagnosis
seronegative polyarthritis as remissions are obtained more the criteria merely provide helpful guidelines for reaching
often and residual joint lesions may be minimal. a diagnosis. In many patients, especially children,
treatment may have to be initiated even when they do not
The course of systemic onset disease can be extremely
fulfil the requisite criteria.
variable and response to therapy is not always satisfactory.
The malar rash, which is virtually pathognomonic of
Inappropriately treated or untreated patients with JIA
SLE, may not be apparent initially. It involves the cheek,
may develop flexion contractures of hips, knees and
bridge of nose and lower eyelids but characteristically
elbows, resulting in permanent disability. Neck stiffness
spares the nasolabial folds (Fig. 22.la). Discoid lesions are
is an especially debilitating problem and can result in
rare in childhood onset SLE. Oral ulcerations may involve
torticollis. Temporomandibular joint involvement results
the buccal mucosa or palate and are usually painless. Some
in restricted opening of the mouth and may require
children may have prominent frontal alopecia (Fig. 22.lb).
surgical intervention.
Arthritis is generally mild and always non-erosive.
Renal involvement is a dreaded complication of SLE
Complications and one of the commonest causes of mortality in children.
Anemia, due to chronic ongoing inflammation, is almost Lupus nephritis is conventionally classified as follows:
always present in children with persistent active arthritis Class I: Minimal mesangial; Class II: Mesangial proliferative;
and serial hemoglobin levels mirror disease activity. Blood Class III: Focal proliferative; Class IV: Diffuse proliferative;
loss induced by NSAIDs can also be a contributory factor Class V: Membranous; Class VI: Advanced sclerosing.
for the anemia. Chronic anterior uveitis may be clinically Class III and Class IV lesions (i.e., proliferative glomerulo
silent and potentially blinding. Girls below 6 years of age nephritis) require the most aggressive forms of therapy.
with oligoarthritis, and who have antinuclear antibodies,
are at the highest risk of developing this complication.
Children with sJIA are especially prone to develop
Table 22.4: SLICC Classification Criteria for SLE
macrophage activation syndrome. This is a potentially Requirements: �4 criteria (at least 1 clinical and 1 laboratory
fatal complication that presents with unremitting fever, criteria) OR biopsy-proven lupus nephritis with positive ANA
sudden onset icterus, bleeding tendency, leukopenia, or anti-dsDNA
thrombocytopenia, hypofibrinogenemia, elevated Clinical criteria
triglycerides and raised ferritin levels. Prompt adminis Acute cutaneous lupus
tration of intravenous methylprednisolone pulses can be Chronic cutaneous lupus
life saving. Oral or nasal ulcers
Growth disturbances, limb length discrepancies and Non-scarring alopecia
joint contractures can be seen in children with long Arthritis
standing disease. Growth failure may occur secondary to Serositis
severe inflammation or treatment with glucocorticoids. Renal involvement
Treatment with recombinant human growth hormone Neurologic involvement
may be an option in children with growth disturbances. Hemolytic anemia
Secondary amyloidosis is a rare complication that presents Leukopenia
with asymptomatic proteinuria and hypoalbuminemia, Thrombocytopenia (<100,000/cu mm3)
and is often irreversible. Immunologic criteria
Antinuclear antibody (ANA)
SYSTEMIC LUPUS ERVTHEMATOSUS Anti-dsDNA
Anti-Smith
Systemic lupus erythematosus (SLE) is an autoimmune
Antiphospholipid antibody
disorder characterized by inflammation of connective
Low complement (C3,C4,CH50)
tissues and blood vessels resulting in multisystem Direct Coombs' test (do not count in presence of hemolytic
involvement. Clinical manifestations are variable and the anemia)
course unpredictable. Childhood SLE is usually more
Rheumatological Disorders ls2s-
Fig. 22.1: Systemic lupus erythematosus. Note (a) Molar rash; and (bl Frontal alopecia
Neurological features include psychosis, seizures, Use of monthly pulses of IV cyclophosphamide (500 mg/
alterations in sensorium, focal deficits and chorea. There m2) has considerably improved the long-term outcome in
may be no correlation between severity of clinical involve children with severe forms of lupus nephritis. Once
ment and findings on neuroimaging. Hematologic remission is achieved, the patient can be maintained on
abnormalities include Coombs' positive hemolytic anemia, mycophenolate mofetil or azathioprine. Mycophenolate
leukopenia, lymphopenia and thrombocytopenia. In mofetil is being increasingly used for therapy of severe
addition, there may be coagulation abnormalities due to forms of lupus nephritis in children.
presence of antiphospholipid antibodies. Cardiac Low dose prednisolone (2.5-5 mg/day) and hydroxy
manifestations include pericarditis, myocarditis, or chloroquine (5-6 mg/kg/day) may need to be continued
verrucous (Libman-Sacks) endocarditis. A few autoimmune for several years depending on the clinical response.
diseases may coexist with lupus including autoimmune Infections must be treated aggressively with appropriate
thyroid disease, celiac disease and overlap syndromes. antimicrobials and the steroid dose increased during such
episodes. With appropriate therapy, the long-term outlook
Serology
of SLE in children is quite encouraging.
Almost all patients with SLE have demonstrable ANA.
Presence of anti-double stranded (anti-ds) DNA antibodies Antiphospholipid Syndrome
is highly specific of SLE and usually correlate with disease
Antiphospholipid syndrome is a common accompaniment
activity. Anti-histone antibodies are present in neonatal
of SLE but can be seen in association with other
lupus especially those associated with characteristic of
rheumatological disorders as well. The syndrome can, at
drug-induced lupus. Anti-Ro antibodies are present in
times, arise de nova when it is known as primary
neonatal lupus especially those associated with congenital
antiphospholipid syndrome. It is a common cause of
heart block. Anti-Sm antibodies are a marker for CNS
acquired hypercoagulable states in children and is manifest
lupus.
with venous and arterial thrombosis, livedo reticularis and
Treatment thrombocytopenia. The presentation is sometimes
catastrophic and may result in fatality. Laboratory diagnosis
Glucocorticoids and hydroxychloroquine form the
is suggested by a typical coagulation profile (normal
mainstay of therapy. Prednisolone is started at doses of
prothrombin and prolonged partial thromboplastin times)
1-2 mg/kg/day and gradually tapered over several
and confirmed by detection of anticardiolipin antibodies
months, according to disease activity. Arthritis usually
(IgM and IgG), anti-f32 glycoproteinl antibodies (IgM and
responds to NSAIDs. Sunscreen lotions (with sun
IgG) and the lupus anticoagulant test. Treatment is with
protection factor of 15-20) must be prescribed for all
long-term oral anticoagulation.
children with lupus and applied 3-4 times/day, even on
cloudy days.
JUVENILE DERMATOMYOSITIS
Life-threatening complications (e.g. class IV lupus
nephritis, mycocarditis, encephalopathy) require the use Juvenile dermatomyositis ODM) is not merely a disorder
of intravenous pulses of methylprednisolone (30 mg/kg/ of muscle and skin, but a multisystem disease
day) for 3-5 days. Rituximab, a monoclonal antibody to characterized by nonsuppurative inflammation of striated
CD20, has also been found to be effective in such situations. muscle and skin, and systemic vasculopathy. Unlike
626 I Essential Pediatrics
adults, pure polymyositis (i.e. with no accompanying skin iv. Chemically induced scleroderma (e.g. with polyvinyl
involvement) is uncommon in children. The diagnosis of chloride, pentazocine, bleomycin)
JDM can be made on basis of the following criteria: v. Pseudosclerodermas (e.g. phenylketonuria, sclere
i. Characteristic heliotrope discoloration over the upper dema, progeria and porphyria cutanea tarda)
eyelids (Fig. 22.2a) or a scaly, erythematous rash over Diffuse cutaneous systemic scleroderma is usually
dorsal aspects of metacarpophalangeal and proximal associated with widespread visceral involvement
interphalangeal joints (Gottron papules; Fig. 22.2b) including the gastrointestinal tract, heart, lungs and
ii. Symmetrical proximal muscle weakness kidneys. It is believed that fetomaternal graft-versus
iii. Elevated levels of muscle enzymes (creatine kinase, host reactions are involved in pathogenesis of this
alanine and aspartate aminotransferases aldolase) condition. Onset of disease is insidious and may be
iv. Electromyographic evidence of myopathy difficult to recognize in initial stages. The child presents
with skin tightening (edema, atrophy and acrosclerosis),
v. Muscle biopsy showing myonecrosis, myophago
Raynaud phenomenon (i.e. blanching, cyanosis and
cytosis and perifascicular atrophy
erythema), soft tissue contractures, arthralgias and
A definite diagnosis of JDM can be made, if a child myalgias, dysphagia (regurgitation, reflux and
fulfils the first criterion along with any three of the aspiration), dyspnea (interstitial fibrosis, low diffusing
remaining four and it is considered probable if two of the capacity) and characteristic subcutaneous calcifications.
four criteria are met. Other dermatological changes Many children have abnormalities of nailfold
include edema over eyelids, photosensitivity, truncal capillaries, which can be seen as capillary dropouts and
rash and calcinosis. Magnetic resonance imaging (MRI) dilated loops with a nail-bed capillaroscope or +40 lens
shows characteristic hyperintense signals on T2- of an ophthalmoscope. Onset of hypertension and
weighted images suggestive of muscle edema and proteinuria usually indicates renal involvement, and
inflammation while Tl weighted images may show should be a cause for concern.
fibrosis, atrophy and fatty infiltration. Muscle biopsy is
Investigations show presence of ANA (with nucleolar
rarely required for diagnosis.
pattern on immunofluorescence) and antibodies to Scl70
Treatment is with pulse intravenous methylprednisolone (DNA-topoisomerasel) or centromere. No form of drug
(30 mg/kg/ day) for 3-5 days followed by gradually therapy is curative. Penicillamine and colchicine can
tapering doses of oral prednisolone (1.5-2 mg/kg/ day). produce beneficial results in some patients, especially if
Weekly methotrexate (15-25 mg/m 2/week given used early in the course of disease. Monthly pulses of IV
subcutaneously or orally) is the mainstay of maintenance cyclophosphamide (followed by maintenance daily
therapy. Usual duration of therapy is 18-24 months. Rapid azathioprine or weekly methotrexate) can be life saving
tapering of steroids may result in disease relapse. Long in patients with interstitial lung disease. Nifedipine is
term prognosis is excellent, if treatment is started early. useful for management of Raynaud phenomenon while
enalapril can result in control of blood pressure and
SCLERODERMA stablization of renal function. The latter is also the drug
Scleroderma refers to hardening of the skin. It can be of choice for scleroderma renal crises. With appropriate
classified as follows: management, 10 years survival rates of up to 90% have
i. Systemic scleroderma (e.g. diffuse cutaneous, limited been reported in children.
cutaneous) Scleredema is a benign, self-limiting condition
ii. Overlap syndromes characterized by non-pitting indurated edema over face,
iii. Localized scleroderma (e.g. morphea, linear sclero neck, shoulders and chest, but excluding the hands and
derma, eosinophilic fasciitis) feet.
Fig. 22.3: Findings in acute phase of Kawasaki disease. (a) Red cracked lips; (b) Strawberry tongue; (c) Swelling on dorsum of
hands; and (d) Periungual desquamation.
Fig. 22.5: Findings in polyarteritis nodosa include (a) Livedo reticularis; and (b) Microaneur ysm (black arrow) on angiography
Table 22.6: Classification criteria for childhood polyarteritis Table 22.7: Classification criteria for childhood Henoch
nodosa Schonlein purpura
A childhood illness characterized by the presence of either a Palpable purpura with at least one of the following:
biopsy showing small and mid-size artery necrotizing vasculitis
Diffuse abdominal pain
or angiographic abnormalities (aneurysms or occlusions),* plus
at least 2 of the following: Any biopsy showing predominant lgA deposition
Arthritis or arthralgia
Skin involvement
Renal involvement (any hematuria and/or proteinuria)
Myalgia or muscle tenderness
Systemic hypertension CNS vasculitis, coma, Guillain-Barre syndrome,
Abnormal urinalysis and/or impaired renal function pulmonary hemorrhage, carditis and orchitis.
Mononeuropathy or polyneuropathy
Testicular pain or tenderness Laboratory Investigations
Signs or symptoms suggesting vasculitis of any other major IgA vasculitis is a clinical diagnosis and none of the
organ systems (gastrointestinal, cardiac, pulmo laboratory features are pathognomonic. There may be a
nary or central nervous system) nonspecific increase in total serum IgA levels. Many
*Should include conventional angiography if magnetic resonance children may have microscopic hematuria and
angiography is negative proteinuria. Skin biopsy from the involved sites shows
leukocytoclastic vasculitis. On indirect immuno
the first few days of illness. Glomerulonephritis is seen in fluorescence, there are deposits of IgA in skin as well as
approximately one-third, but only 10% patients have renal biopsies. Ultrasound examinations may need to be
azotemia or nephrotic range proteinuria. Clinically, it may repeated for evolving abdominal findings.
manifest as isolated hematuria, hypertension or a
nephritic/nephrotic syndrome. Significant renal Treatment
involvement is uncommon in children below 6 years old. Management is generally supportive with maintenance
Gastrointestinal manifestations usually occur in first of hydration and pain relief. Prednisolone (1-1.5 mg/kg/
7-10 days of the illness. Affected children may be erroneously day) is often given in children with gastrointestinal
diagnosed as having a 'surgical abdomen'. Abdominal involvement and is usually continued for 2-3 weeks (in
pain is usually intermittent, colicky and periumbilical. gradually tapering doses) depending on the clinical
Vomiting occurs in about 60% of patients but hematemesis response. There is, however, no clear evidence that
and malena are relatively less common. lntussusception steroids alter the natural course of disease.
(ileoileal or ileocolic) can be seen in the acute phase. Nephritis due to IgA vasculitis may need aggressive
Most clinical features of IgA vasculitis are self-limiting management with immunosuppressants (prednisolone
and resolve in a few days. Rare manifestations include and azathioprine).
630 Essential Pediatrics
23
Genetic Disorders
Neerja Gupta • Madhulika Kabra
• •
Gene at locus 2 • B • B Gene with 2 Homozygous
Centro mere same
alleles, BB
Dark and light bands
Fig. 23. l: Schematic structure of a chromosome Fig. 23.2: Concept of locus, gene, allele and genotype
631
632 Essential Pediatrics
L
n Gamete Gametes
Fertilization / /
/ I
1 /
ii,',
/
\ l- , '
\•
/ / Fertilization
/
\ I /
',�
CD (i)
/
Zygore
Monosomy Trisomy
Normal separation Nondisjunction at meiosis I
a b
Fig. 23.3: (a) Normal separation; and (b) Nondisjunction of chromosomes
Genetic Disorders 1633-
-
_17_ _ -- -
@-1- 4 -15- -16- 18
19 20 21 22 X y
a Interstitial deletion Terminal deletion
Fig. 23.4: Aneuploidy of chromosome 13 (trisomy 13)
--+
I
_1_3__1_4 _ --15- 16 17 18
lffl\ -
v
a
Translocation
@-
Fig. 23.6: (a) Schematic diagram of deletion; (bl Karyotype
®)
with deletion of long arm of X chromosome
21 22 X y
b�
Fig. 23.5: Translocation. (a) Cartoon indicating exchange of
parts of chromosomes. (bl Karyotype showing translocation
between chromosomes 2 and 20 [t(2;20)]
consistent pattern of anomalies and developmental
problems. Examples are William syndrome (7qll.23);
retinoblastoma with mental retardation and dysmorphic
fades (13ql4.l); Prader-Willi syndrome (hypotonia,
mental retardation and obesity, 15qll); Rubinstein Taybi
syndrome (microcephaly, broad thumbs, big toes,
dysmorphism and mental retardation; 16q13); and Fig. 23.7: Signals on fluorescent in situ hybridization (FISH) testing.
DiGeorge syndrome (congenital heart defect, hypoplasia Reduced or increased number of signals indicates aneuploidy
sa4 I Essential Pediatrics
Duplications are abnormal duplication or copy of part of on maternal side or inheritance of both copies from
a particular chromosome that result in extra genetic paternal side).
material. Chromosomal abnormalities are generally sporadic and
therefore, the risk of their recurrence in offsprings is low,
Ring chromosome (Fig. 23.8) occurs due to a two
except when either parent is carrying a balanced trans
breakpoint event involving the ends of the p and q arm
location.
which leaves two sticky chromosomal ends that join to
form a ring.
Testing for Chromosomal Disorders
Inversion (Fig. 23.9a) results from one or two breaks along Laboratory testing for chromosomal disorders includes
the length of the chromosome arm. The broken pieces conventional karyotyping, fluorescent in situ hybridization
rotate by 180 degrees and reinsert in a novel way. If there (FISH), quantitative PCR (qPCR), multiplex ligation probe
is no loss or gain of genetic material, there may be no amplification (MLPA) and chromosomal microarray
significant clinical manifestations. Break point is important (CMA).
if it disrupts a vital gene.
The process of making chromosome preparations by
Isochromosome (Fig.23.9b). During mitotic cell division, in vitro culture, staining, identification and classification
the chromosome divides longitudinally. Rarely it divides of chromosomes is called karyotyping. Karyotyping can
transversely across the centromere, with half of the be performed on peripheral blood lymphocytes, bone
chromosome replicating to form its complement. Thus marrow aspirate and tissue biopsy material. The process
instead of normal chromosomes, two new types of is labor intensive and involves culture, followed by
chromosomes are formed, one having both the long arms harvesting chromosomes after the cells are arrested in
and the other with both the short arms. These are known mitosis. After preparation of slides, staining (usually
as isochromosomes. Each isochromosome has excess of Giemsa stain) is done to produce a banding pattern unique
some genetic material and deficiency of other genetic for each chromosome (Fig. 23.10). This enables detection
material. For example, isochromosomes cause some cases of numerical and structural abnormalities through the
of Turner syndrome. genome at a resolution of approximately 5 Mb. The
Genomic imprinting: Maternal and paternal sets of genes chromosomes from one metaphase figure (a single cell)
are not always functionally equal. Some genes are are classified according to their length (chromosome one
preferentially expressed from maternal or paternal side. is the longest) and banding features into groups called a
Examples include Prader-Willi syndrome (microdeletion karyotype.
on paternal side or inheritance of both copies from Molecular cytogenetic techniques include FISH,
maternal side) and Angelman syndrome (microdeletion quantitative polymerase chain reaction (qPCR) and
•
2 3 4 5
6 7 8 9 10 11 12
a b 19 20 21 22 X y
Fig. 23.8: (a) Schematic representation; and (b) Karyotype showing ring chromosome 18 in a child with developmental delay and
seizures (see red arrow)
Genetic Disorders 1635-
N
N
3.5
N
::.
3
2.5
0
2
1.5
0.5
Fig. 23. l 0: MLPA analysis showing hemizygous deletion (indicated in red) in a patient with Smith-Magneis syndrome
, I �. �
Atlanto-occipital subluxation: The incidence is variable,
reported in 10 -30%. Lateral neck radiograph is
Mosaic: 1% recommended once at 3-5 years, before surgery, for
participation in special games, or earlier, if signs and
21' symptoms suggest cord compression.
Fig. 23.11 : Three 1ypes of chromosomal abnormalities found Physical growth: Regular follow up for height and weight
in children with Down syndrome. Arrows indicate the additional is necessary. Linear growth is retarded as compared to
genetic material that results in the characteristic features normal; children tend to become obese with age. Muscle
tone tends to improve with age, while progress with
Clinodactyly (hypoplasia of middle phalanx of fifth finger) development slows with age.
and simian crease are usual. There is a wide gap between
Malignancies: Patients with Down syndrome are at
the first and the second toe (sandle gap).
increased risk of development of lymphoproliferative
Associated Abnormalities disorders, including acute lymphoblastic leukemia, acute
myeloid leukemia, myelodysplasia and transient
Congenital heart disease: Approximately 40% children lymphoproliferative syndrome.
have congenital heart disease. Endocardial cushion defects
account for 40-60% cases. Presence of heart disease is the Management and Prognosis
chief factor in determining survival. All children should The principles of management are early stimulation,
have a cardiac evaluation before 9 months of age, physiotherapy and speech therapy. Associated problems
including echocardiography. need to be treated as required. Social performance is
Gastrointestinal malfonnations: Atresias are present in 12% usually achieved beyond that expected for mental age.
of cases, especially duodenal atresia. There is an increased Generally, they behave as happy children, like mimicry,
risk of annular pancreas and Hirschsprung disease. are friendly, have good sense of rhythm and enjoy music.
The chief cause for early mortality is congenital heart
Ophthalmic problems: There is an increased risk of disease; almost 50% with cardiac anomalies die in infancy.
cataract, nystagmus, squint and abnormalities of visual Chronic rhinitis, conjunctivitis and periodontal disease are
acuity. Routine evaluation is performed in infancy and common. Lower respiratory tract infections pose a threat
then yearly. to life. Hematological malignancies are another cause of
Hearing defects: 40-60% patients have conductive hearing mortality. Table 23.1 outlines the protocol for care of
loss and are prone to serous otitis media (commonly children with Down syndrome.
Fig. 23. 12: Children with Down syndrome at (a) 3 months; (bl 15 months; and (c) 2 years of age. Note the flat facies, upward eye
slant and open mouth appearance
Genetic Disorders 1637-
Counseling Options for couples who come late or opt for initial
Parents of a child with Down syndrome should be screening with serum markers and ultrasonography are
counseled with tact, compassion and truthfulness. Briefy, karyotyping by amniocentesis at 16-18 weeks, trans
one should: (i) Inform about the disorder as early as abdominal chorionic villus sampling and cordocentesis
possible after diagnosis is confirmed; (ii) counsel in after 18 weeks. Karyotype results are available within a
presence of both the parents in privacy; (iii) talk in simple week with cord blood samples and direct chorionic biopsy
and positive language giving hope and allow sufficient preparations. The results of amniotic fluid cultures take
time to the parents to ask questions; (iv) discuss known about two weeks. Rapid testing using FISH and
problems and associated disorders; (v) highlight the quantitative PCR is very reliable and results are available
importance of early stimulation; (vi) not discuss in 24-48 hours.
institutionalization and adoption, unless asked, and
discourage both the options; (vii) ask parents to contact TURNER SYNDROME
the local Down syndrome association, if one exists; Turner syndrome, with 45 X chromosomal constitution,
(viii) talk about genetics only after chromosomal analysis; has an incidence of -1:3000 newborns. However,
(ix) inform about recurrence risks and possibilities of chromosomal studies of spontaneous abortions have
prenatal diagnosis; and (x) schedule future appointments. clearly shown that majority of 45 X fetuses are likely to be
aborted. Since there is no apparent relationship to
Risk of recurrence: Women 35 years of age or less who
advanced maternal age, it is likely that the condition does
have a child with trisomy 21 have a 1 % risk of having
not arise from gametic nondisjunction.
another, which is significantly greater than the general
population. The risk is little increased, if any, over the Cyfogenetics
usual maternal age dependent frequency if the mother at
Many patients with Turner syndrome show considerable
risk is 35 years or older. For translocations inherited from
degree of chromosomal mosaicism, i.e. 45, XI 46, XX or
the mother, the risk is about 10%, whereas it is about
other karyotypes with multiple cell lines. Formation of
4-5% when father is the carrier. Balanced translocation
isochromosome of long arms of X chromosome may lead
21; 21 is the only situation where all viable fetuses will
to Turner phenotype with 46 chromosomes because of
have Down syndrome.
absence of short arms. Figure 23.6b shows a karyotype of
Prenatal screening and diagnosis (also section: Prevention a child with Turner syndrome with deletion of long arm
of Genetic Disorders). Parents who wish to get a prenatal of X chromosome
diagnosis have a number of options. They can directly get
a fetal karyotype either by chorionic villus sampling (by Clinical Features
transcervical or transabdominal route) or amniocentesis. Turner syndrome may be recognizable at birth.
Alternatively (if the parents do not want invasive testing) Lymphedema of the dorsum of hands and feet and loose
an initial screening may be performed with maternal skin folds at the nape of neck may be present. Other
serum markers and ultrasonography (as discussed later). manifestations include short stature, short neck with
-6381 Essential Pediatrics
Management
Height monitoring should be done using growth charts for
Turner syndrome. Cardiac evaluation and measurement of
blood pressure is recommended at baseline and every year.
Fig. 23.13: Turner syndrome. Note (a) Ptosis in right eye, shield Treatment with growth hormone is recommended. While
chest, increased carrying angle, webbed neck and short neck;
therapy may increase the final height by 8-10 cm, the cost
and (bl Low posterior hair line
is prohibitive. Thyroid testing should be done in infancy
webbing and low posterior hair line. Anomalous ears, or early childhood, if the child is lagging in growth. Routine
prominent narrow and high arched palate, small mandible evaluation is required after 10 years of age. Counseling
and epicanthic folds may be noted. Chest is broad shield regarding behavioral problems due to short stature,
like with widely spaced hypoplastic nipples (Fig. 23.13a amenorrhea and sterility is an integral part of management.
and b). There is increased carrying angle at elbow. Bony Ovarian hormone replacement is advised around 14 years.
anomalies include medial tibial exostosis, and short fourth Conjugated estrogen (0.3 mg/ day) or ethinyl estradiol (5-
metacarpals and metatarsals. Pigmented nevi may appear 10 ug/ day) are given for 3-6 months; the dose of
in older patients. At puberty, sexual maturation fails to medications may be increased. After 6-12 months, cyclical
occur. The phenotype is highly variable. It has been therapy with estrogen and progesterone is started.
recommended that the diagnosis of Turner syndrome Regular audiometry is advised in adulthood or earlier,
should be considered in all girls with short stature. if indicated. Evaluation for renal malformation by ultra
Ultrasound may show streak ovaries and hyp oplastic sonography should be done at first contact. Prophylactic
uterus. Levels of FSH and LH are increased (hyper gonadectomy is advised for patients with Y chromosome
gonadotropic hypogonadism). Adult stature is usually due to the risk of developing gonadoblastoma.
below 145 cm. Associated congenital defects are common Table 23.2 gives brief description of some common
in kidneys (horseshoe kidney, double or cleft renal pelvis), aneuploides.
Table 23.2: Clinical features of common aneuploidies
Aneuploidy Clinical features Management
Trisomy 18 Failure to thrive, developmental retardation, hypertonia, micro Symptomatic, supportive
Edward syndrome gnathia (Fig. 23.14a), shield-shaped chest, short sternum, joint
abnormalities including flexion deformity of fingers (Fig. 23.14b and c),
limited hip abduction and short dorsiflexed hallux. Congenital heart
disease is common
Trisomy 13 Development and physical retardation, microcephaly, sloping Symptomatic, supportive
Patau syndrome forehead; cleft lip with/without cleft palate common
Holo-prosencephaly; varying degree of incomplete development
of forebrain, olfactory and optic nerves
Microphthalmia, iris coloboma, retinal dysplasia and cataract; deafness
Capillary hemangiomata (Fig. 23.15); polydactyly, flexion deformities
Congenital heart disease (80%); most die by 6 months of life
Klinefelter syndrome Hypergonadotropic hypogonadism, small testes, fail to develop Behavioral and psychosocial
47,XXY secondary sex characters; tall stature, gynecomastia rehabilitation
Borderline intellectual disability, behavioral problems Testosterone therapy in middle
Consider diagnosis in boys with mental retardation, psychosocial or late adolescence
learning disability, or problems in school adjustment
Genetic Disorders 1639-
X-Linked Recessive Inheritance Fig. 23.19: X-linked dominant inheritance and its characteristics
Since in males, there is no corresponding locus for a
affected males are seldom born alive. Majority of patients
mutant allele of the X chromosome on the shorter Y
are heterozygous females (Fig. 23.19).
chromosome, the mutant X-linked recessive gene
expresses as a clinical disorder in the male child because Mitochondrial Inheritance
it is not suppressed by a normal allele. In the female, the
Mutations within a mitochondrial gene can lead to
disorder does not manifest clinically since the mutant gene
phenotypic defects and show a pattern of maternal genetic
is compensated for by the normal allele in the other X
transmission. Since mitochondria are only present in ovum
chromosome. Females thus act as carriers of the mutant
and not sperms, the inheritance is maternal. All offspring
allele. Half of their male children inherit the mutant allele
of an affected female are affected. All affected daughters
and are affected. Figure 23.18 shows a family with X-linked
transmit the disease. Sons are affected but do not transmit
recessive inheritance. It is now possible to detect carrier
the disease (Fig. 23.20). Examples include Leigh disease
state in females in some disorders, e.g. hemophilia,
and mitochondrial encephalopathy, lactic acidosis and
Duchenne muscular dystrophy and mucopoly
stroke (MELAS) like syndrome.
saccharidosis type II (Hunter syndrome). Color blindness
also has an X-linked recessive inheritance.
and is used mainly for metabolic disorders. The intake of environmental hazards to prevent excessive bleeding and
substances which cannot be metabolized by the body fractures, respectively. Supportive care includes physical
should be reduced, especially if their accumulation is therapy, stimulation and rehabilitation. Bisphosphonate
potentially toxic, e.g. in galactosemia, galactose cannot be therapy has been found useful in patients with osteogenesis
metabolized adequately. As lactose in the milk is imperfecta by reducing osteoclastic activity.
hydrolyzed in the body to glucose and galactose, milk in Targeted therapies for certain disorders, e.g. cystic
the diet of the affected infant is substituted by lactose free fibrosis with specific mutations (Ivacaftor for G551D and
dietary formulae to obviate damage due to excess of Lumacaftor for delta F508del CFTR mutations) and
galactose in tissues. The phenylketonuric infants placed hematological cancers (imatinib for chronic myeloid
on restricted phenylalanine in the diet may escape leukemia) have paved the way for research for several
irreversible neurological damage. genetic and somatic disorders.
Providing deficient proteins: Deficiency of the metabolic Gene therapy is possible in patients with adenosine
end product is managed by its replacement. Thus, deaminase deficiency, familial hypercholesterolemia and
thyroxine restores the thyroid function in familial some cancers. The normal gene is introduced in affected
hypothyroidism; cortisone suppresses excess ACTH individuals using viral or nonviral vectors.
production and androgen synthesis in adrenogenital
syndrome and administration of factor VIII/IX prevents PREVENTION OF GENETIC DISORDERS
bleeding in cases of hemophilia. Enzyme replacement
therapy, although expensive, has become feasible with the Carrier Screening
availability of deficient enzymes for Gaucher disease, It is now possible to detect the carrier state in a large
Hurler syndrome, Hunter syndrome, mucopoly number of autosomal recessive or X-linked recessive
saccharidosis type VI, Fabry disease, MPS IV and Pompe disorders. HbA2 levels are highly useful in identifying
disease. carriers of thalassemia trait pre-pregnancy or early in
Promoting excretion of toxic substances: The excretion of pregnancy. In India ideally all partners should be tested
certain metabolites can be promoted by chelating agents, for beta-thalassemia carrier status as the condition is very
e.g. penicillamine promotes excretion of copper in patients common in North India. Female carriers of Duchenne
with Wilson disease and desferrioxamine is used to chelate muscular dystrophy may show high serum levels of the
iron in patients with thalassemia and hemochromatosis. enzyme creatinine phosphokinase, but can be tested more
precisely using molecular techniques. Such techniques are
Augmenting enzymes: Certain enzyme systems, which increasingly used for detection of individuals who are
may be immature or reduced at certain phases of life may likely to give birth to offspring with hereditary disorders.
be induced or stabilized by the use of chemical agents.
Phenobarbitone is used to induce hepatic microsomal Newborn Screening
enzymes like glucuronyl transferase in cases of neonatal
This is an example of secondary prevention by early
hyperbilirubinemia or Crigler-Najjar syndrome. In some
diagnosis and treatment. Newborn infants are screened
metabolic disorders, enzymatic block can be bypassed by
routinely for some endocrine disorders and inborn errors
administration of large quantities of the coenzyme, e.g.
of metabolism in developed countries. This is of special
pyridoxine in homocystinuria.
value for detecting affected cases in the newborn period,
Avoid precipitating factors and drugs: Certain drugs, so that handicap can be prevented or minimized by early
which precipitate adverse symptoms in metabolic treatment, e.g. congenital hypothyroidism, congenital
disorders, such as barbiturates in porphyria and oxidating adrenal hyperplasia, phenylketonuria, galactosemia and
agents in glucose-6-phosphate dehydrogenase deficiency, tyrosinemia.
should not be given to affected patients.
Stem cell transplantation is recommended for many Prevention of Neural Tube Defects
genetic disorders like thalassemia major, severe Hurler Folic acid supplementation is recommended at a dose of
syndrome and some primary immunodeficiencies. 0.4 mg daily from 1 month before to 3 months after
Surgery helps to reduce the functional or cosmetic conception to prevent neural tube defects. Expectant
disability in some structural defects, e.g. removing the mothers at high-risk of such defects (e.g. previous fetus
spleen in hereditary spherocytosis. Solid organ transplan with neural tube defects) should consume 4 mg of folic
tation, of liver, kidney and heart, is available across India. acid daily to prevent recurrence.
Conditions where transplantation may be useful include
ornithine transcarbamylase deficiency, maple syrup urine Maternal Serum Screening
disease, cardiomyopathies and polycystic kidney disease. Estimation of pregnancy associated plasma protein A
Supportive care: Patients with hemophilia and osteogenesis (PAPP-A) and free human chorionic gonadotropin (hCG)
imperfecta should be protected from trauma and other in the first trimester and serum alpha-fetoprotein, hCG,
Genetic Disorders 1643-
unconjugated estriol and inhibin A in second trimester based tests. Single gene disorders, e.g. thalassemia, sickle
are useful biochemical markers to detect aneuploidies. If cell anemia, hemophilia, Duchenne muscular dystrophy
the risk of bearing a child with Down syndrome is more and cystic fibrosis can be diagnosed prenatally.
than 1:250, prenatal fetal karyotyping can be offered. Fetal
ultrasonography helps to detect fetuses at high-risk for Genetic Counseling
chromosomal abnormalities. Findings in the second Genetic counseling is a communication process, which
trimester which suggest Down syndrome are increased deals with problems associated with occurrence and
nuchal fold thickness, short femur and humerus length recurrence of a genetic disorder in a family. It is the process
and duodenal atresia. In the first trimester, nuchal by which patients or relatives are advised of the risk of
translucency and nasal bone are robust markers. transmission, occurrence and consequences of the
Alpha-fetoprotein and estriol are low, whereas hCG is disorder, and how this can be ameliorated or prevented.
high, in pregnancies with Down syndrome fetuses. The Genetic counseling is an important component of
detection rate of Down syndrome by triple test in the management of genetic disorders, since definitive therapy
second trimester is about 65% with a false positive rate of is not available for most cases.
5%. All three markers are reduced in fetuses with The objectives of genetic counseling are:
trisomy 18. Ultrasound findings help in counseling, • To provide information about the disease to the
particularly if the parents have opted for initial screening individual and the family
with maternal serum markers. First trimester screening • Help the individual or family to choose a course of
using dual markers has high detection rates, which action that seems appropriate in view of disease risk,
improves further if ultrasound markers are combined. family goals, and ethical and religious standards
Elevated maternal serum alpha-fetoprotein level is a
• To make the best possible adjustment to the illness in
sensitive marker for fetuses with open neural tube defects.
an affected family member, and risk of recurrence.
Prenatal Diagnosis and Selective Termination of Counseling should be undertaken by a physician with
Affected Fetuses proper understanding of the genetic mechanisms.
Indications for genetic counseling include: (i) Known or
This is a successfully used modality for preventing birth suspected hereditary disease in a patient/ family; (ii) birth
of affected babies and reducing the load of lethal, defects in previous children; (iii) unexplained mental
chronically disabling, untreatable or difficult-to-treat retardation, dysmorphism, multiple malformations;
genetic disorders in the community. Non-invasive
(iv) consanguinity; (v) exposure to a teratogen during
prenatal screening (NIPS) is also being used for screening
pregnancy; and (vi) identification of malformation(s) by
high risk pregnancies for aneuploidies. This NGS-based ultrasonography during pregnancy.
technique evaluates mother's blood for common fetal
aneuploidies after 10 weeks of gastation and has negative Suggested Reading
predictive value of 98-99%. Positive tests would need
• Cassidy SB, Allanson JE. Management of genetic syndromes, 3rd
confirmation by invasive testing. edn. Wiley Blackwell, USA, 2010.
Invasive Prenatal Testing • Harper PS. Practical Genetic Counseling, 7th e dn. Wright
Publishers, Bristol, 2010.
This includes chorionic villus biopsy (at or after 10-12 • Jamuar SS, Tan EC. Clinical application of next-generation
weeks gestation), amniocentesis (16-20 weeks) and cord sequencing for Mendelian diseases. Human Genomics 2015; 9:10.
blood sampling (after 18 weeks). Procedure related risk is • Miller DT, Adam MP, Aradhya S, et al. Consensus statement:
lowest with amniocentesis (-0.5%), while chorionic villus chromosomal microarray is a first-tier clinical diagnostic test for
individuals with developmental disabilities or congenital
biopsy has a risk of fetal loss in about 1%. These samples anomalies. Am J Hum Genet 2010; 86, 749-64.
can be used for chromosomal studies, DNA based tests or • Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA analysis
enzyme assays. Amniotic fluid is the preferred sample for for noninvasive examination of trisomy. N Engl J Med
chromosomal studies and chorionic villus tissue for DNA 2015;372:1589-97.
Chapter
24
Inborn Errors of Metabolism
Neerja Gupta • Madhulika Kabra
Inborn errors of metabolism (IEM) are conditions caused with slow progression. They usually have characteristic
by the genetic errors related to synthesis, metabolism, findings that enable a specific clinical diagnosis.
transport or storage of biochemical compounds. The
metabolic error usually results in the accumulation or Clinical Suspicion
deficiency of a specific metabolite. These disorders are The diagnosis of IEM is often delayed, and requires a high
individually rare, but collectively common, and manifest index of suspicion. Symptoms are often nonspecific,
at any time from the fetal life to old age. Early recognition leading to evaluation for other disorders. Clues that
of signs and symptoms, prompt evaluation and suggest the presence of an IEM are listed in Table 24.1.
management results in optimal outcome.
Classification
Table 24.1: Clinical clues suggessting IEM
Intoxication group includes disorders of intermediary
Neonates
metabolism, with accumulation of toxic compounds
resulting in acute or progressive symptoms. Amino Unexpected deterioration after normal initial period
acidopathies (e.g. phenylketonuria, maple syrup urine Nonspecific, unexplained features such as poor feeding,
disease), organic acidurias, urea cycle defects, disorders lethargy, vomiting, hypotonia, failure to thrive, respiratory
abnormalities, apnea, bradycardia and hypothermia
of carbohydrate and copper metabolism and porphyrias
belong to this category. Symptoms are precipitated by Children
catabolic state (fever, infections, immunization, Sudden and rapid illness in a previously well child precipitated
dehydration or fasting). by fever, infection or fasting
Acute encephalopathy; previous similar episodes
Defects of energy metabolism include conditions with Recurrent coma, stroke, ataxia, cramps
deficient energy production or utilization within liver, Worsening with intercurrent febrile illness
muscle, heart and brain, e.g. mitochondrial disorders, History of aversion to sweets, high protein
disorders of glycolysis, glycogen metabolism and Developmental regression
gluconeogenesis, and hyperinsulinism. Failure to thrive, Facial dysmorphism, structural anomalies of brain, cataract,
hypoglycemia with high lactate, hepatomegaly, retinopathy, deafness cardiomyopathy, hepatomegaly,
hypotonia, cardiomyopathy, myopathy, neurological myopathy
symptoms and circulatory collapse may occur. Peculiar odor (musty in phenylketonuria; cabbage like in
tyrosinemia; maple syrup like in maple syrup urine disease;
Disorders of complex molecules include lysosomal storage sweaty feet in isovaleric acidemia or glutaric acidemia type II;
diseases, peroxisomal disorders, al-antitrypsin deficiency cat urine in multiple carboxylase deficiency)
and congenital disorders of glycosylation. Symptoms are Persistent or recurrent hypoglycemia, intractable metabolic
progressive and permanent and do not have precipitating acidosis, hyperammonemia, hyperkalemia
factors. Most disorders have multisystem involvement. Reye syndrome like illness
Common features include developmental delay, E. coli sepsis
organomegaly, coarse fades and arthropathy.
Others
The onset of illness in the intoxication group and in
Family history of similar illness, unexplained sib deaths, or
defects of energy metabolism is often sudden, with
progressive neurological disease
nonspecific physical findings. The course may be recurrent
Parental consanguinity: Most acutely presenting metabolic
and episodic, and response to supportive therapy is rapid. disorders are autosomal recessive.
In disorders of complex molecules, the onset is gradual
644
Inborn Errors of Metabolism 1645-
Plasma amonia
I I
High Normal
t .----------_---.
_,t'----,
No acidosis Acidosis No acidosis
Urea cycle Organic aciduria Pyruvate carboxylase Maple syrup urine disease Aminoacidopathies
Fatty acid oxidation defect deficiency Short chain acyl CoA Nonketotic hyperglycinemia
defect
Glycogen storage disease Multiple carboxylase dehydrogenase deficiency Galactosemia
type 1 deficiency Peroxisomal disorders
Hereditary fructose Respiratory chain or
intolerance mitochondrial defects
Organic aciduria
Table 24.3: Specimens taken in critically sick children with ii. Provide adequate calories (0.2% saline in 10% dextrose
undiagnosed IEM IV); intralipids (2-3 g/kg/day) may be infused if fatty
Clinical photograph and infantogram
acid oxidation defect is not suspected.
iii. Correct metabolic acidosis, dehydration and electrolyte
Blood:5 ml in heparin, separated and stored at-70 ° C;5-10 ml
EDTA blood (leukocytes), refrigerated and not frozen; few blood imbalance. Treat intercurrent illness, if any.
spots on filter paper (acyl carnitine analysis) iv. Enhance excretion of toxic metabolites. Immediate
measures to reduce blood ammonia are necessary as
Urine:5-1 O ml frozen in plain sterile tubes
the risk for irreversible brain damage is related to its
Cerebrospinal fluid: 3-5 ml in 1-2 aliquots frozen and stored concentration. IV phenylacetate and sodium benzoate
at-70 ° C with L-arginine (Table 24.4) are used as detoxifying
Skin biopsy: -3 mm diameter skin (include dermis) from the agents, in urea cycle defects and organic acidemias.
flexor aspect of the forearm or anterior aspect of thigh. Store Dialysis is initiated if plasma ammonia levels >500-
at 37 ° C or refrigerate (not freeze) in culture medium or saline 600 µg/dL, or if levels do not fall within 2 hours after
with glucose. initiation of IV treatment. Hemodialysis is preferred
Liver, muscle, kidney, heart biopsy: At least two tissue biopsies to peritoneal dialysis and exchange transfusion.
of about 1 mm3 , one immediately frozen in liquid nitrogen and Carnitine eliminates organic acids as camitine esters,
other in the glutaraldehyde and is used in life-threatening situations associated
with its deficiency, at a dose of 25-50 mg/kg IV over
for a biochemical autopsy for confirmation of diagnosis 2-3 minutes, followed by 25-100 mg/kg/day orally.
(Table 24.3). Specimens should be obtained before or L-carnitine should not be administered with sodium
within 1 to 2 hours of death to facilitate diagnosis. benzoate. Intractable seizures without metabolic
acidosis or hyperammonemia are treated with
Principles of Management pyridoxine 100-200 mg IV.
Specific treatment is directed towards reversing the basic v. Empiric cofactor or coenzyme therapy may be
pathophysiological process causing the disease. It administered (Table 24.5) to maximize residual enzyme
includes reduction of substrate accumulation for a activity. Long-term adherence to dietary and
deficient enzyme, reduce accumulated toxic metabolites, pharmacologic regimen is recommended. Prompt
supplement metabolites, replace deficient enzyme or recognition and avoidance of physiologic stresses
enhance residual enzyme activity (Fig. 24.2). Treatment (fever, infection, trauma, surgery, fasting) and changes
is symptomatic, supportive and often instituted in diet that may precipitate symptoms is important in
empirically. preventing metabolic decompensation.
i. Eliminate dietary or parenteral intake of potentially vi. If clinical improvement is observed and a final diagnosis
toxic agents (e.g. protein, fat, galactose, fructose). is not yet established, some amino acid intake is provided
Inborn Errors of Metabolism 1647-
ts I
C
tA
E
Precursors accumulate;
toxicity �
Deficient
enzyme
I Deficient product I
�
D
I Alternate metabolites; accumulation of toxic metabolites I
Fig. 24.2: Effect of deficient enzyme (El on A, B and C of an affected pathway (lower panel) and different therapeutic modalities
(upper panel)
after 2-3 days of complete protein restriction. Essential organomegaly, coarse fades, cataract, dislocated lens,
amino acids or total protein is provided orally or IV (begin chronic skin lesions, abnormal hair or urine color, and
at 0.5 g/kg/day, increased to 1-1.5 g/kg/day) until failure to thrive are useful clues. These forms are divided
diagnostic evaluation is complete. Appropriate amino into subgroups depending upon the involvement of
acid formula (free of precursor amino acids) or protein specific system (Fig. 24.3).
free infant formula with breast milk is introduced with Neurologic findings are developmental delay or
clinical and laboratory monitoring. Expressed human progressive psychomotor retardation, seizures, ataxia,
milk is preferred as it can be measured and total protein spasticity, variable hearing and visual impairment, and
intake can be quantified. extrapyramidal symptoms. Psychomotor or developmental
delay is the chief manifestation and tends to be global and
CHRONIC AND PROGRESSIVE PRESENTATION
progressive; regression of milestones may be present.
This group of disorders is characterized by variable but Severe irritability, impulsivity, aggressiveness,
insidious onset from birth to adulthood. Unexplained hyperactivity and abnormal behavior (automatism,
developmental delay with or without seizures, stereotypes, compulsive chewing of thumbs and fingers,
-648 Essential Pediatrics
Chronic encephalopathy
Psychomotor regression
Seizures
Neurological signs
+ +
Yes No
l
Dementia Gaucher disease disorders Homocystinuria
Fig. 24.3: Initial approach to a chronic encephalopathy. MLD metachromatic leukodystrophy; NCL neuronal ceroid lipofuscinosis;
NPD Niemann-Pick disease; MPS mucopolysaccharidoses. Modified from: Clarke JTR. A clinial guide to inherited metabolic disease
(Reference 1 )
self-mutilation, nocturnal restlessness) are common. Hepatic presentations include presence of un
Complex partial or myoclonic seizures occur early in conjugated or conjugated jaundice, hypoglycemia and
course of the disease and are often resistant to therapy. hepatomegaly with or without hepatocellular dysfunction.
Differentiating between predominant involvement of grey Deranged lipid profile is seen in GSD types I and III, and
and white matter helps in narrowing the diagnosis hepatosplenomegaly in lysosomal storage disorders.
(Table 24.6). Movement disorders are intermittent or Hepatocellular dysfunction is seen in galactosemia, GSD
progressive, in form of ataxia, dystonia, choreoathetosis IV and III, Niemann-Pick type B and a 1 -antitrypsin
and Parkinsonism. Underlying conditions include late deficiency. Disorders leading to cirrhosis include
onset organic aciduria, neuronal ceroid lipofuscinosis and tyrosinemia, galactosemia, hereditary fructose intolerance
lysosomal storage disorders. and Wilson disease.
Muscular disorders presenting with myopathy are
Cardiac manifestations may occur in fatty acid
usually due to defects in energy metabolism. Myopathy
oxidation defects, mitochondrial disorders, GSD type II,
may be progressive (glycogen storage disease, GSD types
methylmalonic acidemia, Fabry disease, Kearns-Sayre
II and III), exercise intolerance with cramps and
syndrome, familial hypercholesterolemia, mucopoly
myoglobinuria (GSD V, VI) or part of multisystem disease
saccharidoses and GMl gangliosidosis.
(mitochondrial myopathies).
Table 24.6: Differentiating features of gray matter and white matter disorders
Clinical features Gray matter disease (poliodystrophy) White matter disease (/eukodystrophy)
Age of onset Early Usually late (childhood)
Head size Microcephaly (more common) May have macrocephaly
Seizures Early, severe Late, uncommon
Cognitive functions Progressive decline Initially normal
Spasticity At a later stage Early, severe
Reflexes Normal or brisk Absent (neuropathy) or brisk (long tracts involved)
Eye Retinal degeneration Optic atrophy, cataract, cherry red spot
Peripheral neuropathy Late Early demyelination
Electromyography Usually normal Slowed nerve conduction velocity
Evoked potentials (VEP) Usually normal Prolonged or absent
Electroretinography Abnormal Normal
MRI brain Cerebral atrophy mainly White matter involvement (demyelination, dysmyelination)
Inborn Errors of Metabolism 1649-
Dysmorphic features are present in Zellweger Since most IEMs are inherited in an autosomal recessive
syndrome, glutaric aciduria type 2 and storage syndromes. manner, the risk of recurrence in subsequent pregnancies
Renal manifestations are seen in patients with is 25%. Few disorders show X-linked, autosomal dominant
cystinosis, galactosemia, hereditary fructose intolerance and mitochondrial inheritance. Prenatal diagnosis is
and tyrosinemia (renal tubular acidosis); progressive renal possible by enzyme assays or mutation testing on fetal
failure is common in cystinosis. Enlarged kidneys are seen DNA, obtained through amniotic fluid or chorionic villus
in patients with GSD type I. biopsy (Chapter 22).
Ocular findings may be useful in ascertaining a
diagnosis. Presence of cataract(s) suggests galactosemia, Specific Disorders
peroxisomal disorders, Lowe syndrome and Wilson Aminoacidopathies do not show a common phenotype
disease; lens dislocation is seen in homocystinuria. Corneal but may have unique features (Table 24.7). Table 24.8
abnormalities are seen in mucopolysaccharidoses, Wilson briefly describes urea cycle disorders and organic
disease and Fabry disease. Cherry-red spots are found in acidemias. Figures 24.5 and 24.6 indicate the enzymatic
various lysosomal storage diseases (Tay-Sachs disease, defects and an algorithmic approach to the diagnosis.
GMl gangliosidosis and Niemann-Pick disease). Skin may
show an eczematous rash associated with alopecia in Defects of Carbohydrate Metabolism
biotinidase deficiency. Angiokeratoma are characteristic
These disorders include galactosemia, hereditary fructose
of Fabry disease, but are also seen in fucosidosis and
intolerance and glycogen storage disorders. Major features
13-mannosidosis.
include hypoglycemia, liver dysfunction with or without
skeletal and/ or cardiac muscle involvement.
Laboratory Investigations
Investigations include complete hemogram, liver and Galactosemia
renal function tests and electrolytes. Anemia and There are three disorders of galactose metabolism
thrombocytopenia are important features of Gaucher (Fig. 24.8), but it is the deficiency of the enzyme galactose-
disease; pancytopenia may be seen in propionic and 1-phosphate uridyltransferase (GALT), that is referred to
methylmalonic acidemia. Peripheral smear may show as classical galactosemia. Deficiency of GALT results in
vacuolated lymphocytes in neuronal ceroid lipofuscinosis, accumulation of galactose-1-phosphate and other
fucosidosis and sialidosis; acanthocytosis in abetalipo metabolites (e.g. galactitol) that have toxic effects on the
proteinemia and Hallervorden Spatz disease. Adrenal liver and other organs.
insufficiency is frequent in patients with adreno
Patients are normal at birth, but by 3-4 days of breast
leukodystrophy. Metabolic acidosis with proximal tubular
milk or formula feeding show life-threatening disease with
dysfunction is present in patients with Lowe syndrome,
vomiting, diarrhea and poor weight gain. Jaundice and
cystinosis, Wilson disease and galactosemia. Neuro
liver dysfunction are progressive and appear at the end
imaging, electrophysiological studies and skeletal survey
of first or second week of life. The disease may present
are useful for various neurodegenerative and storage
initially with indirect hyperbilirubinemia due to hemolysis
disorders.
secondary to high levels of galactose-1-phosphate in
Bone marrow aspirate is useful to rule out specific erythrocytes. Many affected infants die of E. coli sepsis in
storage disorders. Enzyme assays for various storage the neonatal period. Untreated infants, if surviving the
disorders are now available and provide definitive neonatal period, have persistent liver disease, cataracts
diagnosis. Estimation of plasma levels of lactate, ammonia, and mental retardation. Acute galactose toxicity may
very long chain fatty acids and amino acids are useful in rarely cause chiefly neurologic symptoms. Proximal renal
certain cases. DNA molecular testing is the most specific tubular disease presents with metabolic acidosis,
form of diagnostic testing and is useful for prenatal galactosuria, glucosuria and aminoaciduria (Fanconi
diagnosis. syndrome).
The diagnosis is confirmed by either enzyme or specific
Management
mutational analysis. A negative urine dipstick by glucose
A multidisciplinary team of metabolic specialists, pediatric oxidase method with positive Benedict reaction indicates
neurologists, clinical geneticist, cardiologist, orthopedic non-glucose reducing substances, e.g. galactose or
surgeon and physiotherapist is required to maximize the fructose. A negative test does not eliminate the possibility,
supportive care in these patients. Supply of deficient especially if the patient has received IV glucose for more
enzyme (enzyme replacement), enhancing residual than a few hours.
enzyme activity through cofactor and megavitamin
therapy (enzyme enhancement/ organ transplantation), or Management: If the diagnosis is suspected, whether or not
reduction of substrate accumulation (substrate reduction) urinary reducing substances are found, galactose
are available for these disorders (Fig. 24.2). containing feedings should be discontinued and replaced
sso I Essential Pediatrics
by soy based or lactose free formula pending results of Hereditary Fructose Intolerance
confirmatory enzyme assay or genetic studies. Galactose The condition occurs due to deficiency of the enzyme,
restricted diet is required throughout life. aldolase B. Symptoms occur following ingestion of
Galactokinase deficiency: This deficiency is rare. The only fructose or sucrose and present with intractable vomiting
significant abnormality is cataract due to accumulation and symptomatic hypoglycemia. Prolonged exposure
of galactitol. Liver, kidney and brain symptoms are not results in failure to thrive, dislike for fruits and sweets,
seen. Galactose free diet, leads to improvement and irritability, hepatomegaly, abdominal distension, edema
prevents further damage. Galactose restricted diet is and jaundice. Investigations show hypoglycemia, lactic
required throughout life. acidosis, hyperuricemia and deranged liver function tests,
Inborn Errors of Metabolism lss1-
N-acetyl glutamate
synthase!
!1�
N-acetyl glutamate
Aspartate
·��
including prolonged pro thro mbin and partial Arginosuccinate
thromboplastin time. Proximal renal tubule dysfunction
manifests as F anconi syndro me. The diagnosis is
confirmed by demonstration of deficiency of aldolase B
in fresh liver biopsy. Fructose free diet is therapeutic. Fumarate Arginosuccinate lyase (4)
Glycogen Storage Diseases Fig. 24.5: Pathways for ammonia disposal and ornithine
metabolism. Deficiency of enzymes results in the following:
Glycogen is an extensively branched polysaccharide (1) CPS deficiency, (2) OTC deficiency, (3) citrullinemia,
macromolecule formed by thousands of glucose units (4) arginosuccinic aciduria and (5) argininemia
652 Essential Pediatrics
T
Elevated citrulline: Citrullinemia
Normal or low Elevated ornithine: Hyperammonemia,
hyperornithinemia, homocitrullinemia
+
Low plasma citrulline
C
glycogen is depolymerized, bonds at branch points are Galactose-1-phosphate
UDP-galacto se
split and free glucose is released into blood by hydrolytic 4'-epimera se uridyltran s fera s e
I
I
,---------------- I Glycogen I l
Phosphorylase kinase
liver
Muscle
�IG-S-D-Vl�III
I GSD IX I
I +
I
Lysosome�� Phosphorylase
_ �
Glycogen Liver I GSD VI I
Glycogen synthetase
I l
Glucose
Pyrophosph��------,�
""'' ) Glucose -1-phosphate
: UTP
Debranching
Phosphoglucomutase enzyme
I GSD 111 I
,+
l
I Glucosej-----------1 Glucose-6-phosphate Ii.,.-----I �lucose I
�--� Glucose-6-phosphatase Glucokinase
GSD I q
'"oo'""''"'"wmera�
l
F ructose-6-phosphate
f
'"ooe•om""'""" I GSD VII I
Frnotose-1 phosphate
IPyruvate!,.,._____
., Lactate
Fig. 24. 9: Schematic glucose and glycogen metabolism in liver and lysosomes. Common enzyme defects and corresponding
glycogenoses are depicted
myopathy and nonsyndromic aminoglycoside-induced and ketosis. Muscle biopsy shows ragged red fibers as well
sensory neural hearing loss. as subsarcolemmal accumulation of mitochondria.
A markedly elevated blood lactate and lactate-to Staining for succinate dehydrogenase and cytochrome C
pyruvate ratio >30 suggests an OXPHOS defect. Other oxidase is useful. Brain magnetic resonance imaging (MRI)
biochemical features are metabolic acidosis, hypoglycemia and/ or spectroscopy are helpful in diagnosis.
Inborn Errors of Metabolism lsss-
Fig. 24.10: (a) A 4-year-old child with glycogen storage disease type I. Note the doll-like facies and protuberant abdomen due to
hepatomegaly. (b and c) Pompe disease (type II) with marked hypotonia; and (d) Cardiomegaly
No specific therapy is available. Supportive treatment mucopolysaccharides are excreted in urine. Six different
includes supplementation with cofactors such as types of mucopolysaccharidoses with their subtypes are
riboflavin, coenzyme Q, folinic acid, vitamin E, vitamin C, recognized. Their distinguishing features are described
camitine, high lipid, low carbohydrate diet and avoiding in Table 24.11 and are shown in Fig. 24.11.
mitochondrial toxins such as sodium valproate and statins. Urinary excretion of glycosaminoglycans (GAG) by 2D
electrophoresis is a useful screening test. Specific enzyme
Lysosomal Storage Disorders assays and DNA analyses confirm the diagnosis. Palliative
Lysosomes are one of the important cellular organelles care and multidisciplinary management are important.
responsible for degradation of complex cellular molecules Enzyme replacement therapy is available for types I, II,
using various acid hydrolases. Deficiency of these IV, and VI, but the cost is prohibitive. An early bone
enzymes results in the accumulation or storage of an marrow transplantation has been found to be effective in
intermediate compound. Deposition of this stored material MPS IH.
in several body tissues leads to cellular damage and
Sphingofipidoses
disease symptoms.
Enzyme deficiencies in the degradation pathway of These are clinically heterogeneous disorders and include
glycosaminoglycans cause mucopolysaccharidoses. In some GMl and GM2 gangliosidoses, Gaucher disease,
glycolipid storage disorders, neurological functions are Niemann-Pick diseases, Fabry disease, Farber disease, and
impaired due to abnormal deposition in the brain. The Krabbe and metachromatic leukodystrophy. The most
second category of oligosaccharidoses is the result of consistent feature is enlarged liver and spleen, with or
deficiencies of enzymes responsible for degradation of without neurological involvement (Gaucher disease I and
glycoproteins with a less complex polysaccharide III, Niemann-Pick disease A and B, and GMl
(oligosaccharides) than glycosaminoglycans. The third gangliosidosis). Metachromatic leukodystrophy and
category, sphingolipidoses is caused by deficiency of Krabbe disease are characterized by white matter
sphingolipid degrading enzymes. Accumulation of lipid involvement and demyelination without organomegaly.
inside the cells gives them a foamy appearance, chiefly Gaucher disease: This is the commonest autosomal
seen in liver, spleen, lungs and marrow, with enlargement recessively inherited lysosomal storage disease. It occurs
of these organs. All conditions have autosomal recessive due to the deficiency of the tissue enzyme gluco
inheritance except mucopolysaccharidosis II and Fabry cerebrosidase that splits glucose from glucosylceramide,
disease (X-linked). Common disorders are discussed resulting in accumulation of the latter in cells of the
below and summarized in Table 24.10. reticuloendothelial system. Cerebroside-laden cells are
large and have eccentric nuclei with vacuolated cytoplasm
Mucopo/ysaccharidoses and 'wrinkled tissue paper' appearance (Gaucher cells). It
Mucopolysaccharides constitute a major part of connective is characterized by visceral (hepatosplenomegaly), and
tissue and consist of units of disaccharides, nitrogen and bone marrow involvement leading to anemia,
esters. In mucopolysaccharidoses, acid mucopoly thrombocytopenia, leukopenia, bony pains, fractures.
saccharides are deposited in the tissues and excreted in There may be associated neurological symptoms like
the urine. Due to lack of degradation, mucopolysaccharides developmental delay, seizures and ocular involvement.
accumulate in the lysosomes causing disorganization of Non-neuronopathic (type I) is the commonest form and
the cell structure and function. Partially degraded characterized by absence of neurological symptoms. Signs
-656 Essential Pediatrics
and symptoms can develop at any age and include anemia, and swallowing difficulty, opisthotonus, head
fatigue, poor growth, delayed puberty, easy bleeding and retroflexion, spasticity and trismus, abnormal eye
bruising, weak bones, bone and joint pain, fractures and movements, oculomotor apraxia (trouble in moving eyes
enlarged liver and spleen (Fig. 24.12a). to look side-to-side, need to turn head to see things on the
Neuronopathic forms show involvement of the central side), saccadic initiation failure (failure in starting fast eye
nervous system. Two types are distinguished by the rate movements) and optokinetic nystagmus, dementia and
of neurological progression. Type II (acute neuronopathic) ataxia, generalized tonic-clonic seizures and progressive
presents early in fetal life as hydrops or in early infancy myoclonic epilepsy.
with neurological signs and involvement of spleen and Diagnosis is made by measuring glucocerebrosidase
liver involvement. Course is rapidly progressive leading levels in leukocytes or skin fibroblasts. Serum chitotrio
to early death by 2-4 years. Type III Gaucher disease sidase levels are elevated. Neuro-ophthalmological
(chronic neuronopathic, Fig. 24.12b) a chronic form with investigations, hearing assessment by brain evoked
indolent course and manifestations in early childhood. response audiometry, EEG and neuropsychometry tests
Signs and symptoms are same as in type 1 except that are required. DNA analysis is helpful in assessment of
neurological involvement is slowly progressive and leads phenotype and prenatal diagnosis.
to death by second or third decade. Neurological This was the first storage disorder for which treatment
symptoms include developmental delay, stridor, squint was available, chiefly as enzyme replacement therapy and
Inborn Errors of Metabolism 1657-
Fig. 24.11: Mucopolysaccharidoses: (a) Patient with type IH disease showing corneal clouding and coarse facial features; (b) MPS,
type II without corneal clouding but with facial coarseness; (c) MPS IHS (milder phenotype) with restriction of joint movements;
(d) Short trunk with barrel-shaped chest and sternum protruding forward in MPS IV (morquio disease); (e) Mild facial coarseness in
A child with MPS Ill; (f) MPS VI (Marotaeux-Lamy) with abnormal skull and facial coarseness; (g) Beaking of the inferior margins of
vertebrae and proximal pointing of metacarpals In MPS type I; (h) Central beaking of the lumbar vertebrae with proximally pointed
metacarpals and short ulnae in MPS IV
substrate reduction therapy. The former provides deficient with type I Gaucher disease with mild to moderate
enzyme to allow breakdown of fat in cerebroside laden manifestations for which enzyme therapy is not an option.
cells. Enzyme replacement does not have much effect on Splenectomy increases the risk of progressive skeletal and
neurons so CNS manifestations are irreversible. Therapy pulmonary disease. Stem cell transplantation is a potential
is recommended in types I and III but not in type II. option.
Substrate reduction therapy means reducing the
production of fatty material, thereby avoiding cellular Metachromatic leukodystrophy: Sulfated glycosphingolipids
accumulation. Miglustat is oral treatment for adult patients accumulate in white matter of the central nervous system,
ssa I Essential Pediatrics
Peroxisomal Disorders
Peroxisomes are involved in the oxidation (!3-oxidation of
phytanic acid and of very long-chain fatty acids, VLCFA)
as well as synthesis of plasmalogens. Based upon their
functioning, peroxisomal disorders can be divided into
two major groups.
Disorders of peroxisomal biogenesis or importation are
Fig. 24.12: (a) Gaucher type l : Note protuberant abdomen caused by defects in the transfer of proteins produced in
due to hepatosplenomeagly; and (b) Gaucher type Ill: Note the cytosol into the peroxisomes. This includes Zellweger
trismus and ophthalmoplegia syndrome (Fig. 24.13), neonatal adrenoleukodystrophy
and infantile Refsum disease and rhizomelic chondro
stains them purple with a brown background, resulting in d ysplasia punctata (Fig. 24.14). These disorders have
metachromatic staining. autosomal recessive inheritance and are caused by defects
The disorder has infantile and juvenile forms. Early in genes coding for peroxins (PEX). Defects interfere with
manifestations include disturbances of gait, incoordina peroxisomal biogenesis and import of proteins into
tion and progressive mental deterioration in the second peroxisome.
year of life. Knee jerk is brisk but ankle reflex and plantar Disorders of individual peroxisomal enzymes include
response may be absent because of involvement of X-linked adrenoleukodystrophy and classical Refsum
peripheral nerves. Diagnosis is confirmed by level of the disease.
enzyme, arylsulphatase A in white cells. There is no X-linked adrenoleukodystrophy (ALD) is an X-linked
effective treatment; bone marrow transplantation has been recessive disorder caused by tissue accumulation of
tried. VLCFA with a carbon chain length of 24 or more due to
GM2 gangliosidosis: Inborn errors of GM2 ganglioside deficient peroxisomal degradation of fatty acids. The
metabolism result in accumulation of the metabolite defective gene (ABCDl gene) is located on Xq28. The
within lysosomes of nerve cells. Most infants with Tay childhood cerebral form usually manifests between 4 and
Sachs form (type I) of the disease have severe deficiency 8 years of age with subtle initial manifestations of
of 13-N-acetylhexosaminidase A (hexosaminidase A). worsening school performance and behavioral problems
Hexosaminidase A and B are deficient in Sandhoff disease such as hyperactivity and emotional lability. Auditory and
(type 11). visual disturbances may be associated. Seizures are often
Tay-Sachs disease is an autosomal recessively inherited the initial manifestation. In most patients, adrenal
defect, which results from deficiency of hexosaminidase dysfunction is noticed after the cerebral symptoms. Rapid
enzyme leading to accumulation of GM2 ganglioside neurological progression ensues causing increasing
within ganglion cells of the nervous system. The disorder spasticity, visual and hearing impairment. MRI brain
manifests by 6 months with loss of head control and the typically shows demyelination in the parieto-occipital
ability to sit. The head is disproportionately large. This is areas (Fig. 24.15).
followed by progressive course with eventual spasticity, In adolescents, the usual age of manifestation is
deafness and blindness. Fundus shows cherry-red spot. between 10 and 21 years and progression is much slower
Death occurs within 4-5 years. In Sandhoff disease, than the above form. Adrenomyeloneuropathy is a milder
visceral involvement is present in addition to features of form with onset in late adolescence or adulthood and is
Tay-Sachs disease. characterized by progressive paraparesis due to long tract
Niemann-Pick disease: This is an autosomal recessive degeneration in the spinal cord.
disorder of sphingomyelin and cholesterol in the Elevated plasma levels of VLCFA can identify patients
lysosomes. In the classical form (type A), clinical features and 85% of female carriers of X-adrenoleukodystrophy.
begin in early life with feeding difficulties, failure to thrive Mutation analysis is the most reliable method to identify
and developmental delay and later neuroregression. There carriers. Corticosteroid replacement should be given for
is protuberant abdomen with hepatosplenomegaly. adrenal insufficiency. Bone marrow transplantation is
Cherry-red spot on fundus examination is seen in about curative but needs to be performed early in the disease.
half the cases. Diagnosis is confirmed by measurement of The role of Lorenzo oil is controversial.
Inborn Errors of Metabolism lssg-
Fig. 24.15: Brain MRI findings in X-linked adrenoleukodystrophy. T2-weighted axial images show symmetrical hyperintense signal
changes in bilateral perieto-occipital white matter and splenium of corpus callosum (Courtesy: Dr. Atin Kumar, AIIMS, New Delhi)
Suggested Reading
• Clarke JTR. General principles. In: A clinical guide to inherited • Saudubray JM, van den Berghe G, Walter JH. Inborn metabolic
metabolic diseases, 3rd edn. New York: Cambridge University diseases: Diagnosis and treatment, 5th edn. Springer Medizin;
Press, 2006. 2011.
Chapter
25
Ophthalmic Disorders
Radhika Tandon
Children may present with varied primary eye problems. II. Family history of any of the following
Several systemic diseases have ocular manifestations, • Retinoblastoma
some of which are very useful in making the correct • Childhood cataract
diagnosis and instituting appropriate management. Also, • Childhood glaucoma
therapies for some diseases are known to have ocular side • Refractive errors in early childhood
effects which need to be recognized. Rarely, medications • Retinal dystrophy or degeneration
for eye diseases can have systemic side effects. Finally • Strabismus and/or amblyopia
diseases beginning in the eyes and adnexa can have • Sickle cell disease
systemic complications. • Syndromes with ocular manifestations
• Nontraumatic childhood blindness
PEDIATRIC EYE SCREENING III. Signs or symptoms reported by the family, health care
The concept of screening children for eye diseases is based provider or school teacher
on the awareness that infants and young children cannot • Defective ocular fixation or visual interactions
communicate their symptoms and visual difficulties. In • Abnormal appearance of the eye(s)
addition, several potentially blinding diseases manifest in • Squinting or tendency to close one eye in certain
this age group; their early detection and treatment can limit situations
ocular morbidity and prevent irreversible blindness. • Any obvious ocular alignment, movement abnor-
mality, head tilt or nystagmus
The goal of pediatric eye screening is to detect eye and
• Large and/or cloudy eye(s)
visual disorders in children or identify their risk factors
• Drooping of the eyelid(s)
so that the child can be referred for detailed ophthalmic
• Lumps or swelling around the eye(s)
evaluation, confirmation of diagnosis and appropriate
• Persistent or recurrent tearing, sticky discharge,
medical management.
redness, itching or photophobia
Comprehensive Pediatric Eye Evaluation • Learning disabilities or dyslexia
Presence of any of the following risk factors is an indication
Guidelines for Examination
for referral for comprehensive ophthalmic evaluation.
I. General health condition, systemic disease or use of Children are best examined in a comfortable and friendly
medications associated with eye disease environment. Very young children can remain in the lap
• Extreme prematurity (gestational age :s;30 weeks); of their mother while older children can be distracted with
suspected retinopathy of prematurity toys and colorful objects. When the child first enters the
• Intrauterine growth retardation room, simple observation of behavior, fixation, movement
• Perinatal complications and general awareness of the surroundings are good
• Neurological disorders indicators of the child's visual status, and gross abnor
• Juvenile rheumatoid arthritis malities can be detected.
• Thyroid disease Steady fixation and uniform steady alignment of the eyes
• Craniofacial abnormalities develop in the first 4-6 weeks. Visual acuity assessment in
• Diabetes mellitus children less than 6 months of age is limited to seeing if the
• Syndromes with known ocular manifestations child attempts to fix and follow light. A child 6-12 months
• Chronic steroid therapy; use of hydroxychloroquine of age can follow and even reach out towards colorful
or other medications known to affect eyes objects, and this permits a very crude assessment of gross
• Suspected child abuse visual ability. A more objective assessment can be made
660
Ophthalmic Disorders I 661
with electrophysiological tests using a pattern-induced through the undilated pupil to view the disc and macula.
visual evoked response (pattern VER) using chequered In case required, more detailed examination of the fundus
patterns of varying degrees of resolution or by observing and retinal periphery can be carried out after dilating the
the optokinetic response or nystagmus induced by the pupils with mydriatic eye drops such as 2.5%
child's attempt to view a striped pattern on a moving drum phenylephrine or short-acting cyloplegic-mydriatic drops
(OKN). Both these tests are an assessment of the resolution such as 0.5% tropicamide or 1 % cyclopentolate eye drops.
acuity or power of the eye to distinguish patterns of varying The retina is best viewed with an indirect ophthalmoscope
degrees of separation or width. These tests are expensive as this gives the maximum field of view and the exami
and not readily available in routine clinics. For most nation can be completed efficiently. In general, as far as
preverbal children up to the age of 3 years, a simple obser possible, most of the examination should be completed
vation of fixation pattern and behavior, ability to see, follow without touching or going too close to the child so that the
or pick-up small objects like toys or candy beads, preferen child is comfortable and does not feel intimidated. Digital
tial looking tests using Teller acuity cards or preferential assessment of the intraocular pressure, eversion of the lids
looking cards are used to estimate the visual status. and slit lamp examination are occasionally required. In
Unilateral loss is also tested for by observing if the child certain situations, an examination under anesthesia is
resists closure or occlusion of one eye over the other. required and should be done only after obtaining the
Vision of children 3-5 years of age can be assessed using parents' informed consent.
picture tests and symbols with matching cards such as the
Kays symbols, tumbling E or HOTV card tests where one CONGENITAL AND DEVELOPMENTAL ABNORMALITIES
relies on the child's ability to recognize the shape and match
This group of diseases may or may not manifest at birth.
the shape with a similar one on a card. Children 5 years or
If the disease is detected at birth, it is 'congenital' such as
older can be tested with more conventional vision testing
lid coloboma, severe corneal opacity or total cataract with
methods using a Snellen visual acuity chart with either
a white opaque lens. Sometimes the disease is present at
alphabets or tumbling E or Landoldts C symbols (Fig. 25.1 ).
birth, but is detected later on, for example, a partial cataract
Ocular movements and external examination of the eye or mild congenital glaucoma. Sometimes the disease is a
can be performed by using adequate illumination with a defect of development but manifests later, such as deve
torch and aided by toys or colorful pictures to capture the lopmental cataract or juvenile glaucoma.
child's attention and interest to cooperate with the examiner.
Pupillary reactions must be tested and fundus examination Disorders in Development of the Whole Eyeball
should be attempted with a direct ophthalmoscope (Globe Abnormalities)
A child may be born with a small eye (microphthalmos or
C
nanophthalmos), absent eyeball (anophthalmos) with or
T E
without an orbital cyst, or more complex abnormalities
associated with craniofacial dysgenesis.
Infections
Preseptal cellulitis and orbital cellulitis manifest as swelling
and inflammation of the eyelids, are differentiated clini
cally, and often occur due to spread of infection from the
lids, adnexa or paranasal sinuses or following trauma.
These are potentially dangerous infections as they involve
the anatomical 'dangerous area of the face' and if not trea
ted promptly and adequately, can spread intracranially,
Fig. 25.2: Child with bilateral congenital corneal opacity due resulting in meningitis or cavernous sinus thrombosis.
to anterior segment dysgenesis. Differential diagnoses include Ultrasonography is required to detect an orbital abscess,
all causes of congenital corneal opacity, congenital glaucoma
with buphthalmos and corneal edema due to raised intraocular which has to be drained. CT scan or MRI is required if
pressure involvement of adjacent paranasal sinuses or intracranial
involvement is suspected. Treatment requires systemic
ACQUIRED EVE DISEASES antibiotics and anti-inflammatory agents, supplementation
with topical antibiotics, and supportive measures, inclu
Nutritional Disorders ding lubricating eyedrops to prevent corneal damage.
The most important condition in this category is vitamin A Other infections involving the eyelids include blepha
deficiency which can be catastrophic in young children if ritis, hordeolum externum (stye), hordeolum internum
severe enough to produce keratomalacia. Up to the age of (infected chalazion), molluscum contagiosum and phthiri
six months, children have adequate hepatic reserves of asis of the eyelashes. Lid hygiene, hot fomentation and local
vitamin A. However, if the mother's nutrition is poor or antibiotic ointments are useful along with instructions for
the infant is not properly fed afterbirth, severe vitamin A personal hygiene. Phthiriasis will require mechanical
deficiency may be precipitated by an attack of acute removal of nits adhering to the eyelashes, local application
respiratory infection such as measles, pneumonia or acute of 20% fluorescein sodium to the lid margins and systemic
gastroenteritis, which could lead to bilateral blindness ivermectin therapy for recalcitrant cases, along with advice
due to severe keratomalacia (Fig. 25.3). Milder forms of on hygiene and treatment of other affected family
vitamin A deficiency may manifest with xerosis of the members.
conjunctiva, Bitot spot and nyctalopia or night blindness. Common infections of the ocular surface include con
Adequate nutritional advice to the pregnant and lactating junctivitis which could be bacterial, viral or chlamydia!.
mother and proper weaning with vitamin A rich fruits Conjunctivitis occurring within the first month after birth
and vegetables is advised. Keratomalacia is treated with is called ophthalmia neonatorum. Every effort should be
oral vitamin A 200,000 IU stat followed by a second dose made to identify the etiologic agent, especially in cases of
after 24 hours and a third dose after 2 weeks. In case the ophthalmia neonatorum, since gonococcal conjunctivitis can
Ophthalmic Disorders I 663
cause loss of vision in the newborn. Conjunctiva! smears natamycin (5%) 1 hourly with supportive measures. Herpes
and swabs can be sent for microbiological evaluation. simplex viral keratitis is treated with topical acyclovir 3%
Mucopurulent conjunctivitis is treated with topical anti eye ointment for epithelial involvement and systemic
biotic eyedrops and supportive measures such as cleansing acyclovir for herpetic keratouveitis or recurrent disease.
the eye with clean water, lubricating eyedrops and cold Other infections include endophthalmitis (traumatic,
compresses. metastatic, or iatrogenic following intraocular surgery)
More severe infections include keratitis and corneal and parasitic infestations, such as toxoplasmosis, toxo
ulcers (Fig. 25.4). Trauma is the most common underlying cariasis, and cysticercosis of the eye, extraocular muscles
predisposing factor, but poor hygiene and lowering of or orbit.
local immunity secondary to chronic inflammation, viral
infections or use of topical steroids are other risk factors Allergic and Inflammatory Diseases
for bacterial and fungal infections of the cornea. Trauma Children may develop allergic diseases of the skin around
with vegetative matter, such as a thorn, tree branch or the eye and the ocular surface and conjunctiva. Dermatitis
wooden broomstick (often used for making 'bows and may be an allergic reaction to local ophthalmic medication
arrows' for playing), predisposes to fungal infections. or sometimes secondary to insect bite, application of
Corneal ulcers require an examination under anesthesia traditional eye medicines or herbal remedies and use of
for detailed evaluation and corneal scraping for micro local creams or lotions. In addition, a variety of environ
biological analysis. Empirical therapy for bacterial corneal mental and hereditary factors may interplay to produce a
ulcers is started with a combination of freshly prepared variety of allergic conjunctiva! manifestations such as
fortified topical antibiotics such as 5% cephazolin and 1.3% seasonal allergic conjunctivitis, hay fever conjunctivitis,
tobramycin eye drops hourly and half hourly alternately perennial or chronic allergic conjunctivitis, atopic allergic
round the clock for the first 48 hours. After 48 hours, the conjunctivitis and vernal keratoconjunctivitis. Itching,
culture report and clinical response are reviewed. If there redness, discomfort, gritty or foreign body sensation,
is no substantial clinical improvement, the antibiotic is watering, mucoid or thick ropy discharge, photophobia
changed based on microbiology results. If clinically and blepharospasm are all seen in different combinations
responding to therapy, the frequency of antibiotics can be and varying degrees of severity. Treatment includes cold
reduced to use during waking hours only, followed two compresses, topical antihistaminic eyedrops for mild cases
days later by two hourly application, then reduced to and counseling to avoid rubbing the eyes. Topical
4 hourly or 6 hourly, and discontinued a week after the corticosteroid eyedrops give quick relief but are best
ulcer has healed. Supportive measures include topical avoided in mild cases because of the danger of self-medi
cycloplegics, hot fomentation, analgesics, antiglaucoma cation and unsupervised chronic topical use complicated
medication if secondary glaucoma is present, and antibiotic by steroid induced glaucoma and secondary corneal
ointment at night. Fungal keratitis is treated with topical infection and ulceration. More severe allergies may have
secondary consequences in the form of dry eye, kerato
pathy and corneal ulceration. These are best referred to
ophthalmologists for expert management and careful
follow-up.
Other inflammatory diseases include phlyctenular
conjunctivitis or keratoconjunctivitis (believed to be an
'allergic' immunological reaction to tubercular antigen);
interstitial keratitis secondary to infections like rubella,
syphilis, leprosy and tuberculosis; and uveitis, either
idiopathic or associated with juvenile chronic arthritis,
psoriasis, tuberculosis, sarcoidosis and toxoplasmosis.
Acute anterior uveitis (iritis, cyclitis and iridocyclitis)
usually presents with a red inflamed eye with photophobia
and diminution of vision. Chronic uveitis may be less
symptomatic with decreased vision due to complicated
cataract. Intermediate and posterior uveitis (pars planitis,
vitritis, retinitis, choroiditis and retinochoroiditis) are
usually painless with symptoms of decreased vision (due
to hazy media and retinal or optic nerve swelling and
Fig. 25.4: A partially treated hypopyon corneal ulcer. The inflammation) and floaters (due to inflammatory cells in
overlying epithelial defect has healed, but there is a deep the vitreous). Treatment is with topical cycloplegic agents
corneal abscess, corneal edema and purulent fluid, i.e. and steroids, supplemented with systemic steroids and
hypopyon in the anterior chamber specific therapy for any underlying disease, such as
664 I Essential Pediatrics
tuberculosis. Patients with uveitis need detailed exami Sturge-Weber syndrome and nevus of Ota may be
nation with a slit lamp biomicroscope to identify the associated with cafe au lait spots, plexiform neurofibromas
inflammatory response, ophthalmoscopy to view the of the lids and orbit and Lisch nodules on the iris and
fundus and specialist ophthalmic care and follow-up to glaucoma.
control the inflammation and minimize the morbidity Muscular dystrophies or degenerations such as chronic
related to the disease and its treatment. progressive external ophthalmoplegia result in ptosis and
Intraocular (retinoblastoma or juvenile xanthogranu restriction of eye movements. Duchenne muscular
loma) or systemic malignant disorders may sometimes dystrophy may be associated with cataracts.
mimic uveitis syndrome due to malignant cells in the eye
and vascular uveal tracts. Tumors and Neoplastic Diseases
Optic neuritis is another important inflammatory Benign tumors include dermoids of orbit, lids or on cornea,
disease which could be idiopathic, secondary to infections hamartomas, osteoma, vascular malformations or heman
or associated with demyelinating disorders. Classical giomas of various types and neurofibromas. Malignant
features include a rapid drop in vision, usually in one eye, intraocular tumors are confined to retinoblastoma
which is accompanied by a relative afferent pupillary (Fig. 25.5), juvenile xanthogranuloma, medulloepithe
defect and normal fundus (retrobulbar neuritis) or inflam lioma and metastatic lesions from neuroblastomas, Ewing
matory swelling of the optic disc (papillitis) and retinal sarcoma, leukemias and lymphomas. Orbital tumors
edema and/ or exudates (neuroretinitis). Patients need to include rhabdomyosarcoma, Langerhans cell histiocytosis,
be treated in consultation with a neuro-ophthalmologist extraocular spread of retinoblastoma, metastatic spread of
after investigations to identify the cause. Ewing sarcoma, neuroblastoma, leukemia and lymphoma.
Glaucoma
Primary congenital and developmental juvenile glaucoma
are now recognized to be inherited diseases. Primary
congenital glaucoma is associated with CYPlBl gene, (2p21)
with a predominantly autosomal recessive mode of inheri
tance, and mutations in the myocillin (MYOC) gene.
Photophobia, blepharospasm, watering and an enlarged
eyeball are classic symptoms. Suspicion of glaucoma or
buphthalmos warrants urgent referral to an ophthal
mologist. An examination under anesthesia is required to
measure the corneal diameter and intraocular pressure, and
to visualize the optic disc. Once glaucoma is confirmed,
medical therapy is started to lower the pressure and patient
prepared for surgery. If the cornea is clear enough to allow
visualization of the angle structures, a goniotomy is attemp
ted. If the glaucoma is more severe or the cornea very edema
tous, a drainage procedure is undertaken to open alternative Fig. 25. 7a: The sequelae of ocular trauma. Following injury with
aqueous drainage channels such as trabeculectomy and a wooden stick, the child had corneal perforation, which was
trabeculotomy. If the cornea fails to clear after adequate repaired. Traumatic cataract was surgically removed. Note the
control of the intraocular pressure, corneal transplantation irreversible anatomical damage with corneal scar, distorted iris
is required to restore vision and prevent irreversible sensory and pupil and lens capsular opacification
deprivation amblyopia.
Children can also develop secondary glaucoma due to
chronic use of topical corticosteroid eyedrops, following
eye trauma particularly if associated with traumatic
hyphema (blood in the anterior chamber) or angle
recession, after surgery for developmental cataract and
after chronic uveitis.
Eye Trauma and Related Problems
Eye injuries are common in children (Fig. 25.7). Eye injuries
are considered to be an important cause of preventable
blindness. Effort must be made to educate the community
in general, and mothers in particular, about the importance
of not allowing children to play with sharp pointed toys
like bows and arrows, firecrackers, chemicals including
colors during Holi festival or other chemicals like edible
Fig. 25. 7b: The sequelae of chemical injury, due to edible
'chuna'. Sharp and dangerous household objects like 'chuna'. Despite aggressive management, long-term sequelae
knives, scissors and needles, and chemicals like cleaning include residual conjunctiva! inflammation with limbo! stem cell
liquid, acid, whitewash paint and edible 'chuna' should deficiency and a scarred, irregular and opacified corneal
be kept out of reach of children. surface
In case an injury is sustained, the eyes should be
immediately washed thoroughly with locally available normal eye due to sensitization of the immune system to
drinkable water, and the child should be rushed to the the sequestered antigens in the exposed uveal tissue.
nearest hospital.
Perforating injuries of the globe require surgical repair Retinal Diseases
under general anesthesia along with administration of Children may be affected by a wide variety of retinal
systemic and topical antibiotics and tetanus prophylaxis. diseases. Retinal detachment can occur secondary to
The child should be told not to rub the eyes and given only trauma or spontaneously in cases with high or pathological
fluids while rushing the child to hospital so that there is no myopia. Classical symptoms such as sudden loss of vision
unnecessary delay in preparing the patient for general with floaters and photopsia may not be reported by
anesthesia and planning surgery. Meticulous repair of the children and the detachment may not be detected till much
wounds is undertaken as soon as possible to minimize the later. Retinal detachment requires surgical treatment and
risk of secondary complications such as endophthalmitis, the sooner the surgery is performed, the greater are the
expulsion of intraocular contents and later risk of sympa chances of functional recovery of vision. Other diseases that
thetic ophthalmitis or an inflammatory panuveitis in the can affect the retina in childhood include degenerative and
Ophthalmic Disorders I 667
Fig. 25.7c: Following trauma with a compass, this young teenager had to be operated for trauma-induced cataract and retinal
detachment and subsequently developed a conjunctiva! inclusion cyst
hereditary conditions like retinitis pigmentosa and factors by a premature, underdeveloped retinal vascular
different forms of macular degeneration such as Stargardt system. The chief risk factors are prematurity, especially
disease. These diseases lead to gradual, painless, bilateral birth before 32 weeks of gestation, birth weight less than
diminution of vision in the first or second decade of life 1500 g and presence of other contributory risk factors such
which may be accompanied by defective dark adaptation as supplemental oxygen therapy, hypoxemia, hypercarbia
or abnormal color vision. No specific treatment modalities and concurrent illnesses like septicemia. The clinical
are available, but refractive correction, low vision aids, features are graded in stages of severity depending on
visual rehabilitation and genetic counseling are ancillary the retinal signs and the zone of retina involved. Children
measures. at risk should be screened periodically to look for evidence
Vascular abnormalities of the retina such as heman of developing what is considered as 'threshold' disease,
giomas, arteriovenous malformations and exudative i.e. requiring ablative laser treatment of the avascular zone
vitreoretinopathies like Coats disease may be seen. Retinal of the retina to check further progression and prevent
vasculitis may be seen in Eales disease and other inflam blinding stages of the disease which would then require
matory disorders. Diabetic retinopathy and hypertensive surgical intervention to treat the ensuing retinal
retinopathy can occur if these systemic disorders are detachment and other complications.
present in sufficient grade of severity and for an adequate
duration of time. An important disease seen only in Blindness and Low Vision in Children
children is ROP. The World Health Organization (WHO) has categorized
blindness in different levels based on the extent of vision
Retinopathy of Prematurity loss. Vision 2020: The Right to Sight is a global initiative
This condition unique to children is seen in preterm babies for the elimination of avoidable blindness, a program
due to early exposure to oxygen and other environmental jointly run by the WHO and The International Agency for
Fig. 25.8: Low vision and rehabilitation services: (a) Retinoscopyfor refraction; (bl Checking acceptance; (c) Child wearing prescribed
glasses; (d) Teenager using telescope; (e and f) Helping for near vision
26
Skin Disorders
Neena Khanna • Neetu Bhari
BASIC PRINCIPLES
Morphology of Lesions
Macules
Macule is a circumscribed area of change in skin color
without any change in consistency (Fig. 26.1). A macule
may be hyperpigmented (e.g. cafe au lait macule),
hypopigmented (e.g. leprosy), depigmented (e.g. vitiligo),
or erythematous (e.g. drug rash).
Papules and Nodules
Papule is a solid lesion< 0.5 cm in diameter with major part
projecting above the skin (Fig. 26.2a). Papules may be
dome-shaped (e.g. trichoepithelioma), flat-topped (e.g.
verruca plana), conical (e.g. condyloma acuminata),
filiform (e.g. filiform warts) or umbilicated (with crater on
surface, e.g. molluscum contagiosum) or verrucous (with
multiple closely packed firm elevations, e.g. verrucous
warts). A papule which is >0.5 cm in size and with the major
part in the skin is called a nodule (Fig. 26.2b).
Fig. 26.2: (a) Papule: Solid lesion, �0.5 cm; (b) Nodule: Solid
lesion, >0.5 cm
Plaque
Plaque is an area of altered skin consistency, the surface
area of which is greater than its depth (Fig. 26.3). A plaque
can be elevated, depressed or flat.
Wheal
Fig. 26.1 : Macule: Circumscribed area of change in skin color Wheal, the characteristic lesion in urticaria, is an
without any change in consistency evanescent, pale or erythematous raised lesion which
669
s10 I Essential Pediatrics
Fig. 26.3: Plaque: Area of altered skin consistency with a surface Fig. 26.5: Blister: Circumscribed, elevated, superficial fluid-filled
area greater than its depth lesion
disappears within 24--48 hours (Fig. 26.4). Wheals are due
to dermal edema, and when the edema extends into
subcutis, it is called angioedema. When the wheals are
linear, the phenomenon is called dermographism.
Blisters
Blister is a circumscribed elevated, superficial fluid filled cavity
(Fig. 26.5). If �0.5 cm, it is a vesicle and if >0.5 cm, a bulla.
Scales
Scales are flakes of stratum comeum (Fig. 26.6) and are
diagnostic in certain dermatoses, e.g. silver easily
detachable flakes in psoriasis, branny scars in pityriasis
versicolor and fish-like scales in ichthyosis.
Crusts
Crusts are formed when serum, blood or pus dries on the
skin surface (Fig. 26.7). Fig. 26.6: Scale: Appears as flakes of stratum corneum
Atrophy
Atrophy is the reduction of some or all layers of skin. In
epidermal atrophy, thinning of the epidermis leads to loss
of skin texture and cigarette-paper like wrinkling without
depression. In dermal atrophy, loss of connective tissue
of the dermis leads to depression of the lesion.
Lichenification
Fig. 26.9: Lichenification: Thickening and hyperpigmentation
Lichenification, which is caused by repeated scratching, of skin with increased skin markings
consists of a triad of skin thickening, hyperpigmentation
and increased skin markings (Fig. 26.9). Burrow
Burrow is a dark serpentine, curvilinear lesion with a
minute papule at one end and is diagnostic of scabies
(Fig. 26.10).
Comedones
Comedones are due to keratin plugs that form within
pilosebaceous apparatus. Comedones can be open or
closed (Fig. 26.11) and are pathognomonic of acne.
Patterns Formed
Arrangement and configuration of skin lesions can help
in diagnosis (Table 26.1).
Seborrheic dermatitis
Lichen
planus
Scabies
Diaper dermatitis
Psoriasis
lchthyosis
Treatment
Fig. 26.17: Keratinopathic ichthyosis: Brownish, warty, broad Therapy for PPKD includes use of emollients, keratolytics
linear plaques (salicylic acid 6%, urea 30-40%), topical retinoids and
vitamin D (calcipotriol), all used after soaking in water.
In mutilating variants, treatment with oral acitretin may
be warranted.
Treatment
Since collodion babies are frequently at risk of several
complications, they are best managed in a controlled,
humidified environment, carefully monitoring for fluid
and electrolyte imbalance. Skin care (frequent application
of emollients) and eye care are paramount. Oral acitretin
is often needed.
Palmoplantar Keratoderma
PPKD may be inherited or acquired. Hereditary
keratodermas are a heterogeneous group of disorders
with AD or AR inheritance. While diffuse and focal
types of PPKD inherited in an ausomal dominant
manner, the mutilating and transgradiens variants have Fig. 26.20: Palmoplantar keratoderma: Autosomal recessive.
an AR inheritance. They may occur in isolation or be massive thickening and mutilation
Skin Disorders 1675-
Treatment
General measures include avoiding friction and trauma,
wearing soft, well-ventilated shoes and gentle handling.
Prompt and appropriate use of antibiotics for blisters and
infected lesions is necessary. Surgery may be required for
release of fused digits, correction of limb contractures and
esophageal strictures.
Gene therapy, intradermal collagen 7 injections and
stem cell transplantation are being evaluated.
Ectodermal Dysplasias
Ectodermal dysplasias comprise a large, heterogeneous
group of inherited disorders that are characterized by
Fig. 26.21: Palmoplantar keratoderma: Transgradiens variant,
defects in development of 2 or more tissues derived from
with keratoderma spilling onto dorsae of feet
embryonic ectoderm. The disorders are classified based
Epidermolysis Bullosa on either inheritance (AD, AR and XLR) or by structures
involved (hair, teeth, nails, sweat glands).
Epidermolysis bullosa are a heterogeneous group of
disorders defined by a tendency to develop blisters even
on trivial trauma. Several variants of EB are recognized Anhldrotic Ectodermal Hypop/as/a
based on inheritance, gene defects and clinical features The condition is inherited in an XLR manner. Child
(Table 26.3). EB simplex and dominant dystrophic EB have presents with intolerance to heat and episodes of high fever
an AD inheritance, while junctional EB and recessive due to reduced sweating (hypohidrosis) because of
dystrophic EB have an AR inheritance. presence of only a few sweat glands. The facies is distinctive
with prominent forehead, thick lips and a flat nose.
Clinlcal Features Additional features include thin, wrinkled, dark-colored
The hallmark of the disease is tendency to develop periorbital skin. The hairs are sparse, light-colored, brittle
blisters even on trivial injury, predominantly at sites of and slow growing. The teeth may be absent (Fig. 26.26) or
trauma. However, there are differences in type of are peg-shaped.
blistering, their distribution and severity, evolution and
sequelae as well as the degree of mucosal and nail Treatment: There is no specific treatment, but quality of
involvement in the different variants (Table 26.3, life can be improved by maintenance of cool ambient
Figs 26.22 to 26.25). temperature and managing fever by tepid sponging.
Neurocutaneous Syndromes
Neurofibromatoses
Neurofibromatoses encompass eight inherited disorders,
of which neurofibromatosis type 1 (NFl) is most common.
Fig. 26.24: Dominant dystrophic epidermolysis bullosa: NFl is an autosomal dominant disorder with 100%
Localized involvement of trauma prone site, bullae heal with penetrance. The defect is mutation/ deletion of NFl
milia formation gene.
Skin Disorders 1677-
NEVI
Nevus is a developmental disorder characterized by circum
scribed hyperplasia of epidermal or dermal structures.
Fig. 26.29: lncontinentia pigmenti, vesicular phase: Multiple crusted Melanocytic Nevi (MN)
vesicular lesions over the right lower limb of a female child
MN are composed of nests of melanocytic nevus cells
and may be congenital or acquired. Acquired MN may be
junctional (with nevus cells at dermoepidermal junction),
compound (with nevus cells at dermoepidermal junction
and in dermis) and dermal (with nevus cells only in
dermis). Of these, first two are seen in children while
the dermal variant is seen only in adults.
The clinical presentation depends on the type of MN
(Table 26.5, Fig. 26.31).
Treatment
Congenital MN especially those larger than 20 cm, need
to be observed for malignant transformation. Acquired
MN can be left alone.
Dermal Melanocytosis
Mongol/an Spot
Mongolian spot is a dermal melanocytosis, due to
entrapment of melanocytes in dermis during their
migration from the neural crest into the epidermis. These
Fig. 26.30: Xeroderma pigmentosa: Multiple, brown to black spots present at birth (or soon thereafter) as gray blue
freckle-like lesions over the face and lips, associated with macules, in the lumbosacral region and disappear
conjunctival cong estion spontaneously by early childhood.
Nevus of Ota
Presents at birth or infancy (sometimes in adolescence)
and consists of mottled slate-gray and brown hyper
pigmented macules in the distribution of the maxillary
division of trigeminal nerve (Fig. 26.32). Lesion persists
for life and is frequently associated with pigmentation of
sclera (slate-gray) and conjunctiva (brown). Pigmentation
of nevus of Ota frequently impacts child's psychosocial
development and can be reduced by treating with
Nd:YAG laser.
Epidermal Nevi Fig. 26.33: Verrucous epidermal nevus: Multiple, brown popular
lesions, arranged linearly
These nevi usually present at birth, as multiple brown
papules arranged linearly (Fig. 26.33). Several variants Vascular 'Birthmarks'
are described, including verrucous epidermal nevus, Vascular 'birthmarks' are classified based on the
inflammatory linear verrucous epidermal nevus, naevus pathogenesis, evolution, clinical manifestations and on
comedonicus and nevus sebaceous. the presence of associations into vascular tumors and
Topical retinoic acid and dermabrasion are helpful. vascular malformations (Table 26.6).
Fig. 26.34: Infantile hemangioma: Soft bright red nodule with Fig. 26.35: Port-wine stain: Light pink to deep red macule often
pale stippling developing bosselation as child grows
Skin Disorders lsa1-
Atopic Dermatitis
Atopic dermatitis is an acute, subacute or chronic
relapsing, endogenous eczema, characterized by dry
skin and recurrent, pruritic, symmetric dermatitic lesions.
The condition is due to a complex interaction between
genetic susceptibility and immunological changes with
heightened IgE response.
Clinical Features
Lesions develop in infancy, anytime after 3 months of
age. In children, two distinct patterns are recognized.
Fig. 26.38: Childhood pattern of atopic dermatitis. Dry plaques
Infantile pattern: Manifests as itchy, erythematous in the flexures
papulovesicles, on the face (Fig. 26.37), but may become
generalized. The lesions clear by 18 months of age in dust mite (using barriers on pillows and mattresses,
40% and evolve into childhood pattern in the rest. regular vacuuming of rooms) may help. There is no
contraindications to vaccination except in children speci
Childhood pattern: Childhood pattern is characterized
fically allergic to eggs, in whom influenza and yellow
by dry, lichenified and crusted plaques, seen mainly on
fever vaccines are avoided. Dietary restrictions are usually
antecubital (Fig. 26.38) and popliteal fossa, the neck and
not warranted and breast feeding is encouraged as it may
face. Most (70%) clear by 10 years of age.
decrease the chance of the infant developing the disease.
The diagnosis is based on Hanifin and Rajka criteria
(Table 26.8). Secondary bacterial and fungal infections Skin care: Mild soaps and cleansing lotions are to be
are frequent. Viral infections like herpes simplex and used for bathing followed immediately by application of
molluscum contagiosum may become widespread. moisturizers to skin. However, the cost-effectiveness of
moisturizers which claim to replenish natural
Treatment moisturizing factors is debatable.
General measures: Care takers and the child should be Acute lesions are treated with wet dressing and
counseled about the chronicity of the disease and that topical steroids. Antibiotics and antifungals (topical/
the child should avoid contact with irritants (woolens systemic) are used when indicated. Oral antihistaminics
and chemicals). Measures to reduce exposure to house are often prescribed.
682 Essential Pediatrics
Pityriasis Alba
Asymptomatic, ill-defined, hyp opigmented macules with
fine scales are seen on face, in children 2-6 years of age.
The lesions are self-limiting, clearing spontaneously in a
few months to couple of years.
Treatment
The family is reassured regarding the benign nature of
the illness and that it is not vitiligo. Mild emollients may
be used.
Fig. 26.45: (a) Pachyonychia congenita: Massive thickening of the Fig. 26.46: Chronic plaque psoriasis: Well-demarcated,
nail plates resulting in tenting of nails; (bl Leukoplakia of the tongue indurated, erythematous plaques surmounted by silvery scales
-686 Essential Pediatrics
Fig. 26.48: Lichen planus: Polygonal. flat-topped, violaceous Fig. 26.50: Lichen striatus: Hypopigmented atrophic macules
papules configured linearly over left forearm
Pityriasls Rosea
Table 26.12: Treatment of lichen planus in children
Etiology
Type of disease Therapy*
The condition may be triggered by reactivation of human
Localized Topical steroids
herpes viruses (HHV-7, HHV-6).
Extensive Narrow band UVB
Oral steroids Clinical Features
Acitretin PR begins with a 'herald patch' in 80% cases. Lesion is
characteristically oval, wrinkled with a collarette of scales
Scalp lichen planus Oral steroids
at the periphery. This is followed by multiple, smaller,
Mucosal lichen planus Dapsone and topical steroids oval to round scaly secondary eruptions. Their arrange
in orabase ment is characteristic as lesions run downwards and
Oral steroids outwards from the spine (Christmas tree appearance)
Acitretin along lines of cleavage. The condition is self-limiting, with
the lesions resolving spontaneously within 2-10 weeks.
*Oral antihistamines to be added, if lesions itchy
No treatment is usually required. Oral antihistamines,
calamine lotion and topical steroids may be used to
decrease itching. Recalcitrant lesions may be treated with
ultraviolet light.
Erythroderma
Childhood erythroderma may be a manifestation of
several dermatoses including ichthyoses (nonbullous
ichthyosiform erythroderma), dermatitis (atopic
dermatitis, seborrheic dermatitis) and papulosquamous
dermatoses (psoriasis, pityriasis rubra pilaris) and as an
adverse effect to drugs.
Clinical Features
Erythroderma refers to a generalized erythema usually
with, sometimes without, scaling that involves more than
90% of the child's body surface area (Fig. 26.51).
Erythroderma is often complicated by thermodysregula
Fig. 26.49: Lichen nitidus: Multiple, small, monomorphic, tion, sepsis and fluid, electrolyte and nutritional imbalance.
hypopigmented papules over the lower abdomen and shaft Treatment includes addressing the underlying disease
of penis and preventing complications. Treatment should be
688 I Essential Pediatrics
Treatment
General measures: Counseling the caretakers about course
of disease and necessity of continuing therapy during
asymptomatic maintenance phase is important. Supportive
measures including barrier nursing, skin and mucosal care
(measures to augment healing, prevent and treat skin
infections), maintaining fluid and electrolyte balance help Fig. 26.53: Chronic bullous disease of childhood: Tense bullae
to improve response to therapy. on erythematous skin in perigenital area
Skin Disorders I sag-
are also frequently seen on lower abdomen, buttocks, knees Associations
and elbows. Oral mucosa! involvement is seen in 50% of Segmental vitiligo progresses initially for about 6 months
patients. The illness is self-limiting, with lesions generally and then stabilizes. Patients with vitiligo should be
resolving within 2 years of onset. examined for cutaneous associations (alopecia areata,
Patients with mild disease are treated with dapsone atopic dermatitis), endocrine disorders (diabetes mellitus,
(1-2 mg/kg) while in those with extensive disease, oral Addison disease, hypoparathyroidism and thyroid
corticosteroids are administered. disorders) and pernicious anemia.
Extensive disease
New lesions Oral steroids+ PUVA*/PUVA* sol or
NB UVB**
Rapid increase Oral steroids+ PUVA*/PUVA* sol or
NB UVB**
Old lesions Oral PUVA*/ PUVA* sol or NB UVB **
Intolerance to PUVA Oral steroids
*Oral PUVA/PUVA sol: Psoralen + UVA/psoralens + sunlight: not to be
Fig. 26.54: Acrofacial vitiligo: Depigmented, scalloped macules used in children <10 yr of age
on face and acral parts **NB UVB: Narrow band UVB
-690 Essential Pediatrics
Clinical Features
• Cutaneous lesions: Lesions usually appear in a single
crop. Target lesions which consist of 3 concentric areas
of varying degrees of erythema are characteristic
(Fig. 26.57). Central bullous lesions are characteristic
in EM major. Lesions are seen symmetrically on acral
parts especially of upper extremities and on the face.
• Mucosa! lesions are conspicuous in EM major (buccal
erosions and hemorrhagic crusts of lips).
• Constitutional symptoms are present in EM major.
Most patients are managed symptomatically. In
patients with recurrent EM, suppressive therapy with
acyclovir may be instituted.
Fig. 26.58: Furuncle: Firm, red follicular nodules which discharge Fig. 26.59: Impetigo contagiosa: Honey-colored crusted lesions
pus and heal with minimal scarring around mouth
Skin Disorders 1693-
Treatment
General measures include local hygiene, removal of crusts Fig. 26.61 : Staphylococcal scalded skin syndrome: Erythema
and superficial peeling of skin in thin sheets
(in ecthyma), rest and limb elevation (for cellulitis). NSAIDs
are used if pain and constitutional symptoms are present.
Topical antibiotics like mupirocin, sodium fusidate and
nadifloxacin are used for localized lesions. Systemic
therapy is required in patients with extensive lesions, in
spreading lesions (erysipelas and cellulitis), and in
presence of constitutional symptoms and lympha
denopathy. Follicular pyodermas and bullous impetigo
warrant use of antistaphylococcal antibiotics (cloxacillin
or coamoxiclav) while spreading pyodermas should be
treated with injectable penicillins. For impetigo and
ecthyma, macrolides usually suffice.
Cutaneous Tuberculosis
Cutaneous tuberculosis caused by M. tuberculosis is
classified based on host's immune status as well as route
of inoculation into:
• Lupus vulgaris (Fig. 26.62)
• Scrofuloderma (Fig. 26.63)
• Tuberculosis verrucosa cutis Fig. 26.63: Scrofuloderma: Sinus with mouth showing
• Tuberculids undermined edge and fixed to underlying lymph node
694 I Essential Pediatrics
The diagnosis is confirmed by histopathology. Patients presentation depends on the type of leprosy (Table 26.20,
should be evaluated for systemic tuberculosis. Therapy Figs 26.64 and 26.65).
of cutaneous tuberculosis comprises use of four anti
tubercular medications (isoniazid, rifampicin, ethambutol Lepra Reactions
and pyrazinamide) for 8 weeks followed by 2 agents Two types of acute episodes (lepra reactions) are
(isoniazid and rifampicin) for the next 16 weeks. recognized in leprosy. Type 1 reaction (TlR) which
develops in patients with borderline leprosy (BT, BB, BL)
Leprosy is due to alteration in host CMI. TlR manifests as edema
The mode of transmission of M. lep rae is uncertain but and erythema of pre-existing lesions along with neuritis
possibly nasal droplet infection is important. The clinical which may result in development of new sensory and
manifestations depend on the host immunological motor impairment. Typ e 2 lepra reaction (T2R, erythema
response. If the host mounts good cell-mediated immunity nodosum leprosum, ENL) which occurs in highly
(CMI), the infection is localized (tuberculoid pole) while bacillated patients (BL and LL) is an immune complex
if the CMI is poor, the infection is extensive with visceral reaction and manifests as several tender, erythematous,
involvement (lepromatous pole). transient nodules on face, flexures and legs. Patients may
The Ridley-Jopling classification, based on clinical, also show neuritis, orchitis, iridocyclitis, arthralgia and
pathological, immunological and bacteriological fever.
parameters, classifies leprosy into:
• Indeterminate leprosy Complications
• Determinate leprosy Patients may show the following complications:
- Tuberculoid • Trophic ulcers
- Borderline tuberculoid • Deformities: Claw hand, clawing of toes, foot drop and
- Borderline saddle nose deformity
- Borderline lepromatous • Ophthalmologic complications: Diminished corneal
- Lepromatous sensation, lagophthalmos, recurrent iridocyclitis
Tuberculoid and lepromatous leprosy are stable forms, • Renal involvement
while borderline forms of leprosy are unstable.
Prototype skin lesion is a hypopigmented/erythematous Investigations
macule/plaque which is anesthetic/hypoaesthetic/ Slit skin smears: Slit skin smears, from the lesions and
normoaesthetic. Skin appendages (hair, sweating) on the ear lobules, are stained with modified Ziehl-Neelsen
lesions are reduced and there is epidermal atrophy. The method for acid fast bacilli (AFB). The smears are usually
nerves may be thickened and tender and there may be negative in TT/BT/most BB leprosy and usually positive
associated sensory and motor impairment. The clinical in LL, BL and some BB.
Skin Disorders
Fig. 26.64: Indeterminate leprosy: Ill-defined hypopigmented, Fig. 26.65: Borderline tuberculoid: Well-defined erythematous
hypoesthetic lesion on the face plaque with satellite lesions
Skin biopsy: Presence of granuloma (epithelioid cells in For the purpose of treatment, leprosy is classified into
tuberculoid leprosy and foamy cells in lepromatous paucibacillary (PB) and multibacillary (MB) leprosy {Table
leprosy) and nerve involvement are typical. 26.21) and based on this multidrug therapy (MDT) is
Treatment instituted (Table 26.21).
Patient and parents are reassured and counseled regarding Treatment of lepra reactions requires specific treatment
treatment compliance and care of hands, feet and eyes. (Table 26.22).
-696 Essential Pediatrics
Table 26.21: WHO recommendations for treatment of Table 26.22: Treatment of reactions in leprosy
leprosy in children aged 10-15 years Type 1 reaction Type 2 reaction
Paucibocillary Multibacillary Mild NSAIDs NSAIDs
Definition 5 or less lesions >5 lesions Moderate NSAIDs NSAIDs
Duration of 6 months; to be 12 months; to be Oral corticosteroids Thalidomide*
therapy completed in completed in 18 months Chloroquine
9 months Clofazimine
Supervised Rifampicin 450 mg Rifampicin 450 mg +
Severe NSAIDs Thalidomide*
(monthly) clofazimine 150 mg
Oral corticosteroids Oral corticosteroids
Unsupervised Dapsone 50 mg Dapsone 50 mg +
{daily) and clofazimine 25 mg NSAIDs: Nonsteroidal anti-inflammatory drugs
*Thalidomide is a teratogenic agent and avoided in girls in the
Rifampicin 10 mg/kg; clofazimine 1 mg/kg daily, 6 mg/kg monthly;
reproductive age
dapsone 2 mg/kg
Site Any part of body, Face and back of Soles and less often palms Face
most commonly on hands
back of hands, fingers
and knees
Molluscum Contagiosum
Caused by a poxvirus, patients show multiple, pearly
white, dome-shaped papules with central umbilication
(Fig. 26.68). Cheesy material can be expressed from the
lesion. The lesions are seen on any part of the body. The
condition is self-limiting and lesions usually clear within
a year, but widespread lesions are seen in patients with atopic
dermatitis and in those who are immunocompromised.
Treatment modalities used include wart paint or
mechanical extirpation.
Hand-Foot-and-Mouth Disease
The illness is caused by coxsackie virus A16 infection, with
feco-oral route being the predominant mode of transmission.
It most often affects children between 1 and 10 years of
age during the summer and autumn months. The
incubation period is 3-6 days. It manifests as an enanthem
over the tongue and buccal mucosa, followed by painful
vesicular exanthem involving lateral aspects of hands and
feet (Fig. 26.69).
The disease usually runs a self-limiting course of
7-10 days, with a very rare incidence of cardiac and
neurological complications.
Gianotti-Crosti Syndrome
Also known as papular acrodermatitis of childhood, the
conduction is associated with hepatitis B virus and
Epstein-Barr virus.
The condition presents as characteristic lesions
(Fig. 26.70) on the face, buttocks and limbs, associated with
mild constitutional symptoms. The mucous membranes Fig. 26.69: (a) Hand-foot-and-mouth disease: Skin lesions:
are not affected. The eruption fades with mild desquama
Oblong vesicles with erythematous halo on palms; (bl Mucosa!
lesions: Oval, vesicular lesions with erythematous halo
tion in 3-4 weeks.
Herpes Simplex Virus (HSV) Infections In patients with underlying dermatoses like atopic
HSV type 1 infection is often asymptomatic but when dermatitis and ichthyoses, HSV infection may become
symptomatic, the manifestations depend on whether the generalized (Kaposi varicelliform eruption or eczema
infection is primary or recurrent. Primary HSV infection herpeticum). Recurrent HSV infection may trigger
presents as acute gingivostomatitis with tightly grouped episodes of erythema multiforme.
vesicles on an edematous base which rupture to form No treatment is generally required, except in primary
polycyclic erosions (Fig. 26.71). There may be associated infection, severe recurrent infection or in immuno
malaise, fever and lymphadenopathy. Patients with compromised patients where treatment with oral acyclovir
recurrent herpes labialis have a prodrome of burning and may be given for 5-7 days.
stinging followed by appearance of grouped vesicular
lesions (Fig. 26.72) with background of slight erythema.
Dermatophytoses
These lesions may leave area of polycyclic depigmentation Etiology
after healing.
Three genera of fungi cause dermatophytoses: Tricho
phyton, Epidermophyton and Microsporum.
Clinical Features
The infection is given different names depending on the
site affected. Dermatophyte infection of skin is known as
tinea corporis, of groin as tinea cruris, of hands as tinea
manuum, of feet as tinea pedis and of nails as tinea
unguium. The classical lesion is an annular/arcuate/
polycyclic plaque with a clear center and an active edge
showing papulovesiculation and scaling.
Tinea capitis Three patterns are recognized:
• Non-inflammatory or epidemic type caused by anthro
pophilic organisms and so is responsible for epidemics.
It presents as alopeciac patch, in which hairs break off
easily (Fig. 26.73).
• Inflammatory or kerion: Caused by zoophilic
organisms and so does not cause epidemics. It presents
as a boggy swelling (Fig. 26.74) from which hair is easily
pluckable without pain. Usually associated with
Fig. 26.71: Herpes gingivostomatitis: Closed grouped vesicles occipital lymphadenopathy.
on an edematous base which coalesce to form polycyclic • Favus: Caused by T. schoenleinii, presents as yellowish,
erosions foul smelling cup-shaped crusts with matting of hair.
Fig. 26.72: Herpes labialis: Polycyclic area of hypopigmentation Fig. 26.73: Tineo capitis: Area of non-scarring alopecia with
and vesicular lesions minimal inflammation with scaling at periphery
Skin Disorders 1699-
Diagnosis
KOH mount shows budding yeasts and pseudohyphae.
Culture is done in unresponsive cases to speciate the
candida.
Treatment
Fig. 26.74: Kerion: Boggy swelling of scalp which drains pus Predisposing factors should be addressed and the area
from multiple openings kept dry. Topical therapy includes imidazoles
(clotrimazole, miconazole and ketoconazole) nystatin
Investigations cream for folds and lotions for oral mucosa. Systemic
The diagnosis is confirmed by the KOH test that shows therapy with weekly fluconazole is given in patients with
fungal hyphae. Culture helps in identification of species extensive disease.
and this is important in patients with tinea capitis. Wood's
lamp may help in diagnosis during epidemics. Pityriasis Versicolor
The condition is cuased by Malasezzia furfur, a commensal
Treatment yeast. Patient presents with scaly, perifollicular macules
Tinea capitis Washing with ketoconazole shampoo and with variable pigmentation (hypopigmented, erythematous
not sharing combs and head wear help to reduce or hyperpigmented). The fine branny scales are accentuated
transmission. Tinea capitis is always treated with systemic by gentle abrasion with a glass slide. The lesions are
agents; griseofulvin (15 mg/kg/day of ultramicronized frequently seen on upper trunk (both anterior and
formulation) for 6 weeks is treatment of choice. Longer posterior), neck and sometimes also on proximal part of
treatment (8 weeks) is needed for kerion. Terbinafine upper extremities.
(5 mg/kg/day for 4-8 weeks) is effective in trichophyton
(noninflammatory) but not in microsporum tinea capitis. Diagnosis
Moroever, use of terbinafine in children is hindered by its KOH mount shows a mixture of short branched hyphae
unpleasant after taste. and spores (spaghetti and meatball appearance).
Tinea corporis Localized lesions of tinea corporis are
Treatment
managed by topical therapy (azoles available as
clotrimazole, miconazole or ketoconazole in lotion, gel and Topical therapy with imidazoles (ketoconazole, 2%) for
cream formulations). Widespread lesions require systemic 3 consecutive days is sufficient in most cases. Systemic
antifungal therapy with terbinafine (2-6 weeks) or therapy with fluconazole is occasionally required in
griseofulvin (4-8 weeks). Due to resistance to terbinafine, extensive and recurrent disease.
itraconazole is being used frequently.
DISEASES CAUSED BY ARTHROPODS
Candidiasis
Candida albicans, a normal commensal becomes pathogenic Scabies
in the presence of predisposing factors including obesity, Scabies is caused by Sarcoptes s cabei var hominis and
diabetes and immunocompromised states. Less frequently transmitted by close contact with infested humans.
other species like C. glabrata may be involved. Patient presents with itchy (worse at night) lesions,
Candidiasis presents as oral thrush, vulvovaginitis, present in a characteristic distribution. The primary lesion
intertrigo, candidal diaper dermatitis or paronychia. Oral is a burrow, a grey thread-like serpentine line with a
thrust presents as soft, creamy white to yellow, elevated minute papule at the end; papules and papulovesicles may
plaques, that are easily wiped off to leave an erythematous, also be seen. Secondary lesions consist of pustules,
eroded or ulcerated surface. The lesions are seen on buccal eczematized lesions and nodules. Lesions are seen in webs
mucosa, tongue, palate and gingiva. of hands, on wrists, ulnar aspects of forearms, elbows,
100 I Essential Pediatrics
axillae, umbilical area, genitalia, feet and buttocks. Face Permethrin 5%: Overnight single application is treatment
is usually spared, except in infants in whom face, scalp, of choice in children older than 2 months of age.
palms and soles (Fig. 26.75a) are also involved. Nodular Crotamiton 10%: Two applications daily for 14 days is
lesions are seen on genitalia (Fig. 26.75b). recommended for infants less than 2 months.
Secondary infections common. Secondary streptococcal
infection may result in acute glomerulonephritis. Benzyl benzoate 25%: Three applications at 12 hourly
intervals.
Treatment Ivermectin, single oral dose of 200 µg/kg body weight, in
General measures: All close contacts of the patient, even children older than 5 years is the treatment of choice for
if asymptomatic, should be treated. Overzealous epidemics (as in orphanages).
laundering of bed linen and clothes is not warranted.
Specific measure: Antibiotics are given, if secondary Pediculosis
infection is present. Antihistamines are given for 1-2 weeks Louse is an obligate ectoparasite and two species infest
to reduce pruritus. The topical scabicide should be applied humans: Pediculosis humanus (P. humanus capitis, head
all over body below the neck, including on the free edge louse and P. humanus corporis, body louse), and Phthirus
of nails, genitals, soles of feet after hydration of body with pubis (pubic louse). Head louse infestation is transmitted
a bath. Scabicides available include: by close contact and pubic louse infestation is acquired
by children from infested parents.
Head louse infestation is common in children while
pubic louse infestation is infrequent but when it occurs it
also involves eyelashes and eyebrows. Head louse
infestation manifests as severe scalp pruritis or recurrent
pyoderma of scalp. Though adult lice are difficult to find,
nits (egg capsules) are easily seen, firmly cemented to hair
on which they can be slid but not flicked off. Secondary
infection, eczematization and occipital lymphadenopathy
are frequent.
Treatment
All family members should be treated. The chief
pediculicides are:
• Permethrin, l % lotion, single 10 minutes application to
wet hair followed by rinsing. Repeat application after
7 days.
• Gamma benzene hexacloride, l % single overnight
application to dry hair followed by rinsing. Second
application used after 7 days.
• Malathion, 0.5% water-based lotion, applied on dry hair
for 6 hours. Has residual effect, so second application
is not needed.
• Spinosad, 0.9% suspension, single 10 minutes application.
Popular Urticaria
Papular urticaria is due to bites of arthropods such as
mosquitoes and fleas. An initial itchy, urticaria! wheal that
develops at the site of bite evolves into a firm pruritic
papule, which persists for several days. The lesion often
has a central hemorrhagic punctum (Fig. 26.76) and may
be surmounted by a tiny vesicle.
Secondary infection, eczematization, hyper- and
hypopigmentation, particularly in darkly pigmented
• individuals are not uncommon. New bites by the same
Fig. 26.75: (a) Infantile scabies: Multiple papulovesicular lesions species often cause a recrudescence of activity in existing
on soles; (bl Infantile scabies: Nodular lesions of genitalia and even healed lesions.
Skin Disorders 1101-
Fig. 26.76: Popular urticaria: Papule with a central hemorrhagic Fig. 26.78: Acrodermatitis enteropathica: Sharply demarcated
punctum erythematous plaque over the perianal area with fissured margins
Treatment Treatment
Prevention of repeated insect bites through use of Oral administration of zinc sulfate or zinc gluconate.
protective clothings, judicious use of insect repellents and
treabnent of pets with infestation is recommended. Topical Porphyria
steroid-antibiotic combination and oral antihistamines Porphyrias are a group of diseases characterized by
help in reducing pruritus and hypersensitivity reaction. genetic or acquired enzyme deficiencies in the pathway
of haemsynthesis, resulting in accumulation of haem
precursors: 5-aminolaevulinic acid (ALA), porphobilinogen
MISCELLANEOUS DERMATOSES and porphyrins.
Protein-Energy Malnutrition Based on clinical and biochemical parameters,
porphyrias are classified into:
Marasmus is characterized by emaciation and dry, thin, l. Erythropoietic porphyria: Congenital erythropoietic
pale, wrinkled skin while kwashiorkor manifests as porphyria (CEP), erythropoietic protoporphyria (EPP).
generalized edema and areas of hyperpigmentation and 2. Hepatic porphyria: Porphyria cutanea tarda (PCT),
occasional desquamation ('flaky paint appearance')
variegate porphyria (VP), acute intermittent porphyria.
predominantly at sites of pressure and friction (Fig. 26.77).
Porphyrias are characterized by extreme photo
Hairs may show alternate areas of discoloration (flag sign).
sensitivity and blistering and scarring of photo-exposed
Acrodermatitis Enteropathica areas (Fig. 26.79).
Treatment for all porphyrias includes genetic
This is an autosomal recessively inherited disorder
counseling, strict photoprotection and some specific
resulting in deficiency of zinc transporter protein and
measures (Table 26.24).
resultant defective zinc absorption. The condition is
characterized by the dermatitis, diarrhea, alopecia and Mastocytoses
irritability. Characteristics skin lesions include periorificial
sharply demarcated, erythematous crusted plaques with Etiology
fissured margins (Fig. 26.78). Mastocytoses are a heterogeneous group of diseases
characterized by localized or diffuse accumulation of
clonal mast cells in the skin and/or in internal organs.
Urticaria pigmentosa is the most common variant
(70-90%) of childhood mastocytosis. It may be seen at birth
or appear in the first year of life and is characterized by
itchy multiple, discrete, yellowish-brown hyperpigmented
macules and slightly elevated plaques in a generalized
distribution with a truncal predominance (Fig. 26.80).
Dermographism is present in one-third of patients and in
the first 2 years, pathognomonic Darier's sign may be present.
Diagnosis is confirmed with histological and immuno
Fig. 26.77: Protein-energy malnutrition: Generalized, areas of histochemical evaluation of skin biopsy.
hyperpigmentation and occasional desquamation ('flaky paint Treatment is directed at alleviation of symptoms
appearance') in an irritable child (pruritus) with antihistamines and/ or disodium
702 Essential Pediatrics
Fig. 26.79: [a) Congenital erythropoietic porphyria: Hypertrichosis over the face; (b) Congenital erythropoietic porphyria: Hyper
pigmentation, mutilating scarring
27
Poisonings, Injuries and
Accidents
Jhuma Sankar
INJURIES AND POISONING abdominal and thoracic structures. The impact of trauma
is transmitted widely through the body resulting in
Nearly 90% of childhood injuries are unintentional or
multisystem injuries. Early recognition and aggressive
accidental. Injuries account for 6-10% of all childhood
management of emergencies like airway obstruction,
deaths. A significant proportion of these children could
hemorrhage including intra-abdominal and intracranial
be saved, if appropriate injury prevention measures were
hemorrhages improve survival rates after major trauma.
applied. Road traffic crashes, falls, drowning, burns and
Subtle changes in heart rate and peripheral perfusion must
poisoning are the leading causes of child death from
be looked for, as these are signs of impending
injuries. A large proportion (e.g. drowning, burns,
cardiorespiratory failure. Hypotension is a late sign of
falls) occur in or around the home. The following is a
shock and blood pressure may remain normal despite
global resource on intentional injury and its prevention:
25-30% blood loss (Table 27.1).
http ://www.who.int/violence_injury_ prevention/child/injuryI
Blunt injury is common compared to penetrating injury.
world_report/en/
Common visceral injuries include contusions, laceration
or hematoma of liver, spleen, lungs as well as
ROAD TRAFFIC ACCIDENTS AND FALLS
pneumothorax, rib fractures and gastrointestinal tract
Road traffic crashes are the leading cause of death among injury. Head injuries, alone or associated with multiple
children aged 10 to 19 years. India has high rates of road system injuries, are the most severe and cause most deaths.
traffic accidents in the world. Falls account for a significant Head injuries also account for disability in children. Blunt
proportion of visits by children to hospital emergencies. trauma in children often results in airway and breathing
Seat-belts and child-restraints, helmets, pedestrian lanes, compromise rather than bleeding and shock.
daytime running lights for vehicles, speed limits, laws
against drinking alcohol and driving are among the Management
successful interventions to prevent road traffic injuries. Children may not cope well emotionally after an accident.
Severe falls can be avoided by changes in architectural They need to be managed in a calm, child-friendly
designs, and specially designed child products and environment, preferably in the presence of a parent or
playground equipment. guardian. Initial management during 'the golden hour'
in pediatric emergency includes primary survey and
Factors Predisposing Children to Trauma resuscitation by a well-organized team. The goal of the
Children have a pliable skeleton with less fat and more primary survey is to find and relieve immediate life
elastic connective tissue, protecting tightly packed threatening conditions. It starts at the injury scene and
704
Poisonings, Injuries and Accidents 1105-
aims to maintain a patent airway, provide adequate 100000 population. Skin, the largest organ of the body,
breathing, circulatory support, and to assess major neuro insulates and prevents heat and moisture loss and protects
logic disability. Initial stabilization should proceed in ABC from invasion by harmful environmental microbes. Loss
sequence. All patients should receive supplemental oxygen of integrity of the skin exposes the body to harmful agents,
preferably with non-rebreathing mask (see Chapter 28). hypothermia and loss of body fluids. Of all types of bums,
Disability: A rapid neurological examination is carried fire-related bums are the commonest, followed by scalds
out to assess level of sensorium with Glasgow Coma Scale and electrical burns. Fireworks are a seasonal injury and
and pupillary responses may indicate traumatic brain over 40% of those injured by fireworks are children
injury, hypoxemia or cerebral hypoperfusion. Various younger than 15 years. Prevention of child labor in firearm
scores have been used to identify children at high risk of manufacturing units and strict legislative action has
mortality of which the Pediatric Trauma score is widely helped prevent firework-related injury in our country.
used; score �6 significantly predicts mortality and Parental supervision of use of fireworks and community
morbidity (Table 27.2). restriction on certain types of fireworks may further
Secondary survey includes assessment as per the reduce these injuries. Children should use flame retardant
mnemonic, "SAMPLE" (symptoms, allergies, medications, or nonflammable fabrics to prevent bums.
past illness, last meal, and events leading to the illness) Children with severe burns often have associated
and head to toe examination to identify intrathoracic, intra traumatic injuries which might be missed because of
abdominal, and skeletal or skull injuries. Continued edema and charring nature of the burn. Electrical injuries
resuscitation and reassessment should proceed can occur from direct contact or by an arc such as a
simultaneously. Radiologic examination involves use of lightning strike. Direct contact often has entry and exit
X-ray, ultrasonography and CT scan to define anatomy site wound. The extent of injury depends on the voltage
and abnormalities. Focused assessment by sonography in of current, and course of electric current through the body.
trauma (FAST) may be useful in detecting intra-abdominal Current passing in the region of the heart can cause
bleeding that can be performed serially at the bedside. arrhythmias and death. Tissues with high resistance like
Management of injuries requires a specialist multidisciplinary bone and tendons convert more electrical energy into
team involving pediatric emergency physicians, thermal energy and sustain more damage. Inhalation
anesthetists, surgeons, orthopedician, pediatric intensivists injury, associated with large burns, includes upper airway
and trained nursing personnel. Life-threatening chest direct thermal injury, chemical pneumonitis from harmful
injuries, e.g. tension pneumothorax, flail chest, massive chemicals and systemic poisoning from inhalation of
hemothorax and cardiac tamponade should be rapidly cyanide and carbon monoxide.
identified and managed. Abdominal blunt injury may
result in contusions, hematomas or laceration of solid Classification of Burns
organs. Suitable analgesic medication is titrated to
alleviate pain and anxiety. Availability of emergency Thermal burns may be scalds (caused by hot liquid or
medical services, transport systems and advanced trauma steam), contact burns (contact with hot objects), flame
facilities has resulted in significant reduction in accident burns, chemical burns (exposed to strong acids or alkalis)
related mortality in developed countries. Polytrauma may or electrical. Based on depth, burns are classified as:
have significant psychological and social impact on the l. First degree or superficial burns confined to the
developing brain and result in considerable morbidity. epidermis. Characterized as erythematous, painful and
Psychological and social support, during resuscitation and dry burns. They heal within a week not leaving any
afterwards, is important. scar behind.
2. Second degree or partial thickness burns involve part
BURNS, ELECTRICAL AND INHALATIONAL INJURIES
of the dermis, and are characterized by erythematous,
WHO estimates approximately 10% of all unintentional moist and painful burns. (a) Superficial: Take less than
injury related deaths are due to fire related bums. Children 3 weeks to heal; (b) Deep: Take more than 3 weeks to
are at higher risk of death from burns with 3.9 deaths per heal and leave scars.
3. Third degree or full thickness burns damage the full burns, chemical bums and inhalational injury; and (v) bum
thickness of dermis. These are characterized as leathery, patients with concomitant trauma.
dry and insensate burn. They cannot regenerate The goals of resuscitation and early management are:
themselves without grafting. (i) adequate fluid replacement; (ii) correction of hyp oxia
The "rule of nines" for calculating the surface area of and ventilatory disturbances; (iii) prevention of
burn is not applicable to children <15-year-old. The Lund hypothermia; (iv) adequate control of pain and anxiety;(v)
and Browder chart can be used for the same. A practical wound care; (vi) nutrition, and (vii) supportive care. IV
approach is to consider the child's palm together with access is established with the peripheral cannula and may
fingers as representing 1% of total body surface area be performed through bum-injured tissue, if required.
(TBSA). The risk of mortality from burns covering 30% of Children with >10% burns should have urinary
body surface area is -50% and that with more than 50% catheterization to titrate fluid resuscitation.
BSA is -100%. Fluid replacement: The goal of fluid resuscitation is to
replenish the fluid loss and to restore and maintain
First Aid
perfusion, tissue oxygen delivery at optimal levels in order
Fire injuries: At the scene of fire, the child should be to protect the zone of ischemia in burnt tissues without
wrapped with a blanket or coat; attempt is made to overloading the circulation. Monitoring urine output and
extinguish the flames by rolling the victim on the ground. a nasogastric tube for continuous suction to prevent emesis
Running with clothes on fire should be avoided. The and aspiration are essential. The adequacy of fluid
victim is rescued to a safe airy place away from the fire to resuscitation is based on urine output, which should be
prevent exposure to gases like carbon monoxide and maintained above 1 mL/kg/hr in infants and young
cyanide. In the case of minor burns or scalds, pour cold children. The Parkland formula estimates the amount of
water, apply cold-water soaks or submerge the burned fluid to be replaced over 24 hours as follows:
portion immediately in cold water. Application of grease, Volume of Ringer lactate (mL) = 4 mL x weight (kg) x %
soda, oil, powder, butter, toothpaste or herbs should be TBSA burn
avoided. The wound is covered with clean sheets of sterile
dressing and the patient wrapped in a blanket or foil. In addition, the child requires maintenance fluid
Management of patients requires assessment of the extent therapy. Half of the resuscitation volume should be given
of injury, including surface area, depth and cause of burn. in initial 8 hours and the other half in following16 hours.
Potassium is administered after normal kidney function
Electrical injuries: The power supply should be switched is shown. Subsequent fluid management should account
off. Using a nonconductor material (dry wooden stick or for ongoing fluid losses (Fig. 27.1).
dry cotton clothes), the victim is pulled from the electric
source. The surface injury may be smaller and is often not Analgesia: Adequate control of pain is an essential
indicative of the extent of injury to deeper tissues. Children component of bum management; opioids are commonly
should be monitored for arrhythmias, ongoing myolysis, prescribed.
and secondary organ dysfunction. Wound care and topical therapy: Adequate wound care
Inhalational injury: Children with inhalation injury may and topical therapy result in healing of first and second
require to be intubated and provided supportive degree burns, without need for skin grafting. The most
ventilation. Pneumonitis peaks after 3-5 days of injury. commonly used topical agents are 0.5% silver sulfadiazine,
High blood levels of carboxyhemoglobin suggest carbon
monoxide poisoning. Inhalation of 100% oxygen shortens
the elimination half life of carbon monoxide from 4 hours (4 ml/kg x % BSA burn) (Ringer lactate)
to 40 minutes, and is thus recommended. Cyanide Plus
poisoning can occur when significant quantities of plastics Maintenance (5% dextrose & Ringer lactate)
are burned. The antidote, hydroxycobalamin, infused at
Initial 24 hours
I
a dose of 70 mg/kg IV, binds with cyanide forming
cyanocobalamin that is stable and excreted in urine. Amyl Half of resuscitation volume in first 8 hours
nitrite and sodium nitrite may induce methemoglobinemia Other half in next 16 hours
and are not recommended. Subsequent
therapy
Hospitalization
I,
Maintenance
Minor burns can be treated at home with topical Plus
ointments. Indications for inpatient care include: (i) third Hourly ongoing loss calculated as
(25 + % BSA burn) x Total BSA
degree burns at any age group; (ii) second-degree bums (N/5 in 5% dextrose)
involving more than 10% TBSA; (iii) burn injuries
involving the face, hands or genital areas; (iv) electrical Fig. 27 .1: Outline of fluid resuscitation in burns
Poisonings, Injuries and Accidents 1101-
0.5% silver nitrate and mafenide acetate. Application use of life jackets, fencing around swimming pools,
of silver sulfadiazine is painless and has a soothing covering water hazards and prompt first aid.
effect, restricting fluid and heat loss from bum surface.
However, it can cause skin rash, leukopenia, and thrombo CHOKING AND SUFFOCATION
cytopenia. Silver nitrate is not an effective antibacterial
agent because of poor penetration of the bum eschar. The Choking, suffocation and strangulation are important
medication can cause hyponatremia, hypokalemia, causes of unintentional injuries, especially in infants.
hypochloremia and hypocalcemia. Mafenide acetate Complications include anoxic brain damage and
penetrates the bum eschar effectively; its application may esophageal perforations. Food (chiefly nuts), latex
be painful and associated with skin reaction and metabolic balloons, toys, lids and small containers are commonly
acidosis. involved in choking, while suffocation is commonly seen
in a crib, waterbed or with playground equipment.
Daily dressing changes are required; moist exposed Ingestion or inhalation of button batteries is dangerous.
bum ointment (MEBO) is promising. Treatment for small, Most batteries pass through the alimentary tract, but
deep second-degree burns has two components: Excising occasionally are impacted in the esophagus or cause
the burn wound before it is infected and covering the gastric erosion. Batteries have also been inserted into the
excised wound with synthetic or biological wound nose. Ingested small coins are usually passed safely but
dressings. For circumferential burns of the chest, abdomen may became impacted and require surgical intervention.
and extremities, decompressive escharotomy need to be Prevention strategies include enforcing regulatory
performed. standards for baby and child product design and
Nutrition: High caloric and protein intake are crucial for manufacture, appropriate labeling and parental education.
survival and recovery. Caloric requirement in children
with burns is estimated as follows: POISONING
Infants: 2100 Kcal/m2 + 1000 Kcal/m2 burn surface area Acute childhood poisoning is a common and challenging
Children: 1800 Kcal/m2 + 1300 Kcal/m2 burn surface area pediatric emergency. Children are susceptible to
Adolescents: 1500 Kcal/m2 surface area and bum surface area poisoning because of their curious and exploring nature,
Adequate protein intake (2-3 g/kg body weight) and and propensity to put virtually everything in their mouths.
supplementation of trace vitamins and minerals are Common poisoning agents in high-income countries
necessary. Whenever feasible, particularly in children with include pharmaceuticals, household products and
less than 15-20% burns, nutrients are given enterally. Tube chemicals; in low and middle-income countries, pesticides,
feeding is started on the first day of admission with rapid kerosene, cleaning agents and pharmaceuticals are
advancement towards intake goals. Parenteral nutrition commonly involved. Majority of poisonings in children
is considered in children with extensive burns, inhalation <5 years of age are accidental, while in older children and
injury or prolonged paralytic ileus. teenagers, these are largely intentional.
Supportive measures: Assessment of physical abilities and Clinical Approach to Child with Suspected Poisoning
enabling a full range of joint movements by physical and
occupational therapy and play therapy is encouraged. The initial approach includes stabilization and rapid
assessment of the airway, breathing, circulation and
mental status. After initial assessment and stabilization
DROWNING AND NEAR DROWNING
of vital signs, general physical and neurological
Drowning is an asphyxia! death from submersion or examination is done. Physical examination may show
immersion in liquid. It is the leading cause of injury related pallor (hemolysis), cyanosis (methemoglobinemia) or
death for young children under 5 years of age. Drowning icterus (hepatotoxic agents, hemolytic agents). Acidotic
rates in low-middle income countries are 6-time higher breathing suggests poisoning due to alcohols, salicylates
than in high-income countries. Risk factors for drowning or agents causing hypotension, hypoxia or seizures.
include residence in densely populated areas with large Tachycardia or tachyarrhythmia may point towards
amount of open water, young age, male sex and those with sympathomimetic and anticholinergic agents, while
conditions such as epilepsy and autism. While drowning bradycardia and bradyarrhythmia suggest toxicity with
is most frequent in natural bodies like ponds, lakes and digitalis and cholinergic agents. Oral cavity examination
rivers, drowning in swimming pools and bathtubs is may reveal signs of caustic ingestion such as excessive
increasing. salivation and swallowing difficulties or indicate a poison
Management includes immediate resuscitation and by its odor. Characteristic features with commonly
transfer to a tertiary care facility. In case of death due to reported poisoning agents are shown in Table 27.3.
drowning, parents need to be provided psychosocial Often a particular poison produces a constellation of
support, as it is difficult to cope with the unexpected death. features (toxidromes) involving various organ systems
Successful interventions to prevent drowning include the that confirm the likely diagnosis. A history of vomiting,
10a I Essential Pediatrics
diarrhea, excessive sweating or salivation, seizures and in a child with suspected poisoning should include
presence of meiosis, coma and respiratory failure indicate vomitus or gastric aspirate, and urine and blood
anticholinergic (organophosphate) poisoning, while the specimens. Simple bedside tests help in management and
presence of mydriasis, dry mouth, seizures, sensorial monitoring of these patients (Table 27.5).
alteration and hypertension may point towards poisoning
or overdose with cholinergic compounds (Dhatura, Management
atropine or tricyclic antidepressants) (Table 27.4). Emergency cardiorespiratory stabilization is the priority
and should precede diagnostic tests. While the patient is
Laboratory Evaluation being stabilized, a member of the team should contact the
Diagnosis of poisonings is chiefly clinical and quantitative National Poisons Information Centre (NPIC) at AIIMS,
estimation of most toxins is usually not possible or New Delhi which has an emergency helpline available
delayed. Laboratory evaluation is used to support the 24 x 7. Based on the information provided, advice on
clinical diagnosis. Quantitative estimation of selected diagnosis and management of the child or adult patient is
agents, such as heavy metals, salicylates, some provided and the poisoning is recorded in the National
anticonvulsants, digoxin and paracetamol is available at Database. Helpline numbers are 1800-116-117, 011-
the toxicology laboratory at the All India Institute of 26589391, and 011-26593677
Medical Sciences, New Delhi as well as a few private http://www.aiims.edu/aiims/departments/pharmacology/NPIC/
centers in the country. Samples for quantitative assessment home.htm
Poisonings, Injuries and Accidents 1109-
Principles of management of patients with poisoning should be optimized to maintain adequate gas exchange
include: (i) initial assessment and rapid stabilization of and hemodynamics, taking care to avoid nosocomial
airway, breathing and circulation (basic life support) and infections.
supportive care, (ii) decontamination, (iii) enhancement Circulation: Causes for cardiovascular instability in
of excretion, and (iv) administration of antidotes. These poisoned patients include decreased systemic vascular
are discussed below. resistance, myocardial depression (tricyclic antidepressants,
calcium channel blockers) and arrhythmias (digoxin,
Basic Life Support tricyclic antidepressants). Priority is given towards
Airway and breathing: Early elective intubation is optimization of preload before using vasoactive agents.
preferred in patients with high risk of aspiration and In hypotensive patients, it should be remembered that
progression to respiratory failure. Rapid sequence patients are often not hypovolemic; aggressive fluid
intubation is preferred, due to potential loss of protective resuscitation can, therefore, lead to fluid overload. If
airway reflexes and expectation of a full stomach, with hypotension persists after 1 or 2 standard crystalloid
risk for aspiration. Specific indications for intubation boluses, infusion of a direct acting vasopressor, such as
include failure to maintain patent airway due to CNS epinephrine and norepinephrine, is preferred. Arrhythmias
depression or increased secretions; respiratory failure caused by agents that block fast sodium channels (tricyclic
(hypoxemia or hypercapnia) and severe pulmonary edema antidepressants) are managed with sodium bicarbonate
(salicylates). Establishment of airway may be difficult in therapy.
children with poisoning due to caustics and upper airway
burns and/ or angioedema. Adequacy of breathing should Supportive Care
be assessed by respiratory efforts, chest excursions, air The goals of care include post-stabilization care and
entry, and oxygen saturation. Mechanical ventilation monitoring for complications and organ dysfunction.
110 I Essential Pediatrics
Convulsions may occur due to hypoglycemia, hypoxia, Pulmonary edema is non-cardiogenic and occurs with
cerebral edema, direct effect of toxin on the central nervous substance abuse (heroin, cocaine) or with aspirin overdose.
system, and hypo- or hypematremia. Seizure control is Treatment comprises of administration of 100% oxygen
achieved through administration of benzodiazepines and positive pressure ventilation, if required. The use of
(lorazepam 0.1 mg/kg IV, midazolam 0.15 mg/kg IV, frusemide and atropine (for organophosphate poisoning)
rectal diazepam 0.2-0.5 mg/kg/dose). Status epilepticus may be helpful.
is managed as per standard protocol. Pain is common with snake or scorpion bites and with
Acid-base abnormalities are commonly observed with ingestion of corrosives. Analgesics, narcotics (if no
alcohols, salicylates and iron toxicity. The emphasis is respiratory /CNS depression) and local anesthetics are
directed at the underlying etiology rather than excessive often required.
use of sodium bicarbonate. Nausea, vomiting and upper GI bleeding may be observed
Electrolyte and metabolic abnormalities are anticipated with ingestion of corrosives or drugs causing gastric
in poisoning with drugs such as digoxin, beta-blockers, irritation, or due to stress of illness itself. The use of
insulin and potassium chloride. Administration of antiemetics, H2 receptor antagonists and proton pump
antidotes, if applicable, and correction of the underlying inhibitors should be considered.
abnormality is important. Decontamination or Removal of Unabsorbed Poison
Hypothermia is observed in poisoning with narcoleptic Decontamination is an important step that helps reduce
agents such as chlorpromazine. Management comprises further absorption of the poison. The method varies
of keeping the patient warm, administering pre-warmed depending on the type and route of exposure, patient age
IV/nasogastric fluids and monitoring for complications and general condition, and the time elapsed since
of hypothermia, e.g. hyperglycemia and disseminated poisoning. However, decontamination should not be
intravascular coagulation. routinely employed for every patient.
Poisonings, Injuries and Accidents 1111-
Dermal and ocular decontamination: Dermal and ocular of gut of a child with ingestion of heavy metals, iron,
decontamination begin with removal of any contaminated sustained release or enteric-coated tablets and drug packets.
clothing and particulate matter, followed by flushing of Careful attention should be paid to assessment of the
the affected area with tepid water or saline. A minimum airway and abdominal exam before initiating WBI, and it
of 10-20 minutes of flushing is recommended for most should never be done in a patient without bowel sounds
exposures, although some chemicals (e.g. alkaline or signs of obstruction or ileus, or without a protected
corrosives) require longer periods of flushing. Dermal airway. WBI is administered via a nasogastric tube and is
decontamination should include thorough cleansing with continued until the rectal effluent is clear.
soap and water especially in case of organophosphate Syrup of ipecac or use of other emetics is no longer
poisoning. Water should not be used for decontamination recommended as the amount of poison removed is highly
after exposure to highly reactive agents, such as elemental variable and the outcomes do not seem to improve with
sodium, phosphorus, calcium oxide and titanium administration. Induced emesis is also contraindicated in
tetrachloride. infants, comatose patients, and in children with corrosive
Gastrointestinal decontamination: GI decontamination and hydrocarbon ingestion.
strategies are most likely to be effective, if employed
within the first hour after an acute ingestion. However, Surgical decontamination comprises of endoscopic
even rapid decontamination with activated charcoal will, removal of toxins in case of ingestion of large quantities
at best, bind -30% of the ingested substance. Of the of the toxin or substance (body packers) or lethal amounts
methods of GI decontamination, only activated charcoal of heavy metals refractory to WBI.
and whole-bowel irrigation (WBI) are of clinical benefit. Enhancement of Excretion
Gastric lavage may be employed for patients who arrive
within 1 hour of toxin ingestion. Following insertion of a The technique of enhancing excretion is useful only for a
large-bore orogastric tube (preferably 28 Fr in infants and few toxins where prolonged exposure can result in
36 Fr in older children) into the stomach, the gastric hemodynamic and respiratory compromise or organ
contents are aspirated and washed. Child is kept in lateral failure. Commonly used methods for enhancing excretion
decubitus position with head end lowered. Contra are described below.
indications to gastric lavage include unprotected airway, Urinary alkalinization is used for enhancing excretion of
ingestion of corrosive substances or hydrocarbons, and weak bases and acids, respectively. Alkalinization is
patients at risk for GI perforation or hemorrhage. accomplished by continuous infusion of sodium
Complications include pulmonary aspiration, respiratory bicarbonate, aiming for urine pH of 7.5-8. This procedure
compromise, mechanical injury or perforation of is used to enhance excretion of weak acids, e.g. salicylates,
esophagus, and electrolyte imbalances. There is limited isoniazid, phenobarbitone and methotrexate. Sodium
evidence to suggest that its use improves clinical outcome, bicarbonate is given at a dose of 1-2 mg/kg in one liter of
so gastric lavage should not be considered unless a patient NI 5 normal saline and infused at a rate of 0.5 to 1 liter per
has ingested a potentially life-threatening amount of hour until desired pH is achieved. Serum pH should be
poison. closely monitored, since pH >7.5 is potentially dangerous
Activated charcoal is a potentially useful method of GI for cellular function. Acidification of urine is not advised
decontamination. Charcoal is activated by heating to because of associated complications like acidosis,
extreme temperatures, which lead to creation of extensive hyperammonemia and rhabdomyolysis.
network of pores, providing large surface area for
absorption. Charcoal is most likely to be effective when Forced diuresis in order to ensure urine flow -5 mL/kg/
given within 1 hour of toxin ingestion. It adsorbs almost hr facilitates drug elimination. Brisk diuresis reduces drug
all toxins except common electrolytes, iron, mineral acids or concentration in distal tubules and decreases the
bases, alcohols, cyanide, most solvents, most water insoluble concentration gradient, reducing chances of reabsorption
compounds (hydrocarbons), pesticides and lithium. The dose and enhancing elimination. Diuresis is usually combined
of activated charcoal is lg/kg in children or 50-100 g in with urinary alkalinization.
adolescents and adults. A patent and stable airway must Hemodialysis is effective in removal of substances having
be ensured before administering activated charcoal. Its use the following properties: (i) low volume of distribution
is contraindicated in patients with intestinal obstruction, (<1 L/kg), (ii) low molecular weight, (iii) low degree of
ileus, peritonitis and corrosive ingestions. protein binding, and (iv) high degree of water solubility.
Whole bowel irrigation (WBI) involves instilling large Toxins removed by hemodialysis include barbiturates,
volume of polyethylene glycol electrolyte solution (PEG carbon tetrachloride, digitalis, ethanol, ethylene glycol,
ES) rectally or orally to wash out the entire gut. salicylates, theophylline, bromide, lithium and valproic
Recommended doses of PEG-ES are 35 mL/kg/hr in acid. In addition to enhancing elimination, hemodialysis
children and approximately 1-2 L/hr in adolescents. In benefits by correcting metabolic and electrolyte
children, WBI is particularly useful in decontamination abnormalities resulting from ingestion of toxic substances.
712 Essential Pediatrics
Hemoperfusion involves circulating blood through a However, effective antidotes are not available for majority
cartridge with large surface area coated with activated of poisonings, and symptomatic and supportive treatment
charcoal. Hemoperfusion enables removal of substances remains the mainstay of management. Table 27.6 lists
with: (i) low water solubility, (ii) high affinity for the antidotes used commonly for management of various
adsorbent, (iii) faster rate of equilibrium between poisonings. A list of manufacturers of specific antidotes
peripheral tissues and blood, and (iv) low affinity for in India is maintained by the NPIC.
plasma proteins. Toxins eliminated by this technique are http://www. aiims.edu/aiims/departments/pharmacology/NPIC/
carbamazepine, barbiturates and theophylline. masspoisioning.htm
Hemofiltration removes compounds with molecular
weight 500 to 40000 RMM, and is used for removal of
arninoglycosides, theophylline, iron and lithium.
COMMON POISONINGS
Exchange transfusion removes poisons affecting the red Hydrocarbon Poisoning
blood cells, as in methemoglobinemia or arsenic-induced Hydrocarbon ingestions account for -5% of accidental
hemolysis. poisonings and -25% of deaths related to ingestions in
Multiple dose activated charcoal (MDAC) enhances children <5 years globally. Children are often accidental
elimination by 2 mechanisms, interruption of enterohepatic victims of HC poisoning as these products are inappro
circulation and gastrointestinal dialysis where intestinal priately stored in unlabeled containers or drinking glasses
mucosa is used as the dialysis membrane. MDAC is given and are often attractive in color or pleasant smelling like
at a dose of 0.5 g/kg every 4-6 hours, until there is significant furniture polishes. Hydrocarbons are categorized into
decline in serum drug concentrations. Chief complications aliphatic (kerosene), aromatic (benzene), halogenated
include bowel obstruction and perforation. The technique
is recommended for drugs like carbamazepine, dapsone, (carbon tetrachloride) and mixed compounds. Aromatic
phenobarbital, quinine and theophylline. IV infusion of and halogenated compounds have predominant effect on
intralipid may be used for sequestering fat-soluble drugs the central nervous system, while aliphatic hydrocarbons
(calcium channel blockers, tricyclic antidepressants) and have risk of aspiration and pulmonary symptoms. The
reducing their impact on target organs. most important manifestation of hydrocarbon toxicity is
aspiration pneumonitis via inactivation of type II
Administration of Specific Antidotes pneumocytes and resulting surfactant deficiency. The
Antidotes are substances that counteract the effect of propensity of a hydrocarbon to cause aspiration
poisons, and where available, are of immense utility. pneumonitis is inversely proportional to its viscosity, and
I Hydrocarbon ingestion
i
Norma I chest X-ray
i
Abnormal chest X-ray
Admit; Oxygen, IV fluids, beta agonists
Monitor respiratory and neurologic status
No steroids or prophylactic antibiotics
discrete or circumferential ulcers; Grade 3a scattered 3-6 weeks after injury, progressively increasing the size
necrosis; and Grade 3b extensive, circumferential necrosis of bougies passed over endoscopically placed guidewires.
of mucosa. The risk of perforation and aspiration are high. Esophageal
strictures refractory to dilatation may be surgically
Management corrected by resection and esophageal bypass.
Management comprises of emergency care and supportive
care (Fig. 27.3). Nasogastric tube should not be inserted Organophosphate Poisoning
and gastric lavage is contraindicated, as they increase the Organophosphates and carbamates are commonly used
risk of injury and perforation. Exceptions are made in pesticide agents and a common cause of poisoning in
patients with mercury chloride, zinc chloride and phenol developing nations. Organophosphates cause toxicity by
ingestion, as these compounds are associated with severe inactivating acetylcholinesterase, resulting in excess of
systemic toxicity and may be rapidly fatal. Airway nicotinic and muscarinic activity in the peripheral and
protection is a priority as laryngeal edema may rapidly central nervous systems. These agents form an irreversible
progress over minutes to hours and may cause airway bond with and permanently inactivate the enzyme. On the
obstruction and death. Elective intubation might be other hand, carbamates reversibly bind with the enzyme.
required in such cases, or in presence of respiratory
distress or hoarseness of voice. Expertise to perform Clinical Features
emergency tracheostomy or cricothyrotomy should be The symptoms of organophosphate toxicity depend upon
available at the time of elective intubation. There is no the route, duration of exposure, and the absorbed dose.
role for use of intravenous or nebulized corticosteroids or Acute poisoning is characterized by three phases:
epinephrine in reducing the need for intubation. Cholinergic crisis, intermediate syndrome and delayed
neuropathy. The features of acute cholinergic crisis include
Long-tenn management comprises of ensuring nutrition diarrhea, urination, miosis, bronchorrhea/bronchospasm,
and therapy for strictures. Patients are initially kept nil bradycardia, emesis, lacrimation and salivation
orally and managed with IV fluids. Endoscopic grading (DUMBBELS). Some patients show nicotinic features with
helps in planning nutritional support. While patients with hypertension, tachycardia and dysrhythmia, muscle
grade 1 and 2a are allowed oral feeds, those with grade weakness, fasciculations, tremors and hypoventilation.
2b or 3a are fed by nasogastric tube that is inserted by Patients with severe poisoning may present with coma
endoscopy. Patients with grade 3b injury receive enteral and respiratory failure which may rapidly progress. While
feeding through gastrostomy; some patients require total recovering from cholinergic crisis, some patients may
parenteral nutrition prior to gastrostomy. suddenly develop respiratory failure (intermediate
Stricture formation is the most important complication. syndrome). Late complications of poisoning include
Dilatation therapy and surgery are recommended for delayed polyneuropathy and a range of chronic neuro
prevention and treatment of strictures. Dilatation is done psychiatric symptoms.
I Supportive care
I Surface decontamination, airway
protection, circulatory management
'
(SI units) the tissues. The physiologic level of MetHb is <1% of the
µMil µg/ml
total hemoglobin concentration. MetHb is reduced
6000 1000 to hemoglobin by cytochrome b5, nicotinamide adenine
4000 dinucleotide, ascorbic acid, glucose-6-phosphate dehydro
500 genase (G6PD), and glutathione reduction enzymes.
2000 Methemoglobinemia occurs when the capacity of these
mechanisms is overwhelmed by intake of various drugs
1300 200
1000 150
and toxins that cause an oxidative stress (e.g. lidocaine,
C
0 800 prilocaine, antimalarials, pyridium, sulfonamides and
600 100
c probable hypatic metoclopramide). Acute methemoglobinemia may be life
QJ
(.) 400 toxicity threatening when MetHb >50% of total circulating
C
0 300 50
(.) hemoglobin.
Cll
E 200
Clinical and Laboratory Manifestations
Cll
Q.
No hepatic
C
QJ 100 toxicity
.c
a. 80 Clinical features range from asymptomatic with cyanosis
0
C 60 10 to severe anoxic symptoms like lethargy, stupor and
.E
$
QJ 40 seizures. The patient appears cyanosed, which does not
<{
5 respond to 100% oxygen. The severity of symptoms
20 depends upon blood MetHb levels; levels >70% result in
vascular collapse and death. Arterial blood gas reveals
10 normal Pa02 and low Sp02• Bedside tests, such as the filter
paper test, are useful for screening; blood is chocolate
0 4 8 12 16 20 24 colored and does not tum red on exposure to oxygen. The
diagnosis is confirmed by multiple wavelength co
Hours after ingestion
oximetry, which also gives MetHb levels in blood.
Fig. 27 .4: Rumack-Matthew nomogram
Treatment
Management comprises supportive care and administra
Blood for acetaminophen levels at
least 4 hours post-ingestion tion of methylene blue, at a dose of 1-2 mg/kg
followed by bolus of 25-30 mL normal saline. The dose
can be repeated after 1 hr to maximum of 7 mg/kg over
Plot on Rumack-Matthew nomogram 24 hours; at higher dosage, the oxidizing action of
methylene blue exceeds the reducing action of
leukomethylene blue. Even after resolution of symptoms,
patients should be observed for recurrences. Patients with
Acetaminophen levels are below Acetaminophen levels are above
the broken line the solid line G6PD deficiency should not receive methylene blue. Other
therapies include ascorbic acid, hyperbaric oxygen and
exchange transfusions.
Do not give N-acetylcysteine; Therapy with N-acetylcysteine
stop, if already started
ENVENOMATIONS
Fig. 27 .5: Approach to a child with acetaminophen overdose
Snake Bites
orally or intravenously. King's College criteria for The highest burden of envenomations exists in south and
acetaminophen toxicity are used for deciding referral for south-east Asia and sub-Saharan Africa. India has the
liver transplantation: (i) acidemia (serum pH <7.3) after highest number (46000 annually) snake bite-related deaths
adequate fluid resuscitation, (ii) coagulopathy (INR >6), in south Asia. More than one-quarter of these deaths occur
(iii) renal dysfunction (creatinine >3.4 mg/dL), and (iv) in children 5-14-year-old, mostly in rural areas and during
grade III or IV hepatic encephalopathy. The degree of the monsoon season. The four most important venomous
transaminase elevation is not involved in determining snakes in India are Indian cobra (Naja naja), Indian krait
liver transplantation. (Bungarus caeruleus), Russell viper (Daboia russelii) and
saw-scaled viper (Echis carinatus).
Methemoglobinemia
Methemoglobinemia is a condition where iron (within Clinical Features
hemoglobin) is oxidized from ferrous (Fe2+) to ferric As per WHO, the diagnosis of envenomation is based on
(Fe3+) state, resulting in inability to transport oxygen to one or more of the following: (i) history of snake bite, (ii)
Poisonings, Injuries and Accidents 1111-
Investigations, for identifying myocardial dysfunction, cardiovascular manifestations. There is limited informa
include chest X-ray, ECG and echocardiography. tion on the efficacy and safety of scorpion antivenom in
Myocardial perfusion and neurological abnormalities may children. An algorithm based approach for management
be identified on nuclear scintigraphy and CT scans, is given in Fig. 27.6.
respectively. Patients should be hemodynamically stable and show
Local measures: The site of the sting is cleaned. Relief from normal sensorium at discharge. Additional criteria for
pain allays anxiety and avoids myocardial stress. NSAIDs discharge include no respiratory distress and being free
can be used for relief from severe pain. Local ice packs, of complications.
xylocaine infiltration, dehydroemetine (counterirritant)
and streptomycin (neuromuscular blockade) are reported INJURY CONTROL
to be useful.
Principles that deserve emphasis in planning injury
General measures include: prevention strategies are as follows:
i. Oxygen administration by face mask or nasal cannula i. Passive injury prevention, such as automatic locks for
in case of respiratory distress, or impending shock. medicine cabinets, is preferred over active strategies,
ii. Frequent monitoring of vital signs, fluid balance, blood e.g. "yuck" stickers on bottles.
levels of electrolytes, pH, liver and kidney functions, ii. Specific instructions, e.g. keep water heater
and DIC profile. temperature lower than 120° F, are more likely to be
iii. Sedation: Diazepam is recommended (in concert with followed than general advice, e.g. reduce temperature
GABA opens ion channels, antagonizing toxin action); of hot water tap in your home.
long-acting sedatives are avoided. iii. Reinforcement by com munity wide education pr o
Drug therapy: Various agents have been used in grams is more effective than individual education
experimental animals and humans to treat systemic sessions.
manifestations of scorpion envenomation. In our country, Targeted messages for prevention of injuries should be
prazosin is the first-line agent because of predominant discussed with the parents (Table 27.10).
Scorpion Envenomation
Suggested Reading • CDC. National action plan for child injury prevention. https://
w w w . c d c . g o v / s a f e c h i l d / p d f / n a t i o n a l_a c t i o n_
• Murphy K. Management of musculoskeletal injuries. In: Behrman,
Kliegman, Jenson, Stanton (eds) Nelson Textbook of Pediatrics, 20th plan_for_child_injury_prevention-a.pdf.
edn. Philadelphia, Elsevier, 2016 pp 366-74. • Katz A, Kluger Y. Caustic material ingestion injuries-Paradigm shift
• World Health Organization. Children and poisoning. http:// in diagnosis and treatment. Health Care Current Reviews 2015;
www.who.int/violence_injury_prevention/child/injury/ 3:152.
world_report/Poisoning_english.pdf.
• World Health Organization. World report on childhood injury • Kajala P, Jhavar L, Singh S, et al. Demographic and clinical profile
prevention. http://apps.who.int/iris/bitstream/10665/43851/1/ of children presenting with acute poisoning in a tertiary care
9789241563574_eng.pdf. hospital. IJEP 2011; 3: 55-9.
Chapter
28
Pediatric Critical Care
Praveen Narsaria • Rakesh Lodha
Care for critically ill children has an important role in small sample volumes. Portable X-ray and ultrasono
improving child survival. In tertiary care hospitals, 5- 10% graphy units are desirable. In addition to the primary
of pediatric beds are reserved for intensive care; higher disorder, it is necessary to ensure nutrition, sedation and
numbers are required, if the hospital has surgical units. effective analgesia and infection control. Communications
In order to optimize resource utilization in resource with the parents is necessary to keep them informed about
limited settings, it is useful to understand the indications the condition of their child, and ensure their trust and
of admission to PICU (Table 28.1). cooperation.
The optimal number of beds in a PICU is 6--10. Attention
is given to the layout, ensuring 200-250 square feet area Suggested Reading
per bed, with rapid access to head end for airway • Slusher TM, Kiragu AW, Day LT, Bjorklund AR, Shirk A, Johannsen
management. The unit should have uninterrupted power C, Hagen SA. Pediatric critical care in resource-limited settings:
supply and preferably be air-conditioned. A crash cart Overview and lessons learned. Front Pediatr 2018;6:49.
having necessary drugs and resuscitation equipment
should be available. The unit should have a central ASSESSMENT OF A SERIOUSLY ILL CHILD
monitoring station and space for utilities and storage. A sick child who is non-responsive to verbal and physical
Equipment required are cardiorespiratory and ECG stimuli should be immediately checked for breathing
monitors, oximeters, devices for oxygen therapy, efforts (gasping, apneic) and central pulses (present,
mechanical ventilators, nebulizers, infusion pumps, absent). If the child has abnormal respiration (gasping
weighing scales and enough disposables. The ICU should or not breathing) or has absent central pulses, then child
have access to laboratory facilities, including blood counts, should receive CPR (cardiopulmonary resuscitation)
glucose and electrolytes, and blood gases that require immediately.
Further assessment comprises of the ABCDE approach.
Table 28.1: Indications for admission to the pediatric intensive A stands for 'airway assessment' and should categorize
care unit the airway as'clear','maintainable' and'not maintainable'.
• Hemodynamic instability or shock requiring inotropic support, B stands for 'breathing assessment' and includes
e.g. cardiac arrhythmias, cardiorespiratory arrest, severe respiratory rate and effort, abnormal sounds on
anemia or hemorrhage auscultation and pulse oximetry. C stands for 'circulation
• Respiratory distress requiring oxygen therapy and/or assessment' including skin color and temperature, heart
impending or established respiratory failure requiring rate and rhythm, blood pressure, central and peripheral
mechanical ventilation pulses, capillary refill time and assessment of end organ
• Altered sensorium due to any cause, including encephalo perfusion by mental status (brain perfusion), and urine
pathy, status epilepticus, raised intracranial pressure output (renal perfusion). D stands for 'disability' that
• Acute hepatic or renal failure and complications establishes the level of consciousness by AVPU pediatric
• Severe metabolic abnormalities, e.g. dyskalemia, dys response scale or Glasgow Coma Scale and pupillary
natremia, hypoglycemia, diabetic ketoacidosis; acute response to light. E stands for'exposure' where body parts
poisoning
are exposed to look for skin rashes or wounds. Features
• Severe infections, e.g. severe malaria, severe pneumonia
predictive of a serious illness, particularly in young infants
• Procedures: Peritoneal dialysis, exchange transfusion,
central venous cannulation are listed in Table 28.2. The history should focus on the
• Postoperative monitoring underlying illness. Common investigations include blood
counts, glucose, electrolytes and arterial blood gases.
721
722 Essential Pediatrics
Table 28.2: Common danger signs over sternum or forehead for 5 seconds to cause blanching.
Seizure activity
The normal capillary refill time is 3 seconds or lower;
prolongation signifies impairment of microcirculation.
Excessive, inconsolable cry
Another way of determining adequacy of peripheral
Decreased activity or drowsiness perfusion is noting the core-peripheral temperature
Increased work of breathing gradient; gradient >5 ° C indicates hypoperfusion.
Abnormal sound on breathing Continuous ECG monitoring is necessary in children
Apneic episodes or cyanosis admitted to the PICU. Central venous pressure (CVP) is
Cold extremities (particularly in absence of cold environment) monitored by placing a catheter through a large vein into
the right atrium; the pressure informs about venous return
Decrease in the urine output
and preload. Normal right atrial pressure is less than
Decreased feeding, bilious vomiting 6 mm Hg. Low CVP in a child with hypotension signifies
low intravascular fluid volume. CVP may be increased
Monitoring due to myocardial dysfunction, fluid overload or increased
pulmonary artery pressures. Renal perfusion is assessed
Respiratory by monitoring urine output; output <0.5 mL/kg/hr in a
The patient should be observed for respiratory rate and child with normal kidneys signifies poor perfusion.
pattern, nasal flaring, use of accessory muscles and color Monitoring of the sensorium and neurologic status also
(Table 28.3). Examination is done for symmetry of air gives information about brain perfusion.
entry, breath sounds and presence of stridor, rhonchi and
crepitations. Respiratory rate is monitored continuously Suggested Reading
by impedance pneumography. Pulse oximetry allows non • Bronicki RA, Spenceley NC. Hemodynarnic monitoring. In: Nichols
invasive measurement of oxygen saturation. While DG, Shaffner DH, eds. Roger's Textbook of Pediatric Intensive Care,
reliable, some conditions lead to inaccuracies, e.g. 5th edn. Lippincott Williams and Wilkins 2016: pp 1120-36.
dyshemoglobinemia (methemoglobin, carbon monoxide • Cheifetz IM, Lee JH, Venkataraman ST. Respiratory monitoring.
In: Nichols DG, Shaffner DH, eds. Roger's Textbook of Pediatric
poisoning), dyes and pigments (methylene blue), poor Intensive Care, 5th edn. Lippincott Williams and Wilkins 2016:
peripheral perfusion, increased venous pulsations and pp 686-709.
interference with external light (phototherapy unit,
fluorescent light). Chest radiography and arterial blood PEDIATRIC BASIC AND ADVANCED LIFE SUPPORT
gas analyses are performed periodically.
Cardiopulmonary arrest in children is much less common
Hemodynamic than adults and usually represents the terminal event of
Hemodynamic monitoring provides information about progressive shock or respiratory failure rather than a
circulatory status and perfusion of vital organs. The rate primary cardiac cause. The major causes in infants and
and character of pulse should be examined. Blood pressure children are respiratory failure, sudden infant death
can be monitored manually or by oscillometry. The state syndrome, sepsis, neurologic diseases, submersion or
of microcirculation is assessed by capillary refilling time. drowning and injuries. In contrast to adults, sudden
Pressure is applied with the index finger or ball of thumb cardiac arrest in children is uncommon. Basic life
support (BLS) refers to a protocol of procedures performed
in cases of cardiopulmonary arrest to provide
Table 28.3: Respiratory rates (RR) and heart rates (HR) at cardiopulmonary resuscitation (CPR) with or without
different ages devices and bag-mask ventilation till advanced life
Age, years RR, breaths/min HR, beats/min support (ALS) can be provided. The major objectives of
1 30 (22-38) 120 (80-160)
CPR are to preserve organ viability during cardiac arrest
and to help return spontaneous circulation.
2 25 (17-33) 110 (80-130)
4 23 (17-27) 100 (80-120) Basic Life Support
6 21 (15-26) 100 (75-115)
To maximize survival and intact neurological status in
post-resuscitation stage, early recognition of cardiac arrest
8 20 (15-26) 90 (70-110) and strict adherence to the BLS sequence is necessary. BLS
10 18 (15-25) 90 (70-110) includes a series of skills performed sequentially to assess
and restore effective ventilation and circulation to the child
12 18 (14-26) 85 (65-105) with respiratory or cardiorespiratory arrest. Evaluation
14 17 (15-23) 80 (60-100) and interventions in pediatric BLS are performed
simultaneously, in the following sequence: (i) assessment,
16 17 (12-22) 75 (55-95)
(ii) circulation, (iii) airway and (iv) breathing. The
Pediatric Critical Care 1123-
sequence Circulation-Airway-Breathing (C-A-B) has can use one hand to support the infant's body and head
been recommended in 2015 update of Pediatric Basic Life and the other hand to perform chest compression.
Support to maintain uniformity in CPR algorithm across Chest compression technique in the child (1-8 years age)
all ages. Fig. 28.1 indicates how the heel of one hand should be
placed over lower half of sternum, avoiding pressure over
Assessment
xiphoid, and with fingers lifted above the chest wall to
Initial assessment is done to confirm cardiac arrest so that prevent compression of rib cage. Rescuer should position
life-saving measures can be begun promptly to enable him/herself vertically above the victim's chest.
intact neurologic survival. The combination of un
Large children and >8 years of age: The two-hand method
responsiveness and absent or abnormal breathing most
for chest compression should be used to achieve an
accurately identifies cardiac arrest. Palpation of the pulse
adequate depth of compression. This is achieved by
for its absence is unreliable as the sole determinant of
placing the heel of one hand over the lower half of sternum
cardiac arrest. If the victim is unresponsive, not breathing
and the heel of the other hand over the first hand,
normally, and there are no signs of life, lay rescuers should
interlocking the fingers of both hands, with fingers lifted
begin CPR; in such a setting, health care providers should
above the chest wall. External chest compression in
begin CPR unless they definitely palpate a pulse within
children and infants should always be accompanied by
10 seconds.
rescue breathing. Ventilation is relatively less important
Circulation during the first minute of CPR for victims of arrhythmia
induced cardiac arrest than it is after asphyxia-induced
CPR should begin with chest compression. Chest arrest. The lay rescuers should use a 30:2 compression
compressions are serial rhythmic compressions of the ventilation ratio for all (infant, child and adult) victims.
chest that allow blood flow to vital organs (heart, lungs For one healthcare provider, the compression-ventilation
and brain) in an attempt to keep them viable until ALS ratio should be 30:2 for all age groups and for two rescuers,
(advanced life support) is available. The victim should be the compression-ventilation ratio should be 30:2 in adults
aid supine on a hard and flat surface. Adequate chest and 15:2 in infants, children and adolescents. Once an
compression is given by pushing hard, to a depth of at advanced airway (tracheal tube) is placed, chest
least one-third of anteroposterior dimension or compressions should not be interrupted for ventilation.
approximately Ph inches (4 cm) in infants and 2 inches The victim should be reassessed after two minutes. If
(5 cm) in children. The rate should be 100-120 signs of spontaneous circulation have reappeared, chest
compressions per minute, allowing full chest recoil and compression should be discontinued and only ventilation
minimizing interruptions in chest compressions. continued till return of spontaneous breathing.
Compression of the xiphoid process should be avoided.
Chest compression in infants (<1 year) Airway
Two-thumb technique: The infant's chest is encircled with Infants and children are at increased risk of respiratory
both hands; fingers are spread around the thorax and the obstruction and failure compared to adults, for the
thumbs brought together over the lower half of the following reasons: Smaller upper airway in comparison
sternum, avoiding the xiphisternum. The sternum is to adults; large tongue in relation to oropharynx; smaller
compressed with the thumbs and the thorax with the
fingers for counterpressure. The two-thumb-encircling
hands technique is preferred because it produces higher
coronary artery perfusion pressure, consistently
appropriate depth and force of compression, and may
generate higher systolic and diastolic pressures. While one
provider should provide chest compressions, the other ''
> I
/�)
If the rescuer is unable to deliver breathes, the rescuer
may continue with chest compressions only; however, one
must remember that majority of pediatric cardiac arrests
are secondary to hypoxia.
Two-finger technique: If the rescuer is alone or unable to
physically encircle the chest, the chest is compressed with
two fingers, placing them vertically over the sternum just
below the intermammary line (between the two nipples)
ensuring that they are away from xiphoid process. One Fig. 28.1: Chest compression in a child (1-8-year-old)
124 I Essential Pediatrics
and compliant subglottic area more prone for collapse upwards and outwards. This method should be used
and/ or obstruction; relatively compliant chest wall and in all victims with blunt trauma, craniofacial injury,
rib cage; and limited oxygen reserve. and those having Glasgow Coma Score <8. This
Position of the victim: If the child is unresponsive but method is not recommended for lay rescuer because it
breathing or signs of life are present, he should be placed is difficult to learn and perform effectively and safely.
on a hard surface in supine position. If head or neck
Foreign body airway obstruction: The mouth is opened
trauma is suspected, head and torso should be moved as
and examined for presence of foreign body, which is
a unit and the neck immobilized.
removed, if visible; blind sweeping is not recommended.
Open the airway: The tongue is lifted away from the If the victim is an infant who is responsive and has features
posterior pharynx to keep the airway patent. of airway obstruction, back slap and chest thrust are
i. Head tilt chin lift maneuver (Fig. 28.2): If the victim is performed till the foreign body comes out or till the infant
found unresponsive and has signs of life, the airway becomes unresponsive. If the victim is an older child or
is opened by tilting the head back and lifting the chin. adolescent, an abdominal thrust is given by standing
One hand is placed over the forehead and head is behind the victim till the foreign body is expelled out or
gently tilted back. Simultaneously, the fingers of the till the patient becomes unresponsive (Chapter 29). If the
other hand are placed on the lower jaw to lift the chin victim becomes unresponsive, cardiopulmonary
to open the airway. This maneuver should not be used, resuscitation should be begun with an additional
if there is suspicion of trauma to head and/ or neck. maneuver of checking the airway for the foreign body after
ii. Jaw thrust (Fig. 28.3): Two or three fingers are placed giving the chest compression and before breaths are given.
under each side of lower jaw at its angle to lift the jaw Trained healthcare provider should perform a tongue-jaw
lift to look for obstructing objects.
Breathing
After opening the airway, one should check for breathing.
Periodic gasping, also called agonal gasps, is not breathing.
If there is effective spontaneous breathing without evi
dence of trauma, the child is turned to recovery position,
which helps maintain a patent airway and prevents
aspiration.
Pediatric Advanced Life Support (PALS) Table 28.5: Size of ET tube and suction catheter in infants
PALS refers to the assessment and support of pulmonary Age; weight Tracheal tube Suction catheter
and circulatory function in the periods before, during and mm Fr
after an arrest. PALS targets the prevention of causes of Premature newborn; <1 kg 2.5 5
arrest and early detection and treatment of cardio
Premature newborn; 1-2 kg 3.0 5-6
pulmonary compromise and arrest in critically ill or
injured children. Newborn; 2-3 kg 3.0-3.5 6-8
Newborn; >3 kg 3.5-4.0 8
Components of PALS are: (i) Basic life support; (ii) use of
equipment and techniques to establish and maintain effec Infant 3.5-4.0 8
tive oxygenation, ventilation and perfusion; (iii) clinical An appropriate sized endotracheal tube is used
and ECG monitoring with arrhythmia detection and (Table 28.5). Beyond 1 year, the size of the tube is:
management; (iv) establishing and maintaining vascular
access; (v) identification and treatment of reversible causes (Age in year)
Tracheal tube size (in mm)= +4
of cardiopulmonary arrest; (vi) emergency treatment 4
of patients with cardiac and respiratory arrest; and Tubes 0.5 mm smaller and 0.5 mm larger than the
(vii) treating patients with trauma, shock, respiratory estimated size should be available for use. The size of
failure or other pre-arrest conditions. suction catheter is usually twice the internal diameter of
the tracheal tube in mm, e.g. 8 Fr suction catheter for
Adjuncts for Airway and Ventilation tracheal tube of size 4 mm. Cuffed tubes are preferred in
Oxygen should be given to all seriously ill or injured patients with poor lung compliance, high airway
children with respiratory insufficiency, shock and trauma. resistance and large glottic air leak.
During mouth-to-mouth rescue breathings, only 16-17% The depth of insertion of the tube is approximately three
oxygen is delivered, with alveolar oxygen pressure of times its inner diameter. In neonates, the endotracheal tube
80 mm Hg, and optimal external chest compressions is inserted to a depth of:
provide only a fraction of the cardiac output, resulting in Depth of insertion (cm)= birth weight (kg)+ 6
reduced tissue perfusion and oxygen delivery. Ventilation In children >2-year-old, the depth of insertion of the
perfusion mismatch during CPR and underlying endotracheal tube is:
respiratory disorders causes right-to-left shunting that (Age in years)
reduces oxygenation. Depth of insertion (cm)= + 12
2
Tube placement is confirmed by looking for
Endotracheal Intubation
symmetrical chest rise and auscultating for air entry on
If used properly, this is the most effective and reliable both sides. Auscultation over upper abdomen is required
method of ventilation. The advantages of endotracheal to rule out esophageal intubation. Other markers of proper
intubation are: (i) it ensures adequate ventilation; (ii) reduced tube placement are improving heart rate, color, perfusion
risk of aspiration of gastric contents; (iii) inspiratory time and oxygen saturation. The position of the tube should be
and peak inspiratory pressure can be controlled; (iv) suction confirmed on chest radiograph.
can be done to keep airway patent; and (v) positive end
expiratory pressure can be provided. However, a skilled Vascular Access
person is required for intubation. Hence, it is recommended During CPR, the preferred access is the largest easily
that bag and mask ventilation should be continued in accessible vein, cannulating which does not require
children who require ventilatory support in the out-of interruption of resuscitation. Central venous lines provide
hospital setting, when transport time is short or when an secure access, rapid action, higher peak drug levels, and
expert is not available for intubation. Indications for permit administration of drugs that might injure
endotracheal intubation are listed in Table 28.4. peripheral veins (vasopressors, calcium gluconate,
hypertonic solutions like sodium bicarbonate). Femoral
Table 28.4: Indications for endotracheal intubation vein is the safest and easiest to access (Chapter 29). Agents
Excessive work of breathing leading to fatigue with short half-life such as vasopressors, adrenaline and
Inadequate neurologic control of ventilation, and poor respiratory adenosine act better, if given through central venous
effort access. Catheter lengths of 5 cm in infant, 8 cm in a young
Functional or anatomical airway obstruction child and 12 cm in an older child are usually suitable.
Need for high peak inspiratory pressure or positive end Intraosseous access should be tried in patients, if the
expiratory pressure central or peripheral venous assess is not achieved. The
Lack of protective airway reflexes usual site for intraosseous access is upper end of tibia
medial to tibial tuberosity (Chapter 29). Other sites include
For prolonged duration cardiopulmonary resuscitation
the distal end of femur, lower end of tibia above medial
12s I Essential Pediatrics
malleolus and anterior superior iliac spine. Drugs like infusing 40-60 mL/kg of crystalloids. Dextrose solutions
adrenaline, adenosine, and vasopressors can be transfused should not be used for initial resuscitation as they do not
by this route. Samples for chemical analysis, blood expand the intravascular volume effectively and may
grouping and crossmatching may be taken from these cause hyperglycemia, leading to osmotic diuresis and a
sites. vicious cycle of polyuria and hypovolemia. Hypo
Tracheal route is not a preferred route of administration glycemia, if suspected or documented, should be managed
of medications even in emergencies. If intravenous or rapidly with intravenous glucose and measures to prevent
intraosseus access is not established, the tracheal route recurrence.
may be used for lipid-soluble agents like lidocaine,
epinephrine, atropine and naloxone. Arrhythmias
Most pediatric arrhythmias are the consequence of
Post-arrest Care hypoxemia, acidosis or hypotension. Children with
Fever is common after cardiac arrest and should be myocarditis, cardiomyopathy or following cardiac surgery
controlled aggressively. After return of spontaneous are also at risk of arrhythmia. Drugs in therapeutic or toxic
circulation, hypoxia or hyperoxia should be avoided and doses can cause arrhythmia. About 10% of pediatric
oxygen saturation should be maintained between 94 and cardiac arrest patients have ventricular fibrillation (VF)
100%. Continuous arterial pressure monitoring is done to or pulseless ventricular tachycardia (VT).
maintain blood pressure above the 5th centile. Table 28.6 Bradyarrhythmia: Hypoxemia, hypothermia, acidosis,
shows doses for commonly used drugs during resuscitation. hypotension and hypoglycemia depress sinus node
function and slow conduction through the myocardium.
Fluid Therapy
Excessive vagal stimulation, raised intracranial pressure
Early restoration of the circulating blood volume is or brainstem compression may cause bradycardia. Sinus
important to prevent progression to refractory shock or bradycardia, sinus node arrest with junctional or
cardiac arrest. An initial fluid bolus of 20 mL/kg is idioventricular rhythm and AV blocks are usually
recommended in shock, and after each bolus, the patient preterminal rhythms. All slow rhythms resulting in
is reassessed. Volume expansion is best achieved with hemodynamic instability require immediate treatment.
isotonic crystalloid fluids, such as Ringer lactate or normal Epinephrine is the most useful drug in treating
saline. Blood replacement is indicated in patients with symptomatic bradycardia, unless due to heart block or
severe hemorrhagic shock who remain in shock despite vagal overtone. For bradycardia due to vagal overtone,
Humoral receptors: Hypotension-induced release of Hypovolemic shock arises from loss of preload. Clues that
epinephrine and norepinephrine from adrenal medulla suggest hypovolemic shock are (i) fluid losses due to
and systemic adrenergic nerve endings lead to vaso diarrhea, vomiting, blood loss, profuse and prolonged
constriction and inotropic and chronotropic effects. sweating, polyuria or a combination of these, or (ii) reduced
Release of vasopressin from neurohypophysis causes intake due to vomiting, poor appetite or fluid deprivation.
vasoconstriction and stimulates free water reabsorption Physical examination shows dry mucous membranes,
in the distal nephron. absence of tears, delayed capillary refill, diminished peri
Renin-angiotensin-aldosterone system: Reduced renal pheral pulses and poor color. The CVP is low. Investigations
perfusion results in release of renin from the juxta show high blood urea and creatinine, elevated uric acid
glomerular apparatus, that helps convert angiotensinogen and small cardiac silhouette on chest X-ray.
to angiotensin I and angiotensin II. Angiotensin II is a Cardiogenic shock results from loss of cardiac contractility.
potent vasoconstrictor and stimulates release of aldo Clues are history of congenital heart disease, recent cardiac
sterone, enhancing sodium reabsorption. surgery or diseases associated with cardiac disorders (e.g.
Duchenne muscular dystrophy), presence of a murmur,
Diagnosis of Shock S3, gallop or friction rub, elevated JVP and hepatomegaly.
An early diagnosis of shock or impending shock and its CVP is elevated and chest X-ray may show a large cardiac
appropriate management improve outcomes. Early silhouette and pulmonary edema.
diagnosis of shock requires a high degree of suspicion and
knowledge of predisposing conditions. Children who are Distributive shock results from loss of afterload or
febrile, have an identifiable source of infection or are systemic vascular resistance. Clues on history include
hypovolemic due to any cause are at increased risk. Signs recent allergies or spinal cord injury. Examination shows
of early shock include tachycardia, mild tachypnea, bounding pulses, well-perfused skin and low blood
prolonged capillary refill (>2-3 seconds), orthostatic change pressure requiring large volume of fluid.
in blood pressure or pulse, and mild irritability. Decreased Septic shock has components of all aforementioned types:
tissue perfusion is identified by change in body temperature Loss of preload, loss of afterload or systemic vascular
(cold extremities) and decreased capillary refill. Vital organ resistance, and loss of contractility. Apart from fever and
hypoperfusion is assumed in presence of oliguria or altered tachycardia, there may be features of decreased perfusion
mentation. Narrowing of pulse pressure is an early finding in form of altered sensorium, prolonged capillary refill
due to reduced systolic and mild increase in diastolic blood >2 seconds (cold shock) or flush capillary refill (warm
pressures. Patients with early septic shock show increased shock), diminished or bounding pulses, and/ or decreased
peripheral pulses, warm and over perfused extremities, urine output. Hypotension is a late feature. A focus of
wide pulse pressure and hyperdynamic precordium. infection should be looked for.
If shock continues, the compensatory mechanisms are
insufficient to maintain the metabolic needs of tissues. Monitoring
Cellular ischemia and inflammation affect brain, kidney Monitoring of patients who are in shock or impending
and cardiac microcirculation. Tachypnea due to metabolic shock is necessary. Parameters to be monitored are pulse
acidosis leads to respiratory alkalosis. Skin shows features rate and volume, respiratory rate and pattern, tempera
of reduced capillary refill and mottling. Hypotension, ture, skin color, blood pressure, sensorium, urine output,
oliguria and hypothermia set in. Mental changes include ECG and pulse oximetry. Metabolic parameters include
agitation, confusion, stupor and finally coma (Table 28.8). blood glucose, electrolytes and arterial gases.
Classification Therapy
Recognition and treatment of shock depends upon the Therapy depends on the typ e of shock. In hypovolemic
etiology of shock. shock, replacement of intravascular volume by isotonic
fluids is necessary. In cardiogenic shock, inotropic support monitoring and are considered for intubation and
and reduction of afterload by use of vasodilators is mechanical ventilation.
beneficial.
Vasoactive Drugs
Fluid Therapy Vasopressors (Table 28.9) Dopamine is the first-line
Vascular access: Large bore IV cannula or catheter is inotrope for managing shock associated with high cardiac
placed in a large peripheral vein, e.g. femoral vein. In older output and low systemic vascular resistance. The
children and adolescents, cannulation of internal jugular, medication increases cardiac output at doses of 5-10 µg/
external jugular and subclavian veins can be considered. kg/min. Its vasoconstrictor effect of dopamine is seen at
Fluids and blood products: The first choice of fluid for the doses >15 µg/kg/minute and follow release of norepine
acute stage is 0.9% normal saline or Ringer lactate. Large phrine from sympathetic vesicles, which may not be well
volumes of fluid have been used for acute stabilization in developed in young infants (<6 months). Low dose
children without increasing the risk of acute respiratory dopamine (2-5 µg/kg/min) does not significantly affect
distress syndrome or cerebral edema. When fluid require renal blood flow. Dopamine refractory shock responds to
ment is high, colloids (dextran, gelatin, 5% albumin) may norepinephrine or high doses of epinephrine. Some
be used. Packed red cells should be given at 10 mL/kg, to clinicians prefer using low dose norepinephrine as the first
maintain hematocrit -33%. line agent for warm hyperdynamic shock. Use of
vasopressors can be titrated to maintain a perfusion
Volume offluids: Normal saline or Ringer lactate, 20 mL/kg,
pressure, that refers to mean arterial pressure minus CVP,
is infused rapidly over 5-10 minutes, and titrated with
or systemic vascular resistance that ensures adequate
changes in heart rate, capillary refill and sensorium. If no urine output and creatinine clearance.
significant improvement is noticed, repeat boluses of
20 mL/kg are given. Large volume fluid deficits require Inotropes (Table 28.10): After initial fluid resuscitation,
40 to 60 mL/kg and maximum up to 200 mL/kg over first myocardial contractility needs to be augmented to
hour for replenishing the deficit. In situations where improve cardiac output. Dobutamine and mid-dose
availability for ventilator support and inotropic drugs is dopamine are used as initial inotropic agents in adults,
limited, fluid boluses should be administered cautiously. but children are less responsive. Epinephrine infusion
Patients who do not respond to boluses of 40-60 mL/kg usually works in dopamine or dobutamine refractory
in 1 hour are labeled as fluid refractory and should receive shock. Low dose epinephrine is used as first-line choice
inotropic support. These patients require careful for cold hypodynamic shock, i.e. low cardiac output.
Therapy with type III phosphodiesterase inhibitors is O minute Recognize septic shock
considered in patients who are normotensive with low Maintain airway and IV access as per PALS
output and high vascular resistance despite use of
epinephrine and vasodilator. However, these agents have 5 minutes
long half lives and should be discontinued at the first sign
of tachyarrhythmia, hypotension or diminished systemic
vascular resistance. 20 ml/kg normal saline bolus up to 60 ml/kg
Correct hypoglycemia, hypocalcemia
Vasodilators (Table 28.11) Vasodilators are useful in
children with hypodynamic shock with high systemic
vascular resistance shock despite therapy with IV fluids 15 minutes
and inotropes.
Figure 28.4 outlines the management of a child with
Fluid responsive shock Fluid refractory shock
septic shock.
I Observe in PICU I
arterial pH after optimizing perfusion and ventilation in
patients with severe acidemia (pH <7.0). Hypoglycemia Dopamine at 10 µg/kg/min
and hypocalcemia should be corrected. Insert CVP line
Arterial pressure monitoring
Control of Infection
Patients with septic shock require prompt, appropriate
60 minutes Dopamine resistant shock
and adequate antibiotic therapy. Even those without an
obvious focus of infection must receive antibiotics that
cover both gram-negative and gram-positive infections.
Surgical drainage is ensured, if the child has pus collection
(abcess, empyema, collection in soft tissues or abdomen).
Corticosteroids are reserved for catecholamine-resistant
! !
Start norepinephrine Start epinephrine
shock, and suspected or proven adrenal insufficiency.
Adrenal insufficiency is perhaps more common in children
(if shock persists) Catecholamine resistant shock
with septic shock than previously thought. Methylene
Give hydrocortisone, if adrenal
blue, which inhibits nitric oxide release, improves insufficiency suspected
mean arterial pressure in adult patients with septic shock. I
The benefit of activated protein C infusion in severe
sepsis is limited. If available, extracorporeal membrane
+
Cold shock with
+
Cold shock with
+
Warm shock
oxygenation may be offered to neonates with refractory normal BP low BP with low BP
shock. Add vasodilator or Titrate volume and Titrate volume and
type Ill epinephrine norepinephrine
phosphodiesterase
Suggested Reading inhibitor
• Dellinger RP, Levy MM, Rhodes A, et al; Surviving Sepsis
Guidelines Committee. Surviving sepsis campaign: International Fig. 28.4: Guidelines for management of septic shock. BP blood
guidelines for management of severe sepsis and septic shock 2012. pressure; CVP central venous pressure; PALS pediatric advanced
Crit Care Med 2013; 41:580----637. life support; PICU pediatric intensive care unit
• Kawasaki T. Update on pediatric sepsis: A review. J Intensive Care
2017;5:47. • Zingarelli B. Shock, ischemia and reperfusion injury. In:
• Khilnani P, Singhi S, Lodha R, et al. Pediatric sepsis guidelines: Nichols DG, Shaffner DH, eds. Roger's Textbook of Pediatric
Summary for resource-limited countries. Indian J Crit Care Med Intensive Care, 5th edn. Lippincott Williams and Wilkins 2016:
2010; 14:41-52. pp 253-268.
Pediatric Critical Care 1731-
NUTRITION IN THE CRITICALLY ILL Use of TPN requires monitoring of blood glucose 2-3
times a day; electrolytes and urea twice a week; and
Critically ill children are prone to malnutrition, due to
weekly biochemistry, triglycerides and blood counts.
reduced intake and accelerated demands, increased
Complications include catheter-related infections, liver
resting energy expenditure, proteolysis, and glucose and
dysfunction, hyperglycemia, acidosis, hyperlipidemia and
insulin intolerance. It is essential to provide adequate
electrolyte imbalance.
nutrition early in the course of illness in order to improve
outcomes. The enteral route is preferred, since it is safer Suggested Reading
and more cost-effective than total parenteral nutrition.
• de Carvalho WB, Delgado AE, Leite HP. Nutritional support. In:
Enteral nutrition helps maintain the gut barrier, preserves Nichols DG, Shaffner DH, eds. Roger's Textbook of Pediatric
indigenous flora and prevents overgrowth of pathogens, Intensive Care, 5th edn. Lippincott Williams and Wilkins 2016:
reducing the risk of bacteremia and pneumonia. By pp 1615-32.
preventing atrophy of gut mucosa, resumption of oral • Joffe A, Anton N, Lequier L, Vandermeer B, Tjosvold L, Larsen B,
feeds is easier during recovery. Supplementation of Hartling L. Nutritional support for critically ill children. Cochrane
Database Syst Rev. 2016; 5: CD005144.
vitamins and minerals is also best done by the enteral
route.
SEDATION, ANALGESIA, PARALYSIS
Apart from milk-based feeds, commercial formulae are
available to supplement nutrition. Elemental formulae The goal of sedation is safe and effective control of pain,
contain carbohydrates as oligosaccharides, maltodextrins anxiety and motion, allowing necessary procedures to be
or hydrolyzed cornstarch; nitrogen as peptides or amino performed and to provide appropriate amnesia or
acids; and lipids as oils or medium chain triglycerides. decreased awareness. The state of consciousness varies
Low lactose or lactose-free diets are available. Feeding is from mild to deep sedation to general anesthesia. In
initiated at 10-15 mL/kg/day and increased by 10-15 mL/ moderate sedation (conscious sedation), consciousness is
kg/day until targets are achieved. Feeds may be delivered depressed but protective airway reflexes are maintained
directly into the stomach by nasal or oral routes. Bolus and the child responds appropriately to verbal command
feeding is preferred over continuous feeding as it is or to light physical stimulation. Airway is maintained
physiological and requires less expertise to administer. independently and spontaneous ventilation is adequate.
Small bowel feeds are useful in gastroparesis. Continuous Deep sedation refers to a medically controlled state of
feeding is preferred for small bowel feeding. depressed consciousness from which the child is not easily
Conditions where enteral feeding is contraindicated are aroused but responds purposefully to painful stimuli. The
severe gastrointestinal hemorrhage, recent gastrointestinal ability to maintain airway is impaired and requires
surgery and intestinal obstruction. Complications of assistance; spontaneous ventilation may be inadequate.
enteral feeding are intolerance, misplacement of the The child should be carefully assessed before sedation
feeding tube, esophagitis and esophageal ulceration. for underlying medical problems, medication use, allergies
Gastrointestinal reflux can lead to pulmonary aspiration. and time and nature of last oral intake. Monitoring is
Diarrhea may occur because of hyperosmolar formulae, important during sedation and following procedures,
infection or malabsorption. including assessment of vital signs, movement of chest
Parenteral nutrition refers to the delivery of nutrients wall, ECG monitoring and pulse oximetry. Table 28.12
directly into the bloodstream, including amino acid summarizes commonly used drugs for sedation and
mixtures, lipids, glucose, trace minerals and vitamins. analgesia and Table 28.13 lists clinical scenarios requiring
These are infused into a peripheral or central vein. A sedation and analgesia. For children on mechanical
peripheral vein may be used, if the osmolality of infusate ventilation, continuous infusion of midazolam or
is less than 700 mOsm/kg. For delivery of adequate diazepam is used for better control of ventilation.
calories, central venous access is essential. For infants, Intermittent doses or continuous infusion of fentanyl or
glucose infusion is started at 5-6 mg/kg/min and morphine is used for pain control.
increased gradually; insulin may be used, if there is
hyp erglycemia. Amino acids are begun at 1 g/kg/d and
Neuromuscular Blocking Drugs
increased over 2-3 days to 2.5 g/kg/d. Lipids are given The use of neuromuscular blocking drugs is common in
at 0.5 g/kg on day 1 and increased to 2-2.5 g/kg/d over patients with artificial airway who are undergoing
4-5 days. Appropriate combinations can be achieved by mechanical ventilation. Succinylcholine is the only
considering fluid requirements. In a critically ill child, the depolarizing muscle relaxant available. Non-depolarizing
energy requirement is lower, as metabolism may be drugs are pancuronium, atracurium, vecuronium and
decreased, there is decreased activity due to illness, rocuronium. Short-term indications for these drugs
sedation and analgesia, and growth is lacking. The energy include airway instrumentation and invasive procedures.
goal in the initial phase of acute illness is less than for a Long-term use facilitates: (i) mechanical ventilation,
normal child and revised regularly to avoid overfeeding overcoming patient ventilation dyssynchrony, and/or
and underfeeding. ensure high frequency ventilation; (ii) reduction of work
-732 Essential Pediatrics
Table 28.14: Strategies to reduce HAI are prepared by processing large pools of donor plasma
obtained from whole blood or plasmapheresis.
Hand washing, hand hygiene, hand disinfection
Indications for red cell transfusion are listed in
Aseptic precautions during invasive procedures
Table 28.15.
Ensure nutrition: Prefer enteral to parenteral nutrition
Transfusion for acute blood loss: If patient is not stabilized
Appropriate and rational prescription of antibiotics after 2 boluses of 20 mL/kg of isotonic crystalloids, it is
Regular training. Infection control,procedure specific guidelines likely that the blood loss is >30% and the patient should
Surveillance for HAI receive fresh blood.
Health care associated pneumonia: Avoid antacids and H2 Transfusion for chronic anemia: Children with chronic
blockers; disinfect respiratory therapy equipment; sterile fluids anemia usually tolerate hemoglobin levels as low as 4 g/dL.
for nebulization and humidifiers; change ventilator circuit tubing Investigations for the underlying cause of anemia should
every 48 hours; care during suctioning; head end at 3D-45 ° be sent, prior to instituting transfusions. Patients are
elevation; cuffed endotracheal tube; selective decontamination screened for cardiovascular decompensation, an
of gut (tobramycin, gentamicin, polymyxin, nystatin) indication for emergency transfusion.
Bloodstream infection: Care of vascular access; use of Teflon Choice of blood group: For red cell transfusions, the choices
or polyurethane catheters; avoid multilumen catheters; use
are based on the principle that the recipient plasma must
transparent dressings; minimal "break in" into catheter and
not contain antibodies corresponding to donor A or B
intravenous tubing; avoid TPN catheters for other infusions
antigens. For plasma and platelet transfusion, donor
Urinary tract infections: Minimal catheterization; asepsis plasma must not contain A or B antibodies corresponding
during insertion; closed drainage; early removal of catheter
to recipient A or B antigens (Table 28.16). Patients who are
RhD negative should receive only RhD negative red cells.
The risk of HAI is related to the severity of underlying Ideally, the same blood group red cells that are compatible
illness, length of PICU stay, invasive monitoring and with the recipient plasma should be transfused.
diagnostic procedures, and indiscriminate use of Qu antity of transfusion: The quantity of blood
antimicrobials. Almost 90% of bloodstream infections administered depends on hematocrit of the blood unit,
occur in children with central venous lines, 95% of
pneumonia in those on mechanical ventilation and 75% Table 28.15: Indications for red blood cell transfusion in children
of UTI in children with catheters. HAI may be caused by Infants
organisms that originate from exogenous sources in the Hematocrit <20 and asymptomatic with reticulocytes <100000/
hospital or from patient's own flora. Apart from increased cu mm
duration of hospital stay and cost of therapy, mortality Hematocrit <30 and requiring oxygen
attributed to HAI ranges between 10 and 20%. Hematocrit <35 and requiring CPAP or mechanical ventilation;
It is important for ICUs to have infection control heart rate >180/min or respiratory rate >80/min persisting for
programs to reduce the risk of HAI. A team of health >24 hours; weight gain <10 g/day over 4 days while on >100
professionals should ensure implementation and Cal/kg/d; or if undergoing surgery
compliance on part of the PICU team. Infection control
Children
activities (Table 28.14) can reduce HAI rates by -50%.
Hemoglobin level :,;4 g/dl (hematocrit ::;12) irrespective of
Suggested Reading clinical condition
Hemoglobin 4-6 g/dl (hematocrit 13-18) with features of
• Joram N, de Saint Blanquat L, Stamm D, Launay E, Gras-Le Guen
hypoxia, acidosis,dyspnea or impaired consciousness
C. Healthcare-associated infection prevention in pediatric intensive
care units: a review. Eur J Clin Microbiol Infect Dis 2012; 31: Malaria with hyperparasitemia >20%
2481-90. Features of cardiac decompensation
BLOOD TRANSFUSIONS Table 28.16: Choices of ABO blood groups for red cells,
plasma and platelet transfusions
Blood component transfusion is an integral part of
treatment for many patients cared for in PICU. Blood Recipient Acceptable ABO group of component
products are prepared from collected whole blood or blood group
apheresis donation. Whole blood units are separated into Red blood cells Plasma Platelets
red cells (RBC) and plasma and platelet components by 0 0 O,A,B,AB O,A,B,AB
differential centrifugation. Automated apheresis
procedures are used to collect platelets, granulocytes or A A,O A,AB A,AB
plasma. Cryoprecipitate is prepared from a plasma unit. B 8,0 B,AB B,AB
Plasma proteins, e.g. albumin, anti-0 immunoglobulins,
AB AB,A,8,0 AB AB
IV immunoglobulins and concentrated coagulation factors
1a4 I Essential Pediatrics
pretransfusion hemoglobin level and patient weight. If the Table 28.18: Indications for transfusion of fresh frozen plasma
hemoglobin level is �5 g/ dL and citrate phosphate Coagulation factor deficiency when individual factor
dextrose red cells (hematocrit 70-75) are used, a trans replacement is not available
fusion of 10 mL/kg raises hemoglobin level by 2.5 g/dL.
Anticoagulant (vitamin K antagonist) related bleeding
If anemia has developed slowly and hemoglobin level is
<5 g/dL, red cell transfusion should be given slowly or in Severe liver disease with prolonged prothrombin time or
small quantities to avoid precipitating cardiac failure from bleeding tendency
circulatory overload. Disseminated intravascular coagulation with active bleeding
C1 esterase deficiency in hereditary angioneurotic edema
Platelets
Platelet concentrates are prepared from whole blood mL of donor plasma and stored at -20 ° C for up to 1 year.
donation but these may also be collected by apheresis. The This unit contains 80-100 units of factor VIII, 100-250 mg
usual platelet bag (unit) contains 7.0 x 1010 platelets, about of fibrinogen, 40-60 mg of fibronectin, 40-70% of vWF and
50 mL plasma, trace to 0.5 mL of red cells and varying 30% of factor XIII. Indications for use include hemophilia,
number of leukocytes (up to 108). Apheresis platelet units von Willebrand disease and congenital deficiencies of
contain 3 x 1011 platelets, approximately 250-300 mL fibrinogen or factor XIII. Compatibility testing of
plasma, trace to 5 mL of RBCs and 106-109 leukocytes. It cryoprecipitate units is not necessary but ABO compatible
can be stored for 5 days at 20-24 ° C. The need for platelet units should be used. Cryoprecipitate is infused at the rate
transfusions depends on the platelet count, bleeding of 1 unit/5-10 kg of recipient weight, over 2-4 hours.
tendency, etiology and setting of interventions like
invasive procedures or surgery (Table 28.17). Risks of Transfusion
The chief risks of blood products include: (i) transfusion
Plasma reactions; (ii) transmission of infectious agents, including
Plasma is prepared from a whole blood donation by HIV, cytomegalovirus, hepatitis Band C viruses, syphilis
centrifugation or automated apheresis. A unit of plasma and malaria; and (iii) bacterial contamination due to
contains 150-250 mL when prepared from whole blood inappropriate collection or storage.
donations. Immediately following collection, plasma
contains approximately 1 unit/mL of each of coagulation Time limit for infusion: There is risk of bacterial
factors. Coagulation factors V and VIII are labile and are proliferation or loss of function in blood products once
not stable in plasma stored at 1-6 ° C. Plasma frozen within they are removed from storage.
8 hours of donation (fresh frozen plasma, FFP) contains i. Whole blood or packed red cell transfusion should
"'0.7 U/mL factor VIII; this may be stored for 12 months begin within 30 minutes of removing from storage
at -20 ° C. The use of FFP is limited to treatment or temperature (2-6 ° C) and completed within 4 hours, if
prevention of significant bleeding due to deficiency of one ambient temperature is 22-25 ° C. In case of high
or more plasma coagulation factors (Table 28.18). ambient temperature, shorter 'out of refrigerator' times
Compatibility tests before plasma transfusion are not should be used.
necessary and plasma should be ABO compatible with ii. Platelets should be infused within 20-30 minutes of
recipients red cells. Usually, RhD group need not be being received.
considered unless in cases where large volume of FFP is iii. Infusion of fresh frozen plasma should begin within
needed. FFP may be thawed in a water bath at 30-70° C or 20-30 minutes of removal from refrigerator.
in microwaves designed for this purpose. The dose of FFP
The products are infused through a sterile administra
depends on the clinical situation and the underlying disease.
tion set containing a 170-200 µm filter. The set should be
If used at a dose 10-20 mL/kg, it increases the level at
changed every 12 hours, if multiple transfusions are
coagulation factors by 20% immediately after infusion.
needed. For platelet transfusions, a fresh set primed with
Cryoprecipitate saline should be used.
Cryoprecipitate is the precipitate formed when FFP is Transfusion reactions: Tables 28.19 and 28.20 summarize
thawed at 4 ° C. It is then refrozen within 1 hour in 10-15 adverse effects of transfusion of blood products.
Hypersensitivity reactions cause mild and moderate
Table 28.17: Indications for platelet transfusion
reactions; life-threatening reactions can occur due to
Platelet count <1 O x 109/L due to any cause multiple causes, including intravascular hemolysis,
Platelet count <20 x 10 9/L and bone marrow infiltration, severe bacterial contamination, fluid overload, anaphylaxis and
mucositis or anticoagulant use transfusion associated lung injury.
Platelet count <30-40 x 109/L and disseminated intravascular
coagulation
Massive transfusion: This is the replacement of blood
equivalent to or greater than the patients total blood
Platelet count <5o-60 x 109/L and major surgical intervention volume (70 mL/kg in adults; 80-90 mL/kg in children)
Pediatric Critical Care 1735-
29
Important Medical Procedures
Arvind Bagga
the thumb and finger and lifting. Blind finger-sweeps are end, the plunger is depressed rapidly while one auscultates
avoided in infants and young children because they may for gurgling over the stomach. The tube is taped securely
push the foreign body further back into the airway, to the nose.
worsening the obstruction. Children presenting with signs
and symptoms of foreign body aspiration beyond the Complications: The procedure may be associated with
oropharynx into the trachea or bronchus require broncho tracheal intubation, nasal or pharyngeal trauma, or
scopy by experienced personnel. vomiting.
Complications: Chest compressions may cause rib and Central Venous Cannulation
cardiac damage in infants, but are rare, if performed by Indications: Usual indications include: (i) inability to estab
experienced personnel. Uncommon complications of the lish venous access in the peripheral circulation; (ii) access
Heimlich maneuver, if performed incorrectly, include for drugs and fluids that require central administration (e.g.
pneumomediastinum, rupture of spleen or stomach and vasopressors, hyperalimentation fluids, contrast
injury to the aorta. medications); (iii) to monitor central venous pressure; and
(iv) access for hemodialysis, plasmapheresis or continuous
Nasogastric Tube Insertion renal replacement therapies.
Indications: Nasogastric intubation is usually performed
for: (i) administration of medications or nutrients in uncon Procedure: Principles common to all central venous cathe
scious or anorexic children; (ii) gastrointestinal decompres ter procedures, regardless of site, include: (i) strict attention
sion in case of intestinal obstruction or trauma; and (iii) to asepsis; (ii) use of the Seldinger technique (placement
gastric lavage in a patient with upper gastrointestinal over a guidewire minimizes trauma and hematoma forma
bleeding or toxin ingestion. tion and enhances successful cannulation); (iii) adequate
sedation to minimize movements; (iv) attention to appro
Contraindication: (i) Suspected basilar skull fracture, priate location of catheter tip, avoiding high-risk sites such
(ii) maxillofacial trauma as ventricles and left atrium, verifying tip position with a
Procedure: The largest size tube that does not cause undue radiograph; (v) avoiding placement in presence of a
discomfort to the child is chosen. Typically, an 8 Fr tube is bleeding diathesis; and (vi) continuous monitoring of vital
used in neonates, 10 Fr for a 1-year-old and increasing sizes signs and oxygen saturation.
in childhood up to 14-16 Fr tubes in teenagers. The length Sit es: The site of access depends on the indication
of tubing to be passed is estimated by adding 8-10 cm to (Table 29.1).
the distance between the nostrils to the xiphoid process.
The child is prepared by explaining the procedure as fully i. External jugular vein. The external jugular vein can be
as possible; sedation is rarely needed. identified easily. There is less risk of pneumothorax.
Complications are minimal because of the superficial
Infants and obtunded children are placed supine with
position of the vein and the ability to compress the
the head turned to one side. The curved tube is straightened
vein to prevent hemorrhage.
and its patency checked with a syringe. Application of a
lubricant facilitates atraumatic nasal passage. The tube is ii. Internal jugular vein. Internal jugular vein cannulation
grasped 5-6 cm from the distal end and advanced poste provides an excellent approach to the central circula
riorly along the floor of the nose. It is inserted with its tion with a high success rate and minimal compli
natural curve pointing downward in order to go past the cations. Carotid artery puncture and pneumothorax
bend of the posterior pharynx easily. The procedure is are the most common complications. With left-sided
discontinued temporarily, if the child coughs or gags or if cannulation, there is potential for injury to the thoracic
the tube emerges from the mouth. When the tube is passed duct and there is a higher risk for pneumothorax
successfully to the measured length, its position is checked. because the apex of the left lung is higher than on the
Using a 5 mL syringe filled with air attached to the proximal right.
iii. Subclavian vein cannulation. This vein is the preferred site Complications: The following complications may occur:
in patients with long-term catheter requirements because (i) puncture of the calcaneus, resulting in necrotizing
of its relatively high level of patient comfort and ease of chondritis or osteomyelitis; (ii) calcified nodules of the
catheter maintenance. In patients with hypovolemia, the heel; (iii) hemolysis, resulting in falsely elevated bilirubin
subclavian vein does not collapse as readily as other and potassium levels from mechanical trauma;
major vessels. Major complications include pneumo (iv) erroneously high glucose values due to alcohol in the
thorax, subclavian artery puncture, or occasionally, swab; and (v) inaccurate pC02 and p02 values from poor
hemothorax. The chief long-term risk is subclavian vein blood flow.
stenosis.
iv. Femoral vein cannulation. Femoral vein cannulation is the Umbilical Vessel Catheterization
most common site for central vein cannulation as it is Indications: The umbilical vein is a convenient route for
easily accessible. Main complications are the risk of vascular access in newborns during the first 7-10 days of
arterial puncture, infection, and rarely, deep vein throm life. The route is used for administration of intravenous
bosis (more common with long-dwelling catheters in fluids or drugs during neonatal resuscitation, when
adolescents). establishing peripheral venous access is technically
difficult. It is also employed as a route for central venous
Capillary Blood (Heel Prick)
pressure monitoring and for performing exchange blood
Indications: Heel prick is a useful technique to obtain arte transfusion. Cannulation of the umbilical artery provides
rialized capillary blood for blood gas analysis, bilirubin, a route for arterial pressure monitoring or arterial blood
glucose, hematocrit and other parameters in newborns. sampling and alternative access for exchange transfusion.
Technique: Figure 29.3 indicates the appropriate areas to
Contraindications: Omphalitis is a contraindication; the
use for heel punctures for blood collection. Prewarming the procedure should also be avoided in presence of peritoni
infant's heel (using a cotton wad soaked in sterile warm tis or necrotizing enterocolitis.
water at 40 °C or a hot towel) is important to obtain capillary
blood gas samples as it increases the flow of blood, allowing Equipment: These include a 5 or 8 Fr catheter or feeding
collection of blood specimen. Hot water should not be used tube, 10 mL syringe, tape or silk suture to tie the base of
since baby skin is thin and susceptible to thermal injury. the cord, normal saline for flushing, intravenous tubing
After ensuring asepsis, a sterile blood lancet or a needle is and three-way connectors, a set of sterile drapes, sterile
punctured at the side of the heel in the appropriate regions instruments (small iris forceps, needle holder and scalpel
as shown in Fig. 29.3. The central portion of the heel is blade) and antiseptic for skin preparation.
avoided as it might injure the underlying bone. Blood
sample is obtained by alternate squeezing and releasing of Procedure: The neonate is placed beneath a radiant
calf muscles. warmer. Anesthesia is not required; the limbs are res
trained gently. The abdomen and umbilicus are cleaned
with chlorhexidine gluconate or povidone-iodine and
sterile drapes placed, leaving the umbilical area exposed.
Vital signs are monitored continuously.
A suture is looped at the base of the cord with gentle
constriction to anchor the cord and limit bleeding. The
cord may need to be immobilized by two artery forceps
grasping cord edges at 3 and 9 o'clock position. Using a
scalpel blade, the cord is trimmed to 1-2 cm above the
skin. The umbilical vessels are easily identified. The
umbilical vein is a single, thin-walled, large diameter
lumen, usually located at 12 o'clock position, while the
two arteries have thicker walls with a small-diameter
lumen (Fig. 29.4). The catheter or feeding tube is flushed
with heparinized saline (1000 U /L) and attached to a three
way connector. A mark is placed at the length of insertion
expected to place the catheter tip above the diaphragm
but below the right atrium; this is calculated as 0.6 times
the shoulder-to-umbilicus distance from the tip of the
catheter. The closed ends of a pair of iris forceps are
Fig. 29.3: Recommended sites for neonatal capillary blood inserted into the lumen of the umbilical vein, and the
sampling. Hatched areas indicate safe areas for puncture sites lumen dilated by separating the ends of the forceps by
Important Medical Procedures 1139-
Arterial Catheterization
Indications: Arterial catheterization may be needed (i) to
monitor blood pressure continuously, especially in hemo
dynamically unstable patients; and (ii) to frequently
monitor arterial blood gas.
Complications:
i. Disconnection of the catheter from the IV infusion.
ii. Ischemia: The radial artery cannula should be with
drawn, if ischemic changes develop.
Fig. 29.4: Umbilical vein cannulation in a newborn. The umbilical iii. Emboli: Blood clot or air may embolize to the digits
vein is located at 12 o· clock position and is identified by its or centrally, resulting in arteriolar spasm or ischemic
large lumen and thin walls necrosis.
iv. Infection may cause septicemia.
opening it gently. Grasping the catheter with iris forceps
1 cm from its distal end, the catheter is inserted into the lntraosseous Infusion
lumen of the umbilical vein and advanced gently inward Indications: The bone marrow cavity is effectively a vascular
until blood returns freely. Resistance to advancement of space that does not collapse even in the setting of shock or
the catheter indicates that the tip is in the portal vein or cardiac arrest. Intraosseous access is the vascular access of
the ductus venosus; the catheter should be withdrawn choice in patients with severe hypotension such as
until free flow of blood is noted. The catheter is flushed cardiopulmonary arrest or decompensated shock. Almost
with saline and secured with a purse string suture. An X any medication that can be administered into a central or
ray is ordered to ensure that the tip of the catheter is in peripheral vein can be safely infused into the bone marrow.
the inferior vena cava and not the hepatic vein or right Crystalloid solutions, colloids and blood products can be
atrium. safely infused, as can hyp ertonic solutions.
A similar procedure is followed for insertion of catheter
Procedure: The technique of intraosseous infusion is rapid
into the umbilical artery. Since the lumen is smaller, the
and simple. The most common sites are the proximal tibia,
vessel is dilated carefully 2-3 times using a curved iris
distal tibia and distal femur (Fig. 29.5). Due to differences
forceps and the catheter inserted gently, taking care
in cortical thickness, the proximal tibia along the flat
to avoid vascular spasm. The catheter is advanced to anteromedial surface of the shaft, 1-2 cm below the tibial
either the high position (above the diaphragm between tuberosity, is the preferred site in infants and young
thoracic vertebrae T6 and T9) or the low position (above children. The distal tibia at the junction of the medial
the aortic bifurcation between lumbar vertebral bodies L3 malleolus and the shaft of the tibia is preferred in older
and L4). children.
Complications: During insertion, vascular spasm, arterial Technique: Using aseptic technique, the site is prepared
injury or air embolism may occur and a false tract may get with an iodine solution. The skin is injected with 1 % lido
created. Other complications include bleeding due to caine for anesthesia in the awake patient. The needle is
accidental disconnection of IV tubing; catheter-related inserted at a 10 ° to 15° angle to the vertical, away from the
infection, thrombosis and embolism; and incorrect position joint space (caudal for the proximal tibia, cephalad for the
of the catheter tip causing cardiac arrhythmias, hepatic distal tibia and femur). Pressure is applied in a 'to and fro'
necrosis or portal hypertension. Vascular complications are rotary motion. As the needle passes into the marrow, a'give
common with the umbilical artery catheter, particularly if away' will be felt. The needle should stand without sup
placed in the low position. port. Evidence for successful entrance into the marrow
740 Essential Pediatrics
Lumbar Puncture
Indications: The procedure is performed to obtain
cerebrospinal fluid (CSF) for the diagnosis of meningitis,
meningoencephalitis, subarachnoid hemorrhage, meta
static leukemia or benign intracranial hypertension.
Procedure: The spinal cord ends at approximately the level
of the L1 and L2 vertebral bodies. Caudal to L2, only the
filum terminale is present. The desired sites for lumbar
puncture are the interspaces between the posterior ele
ments of L3 and L4 or L4 and LS. These spaces are located b
by palpating the iliac crest. If one follows an imaginary
'plumb line' from the iliac crest to the spine, the interspace
encountered is L4 to LS.
Lateral decubitus position: The patient is restrained in Fig. 29.6: Lumbar puncture with the child in (a) Decubitus position;
the lateral decubitus position as shown in Fig. 29.6a. The and (bl Sitting position
Important Medical Procedures 1741-
After the site is chosen, xylocaine is injected with a small Peritoneal Dialysis
needle to produce a skin wheal. The skin is then tilted This modality of dialytic support is used for renal replace
anteriorly so that further infiltration into the subcutaneous ment therapy both in acute kidney injury (AKI) and end
tissue is in a different plane (Z tracking). A needle or over stage renal disease. Catheters placed surgically for chronic
the-needle catheter is then advanced using the Z tracking ambulatory peritoneal dialysis are not discussed here.
technique and at an angle perpendicular to the skin.
Indications: The modality is used in patients with AKI in
Continued aspiration of the needle is used until peritoneal
whom dialysis is indicated (Chapter 17) andhemodialysis and
fluid is aspirated. Approximately 10-15 mL of fluid is
continuous renal replacement therapies are not available,
aspirated for studies. Appropriate studies may include
or if hemodialysis is contraindicated. The technique is widely
cultures and Gram stain, cell count, cytology, amylase, LOH,
available, inexpensive and technically easy to perform even
bilirubin, albumin and protein. If the paracentesis is per
in newborns.
formed for therapeutic purposes, a catheter should be placed.
Contraindications: Relative contraindications to peritoneal
Complications: Complications include hemorrhage, fluid dialysis include recent abdominal and/or cardiothoracic
leak, intestinal or bladder perforation, and hypotension, surgery, diaphragmatic peritoneal-pleural fistula, fecal or
if large volumes are removed. fungal peritonitis and abdominal wall cellulitis.
Catheterization of Bladder Procedure: Access for peritoneal dialysis can be achieved
Indications: Bladder catheterization is done in bedridden by inserting a rigid catheter (Fig. 29.9a) or a single cuff soft
patients who need short-term assistance. It is also required Tenckhoff catheter at the bedside (Fig. 29.9b). The double
in patients with (i) polytrauma, especially for evaluation cuff Tenckhoff catheter, used for chronic peritoneal dialysis
of the urinary tract in an unconscious child; (ii) shock; is placed in the operating room by a surgeon. A rigid acute
(iii) acute urinary retention; (iv) to obtain a urine specimen PD catheter is easily available, inexpensive and relatively
for urinalysis; (v) in acute kidney injury, to monitor urine simple to insert. However, the risks of peritonitis are high,
output; and (vi) for urodynamic studies. particularly if used for more than 48 hours.
The abdomen is cleansed with chlorhexidine and beta
Procedure: The patient is restrained as necessary. The dine and draped. Following administration of sedation and
urethral meatus, penis and the perineal area are cleaned local anesthesia, an 18-22 gauge cannula is inserted below
thoroughly with a povidone-iodine solution. A Foley cathe the umbilicus in the midline or lateral to the rectus abdo
ter of the appropriate size is selected (8 Fr in the newborn, min us muscle at two-thirds the distance between the
10 Fr in most children and 12 Fr in older children). The umbilicus and the anterior superior iliac spine (Fig. 29.9c).
catheter tip should be lubricated with sterile lubricant to About 20-30 mL/kg of peritoneal dialysis fluid is infused
minimize local trauma. till the flanks appear full.
Boys. The penile shaft is gently grasped and extended. The The cannula is removed and the stiff catheter is inserted
catheter is held near the distal tip and advanced up the using the trocar. Once a'give away' sensation is felt, dialysis
urethra unless resistance or an obstruction is encountered. fluid flows freely back into the catheter lumen. The catheter
If resistance is encountered, a smaller catheter is selected. is inserted carefully avoiding injury to viscus by the trocar
Important Medical Procedures 1743-
Fig. 29.9: Peritoneal dialysis: (a) Stiff uncuffed catheter used for acute peritoneal dialysis; (b) Soft single cuff Tenckhoff catheter
inserted bedside for acute dialysis; (c) Usual site of catheter insertion is in midline below the umbilicus or two-thirds of
the distance between umbilicus and anterior superior iliac spine; (d) Device for automated control of dialysis and aseptic han
dling; and (e) Infant undergoing dialysis with soft Tenckhoff catheter
and guiding the tip of the catheter into the left iliac fossa. parameters. Acute manual PD requires constant super
The trocar is removed and the catheter attached to a three vision to ensure accurate inflow, dwell and drain times and
way connection to the peritoneal dialysis fluid and the drain the maintenance of a record of exchange and drain volumes
bag. Once easy inflow and outflow are confirmed, the and net ultrafiltration. By comparison, the use of the
catheter is secured with a purse-string suture and manual automated cycler reduces need for constant supervision
cycles of dialysis are initiated. and record maintenance and decreases the number of
The soft single cuff catheter is inserted using an intro manual interruptions and risk of peritonitis.
ducer kit using the modified Seldinger technique. A tunnel Complications: Abdominal pain or discomfort may occur
is created in the soft tissue so that the exit site is away from due to abdominal distension, improper position of the
the entry point into the peritoneum and the cuff protects catheter or peritonitis. Mild hemorrhage is frequent during
from bacterial migration. This catheter is associated with catheter placement, particularly with rigid acute catheters.
lower risk of peritonitis, particularly if used with an auto Leakage around the PD catheter site is managed by reducing
mated cycler device (Fig. 29.9d). It can be capped when not the exchange volume or placing a suture at the exit site.
in use, allows ease of nursing, and can be used for several Inadequate drainage is due to improper placement of the
weeks (Fig. 29.9e). catheter tip or decreased bowel motility. Bowel perforations
is rare but may be observed with placement of stiff catheters.
Prescription: Acute PD can be performed intermittently or Metabolic complications include hyperglycemia, hypokale
continuously depending upon the desired amount of fluid mia, protein losses and hyp ematremia.
and solute removal, and either manually by nurses or via
an automated device. About 20-30 mL/kg is infused over Bone Marrow Aspiration and Biopsy
5 min, kept in the abdomen for 20--40 min, and then drained A special bone marrow needle is introduced into the bone
out. Ultrafiltration should not exceed 5-10% of body weight marrow space, and a sample aspirated for analysis. A mar
over 24-48 hours. The prescription is modified every row biopsy is taken to ascertain the cellularity and
6-12 hours based on clinical evaluation and laboratory architecture of the marrow.
-744 Essential Pediatrics
Indications: Bone marrow aspiration and biopsy are spines (or for the tibial site, the entire leg up to the distal
indicated in presence of pancytopenia, bicytopenia, unex half of thigh) and draped. The posterior superior iliac spine
plained thrombocytopenia or leukocytosis in order to rule is located by tracing the iliac crest backwards to its most
out significant pathology such as lymphoreticular prominent and elevated point. About 2 mL of 1% lidocaine
malignancy (acute lymphoblastic or myelogenous leuke is injected subcutaneously into the periosteum. The bone
mia, Hodgkin or non-Hodgkin lymphoma, chronic mye marrow needle is held firmly in the dominant hand with
loid leukemia, myelodysplasia, myelofibrosis); hypoplastic the index finger placed over the needle to act as a guard.
or aplastic anemia; megaloblastic anemia; sideroblastic The needle is advanced perpendicularly into the identified
anemia; Langerhans cell histiocytosis; hemophagocytosis area with twisting motion till bone is felt. On advancing
syndrome; suspected metastasis (retinoblastoma, neuro further, a 'give way' is felt that indicates that the needle is
blastoma); infiltrative storage diseases (Gaucher disease) in the bone marrow. The stylet is removed and a 20 mL
or infections involving the bone marrow (kala-azar, syringe attached. The piston is pulled to create negative
tuberculosis). pressure and aspirate slowly around 0.5 mL of marrow. The
syringe is disconnected and the marrow placed on slides.
Sites: The iliac crest is the most commonly used site. The To make a touch preparation, the marrow is spread on the
sternum is not preferred in children because of associated slide by placing another glass slide so as to smear the mar
pain and the risk of injuring underlying vital structures. row gently. Additional slides are prepared similar to a peri
Marrow may be aspirated from the proximal tibia medial pheral smear, using another glass slide at 30 ° angle to spread
to the tibial tuberosity in infants ( <1-year-old). This site is the marrow in a tongue-shaped projection on the slide.
preferred in infants since biopsy from the iliac site in young
children is difficult as the iliac crest is small and carries risk To perform marrow biopsy, the stylet is replaced and the
of injuring pelvic viscera. needle withdrawn slightly. The needle is advanced
through another site in the bone. Once the needle is lodged
Equipment: Various types of bone marrow biopsy needles in the bone, the stylet is removed and the needle advanced
are available (Figs 29.lOa and b). The Jamshidi needle and in rotatory motion through the marrow space. The needle
its modifications are used widely because of their light is withdrawn and biopsy specimen placed in a vial con
weight, sharp bevelled end that allows easy coring of bone, taining formalin. Once the needle is removed, local pressure
a tapering end that facilitates recovery of marrow specimen is applied to allow bleeding to stop. Drapes are removed,
and suitability for both aspiration and biopsy. the skin is cleaned and pressure bandage applied.
Procedure: The child should be fasting for 3-4 hours before Aspiration from the tibia is performed in a similar man
the procedure. The child is positioned prone with face ner. The preferred site is medial to the tibial tubercle, one
turned to a side and the pelvis stabilized by folding a sheet inch below the joint line to avoid the growth plate. The bone
below it. If tibia is to be aspirated, the leg is slightly flexed cortex is thinner and the marrow space is reached more
at the knee joint. Sedation with intravenous midazolam and quickly than with the pelvic site. Obtaining a biopsy is often
ketamine is administered during continuous monitoring of difficult as the marrow is more spongy.
vital signs and oxygen saturation.
Complications: Bleeding and pain at the aspiration site are
The site is cleaned with chlorhexidine and betadine to common. Bone injury with fractures of iliac bone and
include the lumbar spine, iliac crests and posterior iliac subcutaneous infections or osteomyelitis are rare.
Liver Biopsy
Indications: Liver biopsy is used to evaluate hepatic histo
logy in order to: (i) diagnose parenchymal liver disease (e.g.
neonatal hepatitis, suspected metabolic liver disease); (ii)
understand the cause of persistently abnormal liver tests;
(iii) determine the etiology of focal or diffuse abnormalities
on imaging studies; (iv) assess the prognosis of known liver
disease (e.g. extrahepatic biliary atresia, autoimmune hepa
titis, chronic viral hepatitis); (v) determine response to
therapeutic interventions; (vi) develop a treatment plan
based on histology; and (vii) monitor effects of hepatotoxic
drugs. Analysis of the biopsy specimen may include
evaluation of histology, metal content, enzymatic assays
a b and cultures for viral, bacterial, or fungal pathogen.
Fig. 29 .10: Needles for bone marrow aspiration and biopsy. Contraindications: Absolute contraindications include co
(a) Jamshidi needles; (bl Vim Silverman needle agulopathy, as suggested by low platelet count (<60.000 / µL)
Important Medical Procedures 1745-
30
Rational Drug Therapy
Anu Thukral • Kana Ram Jat
746
Rational Drug Therapy 1747-
Closure of ductus arteriosus in neonates: 10 mg/kg/day PO Side effects: Respiratory distress, increased intracranial
followed by 5 mg/kg/day q 24 hr for 2 days pressure, seizures
Side effects: Nausea, vomiting, rashes Contraindication: Respiratory failure, obstructive airway
disease
Naproxen
Juvenile idiopathic arthritis: 10-20 mg/kg/day PO q 12 hr ANTIARRHYTHMICS
Analgesia 5-7 mg/kg/dose PO q 8-12 hr (after meals) Adenosine
Side effects: Nausea, vomiting, rashes 0.1 mg/kg/dose (initial maximum dose 6 mg) rapid IV
(over 1-3 sec); if no response in 1-2 min 0.2 mg/kg bolus
Diclofenac Sodium
To ensure that the drug reaches the circulation, administer
1-3 mg/kg/day PO q 8 hr directly into a vein with a three-way stop cock with 5-10
Side effects: Gastric bleeding, ulcer mL of saline flush ready to push immediately; maximum
single dose 0.25 mg/kg or 12 mg
Mefenamic Acid Side effects: Transient chest pain, dyspnea, flushing,
25 mg/kg/day PO q 6-8 hr bronchospasm. Carbamazepine and dipyramidole
Antipyretic dose: 5-8 mg/kg/dose increase the toxicity/effect of adenosine.
Side effects: Gastric bleeding, rash, seizures Atropine Sulfate
lndomethacin 0.01 mg/kg/dose SC or IV
1-3 mg/kg/day PO q 12-24 hr The dose can be repeated after 2 hr (max 4-6 times a day).
Dose for ductal closure depends on the age of the neonate Organophosphorus poisoning: 0.02-0.05 mg/kg every 10-20
(Table 30.1) min until atropine effect, then q 1-4 hr for at least 24 hours
Side effects: Oliguria, hypoglycemia, platelet dysfunction Side effects: Dry mouth, blurred vision, tachycardia, urinary
retention, constipation, dizziness, hallucinations, restless
ness
Table 30.1: lndomethacin dose (mg/kg) in neonates
Age atfirst dose 1st 2nd 3rd Udocaine Hydrochloride
<48 hours 0.2 0.1 0.1 1 mg/kg/dose (maximum dose: 100 mg) slowly IV; repeat
2-7 days 0.2 0.2 0.2 in 10-15 min for two times; maximum total dose 3-5 mg/
>7 days
kg within the first hr; endotracheal dose is two to three
0.2 0.25 0.25
times the IV dose.
Continuous infusion 20-50 µg/kg/min IV/IO (do not
Tramadol exceed 20 µg/kg/min for patients with shock or CHF);
1-2 mg/kg q 4-6 hr up to maximum of 400 mg/day; avoid administer 1 mg/kg bolus when infusion is initiated (bolus
below 14 yr of age not given within previous 15 min)
Side effect: Seizures, renal and hepatic dysfunction Side effects: Hypotension, seizures, asystole, respiratory arrest
(Contd...)
1s2 I Essential Pediatrics
Faropenem 200 increased to 300 PO 8-12 hr Diarrhea, abdominal pain, loose bowel movement,
nausea, and rash; safety in infants not established
Ertapenem 15-30 IV/IM 12 hr Not approved for children less than 3 months,
diarrhea, nausea, headache
Vancomycin 30-45 in neonate (dosage IV 6-8 hr Ototoxicity and nephrotoxicity (exacerbated with
and frequency varies with concomitant aminoglycosides); adjust dose in renal
gestation age); 40-60 failure
Linezolid 10 mg/kg/dose IV 12 hr Dysgeusia, constipation, diarrhea, dizziness,
PO 8-12 hr headache, anemia, leukopenia, thrombocytopenia
Teicoplanin 10 mg/kg 12 hr for 3 doses; IV, IM 24 hr Long half life. Less nephrotoxic; less catheter-related
then 6-10 phlebitis
T igecycline 1.2 mg/kg/dose IV 12 hr Hypersensitivity reactions, deranged liver function
(Max dose 50 mg) Use with caution in below 8 yrs
Nitrofurantoin 5-7 PO 6 hr Dizziness, hypersensitivity, icterus, interstitial
Prophylaxis: 1-2 pneumonitis, nausea, vomiting
Lansoprazole Clemastine
1 mg/kg/day in a single dose or 2 divided doses for GERD 1-3 yr: 0.25-0.5 mg q 12 hr
in infants 3-6 yr: 0.5 mg q 12 hr
<30 kg: 15 mg, �30 kg: 30 mg 6-12 yr: 0.5-1 q 12 hr
Side effects: Well tolerated, side effects as omeprazole >12 yr: l mg q 12 hr
Suero/fate Contraindication: Patients with ventilator failure,
obstructive airway disease
1 month-2 yr: 250 mg PO 4-6 hr; 2-12 yr: 500 mg 4-6 hr;
12-18 yr: 1 g 4-6 hr Chlorpheniramine Maleate
Side effects: Constipation, headache, dizziness, insomnia,
0.35 mg/kg/day PO q 4-6 hr; 2-5 yr: 1 mg/dose PO q
vomiting
4-6 hr; maximum dose: 6 mg/24 hr; 6-11 yr: 2 mg/dose
Lactu/ose PO q 4-6 hr; maximum dose: 12 mg/24 hr; sustained release
(6-12 yr): 8 mg/dose PO q 12 hr
Constipation: 1-2 mL/kg/ dose in hepatic coma and
Side effects: Hypotension, sedation, urinary retention, oculo
constipation
gyric spasms with high doses and after a few days of
<2 yr 2.5 mL/day PO, PR q 12 hr therapy
>2 yr 5-10 mL PO/ PR q 12 hr; adult dose: 10-15 mL q 12-
24 hr Diphenhydramine Hydrochloride
Side effects: Diarrhea
5 mg/kg/day q PO 6 hr oral; maximum daily dose 300 mg
Bisacodyl Anaphylaxis or phenothiazine, overdose: 1-2 mg/kg IV slowly
5-10 mg bedtime; PO (Max-30 mg/day); Rectal supposi Side effects: Dizziness, drowsiness, loss of co-ordination,
tory: 2-11 yr: 5-10 mg; >11 yr: 10 mg dry mouth, nose or throat
Side effects: Abdominal pain, diarrhea, muscle pain, Fexofenadine
dizziness
<12 yr: 30 mg PO q 12 hr; >12 yr: 60 mg PO q 12 hr or
Vasopressin 120 mg once daily
Catecholamine refractory septic shock: 0.3-2.0 mU /kg/ Side effects: Nausea, diarrhea, drowsiness, headache
minute IV infusion Hydroxyzine Hydrochloride
Diabetes insipidus: 2.5-10 USC/IM q 6-12 hr; 0.5-10 mU/
kg/hr IV infusion 2 mg/kg/day PO q 6 hr; 0.5-1 mg/kg/dose q 4-6 h IM
Side effects:Swelling over face, tremor, confusion, seizure
Bleeding esophageal varices: 20 U IV over 15 min, then
0.2 U/min or 0.33 U/kg/hr Loratadine
Side effects: Hypertension, water intoxication, hypo
3-12 yr: 5 mg/day; >12 yr: 10 mg/day
natremia
Side effects: Diarrhea, epistaxis and flu-like symptoms
ANTIHISTAMINICS Methdilazine Hydrochloride
Astemizole >3 yr: 4 mg q 6-12 hr
0.2 mg/kg/ day taken half-hr before meals; not Side effects: Sedation, urinary retention, leukopenia,
recommended <6 yr agranulocytosis, glaucoma
Side effects: Weight gain with prolonged use
Pseudoephedrine
Cetrizine <12 yr: 4 mg/kg/day PO q 6-8 hr oral; >12 yr: 30-60 mg/
6 months-2 yr: 2.5mg PO once daily; 2-5 yr: 2.5 mg PO dose q 6-8 hr; maximum daily dose 240 mg
once daily, dose may be increased to 5 mg q 12-24 hr; Side effects: Headache, tachycardia and tremor
�6 years: 5-10 mg ; PO q 24 hr
Side effects: Drowsiness, dry mouth and nose ANTIHYPERTENSIVES
Amlodipine
Levocetrizine
0.1-0.2 mg/kg/dose (maximum dose 5 mg) PO q 24 hr,
1-6 years: 0.125 mg/kg/day PO q 24 hr; increase to 0.6 mg/kg/dose up to 20 mg/24 hr
>6 years: 2.5 mg/day PO q 24 hr Side effects: Edema, dizziness, flushing, palpitations;
Side effects: Headache, muscle ache, sleepiness, sore throat reduce dose in hepatic insufficiency
Rational Drug Therapy 1757-
Ciclesonide Note
• Metered dose inhalers (MDI) should be used with large
MDI 80,160 µg/puff: 80-640 µg/day q 12 hr; not approved volume spacers. For infants,the spacer can be used with
below 12 years of age a face mask.
Benefit of less oropharyngeal candidiasis and HPA axis • Rotacap dose is double the inhaler dose; are
suppression administered using a Rotahaler.
Side effects: Benefit of less oropharyngeal candidiasis and • Nebulization: Final volume of 3-5 mL should be made
hyp othalamic-pituitary axis suppression by adding normal saline.
Rational Drug Therapy 1759-
Metolazone Dexamethasone
0.2-0.4 mg/kg/day PO q 24 hr 0.05-0.5 mg/kg/day PO q 6 hr
Side effects: Hyp otension, palpitations and hypovolemia, Congenital adrenal hyperplasia: 0.5-1.5 mg/day
hypokalemia, hyponatremia Cerebral edema 0.5 mg/kg/dose IV/IM q 6 hr
Pulse dexamethasone: 5 mg/kg as slow infusion (maximum
Spironolactone dose 100 mg)
Neonates: 1-3 mg/kg/day q 12-24 hr Side effects: Weight gain, insomnia, mood changes, acne, dry
Children: 1.5-3 mg/kg/day or 60 mg/m2 / day q 12-24 hr; skin, bruising or discoloration, slow wound healing, nausea
not to exceed 100 mg/day Croup: 0.3-0.6 mg/kg IM/oral, single dose
Side effects: Dry mouth, dizziness, headache, irregular periods, Hydrocortisone
gynecomastia, hirsutism, erectile dysfunction, hyperkalemia
Status asthmaticus: 4-8 mg/kg/dose IV q 4--6 hr IV
Triamterene Endotoxic shock: 50 mg/m2 initial dose followed by 50-150
mg/m2 / day q 6 hr IV for 48-72 hr
2-4 mg/kg/day q 12 hr
Side effects: Hyperkalemia, hyponatremia, dry mouth, Acute adrenal insufficiency: 1-2 mg/kg/ dose IV, then
headache 25-150 mg/m2/day IV or IM
Side effects: Hypertension, hyp erglycemia, arrhythmias
Mannito/
0.5-3 g/kg/dose IV given over 30--60 min Predniso/one
Side effects: Hypotension, tachycardia, fluid and electrolyte (Prednisolone, 5 mg = 0.75 mg betamethasone or dexa
imbalance methasone, 4 mg methylprednisolone or triamcinolone,
20 mg hydrocortisone and 25 mg cortisone acetate)
HORMONES Acute asthma: 0.5-2 mg/kg/day PO q 12-24 hr
Anti-inflammatory: 0.5-2 mg/kg/day PO q 8-12 hr
Betamethasone Nephrotic syndrome: 2 mg/kg/day, q 12-24 hr daily; then
Anti-inflammatory: 0.0175-0.25 mg/kg/day or 0.5-7.5 mg/ on alternate days
m2 / day PO q 6-8 hr; 0.0175-0.25 mg/kg/day or 0.5-7.5 Congenital adrenal hyperplasia: 2 mg/kg/day PO q 6-8 hr
mg/m2/day IM q 6-12 hr or single dose in the morning
Fetal lung maturity (24-34 weeks); administer to mother Side effects (immediate): Moon facies, acne, increased
12 mg IM in 2 doses 24 hr apart appetite, gastritis, hyp ertension, electrolyte disturbances,
Side effects (short term): Sodium retention-related weight glaucoma, pseudotumor cerebri
gain, glucose intolerance, hypokalemia, gastrointestinal Side effects (prolonged therapy): Myopathy, osteoporosis,
upset and reversible depression of the hypothalamic stunting, cataract, adrenal cortical suppression
pituitary-adrenal axis
Side effects (long term): Hypothalamic-pituitary-adrenal Methy/predniso/one
activity suppression, cushingoid appearance, hirsutism or 1-2 mg/kg/dose IM or IV
virilism, impotence, cataracts and increased intraocular High dose (pulse) therapy: 15-30 mg/kg daily for 3-5 days
pressure, myopathy, osteoporosis Side effects: Hypertension, sweating, hyperglycemia, mood
changes, dyselectrolytemia, rarely arrhythmias
Cortisone Acetate
Physiological requirement: 0.7 mg/kg/day Triamcinolone
Therapeutic dose: 2.5-10 mg/kg/day q 8 hr 24 mg/day PO q 8-12 hr; deep IM 40 mg or intra-articular
Side effects (immediate): Moon facies, acne, increased 2.5-15 mg; avoid <6 yr
appetite, reduced resistance to infections, headache, Side effects: Fluid retention, hyp okalemic alkalosis, aseptic
gastritis, hypertension, electrolyte disturbances, glaucoma, necrosis of femoral heads, gastritis
pseudotumor cerebri
ACTH
Side effects (prolonged therapy): Myopathy, osteoporosis,
growth retardation, cataract, adrenal cortical atrophy For infantile spasms: 20-40 U/kg/day IM q 24 hr for 6 week
or 150 U/m2 / day q 12 hr for 2 weeks followed by a gradual
tapering, for dynamic testing (short ACTH stimulation test)
Fludrocortisone <6 months: 62.5 µg; 6 months-2 years: 125 µg; >2 years 250 µg
Infants: 0.05-0.l mg/day PO q 24 hr; Children: 0.05-0.2 mg/ Side effects: C/1 hepatic damage, nephropathy, acute
day PO q 24 hr psychosis, CHF, Cushing's disease, peptic ulcer, fungal
Side effects: Hypertension, hypokalemia, acne, rash infections, recent surgery
Rational Drug Therapy 1761-
Lorazepam Midazolam
0.1 mg/kg IV; repeat at 5 minutes; longer duration of action 0.07-0.2 mg/kg/dose IM or IV
than diazepam; 0.03-0.05 mg/kg/dose PO q8-12 hr Pre-operative sedation or conscious sedation (mechanical
Side effects: Confusion, depressed mood, hyperactivity, ventilation) above dose followed by 0.2-1 µg/kg/min for
agitation, hostility neonates and 0.5-3.0 µg/kg/min for infants and children
Status epilepticus 0.2 mg/kg IV or IM followed by 0.1-0.2
Clonazepam mg/kg/hr
Infant and child <10 yr or <30 kg: initial: 0.01-0.03 mg/ Intranasal 0.2 mg/kg may be used for acute seizure control
kg/day PO q 8 hr; increment: 0.25--0.5 mg/day q 72 hr, Side effects: Respiratory depression, shock
up to maximum maintenance dose of 0.1--0.2 mg/kg/day Triclofos
q8 hr
20 mg/kg/dose for sedation PO q12 hr
Child �10 yr or �30 kg and adult: initial: 1.5 mg/24hr PO
q8 hr; increment: 0.5-1 mg/day q72 hr; maximum dose: Side effects: Gastrointestinal disturbance, mild rash
20 mg/24hr
Carbamazepine
Side effects: Drowsiness, dizziness, muscle weakness, loss
of balance or coordination <6 yr: 10-20 mg/kg/day PO q8 hr, increment q5-7 days
up to maximum of 35 mg/kg/24hr; 6-12 yr: 10 mg/kg/
Chloral Hydrate 24 hr PO q 12 hr up to maximum 100 mg/dose q 12 hr;
maintenance 20-30 mg/kg/day q6-12 hr
5-10 mg/kg/dose for sedation; 20-75 mg/kg/dose for
Side effects: Dizziness, drowsiness, nausea, ataxia, and
heavy sedation
vomiting, pruritus, speech disturbance, xerostomia and
Side effects: Nausea and vomiting are more common, amblyopia
diarrhea; dizziness and drowsiness are less common
Clobazam
Chlorpromazine <30 kg: 5 mg PO q24hr, increase to 20 mg q24hr
2.5--6 mg/kg/day PO q6 h >30 kg: 10 mg PO q24hr, increase to 40 mg q24hr
Chorea: Start with 50 mg/day PO; increase by 25 mg/day Side effects: Dizziness, drowsiness, anxiety, suicidal thoughts,
till controlled; maximum dose 300 mg/day withdrawal symptoms, lower doses in liver diseases
Neonatal tetanus: 1-2 mg/kg/dose q2--4 hr
Side effects: Extrapyramidal reactions (e.g. Parkinson-like Pentobarbital
symptoms, dystonia, tardive dyskinesia), drowsiness, Refractory status epilepticus: 10 mg/kg loading IV over
dizziness, skin reactions or rash, dry mouth, orthostatic 1 hr, maintenance 1-5 mg/kg/hr
hypotension, amenorrhea, galactorrhea, weight gain Side effects: Hypotension, respiratory suppression,
arrhythmia
Fluoxetine Hydrochloride
Phenobarbital
5-10 mg/day; maximum 20 mg/day
Side effects: Insomnia, weakness, anxiety, drowsiness, Anticonvulsant: 20 mg/kg loading IV; 3-5 mg/kg/day IV
tremor, diarrhea, dyspepsia, nausea, nervousness, q12-24hr as maintenance
headache, xerostomia Side effects: Dizziness, respiratory depression, hypotension
Phenytoin Sodium
Haloperidol
Arrhythmia: Loading 1.25 mg/kg IV over 3 min and repeat
Psychotic disorder: 0.05--0.15 mg/kg/day PO q 8-12 hr; every 5-10 min to a maximum total dose of 15 mg/kg or
agitation: 0.01-0.03 mg/kg/day q 8-12 hr; chorea: until arrhythmia reverts or hypotension develops;
0.25 mg PO q12 hr; 5-10 mg/day q12 hr maintenance 5-10 mg/kg/day PO q12 hr
Side effects: Extrapyramidal reactions, dyskinesia Status epilepticus: Loading 15-20 mg/kg IV, do not exceed
1-3 mg/kg/min. Maintain with 5-8 mg/kg/day PO or
Ketamine IV q12-24hr
Side effects: Gum hypertrophy, hirsutism, hypersensitivity,
IV induction: 0.5-2 mg/kg at a rate not to exceed 0.5 mg/
megaloblastic anemia, osteomalacia and vestibulo
kg/min; IM, oral, rectal: 3-10 mg/kg/dose; nasal and
cerebellar syndrome
sublingual: 3-5 mg/kg/dose
Minor procedures 0.5-1.0 mg/kg; sedative dose 2 mg/kg Fosphenytoin Sodium
The concomitant use of midazolam is beneficial 15-20 mg/kg/day; then 4--6 mg/kg/day
Side effects: Hypertension, hypertonia, diplopia, increased Side effects: Pruritus, dizziness, ataxia, nystagmus, contra
intraocular pressure, salivary hypersecretion indicated in porphyria
-7641 Essential Pediatrics
Side effects: Hepatotoxicity, irritability, hearing loss, Side effects: Postural hypotension, dizziness, faintness,
nausea, vomiting, pyrexia nasal stuffiness, priapism
Vigabatrin Tolazoline
Infantile spasm: 40-150 mg/kg/day POq 12-24 hr 1-2 mg/kg IV over 10 min followed by 1-2 mg/kg/hour
Side effects: Visual field defects, GI and psychiatric symptoms in continuous infusion
Side effect: Dizziness, faintness
VASODILATORS
lsosorbide Dinitrate Suggested Reading
• de Vries TPGM, Heming RH, Hogerzeil HV, Fresle DA. Guide to
0.1 mg/kg/day POq6-8 hr Good Prescribing-A Practical Manual. Essential Drugs and
Side effects: Flushing, headache Medicines Policy, World Health Organization, 1211 Geneva 27,
Switzerland 2000. Available at http://www.who.int/medicines/
Nifedipine areas/rational_use/en/https://www.drugs.com/
0.3 mg/kg/dose oral q6 hr • Ritter JM, Lewis LD, Mant TGK, Ferro A. A Textbook of Clinical
Antihypertensive: 0.25--0.5 mg/kg/dose (maximumlO mg) Pharmacology and Therapeutics, 5th edn, 2008. London, Hodder
POq6 hr Arnold. Available at http:/ /pharmaresearchlibrary.com/wp
content/uploads/2013/03/A-Textbook-of-Clinical-Pharmacology
Vasodilator: 0.3 mg/kg/dose POq6 hr and-Therapeutics-Sth-edition.pdf
Side effects: Hypotension, dizziness • Singh MB, Deorari AK. Drug dosages in children, 8th edn. New
Delhi, Sagar Publications, 2009.
Prazosin
• Unni JC, Nair MKC, Menon PSN, Bansal CP. IAP Pediatric
Antihypertensive: 0.05--0.l mg/kg/day q 8 hr (maximum Drug Formulary, 3rd edn. Mumbai: Indian Academy of Pediatrics
0.5 mg/kg/dose) 2012.
Chapter
31
Integrated Management of
Neonatal and Childhood Illness
Ajay Khera • Varun Alwadhi
Many well-known interventions like universal immuniza treatment of sick children in an outpatient or primary care
tion, essential newborn care, exclusive breastfeeding setting.
during first 6 months of life, appropriate complementary
feeding, oral rehydration therapy, and timely and Clinical Guidelines
appropriate use of antibiotics in pneumonia have proven The clinical guidelines target children less than 5-year
to be effective in reducing child mortality. While each of old, the age group that bears the highest burden of
these interventions is successful, there is evidence to suggest morbidity and mortality. The guidelines represent an
that an integrated approach is needed to manage sick children. evidence-based syndromic approach to case management
Sick children often present with overlapping signs and that includes rational, effective and affordable use of
symptoms common to different illnesses and often suffer drugs. Careful and systematic assessment of common
from more than one illness, which may necessitate symptoms, using selected reliable clinical signs, helps to guide
different treatments. Another reason for integrated rational and effective actions.
approach is the need for incorporating preventive An evidence-based syndromic approach can be used
strategies such as immunization and nutrition along with to determine: (i) Health problem(s) the child may have;
curative care. (ii) severity of the child's condition; and (iii) actions that
can be taken to care for the child (e.g. refer the child
INTEGRATED MANAGEMENT OF NEONATAL AND immediately, manage with available resources or manage
CHILDHOOD ILLNESS STRATEGY at home). In addition the guidelines suggest the
adjustments required to manage with the capacity of
Integrated Management of Childhood Illness (IMCI)
health system and active involvement of family members
strategy, developed by World Health Organization in
in health care practices.
collaboration with UNICEF and many other agencies in
mid-1990s, combines improved management of common Principles of Integrated Care
childhood illnesses with prevention of diseases and
Depending on a child's age, various clinical signs and
promotion of health by including counseling on feeding
symptoms differ in their degrees of reliability and
and immunization. This strategy has been adapted and
diagnostic value and importance. IMNCI clinical
expanded in India to include neonatal care at home as
guidelines focus on children up to 5 years of age. The
well as in the health facilities and renamed as Integrated
treatment guidelines have been broadly described under
Management of Neonatal and Childhood Illness (IMNCI).
two age categories:
1. Young infants age up to 2 months
Essential Components 2. Children age 2 months up to 5 years
The IMNCI strategy includes both preventive and curative The IMNCI guidelines are based on the following
interventions that aim to improve practices in health principles:
facilities, the health system and at home. At the core of • All children under 5 years of age must be examined for
the strategy is integrated case management of the most conditions which indicate immediate referral
common neonatal and childhood problems with a focus • Children must be routinely assessed for major
on the most common causes of death in children <5 years symptoms, nutritional, quality of interaction with a
of age. child, immunization status, feeding problems and other
The initial guidelines developed in 2003 were adapted problems
in 2009 and have recently been revised again in 2017 and • Only a limited number of carefully selected clinical
this chapter elaborates the clinical guidelines for the signs are used for assessment
766
Integrated Management of Neonatal and Childhood Illness 1767-
• A combination of individual signs is used to classify Outpatient health facility: Assessment; classification and
the severity of illness which calls for specific action identification of treatment; referral, treatment or counseling
rather than a 'diagnosis'. Classifications are color-coded of the child's caretaker (depending on classification(s)
and suggest referral (pink), initiation of treatment in identified); follow-up care
health facility (yellow) or management at home (green)
Referral health facility: Emergency triage assessment and
• IMNCI guidelines address most common, but not all
treatment (ETAT); diagnosis, treatment and monitoring
pediatric problems
of patient progress.
• IMNCI management protocols use a limited number
of essential drugs Appropriate home management: Teaching mothers or
• Caretakers are actively involved in the treatment of other caretakers how to give oral drugs and treat local
children infections at home; counseling mothers or other caretakers
• IMNCI includes counseling of caretakers about home about food (feeding advice, feeding problems); develop
care including feeding, fluids and when to return to ment support care (playing and communication) fluids;
health facility. when to return to the health facility; and the mother's own
The overall case management process is summarized health.
in Fig. 31.1.
Classification Tables
The case management of a sick child brought to a first
level health facility includes a number of important IMNCI classification tables describe the steps of case
elements. management process: ASSESS, CLASSIFY and IDENTIFY
For all sick children age up to 5 years who are brought to a first-level health facility
ASSESS the child: Check for danger signs (or possible bacterial infection/jaundice). Ask
about main symptoms. If a main symptom is reported, assess further. Check nutrition and
immunization status. Check for other problems.
CLASSIFY the child's illness: Use color-coded triage system to classify main symptoms and his or
her nutrition or feeding status
+ +
I
+
Treat the child Treat the child
Give urgent pre-referral treatment(s) needed Give first dose of oral drugs in the clinic and/or
advice caretaker
Teach the caretaker how to give oral drugs
and to treat local infections at home
Refer the child If needed, give immunizations
Explain to caretaker the need for referral +
Calm caretaker fears and resolve problems Counsel the mother
Write referral note Assess child's feeding and development;
Give instructions and support care and solve problems if present.
supplies needed to care for the child on way Advise about feeding, development support,
to the hospital. care and fluids during illness and when to
return to a healthfacility
Counsel mother about her own health
' +
Follow-up care: Give follow-up care when the child returns to the clinic
If necessary, reassess the child for new problems
TREATMENT. There are separate classification boxes for drawing, fever, hypothermia, movement only when
main symptoms, nutritional status and anemia. stimulated or no movement at all.
IMNCI classifications are not necessarily specific This infant should be referred urgently to the hospital
diagnoses, but they indicate what action needs to be taken. after being given the first dose of intramuscular
All classifications are color-coded: pink calls for hospital ampicillin/oral amoxycillin plus gentamicin, treatment to
referral or admission, yellow for initiation of treatment, prevent hypoglycemia, and advice to the mother on
and green means that the child can be sent home with keeping the young infant warm while arranging referral,
careful advice on when to return. and on the way to the hospital.
Classification tables are used starting with the pink A sick young infant with local bacterial infection is
rows. If the young infant or child does not have the severe the one with umbilicus red or draining pus or skin
classifications, look at the yellow rows. For the classification pustules. This infant may be treated at home with oral
tables that have a green row, if the young infant or child antibiotics but should be seen in follow-up after two days.
does not have any of the signs in the pink or yellow rows, Additionally, if the sick young infant has jaundice,
select the classification in the green row. If the young infant classify for jaundice.
or child has signs from more than one row, the more severe There are two possible classifications
classifications is selected (Box 31.1). However, if the • A sick young infant with severe jaundice is one who
classification table has more than one arm (e.g. possible has yellow palms and soles or has jaundice at age
bacterial infection/jaundice, diarrhea in a sick child), one <24 hours or at age 14 days or more. This infant should
may have more than one classification from that box. be referred urgently to the hospital after being given
treatment to prevent hyp oglycemia and advice to the
Box 31. l : Effective communication with care provider
mother on keeping the young infant warm while
It is critical to communicate effectively with the infant's mother arranging referral.
or caretaker. Proper communication helps to reassure the
• A sick young infant with jaundice is one who has
mother or caretaker that the infant will receive appropriate
care. In addition, the success of home treatment depends on jaundice but the palms and soles are not yellow. This
how well the mother or caretaker knows about giving the infant should be given home care, but mother should
treatment and understands its importance. be advised when to return immediately and should be
Parents, if correctly informed and counseled, can play an seen in follow-up in two days.
important role in improving the health status of their children
by following the advice given by a health care provider, by Assessing for Diarrhea
applying appropriate feeding practices and by bringing sick
Diarrhea is a main symptom, which is assessed if the
children to a health facility as soon as symptoms arise.
mother says it is present. Exclusively breast-fed infants
normally pass frequent soft stools. This should not be
OUTPATIENT MANAGEMENT OF YOUNG INFANTS AGE UP confused with diarrhea. A young infant is said to have
TO 2 MONTHS diarrhea if the stools have changed from usual pattern
Young infants have special characteristics that must be and the child is passing many watery stools (more water
considered when classifying their illnesses. They can than fecal matter).
become sick and die very quickly from serious bacterial
infections. They frequently have only general signs such Clinical Assessment and Classification
as few movements, fever or low body temperature. Mild All infants with diarrhea should be assessed for presence
chest in drawing is normal in young infants because their of dehydration. A number of clinical signs are used to
chest wall is soft. The assessment procedure for this age determine the level of dehydration: infant's general
group includes a number of important steps that must be condition (lethargic or unconscious or restless/irritable);
taken by the health care provider, which are given below. sunken eyes and elasticity of skin (skin pinch goes back
very slowly, slowly or immediately).
Communicating with the Caretaker All young infants with diarrhea are classified for degree
It is critical to communicate effectively with the infant's of dehydration. Young infants with severe dehydration
mother or caretaker. Good communication techniques and will need IV fluids while those with some dehydration
an integrated assessment are required to ensure that are treated as plan B with oral rehydration. Young infants
common problems or signs of disease or malnutrition are with no dehydration will require more fluid to prevent
not overlooked. dehydration.
Checking for Possible Bacterial Infection/Jaundice Checking for Feeding Problems or Very Low Weight
A sick young infant with possible serious bacterial All sick young infants seen in outpatient health facilities
infection is one with any of the following signs: not should be routinely evaluated for adequate feeding and
feeding well, convulsions, fast breathing, severe chest in have their weight checked). Infants who are very low
Integrated Management of Neonatal and Childhood Illness 1769-
weight (weight <1800 g) are given pink classification and Non-urgent treatments, e.g. applying gentian violet
should be referred to a hospital. Infants who are low paint on skin pustules, should be deferred to avoid
weight (weight 1800-2500 g) need special attention to how delaying referral or confusing the caretaker.
they are fed and on keeping them warm. • If an infant does not need urgent referral, check to see
To assess the young infant for feeding problems the if the infant needs non-urgent referral for further
mother is asked specific questions about infant feeding to assessment. These referrals are not as urgent. Other
determine if the feeding practices are optimal. If there is necessary treatments may be done before referral.
no indication for referral the mother is observed for
breastfeeding. Breastfeeding is observed to see the signs Treatment in Outpatient Clinic and at Home
of attachment and whether the infant is suckling Young infants who have local infection, feeding problem
effectively. Mothers of infants with problem in feeding or low weight, or diarrhea with some dehydration should
are counseled appropriately. Infants who are not low have treatment initiated in clinic, which is continued at
weight for age and have no feeding problem are classified home. Counseling a mother/caretaker is critical for home
as 'no feeding problem' and counseled about home care care. The health professional should use good communica
of young infant. tion skills while counseling the mother/ caretaker for
treatment (Box 31.2).
Checking Immunization Status
Immunization status should be checked in all sick young Box 31.2: Effective communication and counseling-APAC
infants. A young infant who is not sick enough to be • Ask and listen: Ask the mother/caretaker and listen carefully
referred to a hospital should be given the necessary to find out the young child's problems and what the mother/
immunizations before he is sent home. caretaker is already doing for the young infant
• Praise: Praise the mother/caretaker for what she has done
Assessing other Problems well
All sick young infants need to be assessed for other • Advise and teach: Advise the mother/caretaker how to take
potential problems mentioned by the mother or observed care of young child at home (for tasks which require mother/
during the examination. If a potentially serious problem caretaker to carry out treatment at home: give information,
is found or there are no means in the clinic to help the show an example, and let her practice)
infant, he should be referred to hospital. • Check:Before the mother/caretaker leaves, always check
understanding by asking questions to find out what she
Identify Treatment and Treat understands and what needs further explanation
The next step is to identify treatment required for the
young infant according to the classification (see Charts). Advise when to Return
All the treatments required are listed in the 'Identify Immediately: Return immediately if the infant has any of
Treatment' column of the ASSESS and CLASSIFY THE these signs: breastfeeding or drinking poorly, becomes
SICK YOUNG INFANT. If a sick infant has more than sicker, develops a fever or feels cold to touch, fast
one classification, treatment required for all the breathing, difficult breathing, yellow palms and soles (if
classifications must be identified. The first step is to young infant has jaundice), diarrhea with blood in stool.
determine if there is need to refer the child to hospital.
All infants and children with a severe classification For follow-up visit: Return not later than 2 days if the
(pink) are referred to a hospital as soon as assessment is infant has: Local bacterial infection or, jaundice or diarrhea
completed and necessary pre-referral treatment is or feeding problem or thrush; and not later than 14 days
administered. Successful referral of severely ill infants to if low weight.
the hospital depends on effective counseling of the Next well child visit: For immunization and feeding
caretaker. counseling.
The first step is to give urgent prereferral treatment
(written in bold font in identify treatment section of chart). Counsel the Mother about her Own Health
This may be:
During a sick infant visit, listen for any problems that the
• Administering first dose of antibiotic mother herself may be having. She may need treatment
• Treatment of severe dehydration or referral for her own health problems. If the mother is
• Prevention of hypoglycemia with breast milk; if young sick, provide care for her, or refer her for help. Advise her
infant is not able to swallow give expressed breast to eat well to keep up her own strength and health. Check
milk/ appropriate animal milk with added sugar by her immunization status and give tetanus toxoid if needed.
nasogastric tube Give the mother iron folic acid tablets if she is not taken
• In young infants with diarrhea, giving frequent sips of them. Make sure she has access to family planning and
ORS solution on the way to the hospital. counseling on STD and AIDS prevention.
110 I Essential Pediatrics
OUTPATIENT MANAGEMENT OF SICK CHILD AGE Classification of cough or difficult breathing: Those
2 MONTHS TO 5 YEARS requiring referral for possible severe pneumonia or severe
disease. This group includes children with any general
The assessment procedure is similar to that of young infant
danger sign, or stridor when calm. Children with severe
including: (i) History taking and communicating with the
pneumonia or severe disease most likely have an invasive
caretaker about the child's problem; (ii) checking for
bacterial organisms and diseases that may be life
general danger signs; (iii) checking main symptoms;
threatening. The patient needs urgent referral to a hospital
(iv) checking for malnutrition; (v) checking for anemia;
for treatment, such as oxygen, a bronchodilator or
(vi) assessing the child's feeding; (vii) checking immuniza
injectable antibiotics. Pulse oximeter is used to determine
tion status; and (viii) assessing other problems.
oxygen saturation and patient referred if <90%.
Communicating-History Taking Those who require antibiotics as outpatients because
A sick child brought to an outpatient facility may have they are highly likely to have bacterial pneumonia. A
signs that clearly indicate a specific problem. However, child with cough or difficult breathing who has fast
some children may present with serious, nonspecific signs breathing and or chest indrawing is classified as having
called General Danger Signs that do not point to a pneumonia. This child should not have a general danger
particular diagnosis. For example, a child who is lethargic signs, or stridor and his oxygen saturation is >90%.
or unconscious may have meningitis, severe pneumonia, Those who simply have a cough or cold and do not
cerebral malaria or any other severe disease. Great care require antibiotics. Such children may require a safe
should be taken to ensure that these general danger signs remedy to a relieve cough. A child with cough and cold
are not overlooked because they suggest that a child is normally improves in 1-2 weeks. However, a child with
severely ill and needs urgent attention. chronic cough (more than 14 days) needs to be further
assessed (and, if needed, referred) to exclude tuberculosis,
Assessing for General Danger Signs asthma, whooping cough or another problem.
The following signs should be routinely checked in all
children: (i) History of convulsions during the present Diarrhea
illness, (ii) unconsciousness or lethargy, inability to drink A child with diarrhea passes stools with more water than
or breastfeed when mother tries to breastfeed, or to give normal. A child with diarrhea may have (i) acute watery
child something to drink; (iii) child vomits everything; and diarrhea (including cholera); (ii) dysentery (bloody
(iv) child is presently having convulsions. diarrhea); or (iii) persistent diarrhea (diarrhea that lasts
If a child has one or more of these signs, he must be 14 days or more).
considered seriously ill and will almost always need Clinical assessment and classification. All children with
referral. diarrhea should be assessed for dehydration based on the
following clinical signs: General condition (lethargic or
Assessing for Main Symptoms unconscious or restless/irritable); sunken eyes; child's
After checking for general danger signs, the health care reaction when offered to drink (not able to drink or
provider must enquire about the following main drinking poorly or drinking eagerly/thirsty or drinking
symptoms: (i) Cough or difficult breathing; (ii) diarrhea; normally) and elasticity of skin (skin pinch goes back very
(iii) fever; and (iv) ear problems. If the symptom is present slowly, slowly or immediately). In addition a child with
the child is evaluated for that symptom. diarrhea should be asked how long the child has had
diarrhea and if there is blood in the stool. This will allow
Cough or Difficult Breathing identification of children with persistent diarrhea and
dysentery.
Four key clinical signs are used to assess a sick child with
cough or difficult breathing: Fever
• Fast breathing: Cut-off respiratory rate for fast breathing
All cases with fever are suspected to have malaria after
is ;?.50 breaths per minute for a child 2-12 months and
ruling out other common causes and should be
;?.40 breaths per minute for 12 months up to 5 years
investigated for confirmation of malaria by microscopy
• Lower chest wall indrawing or rapid diagnostic kit (RDK) so as to ensure treatment
• Stridor with full therapeutic dose with appropriate drug to all
• Wheeze confirmed cases.
Patients with wheezing and either fast breathing or History of duration of fever is important in evaluating
chest indrawing are given a trial of rapid acting inhaled fever. If fever has persisted daily for more than seven days
bronchodilator for up to three times 15-20 minutes apart. the child needs to be referred to hospital for assessment
The patient is observed again for respiratory rate and signs and diagnostic tests. The other signs looked for in a child
of chest indrawing, and reclassified as follows: with fever include general danger signs (assessed earlier)
Integrated Management of Neonatal and Childhood Illness 1111-
and signs of meningitis, e.g. stiff neck. Besides these, signs Checking for Anemia
of measles such as cough/difficult breathing, diarrhea, Palmar pallor can help to identify sick children with severe
cornea clouding, mouth ulcers and ear infections. Before anemia. Wherever feasible, diagnosis of anemia can be
classifying fever, one should check for other obvious supported by using a simple laboratory test for
causes of fever. hemoglobin estimation. For clinical assessment of anemia
Ear Problems the color of the child's palm is compared with examiner's
own palm. If the skin of the child's palm is pale, the child
A child with an ear problem may have otitis. It may be has some palmar pallor. If the skin of the palm is very
acute or chronic infection. If the infection is not treated, pale or so pale that it looks white, the child has severe
the ear drum may perforate. The mother is asked about palmar pallor. Pallor is classified as severe anemia, anemia
history of ear pain and ear discharge or pus. The child is or no anemia.
examined for tender swelling behind the ear. Based on
these clinical findings a child can be classified as
Assessing Child's Feeding and
mastoiditis, acute ear infection, chronic ear infection or
Development Support Care
no ear infection. Children with mastoiditis are classified
as severe illness and referred urgently to hospital. Children All children less than 2 years old and all children classified
with acute ear infection are given oral antibiotics and those as moderate acute malnutrition need to be assessed for
with chronic ear infection are advised to keep the ear dry feeding and development support care.
by wicking. Feeding assessment includes questioning the mother
or caretaker about: (i) Breastfeeding frequency and night
Checking for Malnutrition
feeds; (ii) types of complimentary foods or fluids,
After assessing for general danger signs and the four main frequency of feeding and whether feeding is active; and
symptoms, all children should be assessed for malnutrition. (iii) feeding patterns during the current illness. The mother
There are two main reasons for routine assessment of or caretaker should be given appropriate advice to help
nutritional status in sick children: (i) To identify children overcome any feeding problems found.
with severe malnutrition who are at increased risk of
Assessment of development support care includes
mortality and need urgent referral to provide active
assessment of mother's sensitivity and responsiveness
treatment; and (ii) to identify children with suboptimal
nutritional status resulting from ongoing deficits in dietary to the child's needs through questioning the mother or
intake plus repeated episodes of infection and who may caretaker about: (i) Playing with the baby; (ii) talking to
benefit from nutritional counseling. the baby, and (iii) making the baby smile and the learning
pattern of the child. The mother or caretaker should be
Clinical assessment and classification: Edema of both feet; given appropriate advice to help overcome any playing
weight for height; mid-upper arm circumference (only for and communication problems found (for more details,
children 6-59 months) refer to the section on counselling the mother or
The child is classified as Complicated Severe Acute caretaker).
Malnutrition when they have severe acute malnutrition
(edema of both feet, weight for height/length less than Identify Feeding Problems
-3 SD scores, or mid-upper arm circumference less than
It is important to complete the assessment of feeding by
115 mm) and at least one medical complication, including
referring to age appropriate feeding recommendations
any general danger sign, any severe classification, or
and identify all the feeding problems before giving advice.
pneumonia with chest indrawing or a feeding problem
Other common feeding problems are: Difficulty breast
in children under 6 months. Children classified as having
complicated severe acute malnutrition are at high risk of feeding, use of feeding bottle, lack of active feeding and
death from pneumonia, diarrhea, measles, and other not feeding well during illness.
severe diseases. These children need urgent referral to
hospital where their treatment can be carefully monitored. Identify Developmentally Supportive
[Family Interaction} Problems
If the child has at least one sign of severe acute mal
nutrition, but does not have other signs of complication, It is important to complete the assessment of family
they are classified as Uncomplicated Severe Acute interaction and identify all the problems before giving
Malnutrition. A child is classified as Moderate Acute advice. Based on the mother's answers to the questions,
Malnutrition if the weight-for-age is between -3 and -2 identify any differences between the family's actual
Z-scores or MUAC is between 115 and 125 mm. The child interaction (sensitivity and responsiveness) and the
is classified as No Acute Malnutrition if the child has a recommendations. These differences are problems.
weight-for-age over -2 Z-scores, and has no other signs Some examples of interaction problems are listed in
of malnutrition. Box 31.3.
-772 Essential Pediatrics
Box 31.3: Examples of interaction problems necessary pre-referral treatment is administered. If a child
only has severe dehydration and no other severe
Family interaction Recommended action
classification, and IV infusion is available in the outpatient
Mother reports, "she does Discuss ways to help baby see, clinic, an attempt should be made to rehydrate the sick
not play with baby" hear, feel and move, appropriate child. The principles of referral of a sick child are similar
for age, ask caregiver to do play
or communication activity,
to those described for a sick young infant.
appropriate for age
Referral of Children Age 2 Months to 5 Years
Mother reports, "she does If baby is less than 6 months ask
not talk to child or talks caregiver to looks into baby's eyes For all children before referral
harshly to child" and talk to baby. For older 1. Prevent low blood sugar by giving breast milk or sugar
children give caregiver and child water.
an activity to do together. Help 2. For convulsions give diazepam (10 mg/2 mL solution)
mother interpret what child is in dose 0.2 mg per kg (0.05 ml/kg) IV or rectally; if
doing and thinking and see child convulsions continue after 10 minutes, give a second
respond and smile. If the mother dose of diazepam.
scolds child, help caregiver
distract child from unwanted 3. For severe pneumonia or severe disease (as also for
actions by giving alternative toy or mastoiditis), give first dose of IV or intramuscular
activity. If the mother is not able antibiotic. Options for an intramuscular antibiotic for
to comfort child and child does not pre-referral use include (ampicillin plus gentamicin
look at the mother for comfort: combination, OR ceftriaxone).
help mother look into child's eyes 4. For very severe febrile disease, give one dose of
and gently talk to child and hold paracetamol for high fever (38.5°C or above); give first
child. dose of intramuscular quinine/artesunate for severe
Mother tries to force smile Ask mother to make large gestures malaria in high Plasmodium falciparum area, and give
or is not responsive to baby and cooing sounds; copy baby's first dose of an appropriate antibiotic.
sounds and gestures and see 5. For severe complicated measles, give first dose of
baby's responses.
appropriate antibiotic, give vitamin A, and if there is
Mother says the child is Encourage more activity with the clouding of the cornea or pus draining from the eye,
slow to learn child, check hearing and seeing. apply tetracycline eye ointment.
Refer child with difficulties
6. For severe dehydration, IV fluids should be given in
the outpatient clinic according to WHO Treatment
Plan C. Give 100 mL/kg IV fluids. Ringer's lactate
Checking Immunization, Vitamin A and Follc Acid solution is the preferred commercially available
Supplementation and Dewormlng Status solution.
The immunization status of every sick child brought to a 7. For severe persistent diarrhea, treat dehydration before
health facility should be checked. After checking referral using WHO Treatment Plan B for some
immunization status, determine if the child needs vitamin dehydration and Plan C for severe dehydration.
A supplementation and/or prophylactic iron folic acid 8. For severe acute malnutrition, give first dose of
supplementation or deworming administration. intramuscular antibiotics. Options for an intramuscular
antibiotic for pre-referral use include ampicillin plus
Assessing other Problems gentamicin combination OR ceftriaxone. Oral amoxicillin
The IMNCI clinical guidelines focus on five main can be an option.
symptoms In addition, the assessment steps within each
Treatment in Outpatient Clinics and at Home
main symptom take into account several other common
problems. For example, conditions such as meningitis, Identify the treatment associated with each nonreferral
sepsis, tuberculosis, conjunctivitis, and different causes classification (yellow and green) in the IMNCI chart.
of fever such as ear infection and sore throat are routinely Treatment uses a minimum of affordable essential drugs
assessed within the IMNCI case management process. (Box 31.4).
knows how to give treatment, understands its importance • Reduction of signs of possible severe vacterial infection
and knows when to return to a health care provider. (PSBI) in young infants
Table 31.1 lists the specific times to advise a mother or • Revised drug dosages for pre-referral treatment of
caretaker to return to a health facility. possible severe bacterial infection
• Simplified classifications of diarrhea in young Infants
Table 31.1: Follow-up visits • Mandatory assessment of breastfeeding in all young
When to return infants
Immediately • Revised immunization schedule and addition of
• Any sick child not able to drink or breastfeed, or becomes deworming as per immunization and deworming
sicker or develops a fever policy of India
• If child has no pneumonia: Cough or cold, also return if fast • Removed weight for age as criteria for referral and
breathing or difficult breathing referral of low birth weight aligned with other existing
• If child has diarrhea, also return if blood in stool or drinking new-born training packages
poorly • Added classifying danger signs as severe disease with
For follow-up visit (not later than . . . ) addition of convulsing now
• 2 days: Pneumonia, dysentery, malaria/suspected malaria/ • Added use of rapid acting bronchodilator before
fever; malaria unlikely if fever persists; measles with eye or classifying wheeze with fast breathing/ chest indrawing
mouth complications. in children presenting with cough or difficult breathing
• 5 days: Diarrhea, if not improving, persistent diarrhea, acute • Revised signs for classifying pneumonia as per WHO
ear infection, chronic ear infection, uncomplicated acute recommendations
malnutrition/feeding problem, any other illness, if not • Added use of pulse oximetry for classifying pneumonia
improving.
• Revised classification of fever as per National Anti
• 14 days: Anemia
Malaria Program guidelines including use of RDT and
• 30 days: Moderate acute malnutrition
drugs for treating malaria
Advise when to return for the next immunization according to
• Signs for severe acute malnutrition revised
immunization schedule.
• Added early child development in the section on
Salient Adaptations in IMNCI (2017) feeding counseling
In general the adaptations were undertaken to update as Suggested Reading
per global advancements and in line with the various • IMCI: Global Survey report. World Health Organization; 2017
guidelines of India released from time to time. The • Integrated Management of Childhood Illness Chart Booklet.
adaptation took into consideration revised WHO IMCI Geneva: World Health Organization; 2014
charts released in 2014 and antimicrobial therapy • Oxygen therapy for children: a manual for health workers. Geneva:
World Health Organization; 2016
advancements. A major adaptation included incorporation • Pediatric emergency triage, assessment and treatment: care of
of Early Child Development messages along with critically ill children: Updated guideline. Integrated Management
nutritional counseling. of Child Illness. World Health Organization; 2016
IDENTIFY TREATMENT
SIGNS CLASSIFY AS (Urgent pre-<eferral treatments are in bold print.)
CHECK FOR POSSIBLE BACTERIAL
::::,
INFECTION/ JAUNDICE • Not able to feed or ;.. Give first dose of ampicillin !oral amoxycillin and
Classify • Convulsions or intramuscular gentamicin. cc
ALL • Fast breathing (60 breaths per minute or POSSIBLE
ASK: LOOK, LISTEN, FEEL: more) or
YOUNG SERIOUS ;.. Treat to prevent low blood sugar.
INFANTS • Severe chest indrawing or BACTERIAL Q.
• Is the infant • Count the
having • Axillary temperature 37.5'C or above (or INFECTION ;.. Warm the young infant by skin to skin contact
breaths in one while arranging referral.
feels hot to touch) or s:
diffirulty io mi"""· I»
• Axillary temperature less than 35.5'C (or
feeding?
• Has the
Repeat the court
if elevated.
INFANT
MUST
> feels cold to touch) or ;.. Advise mother how to keep the young infant
warm on the way to the hospital
::::,
I»
BE • Movement only when stimulated or no
ccCl>
infant • Look for severe chest indrawing.
had CALM movement at all. 3
;.. Refer URGENTLY to hospital
convulsions?• Look at the umbilicus. Cl>
::::,
Is it red or draining pus? }
'°"'' ....
• Umbilicus red or draining pus or LOCAL }>Give oral amoxycillin for 5 days.
• Look for skin pustules BACTERIAL ;.. Teach mother to treat local infections at home.
• Skin pustules. a
• Measure axillary temperature INFECTION }>Follow up in 2 days.
(if not possible, feel for fever or low body z
Cl>
temperature). 0
• Look at the young infant's movements ::::,
If infant is sleeping, ask the mother to awake >--
him/her. • Palms and soles yellow or ;.. Treat to prevent low blood sugar. i
- Does the infant move on his/her own? • Any jaundice at age < 24 hours or age SEVERE I»
If the young infant is not moving,gently 14 days or more }> Warm the young infant by skin to skin contact ::::,
stimulate him/her. And if the infant JAUNDICE Q.
while arranging referral.
- Does the infant not move at all? has jaundice 0
• Look for jaundice? ;.. Advise mother how to keep the young infant :::r
Are the palms and soles yellow? warm on the way to the hospital 0:
:::r
0
C> ;.. Refer URGENTLY to hospital
0
Q.
• Palms and soles not yellow JAUNDICE }>Advise mother to give home care for the young 5'
infant. Cl>
0
}>Follow up in 2 days. 0
-..a
-..a
AGE UP TO 2 MONTHS
THEN ASK:
Does the young infant have diarrhoea?*
IF YES LOOK AND FEEL: Two of the following :,.. Give first dose of intramuscular ampicillin (Oral Amoxycillin)and
signs: gentamicin.
• Look at the young infant's general condition: SEVERE
• Movement only when DEHYDRATION "'" infant also has another severe classification:
Infant's movements
- Refer URGENTLY to hospital with mother giving frequent sips o
+ Does the infant move on his/her own? stimulated or no
ORS on the way.
+ Does the infant move only when stimulated but movement at all -Advise mother to continue breastfeeding.
• Sunken eyes
then stops? -Advise mother how to keep the young infant warm on the way
Classify • Skin pinch goes back
+ Does the infant not move at all? to the hospital.
very slowly.
+ Is the infant restless and irritable? DIARRHOEA
:,..11 infant does not have any other severe dassification:
- Give fluid for severe dehydration (Plan C) and then refer to hospital
• Look for sunken eyes.
t> after rehydration
• Pinch the skin of the abdomen. Two of the following ;,. ff infant also has another severe classificatioo or Low Weight:
Does it go back: signs: -Give first dose of intramuscular ampicillin (Oral Amoxycillin)
+ Very slowly (longer than 2 seconds)? SOME and gentamicin
+ Slowly? • Restless, irritable. DEHYDRATION - Refer URGENTLY to hospital with mother giving frequent
• Sunken eyes. sips of ORS on the way.
-Advise mother to continue breastfeeding.
• Skin pinch goes back
-Advise mother how to keep the young infant warm on the way to m
slowly. tll
the hospital.
;,. ff infant does not have low weight or another severe classification-
- Give fluids for some dehydration (Plan B).
-Advise mother when to return immediately.
- Follow up in 2 days '"ti
CD
Q,
• Not enough signs to ;,.Give fluids to treat diarrhea at home (Plan A).
classify as some or NO
severe DEHYDRATION ;,.follow up in 5 days if not improving.
dehydration.
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....a
....a
....a
I
AGE UP TO 2 MONTHS �
AGE VACCINE
m
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"'ti
CD
*Rotavirus to be given wherever included in the immunization schedule. Q,
c;·
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::::,
CHECK FOR GENERAL DANGER SIGNS SIGNS CLASSIFY AS IDENTIFY TREATMENT
• Any general danger sign VERY )> Give diazepam if convulsing now and
ccS'
ASK: LOOK: Urgent SEVERE DISEASE maintain airway
attention i
Q.
• Is the child able to drink or breastfeed?
• Does the child vomit everything?
• See if the child is lethargic or
unconscious.
> )> Quickly complete the assessment
s:
• Has the child had convulsions? • Is the child convulsing now? )> Treat to prevent low blood sugar I»
::::,
I»
)> Refer URGENTLY to hospital. ccCl>
3
Cl>
A child with any general danger sign needs URGENT attention; complete the ::::,
assessment and any pre-referral treatment immediately so referral is not ....
delayed. a
z
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0
::::,
i
I»
::::,
Q.
0
:::r
0:
:::r
0
0
Q.
5'
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0
0
"'-I
u:t
ASSESS AND CLASSIFY THE SICK CHILD �
AGE 2 MONTHS UP TO 5 YEARS
ASSESS CLASSIFY IDENTIFY
ASK THE MOTHER WHAT THE CHILD'S PROBLEMS ARE TREATMENT
USE ALL BOXES THAT MATCH THE
• Determine if this is an initial or follow-up visit for this problem. CHILD'S SYMPTOMS AND PROBLEMS
- if follow-up visit, use the follow-up instructions on TREAT THE CHILD chart. TO CLASSIFY THE ILLNESS.
- if initial visit, assess the child as follows:
I *In settings where inhaled bronchodilator is not available, oral salbutamol may be tried but not recommended for treatment of severe acute whee"E!
I Ensure availability of pulse oximeter, determine oxygen saturation and refer if <90%.
AGE 2 MONTHS UP TO 5 YEARS
Does the child have diarrhoea?
Two of the following signs: l>If child has no other severe classification:
IF YES, ASK: LOOK AND FEEL: for - Give fluid for severe dehydration (Plan C).
DEHYDRATION • Lethargic or unconscious
• Sunken eyes l> If child also has another severe classificatia, :
SEVERE
• Look at the child's general • Not able to drink or Refer URGENTLY to hospital with mother giving frequent
• For how long? DEHYDRATION
drinking poorly sips of ORS on the way. Advise the mother to continue
condition.
Is the child:
[> breastfeeding.
• Is there blood in • Skin pinch goes back
the stool? very slowly. l>lf child is 2 years or older and there is cholera in your area,
- Lethargic or unconscious? give doxycycline for cholera.
- Restless and irritable? ::::,
• Look for sunken eyes. Two of the following signs: l>Give fluid, zinc supplements and food for some dehydration {Plan cc
Classify B).
• Offer the child fluid. Is the child: • Restless, irritable l> If child also has a severe classification:
DIARRHOEA SOME Refer URGENTLY to hospital with mother giving frequent sips Q.
• Sunken eyes
- Not able to drink or drinking DEHYDRATION of ORS on the way. Advise the mother to continue
poorly? • Drinks eagerly, thirsty s:
• Skin pinch goes back breastfeeding. I»
l>Advise mother when to return immediately. ::::,
- Drinking eagerly, thirsty? slowly. I»
l> Follow-up in 5 days if not improving. ccCl>
• Pinch the skin of the abdomen.
Does it go back: Not enough signs to NO l>Give fluid, zinc supplements and food to treat diarrhoea at home 3
- Very slowly (longer seconds)? classify as some or severe DEHYDRATION (Plan A). Cl>
-Slowly? dehydration . l>Advise mother when to return immediately. ::::,
;, Follow-up in 5 days if not improving.
....
and if diarrhoea
a
14 days or more • Dehydration present. SEVERE ;, Treat dehydration before referral unless the child has another
z
Cl>
PERSISTENT severe classification. 0
DIARRHOEA ;, Refer to hospital. ::::,
• No dehydration. PERSISTENT l>Advise the mother on feeding a child who has PERSISTENT i
DIARRHOEA I»
> DIARRHOEA.
;, Give single dose of vitamin A.
l>Give zinc supplements daily for 14 days.
::::,
Q.
;, Follow-up in 5 days. 0
:::r
and if blood 0:
in stool • Blood in the stool. DYSENTERY l> Treat for 5 days with cefixime. :::r
l> Treat dehydration 0
l>Give zinc supplements for 14 day., 0
Q.
;, Follow-up in 2 days.
I> 5'
Cl>
0
0
�
.....
I
AGE 2 MONTHS UP TO 5 YEARS �
• Any general danger sign or )> Give first dose of ampicillin I oral amoxycillin and
• Stiff neck VERY SEVERE intramuscular gentamicin.
Does the child have fever? FEBRILE ,- If PF Predominant area give first dose of IM quinine
(by history or feels hot or temperature 37.5'C* or above) DISEASE !artesunate after making a smear!RDT
)> Treat the child to prevent low blood sugar.
)>Give one dose of paracetamol in clinic for high fever( temp
38.S'C or above).
IFYES: ,-Refer URGENTLY to hospital.
Is it a PF (p.falciparum ) predominant area? Yes/No
• Positive ROT ,-Give antimalarial as per NAMP guidelines
THEN ASK: LOOK AND FEEL: Classify MALARIA ,-Give one dose of paracetamol in clinic for high fever.
FEVER )>Advise extra fluids, continue feeding and advise about danger
• Fever for how long? • Look or feel for stiff neck. signs.
• If more than 7 days, has fever • Look for runny nose. )>Follow-up in 2 days if fever persists.
• Negative ROT/ ROT Not
been present every day? • Look for any bacterial cause of Available and SUSPECTED )>If fever is present every day for more than 7 days, refer for
fever.
> •No other cause of fever. MALARIA assessment.
• Has the child had measles • Negative ROT/ ROT Not )> Give one dose of paracetamol in clinic for high fever(temp.
Available and FEVER 38.S'C or above).
within the last 3 months? Look for signs
of MEASLES • Other cause of fever MALARIA )> Advise mother when to return immediately.
PRESENT .. UNLIKELY )> Follow-up in 2 days if fever persists
+ Generalized rash and )> If fever is present every day for more than 7 days, refer for
+ One of these: cough, runny
nose, or red eyes. • Any general danger sign a- SEVERE ,- Give first dose of Vitamin A.
• Clouding of cornea or COMPLICATED ,- Give first dose of ampicillin I oral amoxycillin and
• Deep or extensive mouth MEASLES intramuscular gentamicin. m
Test POSITIVE /NEGATIVE/NA ulcers. )> If clouding of the cornea or pus draining from the eye, apply
tll
P falciparum/ P vivax tetracycline eye ointment
Classify ;. Refer URGENTLY to hospital
MEASLES
�
• Pus draining from the eye or MEASLES WITH ;. Give first dose of Vitamin A. eI
If the child has measles • Look for mouth ulcers. • Mouth ulcers. EYE OR MOUTH )> If pus draining from the eye, treat eye infection with
now or within the last 3 Are they deep and / "'ti
COMPLICATIONS tetracycline eye ointment CD
months: extensive? Q,
)> If mouth ulcers, treat with gentian violet
• Look for pus draining from the eye .
J;.. Follow-up in 2 days. a
• Look for clouding of the cornea.
• Measles now or within the last 3 MEASLES J;.. Give first dose of Vitamin A.
months.
c;·
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• Pus is seen draining from the CHRONIC EAR J;.. Dry the ear by wicking.
ear and discharge is reported INFECTION )> Topical ciprofloxacin ear drops for 2 weeks
for 14 days or more. )> Follow-up in 5 days.
• No ear pain and NO EAR
No pus seen draining from the INFECTION No additional treatment
ear.
I
;;-Other causes of;;,;;, include co�gh �;-;;;,Id, pneumonia:diarrho;;;:·dysentery and skin infections. I
AGE 2 MONTHS UP TO 5 YEARS
THEN CHECK FOR ACUTE MALNUTRITION
• Oedema of both feet or l>Give first dose of appropriate antibioti:
LOOK AND FEEL: • WFH/L less than -3SD scores l> Treat the child to prevent low blood sugar.
• Look for oedema of both feet. or MUAC less than 115 mm, COMPLICATED
• Determine weight for heighUlength•.--Z score AND any one of the following: SEVERE l>Refer URGENTLY to hospital
• Measure MUAC** mm in a child 6 months or older. + Medical complication ACUTE )> While referral is being organized, warm the child.
If MUAC less than 115 mm, then: present or MALNUTRITION
l>Keep the child warm on the way to hospital.
+ Breastfeeding problem.
• Check for any medical complication present: Classify [�
• Any general danger signs NUTRITIONAL • WFH/L less than-3SD scores
/ UNCO MPLICATED J>Give appropriate antibiotic for 5 da)S
+ Any severe classification STATUS ACUTE ::::,
Or l>Counsel the mother on how to feed the child.
• Pneumonia with chest indrawing
I MALNUTRITION
l>Assess for possible TB infectiort cc
• MUAC less than 115 mm
• If no medical complications present: l>Advise mother when to return immediately
+ Child is less than 6 months, assess breastfeeding. l> Follow-up in 5 days. Q.
Does the child have a breastfeeding • WFH/L between-3 and -2 SD MODERATE l>Assess the child's feeding & development support care and s:
problem? scores ACUTE counsel the mother. I»
::::,
MALNUTRITION l> if feeding problem, follow-up in 5 days. I»
Or l>Assess for possible TB infectiort
cc
Cl>
• MUAC 115 up to 125 mm l>Advise mother when to return immediately 3
Cl>
l> Follow-up in 30 days. ::::,
....
l> If child is less than 2 years old, assess child's feeding &
• WFH/L -2 SD scores or more NO ACUTE
a
MALNUTRITION development support care
z
Cl>
Or 0
l> If feeding problem, follow-up in 5 days. ::::,
• MUAC 125 mm or more
i
I»
::::,
THEN CHECK FOR ANEMIA • Severe palmar pallor SEVERE ANEMIA l>Refer URGENTLY to hospital. Q.
0
:::r
LOOK: • Some palmar pallor l>Give iron folic acid therapy for 60 days.
0:
• Look for palmar pallor. Is it: l> Assess the child's feeding & development support care and :::r
- Severe palmar pallor? Classify ANEMIA counsel the mother. 0
- Some palmar pallor? ANAEMIA - If feeding problem, follow-up in 5 days. 0
Q.
l>Advise mother when to return immediately.
If possible get Hb testing
[> l>Follow-up in 14 days. 5'
Cl>
• No palmar pallor NO ANEMIA l> Give prophylactic iron folic acid if child 6 months or older. 0
0
MAKE SURE CHILD WITH ANY GENERAL DANGER SIGN IS REFERRED after first dose of an appropriate antibiotic and ·wFH/L is Weight-for-Height or Weight-for-Length determined by using the WHO growth
other urgent treatments. standards charts.
Exception: Rehydration of the child according to Plan C may resolve danger signs so that referral is no longer needed •• MUAC is Mid-Upper Arm Circumference measured using MUAC tape in all children
6 months or older.
I
AGE 2 MONTHS UP TO 5 YEARS
THEN CHECK THE CHILD'S IMMUNIZATION *, PROPHYLACTIC VITAMIN A and IRON-FOLIC ACID SUPPLEMENTATION and
DEWORMING STATUS
c;·
tll
* A child who needs to be immunized should be advised to go for immunization the day vaccines are available at AWC/SC/PHC
# Wherever included in the immunization schedule.
• Breastfeed as often as the • Breastfeed as often as the child wants • Breastfeed as often as the child wants • Breastfeed as often as the child wants • Give a variety of family foods to
child wants, day and night • Start by going 2 to 3 tablespoons of food • Give at least half cup serving at a time • Offer food from the family pot your child including animal
at least 8 times in 24 hours Gradually increase to Y, cups (1 cup= of: • Give at least 3/4 cup serving at a time of source foods and vitamin A-rich
250 ml). - Mashed roti/rice/bread/biscuit mixed - Mashed roti/rice/bread mixed in thick dal fruits and vegetables. ::::,
- Mashed roti /rice/bread/biscuit mixed in sweetened undiluted milk OR with added ghee/oil or khichri with added
• Do not give any other foods or -Mashed roti/rice/bread mixed in thick
in sweetened undiluted milk or thick oil/ghee. • Give at least 1 full cup (250ml) cc
fluids not even water dal with added ghee/oil or khichri with
dal with added ghee/oil or Khichri - Add cooked vegetable also in the servings at each meal.
with added oil/ghee. added oil/ghee. OR • Give 3 to 4 meals each day.
Remember -Add cooked vegetables also in the -Add cooked vegetables also In the Q.
- Mashed roti/rice/bread/biscuit mixed in
•Continue breastfeeding if the servings. servings sweetened undiluted milk Or
child is sick OR OR • Give 1 or 2 nutritious food 3:
- Sevian/daliah/halwa/kheer prepared in I»
- Servian/dalia/halwa/kheer prepared in - Sevian/dalia/halwa/kheer prepared in
milk OR between meals, such as; ::::,
mild OR milk OR banana/biscuit/cheeko/ I»
- Any ceral porridge cooked in milk OR
-Any cereal porridge cooked in milk, -Any cereal porridge cooked in milk OR mango/papaya as snacks
ccCl>
OR Mashed boild/fried potatoes - Mashed boiled/fried potatoes
Offer banana/biscuit/cheeko/mango/ 3
-Mashed boiled/fried potatoes. Remember Cl>
• Give 3 to 4 meals each day. Offer 1 papaya ::::,
Give 2 to 3 meals each day. Offer • Ensure that the child
or 2 snacks between meals. The ....
1 or 2 Snacks each day between • Give 3 to 4 meals each day. Offer 1 to 2
child will eat if hungry. finishes the serving
meals when the child seems hungry. snacks between meals. Continue to feed a
• For snacks, give small chewable items • Teach your child was
your child slowly patiently. his hands with soap
z
Remember that the child can hold. Let your child Cl>
• Encourage your child to eat.
try to eat the snack but provide help and water every time 0
• Keep the child in your lap and feed ::::,
if needed. before feeding
with your own hands.
• Wash your own hand child's hand Remember
Remember i
with soap and water every time • Sit by the side of child and help him to • Play: Make simple toys for your I»
• Play have large colourful before feeding. • Keep the child in your lap and feed finish the serving child. ::::,
things for your child to reach with your own hands. • Wash your own hand child's hand with Q.
• Wash your own hand child's hand • Communicate: Help your child
for and new things to see • Play: Actively play with your child. soap and water every time before count, name and compare 0
with soap and water every time before feeding. :::r
Give your child clean, safe household things.
feeding.
things to handle, bang and drop. 0:
•Communicate: Respond to your child's
:::r
• Communicate: Talk to and • Play: Give your child things to stack up, 0
respond to your child. Get a sounds and interests. Tell the child the • Play: Actively play with your child. 0
Give your child clean, safe household and to put into containers and take out. Q.
conversation going with names of things and people.
sounds or gestures things to handle, bang and drop. • Communicate: Ask your child simple
(copy your child) • Communicate: Respond to your child's questions. Respond to your child's 5'
attempts to talk. Play games like Cl>
sounds and interests. Tell the child the 0
names of things and people. "bye-bye" and" peek a boo". 0
* A good daily diet should be adequate ion quantity and include an energy-rich food (for example, thick cereal porridge with added oil); Meat, fish, eggs or pulses; and fruits and vegetables
I
Chapter
32
Rights of Children
Rajeev Seth
The Constitution of India guarantees equality before the Table 32.1: Articles of the UN Child Rights Convention
law to all citizens, and has pledged special protection for that apply to child health
children. In 1992, India accepted the obligations of the UN Article Purpose
Convention on the Rights of the Child and the Government
Article 2 Protection from discrimination
has taken steps towards advancing child rights. These include
formation of the National Commission for Protection of Article 3 Best interests of the child a primary considera
Child Rights (2005), National Policy for Children (2013), tion: institutions, services and facilities responsible
for the care or protection of children shall conform
Right to Education (2009), Protection of Children from
to the standards established by competent
Sexual Offences (2012) and amendment to Juvenile Justice
authorities
Act (2015) to protect, promote and defend child rights.
Article 5 Parents responsible for ensuring that child rights
United Nations Convention of Child Rights and are protected
Child Health Care Article 6 Right to survival and development
The UN Convention has implications at policy and Article 9 Right of the child who is separated from one or
decision-making level and for practice or health care both parents to maintain personal relations and
provision. It has positively influenced child rights direct contact with both parents on a regular
pertaining to health and well-being. Physicians should basis
have adequate knowledge of rights of every child in the Article 12 Right of a child to express their views, considering
area of child survival, identity, development, protection the maturity of the child
and participation. Pediatricians should understand the Article 14 Freedom of expression inc luding seeking,
social determinants of child health and align themselves receiving and imparting information
with child right organizations in advocacy efforts and Article 16 Protection of privacy
lobby their local, state and national elected representatives
Article 17 Access to information from mass media, with
to advance child rights (Table 32.1). protection material injurious to child well being
The 2030 Agenda for Sustainable Development Article 18 Assistance to parents with c hild rearing
Goals (SDG) responsibilities
Article 19 Protection from physical and mental violence,
The UN General Assembly adopted the 2030 Agenda for
abuse or neglect
SDG in September 2015. The SDG are for universal,
integrated and transformative vision for a better world. Article 20 Special protection to children deprived of their
They comprise 17 goals and 169 targets to wipe out families
poverty, fight inequality and tackle climate change over Article 22 Protection of children seeking refugee status
the next 15 years. The SDG aims to build on work of the Article 23 Rights of disabled children to special care
millennium development goals (MDG) which, in Article 24 Right to health and access to health care
September 2000, rallied the world on a 15-year agenda to
tackle the indignity of poverty. Article 27 Right to an adequate standard of living
Article 28 Right to education
India's Approach to Promotion and Article 30 Right to own culture and religion
Protection of Child Rights
Article 31 Participation in leisure and play
The Government of India upgraded an independent
Article 34 Protection from sexual exploitation
Ministry of Women and Child Development (2006) in
786
Rights of Children 1787-
order to provide focus to the issues of women and (2005), Child Labor (Prohibition & Regulation) Act (1986;
children. The National Commission for Protection of Child notifications in 2006 & 2008 expanded the list of banned
Rights was constituted in 2007, which also provides for and hazardous processes and occupations) and
setting up state level commissions, meant for protection Information and Technology (Amendment) Act (2008).
and promotion of child rights in the country. Besides the
Protection of Children from Sexual Offences Act (POCSO)
institutional, administrative and legislative framework, 2012: India has recently adopted the Protection of
India has a strong presence of non-governmental Children from Sexual Offences Act (2012). This is the first
organizations (NGO), a network of community-based comprehensive law on sexual abuse in India which
people groups, which, along with media, act as watchdogs expands the scope and range of forms of sexual offences,
to protect human and child rights. The Government of makes reporting of abuse mandatory and defines
India released a third and fourth combined periodic report guidelines for child-friendly police and procedures.
(2011), which analysis the overall implementations of the Together with the Juvenile Justice Act (2000), this act has
UN Convention on Child Rights and challenges that created an opportunity to ensure greater protection to
impede the realization of these rights. children who have suffered abuse. Doctors are obliged to
promptly and adequately respond to child victims.
General Measures of Implementation POCSO provides safeguards to the best interest and well
To implement the commitment to child rights, several being of the child at every stage of the judicial process, in
policies, laws and programs have been introduced: collection of evidence, investigation and trial of the
offender. It provides protection of children from sexual
National Plan of Action for Children (2016): The charter offences (penetrative, non-penetrative), sexual harassment
commits to rights of all children by creating an enabling and pornography. The Act defines sexual assault to be
environment for their survival, growth, development and aggravated when the abuse is committed by police, army
protection. personnel, doctor, management or staff of a hospital/
National Charterfor Children (2003): This emphasizes the educational institution or if the abused child is mentally
Government commitment to child rights, while ill or disabled. Since the act defines child as anyone below
enumerating children's duties towards their families, 18 years of age, adolescents are also included.
society and the nation.
Juvenile Justice (Care and Protection of Children) Act
National Policy for Persons with Disabilities (2006): The (2015): This Act replaces the existing Indian juvenile
policy recognizes that majority of persons with disabilities delinquency law and Juvenile Justice Act, so that juveniles
can lead a better quality of life if they have access to equal in conflict with the law in the age group of 16-18 years,
opportunities and effective rehabilitation. involved in heinous offences, can be tried as adults. The
Policy Framework for Children and AIDS in India (2007): Act came into force from 15 January 2016.
This policy seeks to address needs of children affected by National Programs
HIV/ AIDS by integrated services within existing
development and poverty reduction programs. The Government of India is implementing several programs
on social inclusion, gender sensitivity, child rights,
National Rehabilitation and Resettlement Policy (2007): participation and protection. These programs include:
Under this policy, no project involving displacement of Integrated Child Development Services (ICDS), Kishori
families can be undertaken without detailed social impact Shakti Yojana and Nutrition Programme for Adolescent
assessment on lives of children. Girls, Rajiv Gandhi Creche Scheme for children of working
National Urban Housing and Habitat Policy (2007): The mother, scheme of assistance to home for children (Sishu
policy seeks to promote sustainable development of Greh) to promote in-country adoption, Dhanalakshmi or
habitat and services at affordable prices and provide conditional cash transfer schemes for girl child, Program
shelter to children from disadvantaged families. for Juvenile Justice, Child Line (24 hours toll free number
1098 with outreach services for children in need of care and
National Policy for Children (2013): The Government protection), Integrated Child Protection Scheme (ICPS),
adopted this policy to reiterate its commitment to rights Integrated Program for Street Children, Ujjawala (scheme
based approach to children. for prevention of trafficking and rescue, rehabilitation,
reintegration and repatriation), Sarva Shiksha Abhiyan that
National Legislations
addresses educational needs of 6-14-year-old and bridges
The legislative framework for children's rights is being social, gender and regional gaps with active participation
strengthened with the formulations of new laws and of community, National Program for education of girls at
amendments in old laws. These include the Food Security elementary level or Kasturba Gandhi Balika Vidyalaya,
Bill (2011), Right to Free and Compulsory Education Act National Rural Health Mission (NRHM), Mid Day Meal
(2009), Prohibition of Child Marriage Act (2006), scheme, Jawaharlal Nehru National Urban Renewal
Commissions for Protection of Child Rights Act (2005), Mission, Universal Immunization Program and Integrated
Right to Information (RTI) Act (2005), Goa Children Act Management of Neonatal and Childhood Illness (IMNCI).
188 I Essential Pediatrics
Role of Pediatricians in Realizing Child Rights or behavioral problems. To be able to detect child sexual
The status and condition of children is the clearest abuse requires a high index of suspicion and familiarity
indicator of whether nations and societies understand and with the verbal, behavioral and physical indicators of
respect human rights. Survival, early childhood care abuse. Many children will disclose abuse to caregivers or
including health care, nutrition, education, growth and others spontaneously, though there may also be indirect
development, are crucial child rights and must be physical or behavioral signs. Emotional and psychological
prioritized. Prevention of child abuse, neglect, protection abuse has received less attention globally due to cultural
and exploitation (street children, child labor, trafficking) variations in different countries. Moreover, corporal
are intimately linked to poor socioeconomic conditions punishment of children, i.e. slapping, punching, kicking
and cultural attitudes. Parents who are illiterate and often or beating is a significant phenomenon in schools and
ignorant of rights of children, must be made aware to other institutions. Child neglect can manifest as failure to
demand these rights. Pediatricians should join hands with thrive, failure to seek basic health care, immunizations,
professionals, government, elected representatives, policy deprivation of education and basic nutrition needs.
makers and administrators to ensure implementation of
Strategies to Reduce Child Abuse and Neglect
programs.
Child abuse and neglect should be placed on the national
CHILD ABUSE AND NEGLECT agenda, both as a social and a public health problem. The
problems of socially marginalized and economically
The WHO defines 'child abuse or maltreatment as forms backward groups are immense, particularly amongst
of physical and/ or emotional ill-treatment, sexual abuse, children in urban slums, street and working children and
neglect or negligent treatment or commercial or other children of construction workers. Child labor cannot be
exploitation, resulting in actual or potential harm to the abolished in the presence of abject poverty. However, the
child's health, survival, development or dignity. The term Government should make sure that working child is not
child abuse has different connotations in different cultural exploited. The child must get time for education and must
and socioeconomic situations. In the Indian context, it is receive health care. The employer must provide care for
important to include children who are deprived of children. The belief behind the legislation is that protection
education, early development, basic health care or of the children against all forms of abuse and exploitation
nutrition. Child labor and trafficking are the worst kind is a basic child right. Laws should be enforced.
of child abuse. Child Protection services should also reach the rural
Major types of child abuse include: (i) Physical abuse: areas. Panchayat officials should be given responsibility
Acts of commission by a caregiver that cause actual to ensure that basic education, nutrition, health care and
physical harm or have the potential for harm; (ii) Sexual sanitation is available for proper development of every
abuse: Acts where a caregiver uses a child for sexual child in their village. The panchayat should be duty bound
gratification; (iii) Emotional abuse: Failure of a caregiver to to ensure that every child is in school and protected from
provide an appropriate and supportive environment, and agrarian and allied rural occupations as a part of family
includes acts that have an adverse effect on the emotional or individual child labor.
health and development; and (iv) Neglect: Failure of a Pediatricians can do a great deal in recognizing,
parent or guardian to provide for the development of the responding to and reporting child abuse. They are often
child, in one or more of the following: Health, education, the first point of contact of a child with abuse and best
emotional development, nutrition, shelter and safe living advocates for protection of their rights. They should be
conditions. Neglect is distinguished from circumstances sensitized on how to use Protection of Children from
of poverty in that neglect can occur only in cases where Sexual Offences Act. Pediatricians should seek assistance
reasonable resources are available to the caregiver. from special juvenile police units, child welfare
committees, toll-free phone service for children in distress
Features of Child Abuse and Neglect (child line 1098), national and state commissions for
Injuries inflicted by a caregiver on a child can take many protection of child rights and NGOs and direct families
forms. Death in abused children is most often the to these services. The Indian Academy of Pediatrics and
consequence of a head injury or injury to the internal the Indian Child Abuse Neglect and Child Labor group
organs. Patterns of injury to the skin and skeletal have brought out guidelines for pediatricians to respond
manifestations of abuse include multiple fractures at to child abuse and neglect.
different stages of healing. There is evidence that about Suggested Reading
one-third of severely shaken infants die and that the
majority of the survivors suffer long-term consequences • Convention on the R i g hts of the Child, ava ilable from
www.unicef.org/ ere.
such as mental retardation, cerebral palsy or blindness. • Seth R. Child abuse and neglect in India. Indian J Pediatr 2015;
Children who have been sexually abused exhibit 82:707-14.
symptoms of infection, genital injury, abdominal pain, • Srivastava RN. Child abuse and neglect: Asia Pacific Conference
constipation, chronic or recurrent urinary tract infections and the Delhi Declaration. Indian Pediatr 2011; 49:11-12.
Rights of Children 1789-
• Sustainable Developmental Goals(SDG); www.un.org/ of the adoption agency, duly witnessed by any authority
sustainabledevelopment/sustainable-development-goals. of the hospital and a relative. A waiting period of two
• The Protection of Children from Sexual Offences Act, 2012;
months is given to the biological parents to reconsider the
wcd.nic.in/child act/childprotection31072012.pdf.
decision, following which the child is free for adoption.
ADOPTION Prospective Adoptive Parents
Adoption is an important alternative for the rehabilitation A child can be adopted by a married couple having
of children who are destitute and abandoned or, for social infertility or voluntarily opting for adoption. Even single
reasons, cannot be brought up by their parents. Medical persons are eligible to adopt. Couples who have taken a
practitioners and pediatricians play a vital role in decision to adopt should go to a registered agency, that is
influencing health and social decisions of their adoptive licensed to process adoption by both state government
patients and should work closely with counselors and and the Central Adoption Resource Authority, Ministry
allied health professionals. 'Right to a family' is proposed of Women and Child Development, Government of India.
as a fundamental right by the United Nations. Adoption Applications for inter-country adoption, of a child born
agencies need to ensure that these rights are protected. in India, require to be forwarded by an accredited agency
of the country of the adoptive parents, to a recognized
Legal Aspects placement agency in India and the Central Adoption
In India, only specialized adoption agencies recognized Resource Authority.
by the State Government can deal with adoption Social workers from the adoption agency provide
placement. Direct adoption placement by hospitals, guidelines and support to pre-adoptive parents, and help
maternity and nursing homes is not permitted. Central make informed decisions (pre-adoption counseling). A
Adoption Resource Authority is an autonomous body home study is conducted by the professional social
under the Ministry of Women and Child Development, worker. Additionally, parents are required to submit a
Government of India. It functions as a nodal body for document regarding their health and financial status. Once
adoption of Indian children and is mandated to monitor their application is approved, a suitable child is shown to
and regulate in-country and inter-country adoption. them. After they accept the child, placement is legalized.
The placement is followed for 3 years or until legal
Prospective parents should be advised to read the
adoption is complete. The adoptive parents are assured
guidelines from its website and follow the due procedures.
confidentiality and provided support as needed.
The Government has notified guidelines, in pursuance of
the Juvenile Justice Act (2000), that enables citizens of all Role of a Pediatrician
religions the freedom to adopt a minor child, irrespective
of whether he/she is a single parent and/or such adoptive Pediatricians are often asked for advice prior to adoption;
parent/s adopt a child of the same sex, irrespective of their role consists of the following:
• Counsel and teach adoptive parents about the process
whether he/she is a single parent and/or such adoptive
of adoption
parent/s adopt a child of the same sex, irrespective of the • Teach parents who wish to relinquish their child due
number of living biological sonse or daughters. Prior to to any reason, the correct procedure and to not leave
2000, adoption was allowed to Hindus under the Hindu children in public places or in unhealthy surroundings
Adoption and Maintenance Act; other religious groups as this is unsafe and traumatizing
were governed by the Guardianship and Wards Act. • Discourage private adoptions, since these are illegal
• Examine carefully babies brought from placement
Adoption Procedures agencies, and explain a realistic diagnosis and prognosis
A child, who has been relinquished by his/her biological to the adoptive parents
parents or found abandoned, must first be presented to • Repeat all essential tests that have a window period
the Child Welfare Committee. This committee has the sole (HIV, hepatitis B) after 3-6 months, before placement
authority to declare the child free for adoption under the • Provide a supportive attitude to encourage adoptive
current law. In case of an abandoned child, the committee, parents to overcome their fears.
after due investigations, declares the child as destitute and
free for adoption. In case the biological parents want to Suggested Reading
relinquish a child, they have to execute a document in favor • Central Adoption Resource Agency; http://www.cara.nic.in.
Index
Abdominal pain 281 Adenosine 456 Antiviral agents 754
causes of 282 Adolescence: package of interventions 66 Aortic regurgitation 437
Abdominal paracentesis 741 Adolescent health visit 60, 65 Aortic stenosis 425
Abdominal tuberculosis 302 adolescent-friendly health services 66 Apgar score 127
Abetalipoproteinemia 568 Adolescents 62 Aplastic anemia
Abnormalities in red cell glycolysis adolescent pregnancy 64 clinical features 343
autoimmune hemolytic anemia 338 environmental and social challenges 64 congenital syndromes 344
glucose-6-phosphate dehydrogenase genital infections 63 differential diagnosis 343
deficiency 338 health problems 62 etiopathogenesis 343
pyruvate kinase deficiency 338 infections 62 evaluation 345
Acetaminophen legal age definitions 64 laboratory studies 344
clinical stages 715 lifestyle diseases 63 treatment 345
laboratory manifestations 715 problems specific to females 62 Apnea 167
N-acetyl cysteine 715 sexually transmitted infections 63 Approach to a bleeding child
toxicity 715 sleep disturbances 62 coagulation disorders 347
treatment 715 substance abuse 63 platelet and coagulation disorders 348
Acne vulgaris vulnerability 63 disorders of platelet function 347
clinical features 683 Adoption 789 laboratory investigations 349
pathogenesis 683 Adrenoleukodystrophy 658 thrombocytopenia 347
therapy 683 Advanced life support 725 work-up in child with bleeding 349
Acrodermatitis enteropathica 701 Adverse events following vaccination 201 Approach to chronic cough 390
Acute appendicitis 282 Agents for myasthenia 748 Arrhythmias
Acute diarrhea 287 Allergic fungal rhinosinusitis 364 bradyarrhythmia 726
assessment for dehydration 288, 289 Alopecia areata 683 Arterial catheterization 739
clinical findings 287 treatment of 684 Arthritis 620
etiology 287 Amebiasis DMARDS 623
guidelines for treating 290 clinical features 261 IgA vasculitis (Henoch-Schonlein purpura) 628
home available fluids 290 diagnosis 262 iridocyclitis 623
laboratory investigations 288 treatment 262 juvenile dermatomyositis 625
management 289 Amebic meningoencephalitis 263 juvenile idiopathic 621
WHO ORS 289 granulomatous amebic encephalitis 264 Kawasaki disease 627
Acute flaccid paralysis 586 primary 263 Legg-Calve-Perthes disease 621
National Polio Surveillance Project 587 Analgesics 746 mixed connective tissue disease 626
non-polio 587 Anemia 329 polyarteritis nodosa 628
surveillance 586 approach to macrocytic 332 reactive 620
Acute kidney injury 482 approach to microcytic 331 scleroderma 626
acute renal failure in newborn 487 approach to normocytic 332 septic 620
approach to evaluation 482 clinical features 330 SLICC criteria 624
continuous renal replacement therapies 487 diagnosis 330 systemic JIA 622
definition and classification 482 hematopoiesis 329 systemic lupus erythematosus 624
dialysis 485
investigation 330 Takayasu arteritis 626
hemodialysis 486
reticulocyte count 331 transient synovitis 620
incidence and etiology 482
Anion gap 82 treatment 623
management 483
pathophysiology 482 Antenatal hydronephrosis 501 tubercular 620
peritoneal dialysis 485 Anthelminthics 753 Ascites
Acute otitis media Antiarrhythmics 747 causes 315
diagnosis 357 Anti-asthma agents 758 evaluation 315
etiology 357 Antibiotics 748 treatment 316
treatment 357 Anticancer drugs 754 Asphyxia 126
Acute pancreatitis 285 Anticoagulants 754 Aspirated foreign body
Acute pericarditis 445 Anticonvulsants 754 back blows 736
Acute respiratory distress syndrome 393 Antidepressants 762 Heimlich maneuver 736
Acute respiratory tract infection control Antidotes 754 Assessment of physical growth
program 380 Antiemetics 754 dentition 11
Acute viral hepatitis Antiepileptics 762 head circumference 12
clinical features 310 Antifungal agents 749 length 12
complications 310 Antihistaminics 756 mid-upper arm circumference 13
investigations 310 Antihyp ertensives 756 standing height 12
management 310 Antimalarials 753 weight 11
prevention 311 Antimicrobials 748 Assessment of seriously ill child
Acyanotic congenital heart defects Antiprotozoal 753 ABCDE approach 721
atrial septa! defect 409 Antipyretics 746 common danger signs 722
ventricular septa! defect 411 Antitoxins 757 monitoring 722
791
-792 Essential Pediatrics
Conduct disorder 58 Defects of energy metabolism 644 growth hormone deficiency 505
Congenital abnormalities of kidney and Dehydration 71 management 507
urinary tract Delayed clamping of umbilical cord 134 Disorders of renal tubular transport 492
multicystic dysplastic kidney 500 Delayed puberty 532 Bartter syndrome 496
posterior urethral valves 501 in boys 534 Fanconi syndrome 494
Congenital disorders 172,557 in girls 533 Gitelman syndrome 496
agenesis of corpus callosum 557 Turner syndrome 535 nephrogenic diabetes insipidus 496
ankyloglossia (tongue tie) 366 Dengue 219 pseudohypoparathyroidism 517
anorectal malformation 173 clinical manifestations 220 renal glucosuria 496
Arnold-Chiari malformation 557 confirmation of diagnosis 221 renal tubular acidosis 493,495
cleft lip and cleft palate 174,366 differential diagnosis 220 Disorders of sex development 536
macroglossia 366 epidemiology 219 cryptorchidism (undescended testes) 539
micrognathia 366 management 221 evaluation 538
Congenital heart disease 398 pathophysiology 220 management 539
complications of 407 prevention 223 Disorders of the gonadal hormones
cyanotic spells 408 prognosis 223 precocious puberty 529
duct-dependent lesions 402 severe 221 precocious puberty in girls 529,531
epidemiology and etiology 398 tourniquet test 221 puberty 529
fetal circulation 399 Dermatophytoses Disorders of thyroid gland 510
hemodynamic classification of 400 tinea capitis 698 assessment of thyroid function 511
Nadas criteria 403 tinea corporis 699 endemic goiter 514
natural history 408 Development,factors affecting 38 goiter 513
physiology of 398 intrauterine growth restriction 39 hyperthyroidism 515
pretricuspid versus post-tricuspid shunts 401 neonatal 39 hypothyroidism 511,513
prevention of 409 perinatal asphyxia 39 iodine deficiency disorders 514
second heart sound 404 postneonatal 39 National Goiter Control Programme 515
single ventricle physiology 402 prenatal 38 physiology 510
transitional circulation 400 psychosocial 39 Disseminated intravascular coagulopathy 351
Developmental assessment 49 blood component therapy 353
unfavorable streaming and parallel
developmental quotient 50 causes 352
circulation 403
developmental surveillance 51,52 DIC score 353
VSD-PS physiology (Fallot physiology) 402
screening tests 51 disorders which cause 352
Congenital infections
Diabetes mellitus 540 laboratory features 352
CMV 264 classification 541
perinatal HSV 265 pathophysiology 352
complications of DKA 548 Diuretics 759
rubella 264 diabetic ketoacidosis 546
syphilis 265 Drooling 370
diagnostic criteria 540 Drowning,near 707
toxoplasmosis 264 hyp erosmolar non-ketotic state 549
Congestive cardiac failure 394 Drug eruptions
hypoglycemia 546 erythroderma 690
Constipation 278 insulin 542,544
causes of 279 fixed drug eruption 690
insulin regimen 543 photosensitive eruption 690
disimpaction 279 management 547
functional 279 Stevens-Johnson syndrome 690
monitoring 544 Dysentery 292
Hirschsprung disease 280 sick day care 544
management 279,281 Dysphagia 277
type 1 diabetes mellitus 542 achalasia cardia 278
rectal biopsy 281 type 2 diabetes mellitus 550 esophageal 277
Copper 122 Diaper dermatitis 682 foreign bodies in esophagus 277
deficiency 123 Diaphragmatic hernia 174 oropharyngeal or transfer 277
Corrosive ingestion Diphtheria
classification 713 clinical features 236 Eating disorders 57
clinical manifestations 713 diagnosis 237 Ebola virus 233
management 714 etiopathogenesis 236 Ebstein anomaly 420
stricture formation 714 management 237 Ectodermal dysplasias 675
Cow milk protein allergy 298 Diphtheria,pertussis and tetanus vaccine 189 Effect of maternal conditions on fetus and
Craniosynostosis acellular pertussis vaccine 191 neonates
Apert syndrome 37 Disorders of adrenal glands 518 diabetes mellitus 176
cloverleaf skull deformity 37 adrenal insufficiency 522 hepatitis B infection 177
Crouzon syndrome 37 adrenocortical hyperfunction 519 hypothyroidism 177
plagiocephaly 37 congenital adrenal hyperplasia 522 tuberculosis 177
Croup syndrome hyperaldosteronism 521 Eisenmenger syndrome 425
spasmodic 376 pheochromocytoma 521 Emerging viruses 233
Cutaneous tuberculosis physiology 518 Chandipura virus 234
lupus vulgaris 693 21-hydroxylase deficiency 522 Crimean-Congo hemorrhagic fever virus 233
scrofuloderma 693 Disorders of calcium metabolism 516 hantaviruses 233
tuberculids 693 hypercalcemia 518 nipah virus 234
tuberculosis verrucosa cutis 693 hypocalcemia 516 Encephalitis
Cystic fibrosis management 517 acute 559
genetics 392 pseudohyp oparathyroidism 517 autoimmune 563
Cystic kidney diseases 502 Disorders of complex molecules 644 herpes simplex 561
glomerulocystic kidney disease 503 Disorders of pituitary gland 505 Japanese 560
polycystic kidneys 502 approach to short stature and GHD 506 viral 559
Cystinosis 495 diabetes insipidus 508 Encephalopathies 564
-794 Essential Pediatrics
Idiopathic thrombocytopenic purpura 349 neonatal hypothyroidism 124 Level of newborn care
evaluation 350 recommended daily intake 123 newborn care corner 133
management 350 Iron deficiency anemia 124,333 newborn stabilization units 133
Immunity diagnosis 333 special newborn care units 133
adaptive immune system 178 evaluation 333 Levene classification for hypoxic-ischemic
innate immune system 178 non-response to hematinic therapy 333 encephalopathy 163
Immunization treatment 333 Lichen nitidus 686
active immunity 182 Lichen planus 686
passive immunity 182 Japanese B encephalitis vaccine 195,196
Lichen striatus 686
principles 183,185 Jaundice 168,309
Liver abscess
protective efficacy of vaccine 182 approach to a neonate 169
clinical features 307
Immunization programs 184,185 breast milk 168
diagnosis 308
Immunodeficiency 299 breastfeeding 168
management 308
acquired immunodeficiency causes 169,309
Liver biopsy 744
syndrome 224,300 clinical estimation,Kramer 168
Liver failure
primary 178 Crigler-Najjar syndrome 309
acute 311
ataxia-telangiectasia 179 Dubin-Johnson syndrome 309
causes 311
cellular immunodeficiency exchange transfusion 172
clinical features 311
clues to the diagnosis 180 Gilbert syndrome 309
management 312
common variable immunodeficiency 180 management 169
stages of hepatic encephalopathy 312
DiGeorge anomaly 179 pathological 170
treatment of 313
hyper-IgM syndrome 180 phototherapy 171
Liver transplantation 328
hypogammaglobulinemia of infancy 180 physiological 168,169
Liver tumors
IgA deficiency 180 prolonged 170
hepatoblastoma 308,612
IgG subclass deficiency 180 Joubert syndrome 568
hepatocellular carcinoma 308
severe combined immunodeficiency 179 Juvenile delinquency 58
infantile hemangioendothelioma 308
Wiskott-Aldrich syndrome 179 Kangaroo mother care Lowe syndrome 495
X-linked (Bruton) agammaglo- criteria for eligibility 151 Lumbar puncture 740
bulinemia 180 initiation of 151 Lymphoma 602
Inborn errors of metabolism 647 procedure 153 Hodgkin 602
defects of carbohydrate metabolism 649 Keratomalacia 662 non-Hodgkin 604
fatty acid oxidation defects 652 Kussmaul sign 446 Lysosomal storage disorders
galactosemia 649 mucopolysaccharidoses 655
glycogen storage diseases 651 Language 48 peroxisomal disorders 658
hereditary fructose intolerance 650 key milestones 49 sphingolipidoses 655
laboratory investigations 649 Laryngotracheobronchitis 368,376
management 649 Laryngomalacia 369 Macrocephaly 35
mitochondrial disorders 653 Late effects of childhood cancer 618 causes of 36
Incontinentia pigmenti 677 Laws of growth 9 Magnesium 80,121
Infantile seborrheic dermatitis 682 Leishmaniasis 259 hypermagnesemia 80
Infectious mononucleosis 211 clinical features 260 hypomagnesemia 80
clinical features 212 diagnosis 260 physiology 80
diagnosis 212 prevention and control 261 Malaria 254
Infective endocarditis 439 treatment 260,261 clinical features 256
prophylaxis 442 Lentigines 689 control and prevention of 259
Inflammatory bowel disease 300 Leprosy diagnosis 256
clinical features 301 complications 694 epidemiology 254
diagnosis 301 investigations 694 life cycle of the parasite 255
treatment 301 lepra reactions 694 National Vector-Borne Disease Control
Influenza lepromatous 694 Programme 259
clinical features 231 treatment 695 severe 256
diagnosis 232 tuberculoid 694 treatment failures, recrudescence and
epidemiology 231 Leptospirosis 240 relapse 259
treatment 232 clinical features 241 complicated malaria 258
Influenza vaccine 197,198 diagnosis 241 uncomplicated malaria 257
Injury control 719 treatment 241 falciparum malaria 257
do's and dont's of injury prevention 720 Leukemias 593 mixed malaria 258
Insulin pump 544 acute lymphoblastic 594 vivax malaria 257
Integrated Child Development Services 107 acute myeloid 594 Malnutrition 97
Integrated management of neonatal and Down syndrome 600 catch-up growth 101,105
childhood illness 766,774 late effects of treatment 600 dehydration 100,102
classification tables 767 management 598 electrolyte imbalance 103
effective communication and counseling 769 prognosis 599 hypoglycemia 100
principles of integrated care 766 Leukocytosis hypothermia 100,102
Interstitial nephritis 478 basophilia 355 infection 100,103
Intestinal lymphangiectasia 299 eosinophilia 355 micronutrient deficiencies 104
Intestinal nematodes 265 lymphocytosis 355 nutrition rehabilitation centres 99
Intrauterine growth restriction 8 monocytosis 355 post-discharge care at home 106
Intussusception 283 neutrophils 355 prevention 107,292
Iodine Leukopenia 355 refeeding 104
deficiency 123 causes of neutropenia 356 severe acute malnutrition 97,98,106
goiter 124 qualitative defects 356 Malrotation 283
-796 Essential Pediatrics