Article newborn

Transient Tachypnea of the

Newborn
Lokesh Guglani, MD,* Introduction
Satyan Lakshminrusimha, The birth of a child is preceded by several changes to prepare for the transition from
MD,* Rita M. Ryan, MD* intrauterine to extrauterine life. The five major events that establish the lungs as the organ
of gas exchange at birth include: clearance of fetal lung fluid, establishment of spontaneous
breathing, decrease in pulmonary vascular resistance, release of surfactant, and cessation of
Author Disclosure the right-to-left shunting of venous blood returning to the heart. (1) During fetal life, fluid
is secreted into the alveoli to maintain normal growth and function, (2) and fetal lung
Drs Guglani,
volume approximates the functional residual capacity that would be established once air
Lakshminrusimha, and
breathing is initiated. (3) Clearance of lung fluid can be affected by several factors, and its
Ryan have disclosed impairment culminates in tachypnea and could necessitate transfer to an intensive care unit
no financial for monitoring and respiratory support.
relationships relevant Transient tachypnea of the newborn (TTN), which is believed to result from incom-
to this article. This plete resorption of fluid from the lungs of the newborn, presents an important diagnostic
and therapeutic dilemma in the newborn nursery. This review focuses on TTN, with
commentary does not
emphasis on fetal lung fluid mechanics and possible mechanisms of fetal lung fluid
contain a discussion
resorption as well as its pathophysiology, clinical and diagnostic features, and manage-
of an unapproved/ ment. Some neonatologists refer to TTN as retained fetal lung liquid syndrome.
investigative
product/device. Physiology of Fetal Lung Fluid
The lungs are filled with liquid in utero, which increases from 4 to 6 mL/kg body weight
at mid-gestation to about 30 to 50 mL/kg near term in fetal lambs. (4) Jost and Policard
(5) first demonstrated that fluid within the fetal lung arises from the lung and contributes
to the volume of amniotic fluid. The rate of production ranges from 2 mL/kg per hour
in the initial part of pregnancy to 5 mL/kg per hour at term, thereby contributing one
third to one half of the daily turnover of amniotic fluid. The fluid gradually moves up the
trachea and either is swallowed or goes into the amniotic fluid reservoir around the baby.
The volume of fetal lung fluid is regulated by the larynx, which acts as a one-way valve,
allowing only outflow of the lung fluid under normal circumstances (6) and creating a
pressure gradient of approximately 1 cm of water between the airway lumen and amniotic
cavity to keep the lungs distended. Such distention is essential for lung growth, and a
decrease in fetal lung fluid (as reflected by oligohydramnios) can result in pulmonary
hypoplasia. (7)
The pulmonary epithelium in the fetal lung (Fig. 1, left panel) secretes chloride into the
alveolus. Chloride enters the lung epithelial cell across the basolateral membrane via a
Na/K/2 Cl cotransporter, the target transporter for furosemide. The chloride ions are
secreted into the alveolus by various chloride channels. The potassium ion extrudes
through basolateral potassium channels. Sodium follows chloride through paracellular
pathways, with water flowing between or through cells via aquaporins, thus helping to
maintain adequate lung fluid. (8)
Although fetal sheep lung fluid remains fairly constant at 90% to 95% of total lung
weight through much of the third trimester, the fluid begins to decrease a few days before
spontaneous vaginal delivery from approximately 25 to 18 mL/kg. (9) With the onset of
labor, the high circulating concentration of epinephrine activates the switch within the
lungs from net secretion to net reabsorption. (6) Conventionally cited mechanisms related
to vaginal squeeze of the thorax during birth and Starling forces also contribute to a very
small proportion of lung fluid resorption. (10)
The currently accepted mechanism of transepithelial movement of lung fluid at the time

*Department of Pediatrics, University at Buffalo, Women and Childrens Hospital of Buffalo, Buffalo, NY.

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newborn transient tachypnea of the newborn

Epidemiology
Epidemiologic data are scarce, but
studies show that TTN occurs in
3.6 to 5.7 per 1,000 term infants.
(15)(16) Retention of fetal lung
fluid may be more common in pre-
term infants (up to 10 per 1,000
births), but there usually are coex-
isting problems such as respiratory
distress syndrome (RDS) that may
mask its presentation. (17) TTN is
one of the most common causes
of neonatal respiratory distress,
(18)(19) and actually may be un-
derdiagnosed. (20) Risk factors for
TTN include birth by cesarean sec-
tion with or without labor, male
sex, family history of asthma (espe-
cially in mother), (21) lower gesta-
tional age, macrosomia, and mater-
nal diabetes (Fig. 2). For babies
Figure 1. Mechanism of fetal and neonatal lung fluid transport. The left panel shows born by elective cesarean section,
active secretion of chloride ions from alveolar cells into the alveolar space. Sodium (Na) the presence of labor and the tim-
and water accompany chloride (Cl-). Around the time of birth (right panel), type II cell ing of delivery significantly affect
apical epithelial sodium channels (ENaC) become activated by adrenergic stimulation. the presence of respiratory morbid-
Basolateral Na/K ATPase helps move sodium into the interstitium, which brings ity. The incidence of respiratory
chloride and water passively along with it through the paracellular and intracellular morbidity in babies delivered by ce-
pathways. Most interstitial lung liquid moves into the pulmonary circulation; some drains sarean section before the onset of
via the lung lymphatics. Kpotassium, NKCCsodium, potassium, 2 chloride labor is 35.5 per 1,000, compared
cotransporter
with cesarean section with labor, in
which the rate is 12.2 per 1,000.
of birth is by passive movement of sodium through (22) With vaginal delivery, morbidity occurs in 5.3 per
epithelial sodium channels (ENaC) (Fig. 1, right panel), 1,000 births. Even late preterm delivery (between 34 and
which are believed to be closed during fetal life but 37 weeks of gestation) increases the risk for TTN. (23)
become activated by adrenergic stimulation near birth. A significant reduction in respiratory morbidity can be
(11) The epinephrine stimulation of amiloride-sensitive achieved if elective cesarean section is performed after
ENaC channel-mediated alveolar fluid clearance is medi- 39 weeks of gestation. (24)
ated by cyclic adenosine monophosphate (12) and Ca2,
likely acting as an intracellular second messenger. (13)
OBrodovich and associates (14) showed that intralumi- Diagnosis and Clinical Features
nal instillation of amiloride in newborn guinea pigs de- The diagnosis of TTN is based on clinical and radiologic
lays lung fluid clearance and leads to hypoxemia and findings (Table 1). It frequently is a diagnosis of exclu-
respiratory distress. Sodium then moves into the inter- sion; other conditions such as RDS, pneumonia, and
stitium via ouabain-sensitive basolateral Na/K AT- pneumothorax must be excluded. TTN usually presents
Pase, and inhibition of this channel reduces lung liquid within a few hours of birth with tachypnea, retractions,
clearance in animal models. Movement of sodium into and grunting and occasionally with a requirement for
the interstitium helps to move chloride and water supplemental oxygen. Respiratory rates are greater than
passively along with it through the paracellular and 60 breaths/min, often in the range of 80 to 100 breaths/
intracellular pathways. Most interstitial lung liquid min, and sometimes higher. Because many babies expe-
moves into the pulmonary circulation; some drains via rience tachypnea for a period of time after birth, shorter
the lung lymphatics. periods of tachypnea sometimes are referred to as tran-

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 newborn transient tachypnea of the newborn

sitional delay. This may be part of

the spectrum of retained fetal lung
fluid syndromes, with TTN being
more severe than typical transi-
tional delay. Any chosen cutoff for
the length of normal tachypnea
after birth (ie, the minimum num-
ber of hours of tachypnea for a di-
agnosis of TTN) is arbitrary but
could range from 2 to 12 hours. Six
hours may be a practical choice for
the cutoff between transitional de-
lay and TTN because by this time,
the baby may not be able to take
feedings orally, requiring other ar-
rangements.
Tachypnea due to TTN re-
solves by 72 hours in most cases
but can persist longer. Ultimately,
the tachypnea resolves, consistent
with the transient in the name
TTN. In a retrospective review of
95 newborns who had TTN, (25)
clinical and laboratory findings
were compared between two sub-
sets: babies in whom tachypnea
lasted fewer than 72 hours and
those in whom it lasted more than
72 hours. The authors suggested
that a peak respiratory rate of
more than 90 breaths/min at
36 hours of age was highly predic-
tive of prolonged tachypnea. Pro-
longed TTN was associated with
lower white blood cell count and
hematocrit values, longer hospi-
talization, and antibiotic treat-
Figure 2. Risk factors associated with transient tachypnea of newborn. See text for
ment in this study.
details.
Grunting can be common im-
mediately after birth and is consid-
ered part of transition. Among a cohort of 466 new- fected, unless the newborn becomes severely symptom-
borns, 17.4% had grunting respirations at birth, but the atic. (27)
grunting subsided in most by 2 hours of age (68% Occasionally, some infants who have TTN develop
stopped within 30 minutes, 85% by 1 hour, and 93% by severe hypoxemia and may require high concentrations
2 hours). (26) If grunting and other signs of distress of oxygen (60%) to maintain their saturations. Such
persist, the baby may require further assessment and babies may need additional respiratory support (intuba-
intervention. Another clinical sign of TTN is a barrel- tion and mechanical ventilation). Pulmonary hypertension
shaped chest due to hyperinflation, which may push with right-to-left shunting across the ductus or foramen
down the liver and spleen, making them palpable. Aus- ovale may be present because of possible elevation in the
cultation of the chest may reveal crackles, usually with pulmonary vascular resistance associated with retained
associated tachycardia. Blood pressure remains unaf- fetal lung fluid. Rarely, air leaks have been reported.

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newborn transient tachypnea of the newborn

Diagnosis of Transient
Table 1. Causes of Tachypnea in a
Table 2.

Tachypnea of the Newborn Newborn

Symptoms start within the first 6 hours after Transient tachypnea of newborn
delivery Respiratory infections (pneumonia)
Tachypnea and, in some cases, retractions, grunting, Aspiration syndromes (meconium, blood, or amniotic
or nasal flaring; desaturation/cyanosis is uncommon; fluid)
good response to oxygen supplementation (as Congenital malformations (congenital diaphragmatic
verified clinically or by pulse oximetry); mechanical hernia, cystic adenomatoid malformations) and Central
ventilation rarely required nervous system irritation (subarachnoid hemorrhage)
Chest radiograph consistent with retained fetal lung or disease (hypoxic-ischemic encephalopathy)
fluid, showing congestion, perihilar streaking, fluid in Hyaline membrane disease (respiratory distress syndrome)
the interlobar fissure Edema, pulmonary (left-to-right shunts with failure,
Symptoms and radiographic findings transient and anomalous venous drainage)
self-limited, disappearing within the first postnatal Air leaks (pneumothorax) and Acidosis (metabolic)
week (usually within a few days)
Other diagnoses excluded (eg, pneumonia, respiratory
distress syndrome, pneumothorax)
between the two for the diagnosis of TTN compared
with 95% agreement for the diagnosis of RDS and 78%
Radiographic Features for pneumothoraces. (29)
Chest radiography (Fig. 3) typically shows prominent
perihilar vascular markings due to engorged periarterial Differential Diagnosis
lymphatics, edema of the interlobar septae, and fluid in The definitive diagnosis of TTN often is retrospective
the fissures. There may be some degree of hyperinflation, because by definition, the symptoms are transient and
and fluid may be seen at the costophrenic angles, with other conditions have been excluded. The common
widening of intercostal spaces. Findings often become causes of tachypnea in a neonate can be remembered by
normal within 2 days, but complete disappearance of using the mnemonic TRACHEA (Table 2). Besides
perihilar markings may require 3 to 7 days. (28) A retro- RDS and pneumonia, another important disorder that
spective review comparing the interpretation of the first should be considered, based on additional history, is
chest radiograph obtained for 99 neonates admitted to tachypnea related to cerebral irritation from a subarach-
the intensive care unit for mild-to-moderate respiratory noid hemorrhage or hypoxic brain injury (also called
distress, which was read by clinicians and radiologists cerebral hyperventilation). Infants who have the latter
independently, showed agreement only 48% of the time diagnosis tend to have respiratory alkalosis, and chest

Figure 3. Radiographs of two babies who have transient tachypnea of the newborn of differing severity. Note the streaky lung
opacities and fluid in the minor fissure on the right side.

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 newborn transient tachypnea of the newborn

radiography may show some cardiomegaly, with normal Conversely, babies experiencing TTN have an increase in
lung fields. Tachypnea due to metabolic acidosis should physician-diagnosed preschool asthma. (35) Birnkrant
be considered and can be ruled out with measurement of and colleagues (36) examined a database of 18,379 term
a capillary or arterial blood gas. Because it is difficult to infants, from which 2,137 children who had asthma were
exclude pneumonia at presentation, many babies who compared with a similar number of birthday-matched
have TTN are treated with antibiotics for the first 24 to controls, and showed that TTN was associated signifi-
48 hours until the blood culture is negative; by that time, cantly with the diagnosis of childhood asthma. The asso-
clinical symptoms and radiologic findings usually have ciation of TTN and asthma was statistically strongest
resolved significantly, which is highly suggestive of TTN, among male infants, especially among males whose
obviating the need for continued treatment with antibi- mothers lived at urban addresses, males of nonwhite race,
otics. and males whose mothers did not have asthma. The
authors proposed that TTN may be a marker of deficient
Lung Function in TTN pulmonary function, reflecting inherited susceptibility to
Lung function is difficult to measure immediately after asthma. Asthma is a multifactorial disease, and the corre-
birth, and data in newborns are limited. Lee and associ- lation with TTN remains to be elucidated clearly. Some
ates (30) measured the thoracic gas volume by using total factors may predispose to both diseases or TTN itself may
body plethysmography and functional residual capacity be a risk factor for later development of asthma.
by argon dilution at ages 4 to 6 hours and 24 hours in 10
babies delivered vaginally and 10 babies born by elective
cesarean section. They noted lower mean thoracic gas Management
volume at 4 to 6 hours in babies born by cesarean section An important question that arises in the community
compared with those born by vaginal delivery. They also hospital setting is when to refer newborns to a level 2 or
showed a delay of up to 24 hours in the establishment of 3 neonatal intensive care unit for management of early-
final lung volumes in babies born without exposure to onset respiratory distress in newborns, especially babies
labor or passage through the birth canal. They suggested suspected of having TTN. Hein and colleagues (37) have
that this finding may explain the increased respiratory recommended the rule of 2 hours, whereby the new-
morbidity associated with delivery by elective cesarean born is observed for 2 hours after the onset of respiratory
section. (30) distress. If there is no improvement in the degree of
Faxelius and associates (31) looked at the correlation distress, a chest radiograph is obtained. Many newborn
between the catecholamine surge associated with labor nurseries use pulse oximetry as an adjunct to clinical
and lung function at 30 minutes and at 2 hours after birth monitoring. If the baby exhibits desaturation in room air,
by measuring cord pH and catecholamine and cortisol a blood gas measurement may be useful. The baby then
values in term babies born by different modes of delivery. may be referred to a higher facility if the chest radiograph
They found lower tidal volume, minute ventilation, and does not appear normal, the baby is worsening clinically,
dynamic compliance at 30 minutes and 2 hours after the baby requires more than 40% oxygen to maintain
birth in infants delivered by cesarean section compared normal oxygen saturation, or there is no improvement
with those delivered vaginally. The catecholamine and after 2 hours of all feasible interventions.
cortisol concentrations at birth were higher in the vaginal If tachypnea is associated with increased work of
group than in the cesarean section group, with significant breathing and is not resolving, the baby must be kept nil
correlation between the catecholamine concentrations per os (NPO) and requires intravenous (IV) fluids (10%
and lung compliance at 2 hours in this group. Sandberg dextrose in water at 60 to 80 mL/kg per day). After the
and colleagues (32) evaluated newborns who had tachyp- transition period (the first few hours after birth), in-
nea lasting more than 2 hours after birth and showed creased work of breathing, as opposed to isolated tachy-
lower tidal volumes but normal-to-increased total venti- pnea, should heighten concern that TTN may not be the
lation due to increased respiratory rates and hyperinfla- correct diagnosis. Because these are term babies and it is
tion with reduced dynamic lung compliance. easier to observe the respiratory status unbundled, they
usually are observed in open radiant warmers. Typically,
Asthma and TTN chest radiography is performed to support the diagnosis
Literature about the link between asthma and TTN is of TTN and rule out other conditions (eg, pneumotho-
increasing. Babies born to mothers who have asthma are rax). A screening complete blood count with differential
at higher risk for the development of TTN. (33)(34) count and a blood gas analysis (especially in the presence

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newborn transient tachypnea of the newborn

of increased work of breathing or oxygen requirement) Treatment with furosemide was evaluated in a con-
should be considered. trolled, prospective, randomized trial in 50 infants hav-
Although the respiratory rate can be high for the baby ing TTN. (39) The furosemide group was given
who has typical TTN, other signs of increased work of 2 mg/kg orally at the time of diagnosis followed by
breathing (grunting, flaring, retractions) resolve sooner 1 mg/kg 12 hours later if the symptoms persisted; the
than the tachypnea. As the TTN is resolving, and if the control babies received a placebo. No significant differ-
diagnosis is straightforward and the respiratory rate is less ence in the duration of tachypnea or in the length of
than 80 breaths/min, enteral feedings can be given. The hospitalization was observed with furosemide therapy.
feedings should be started on a gentle protocol by ad- A recent randomized, blinded, placebo-controlled pi-
vancing volume in small increments (continuing to sup- lot trial examined the safety and efficacy of racemic
plement total fluids with IV fluids) until the baby no epinephrine for the treatment of TTN based on the
longer exhibits tachypnea and has a respiratory rate of less hypothesis that infants who have TTN may have rela-
than 60 breaths/min. For babies who continue to have tively low concentrations of epinephrine, which is known
tachypnea and are NPO or are receiving low-volume to mediate fetal lung fluid absorption. (40) Although no
feedings for more than 1 day, electrolytes should be infant in either the treatment or control arm experienced
added to the IV fluids, and parenteral nutrition should be an adverse event, including tachycardia or hypertension,
considered to provide optimal nutrition. Babies who there was no difference in the rates of resolution of
have TTN need to be observed closely; in 74%, symp- tachypnea in the treatment and the control groups.
toms subside by 48 hours of age. (18)
If the pulse oximetry or blood oxygen value suggests
that the baby needs oxygen, the preferred initial method Prevention and Scope for Future Research
of delivery is by oxygen hood. The concentration is The ideal approach to preventing TTN is to reduce the
adjusted to maintain a pulse oximetry reading in the low incidence of cesarean section, which has been increasing
90s. With nasal cannula delivery, the actual oxygen con- and contributes significantly to respiratory morbidity in
centration delivered is more difficult to determine; this term newborns. The American College of Obstetrics and
form of oxygen delivery may be used after the first Gynecology (ACOG) recommends scheduling elective
24 hours of age, when the diagnosis is more certain. In cesarean section at 39 weeks gestation or later on the
the uncommon event that a baby who has TTN needs basis of menstrual dates or waiting for the onset of
intubation and higher oxygen concentration, the baby spontaneous labor. ACOG also provides criteria for es-
should remain NPO and an arterial line may be needed. tablishing fetal maturity before elective cesarean section.
Such infants are at risk for persistent pulmonary hyper- However, the safety of this approach in mothers who
tension of the newborn, at times even requiring extracor- previously have delivered by cesarean section has not
poreal membrane oxygenator (ECMO) support. Al- been established in rigorous trials. A recent study dem-
though the total number of neonates requiring ECMO onstrated that antenatal betamethasone administered
support for respiratory failure has declined from 1989 to prior to an elective cesarean section reduced the inci-
2006, the proportion delivered by elective cesarean sec- dence of respiratory morbidity in infants. (41) Although
tion among them is rising. (38) Because there is a higher mortality is not a concern, TTN is very common and is a
occurrence of respiratory morbidity in late preterm and frustrating condition that sometimes requires transfer of
term infants delivered by elective cesarean section, the the baby, separation from the mother if she cannot be
relative numbers of infants who have TTN and require transferred, multiple diagnostic studies, delay in dis-
ECMO may signal a concerning trend. charge, prolonged hospitalization, and increased health-
Some infants finally diagnosed as having TTN can care costs. Also, these babies may have an increased risk
experience prolonged tachypnea. If tachypnea persists of asthma. Thus, additional research to elucidate mech-
beyond 5 or 6 days, echocardiography should be consid- anisms of lung fluid reabsorption that are dysfunctional
ered to rule out congenital heart disease. In general, in TTN and possible therapeutic interventions is war-
babies who have TTN cannot have a definitive diagnosis ranted.
of TTN until the tachypnea resolves. Therefore, babies
are not discharged until the tachypnea resolves (respira-
tory rates 60 breaths/min for at least 12 hours). References
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 Transient Tachypnea of the Newborn
Lokesh Guglani, Satyan Lakshminrusimha and Rita M. Ryan
Pediatrics in Review 2008;29;e59
DOI: 10.1542/pir.29-11-e59

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 Transient Tachypnea of the Newborn
Lokesh Guglani, Satyan Lakshminrusimha and Rita M. Ryan
Pediatrics in Review 2008;29;e59
DOI: 10.1542/pir.29-11-e59

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located on the World Wide Web at:
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Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2008 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601.

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