Ultrasound Obstet Gynecol 2020; 55: 586–592

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Coronavirus in pregnancy and delivery: rapid review

E. MULLINS1 , D. EVANS2,3 , R. M. VINER3,4 , P. O’BRIEN5,6 and E. MORRIS6,7
1 Department of Metabolism, Digestion and Reproduction, Imperial College London, Queen Charlotte’s and Chelsea Hospital, London,

UK; 2 North Bristol NHS Trust, Bristol, UK; 3 The Royal College of Paediatrics and Child Health, London, UK; 4 University College
London, London, UK; 5 University College London Hospitals NHS Foundation Trust, London, UK; 6 The Royal College of Obstetricians
and Gynaecologists, London, UK; 7 Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, Norfolk, UK

K E Y W O R D S: breastfeeding; COVID-19; fetal; miscarriage; neonatal; pregnancy; preterm birth

CONTRIBUTION (RCPCH) and RCOG who provided expert consensus on

What are the novel findings of this work? areas in which data were lacking.
This is the most up-to-date review of COVID-19 in Results From 9965 search results in PubMed and 600
pregnancy, with comparison to previous outbreaks of in MedRxiv, 21 relevant studies, all of which were case
novel coronavirus in pregnancy. We discuss the limited reports or case series, were identified. From reports of
data available, the limited evidence base for clinical 32 women to date affected by COVID-19 in pregnancy,
practice, possible therapeutic options in pregnancy and delivering 30 babies (one set of twins, three ongoing
future research. pregnancies), seven (22%) were asymptomatic and two
(6%) were admitted to the intensive care unit (ICU),
What are the clinical implications of this work? one of whom remained on extracorporeal membrane
A version of this rapid review, with searches up to 25 oxygenation. No maternal deaths have been reported
February 2020, informed the Royal College of Obste- to date. Delivery was by Cesarean section in 27 cases
tricians and Gynaecologists’ guidance on COVID-19 in and by vaginal delivery in two, and 15 (47%) delivered
pregnancy. preterm. There was one stillbirth and one neonatal death.
In 25 babies, no cases of vertical transmission were
reported; 15 were reported as being tested with reverse
ABSTRACT
transcription polymerase chain reaction after delivery.
Objectives There are limited case series reporting the Case fatality rates for SARS and MERS were 15% and
impact on women affected by coronavirus during 27%, respectively. SARS was associated with miscarriage
pregnancy. In women affected by severe acute respiratory or intrauterine death in five cases, and fetal growth
syndrome (SARS) and Middle East respiratory syndrome restriction was noted in two ongoing pregnancies affected
(MERS), the case fatality rate appears higher in those by SARS in the third trimester.
affected in pregnancy compared with non-pregnant
women. We conducted a rapid review to guide health Conclusions Serious morbidity occurred in 2/32 women
policy and management of women affected by COVID-19 with COVID-19, both of whom required ICU care.
during pregnancy, which was used to develop the Royal Compared with SARS and MERS, COVID-19 appears
College of Obstetricians and Gynaecologists’ (RCOG) less lethal, acknowledging the limited number of cases
guidelines on COVID-19 infection in pregnancy. reported to date and that one woman remains in
a critical condition. Preterm delivery affected 47%
Methods Searches were conducted in PubMed and of women hospitalized with COVID-19, which may
MedRxiv to identify primary case reports, case series, put considerable pressure on neonatal services if the
observational studies and randomized controlled trials UK’s reasonable worst-case scenario of 80% of the
describing women affected by coronavirus in pregnancy. population being affected is realized. Based on this
Data were extracted from relevant papers. This review review, RCOG, in consultation with RCPCH, developed
has been used to develop guidelines with representatives guidance for delivery and neonatal care in pregnancies
of the Royal College of Paediatrics and Child Health affected by COVID-19, which recommends that delivery

Correspondence to: Dr E. Mullins, Department of Metabolism, Digestion and Reproduction, Imperial College London, Queen Charlotte’s
and Chelsea Hospital, DuCane Road London, London W12 0HS, UK (e-mail: [email protected])
Accepted: 13 March 2020

© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd REVIEW
on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
Rapid review: coronavirus in pregnancy 587

mode be determined primarily by obstetric indication RESULTS

and recommends against routine separation of affected
mothers and their babies. We hope that this review will be The search of PubMed identified 9965 results; 69 abstracts
helpful for maternity and neonatal services planning their were screened, of which 48 were excluded due to the
response to COVID-19. © 2020 The Authors. Ultrasound study not including pregnant women or humans, or
in Obstetrics & Gynecology published by John Wiley being an in-vitro study. Twenty-one relevant studies were
& Sons Ltd on behalf of the International Society of identified2–22 ; their full texts were reviewed and all 21
Ultrasound in Obstetrics and Gynecology. were included. It is highly likely that there was overlap
in cases reported to be affected by SARS. The search
of MedRxiv identified 600 results; 39 abstracts were
screened and no relevant studies were identified.
INTRODUCTION All studies were case reports or series and all were
The common human coronaviruses 229E (alpha corona- classified subjectively as being of low quality. There was
virus), NL63 (alpha coronavirus), OC43 (beta corona- inconsistent reporting of maternal, perinatal and neonatal
virus) and HKU1 (beta coronavirus) cause the common outcomes. Outcomes of included cases are summarized in
cold. Three human coronaviruses cause more severe, Table 1. A narrative review is presented.
acute illnesses; MERS-CoV causes Middle East respiratory
syndrome (MERS), SARS-CoV causes severe acute Maternal outcome
respiratory syndrome (SARS) and SARS-CoV-2 causes
COVID-19. To date, 32 women affected by COVID-19
COVID-19.
in pregnancy, including one with a twin pregnancy, have
There are limited case series reporting on the impact
been reported, delivering 30 infants (three pregnancies
of coronaviruses during pregnancy. In women affected by
were ongoing)2–5 . Twenty-seven delivered by Cesarean
SARS or MERS, the case fatality rate appeared higher in
and two by vaginal delivery. Women who delivered
those affected in pregnancy compared with non-pregnant
did so within 13 days of onset of illness. In cases in
women.
which maternal morbidity and mortality were reported
Person-to-person spread of COIVD-19 in the UK has
(n = 23), two women required intensive care unit (ICU)
now been confirmed. To guide treatment and prevention
admission and mechanical ventilation, one of whom
in women affected by COVID-19 during pregnancy in the
developed multiorgan dysfunction and was still on
current outbreak, we conducted a rapid review.
extracorporeal membrane oxygenation (ECMO) when
the case was reported. When reported (n = 17), all
METHODS symptomatic women had viral changes apparent on
computed tomographic (CT) chest imaging. There were
Searches were conducted in PubMed and MedRxiv on no maternal deaths to date2,3 .
25 February 2020 (Appendix S1) and updated on 10 SARS. The case fatality rate (CFR) was 15% for all
March to identify primary case reports, case series and reported cases of SARS in pregnancy6–11 . A case–control
randomized controlled trials describing women of any study comparing 10 pregnant and 40 non-pregnant
age affected by coronavirus in pregnancy or the postnatal women affected by SARS in Hong Kong reported an ICU
period. There were no date or language restrictions on admission rate of 60% and a CFR of 40% in the pregnant
the search. References of relevant papers were searched group, compared with respective values of 17.5% and 0%
manually for relevant studies. in the non-pregnant group9 . All women affected by SARS
Due to time constraints, one reviewer (E.M.) conducted had CT or chest X-ray evidence of pneumonia (Table 2).
the search, reviewed full texts and extracted data on MERS. In pregnant women affected by MERS, 7/11
demographics, maternal outcomes, maternal diagnostic (64%) were admitted to the ICU, and CFR was 3/11
testing, maternal imaging, fetal, perinatal and neonatal (27%)12–17 .
outcomes, and neonatal diagnostic testing. Comparison
of outcomes between pregnancies affected by COVID-19, Early pregnancy
SARS and MERS is presented.
The review was not registered in PROSPERO and COVID-19. There are currently no data on first-trimester
corresponding authors were not contacted due to time COVID-19 infection.
constraints. The quality of included studies was assessed SARS. Miscarriage affected 4/7 women with
subjectively and classified as anecdotal, low, medium or first-trimester SARS infection8 , all of whom had an
high. Ethical approval was not required for this review. ultrasound finding at 3–5 weeks of pregnancy of
This review has been used to develop interim unknown location or unknown viability, in which ongo-
guidance on COVID-19 infection in pregnancy, with ing pregnancy at 13 weeks would be expected in 38%
representatives of the Royal College of Paediatrics and 50%, respectively, acknowledging the complexity in
and Child Health (RCPCH) and the Royal College this area23,24 . Those with fetal heart activity recorded
of Obstetricians and Gynaecologists (RCOG) providing (n = 2) did not miscarry, neither did a woman in whom
expert consensus on areas in which data were lacking. the diagnosis was retrospective and did not undergo
This guidance has now been published in full by RCOG1 . ultrasound examination.

© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd Ultrasound Obstet Gynecol 2020; 55: 586–592.
on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
588 Mullins et al.

Table 1 Overview of pregnancy and perinatal and neonatal outcomes in pregnancies affected by coronaviruses, according to gestational age
(GA) at diagnosis

COVID-19a SARS MERS

Second Third First Second Third First Second Third
Variable All trim trim All trim trim trim All trim trim trim

n 32b 2 30 20h 7 5 8 11 1 5 5
Maternal age (years) 30 (25–40) 31 (24–44) 33 (27–39)
GA at presentation 36.5 (25–39) 16 (3–32) 24 (6–38)
(weeks)
Maternal comorbidity 4/19 (21)c NR 4/19 (21)c NR NR NR NR 5 (45) 0 (0) 2 (40) 3 (60)
Asymptomatic at 7 (22) 2 (100) 5 (17) 0 (0) 0 (0) 0 (0) 0 (0) 2 (18) 1 (100) 1 (20) 0 (0)
admission
ICU admission 2/23 (9)d 0 (0) 2/21 (10)d 6 (30) 1 (14) 2 (40) 3 (38) 7 (64) 0 (0) 3 (60) 4 (80)
Maternal mortality 0 (0)c,d 0 (0) 0 (0)c,d 3 (15) 1 (14) 1 (20) 1 (13) 3 (27) 0 (0) 1 (20) 2 (40)
Viral changes on chest 18/19 (95)c 20 (100) 8/9 (89)k
CT/X-ray in
symptomatic women
Miscarriage or IUD 1 (3)e 0 (0)e 1 (3)e 5 (25) 4 (57) 0 1 (13)j 2 (18) 0 (0) 1 (20) 1 (20)
Preterm delivery
Any 15 (47)f 0 (0)f 15 (50)f 4/13 (31)i NR 2 (40)i 2 (25)i 3 (27) 0 (0) 1 (20) 2 (40)
Spontaneous 0 (0) 0 (0) 0 (0)d 1 (5)i NR 0 (0)i 1 (13)i 0 (0) 0 (0) 0 (0) 0 (0)
Post-infection FGR NR NR NR 2 (10) NR 0 (0) 2 (25) 0 (0) 0 (0) 0 (0) 0 (0)
Vertical transmission 0/25 (0)g — 0/25 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
Neonatal death 1/29 (3) — 1/29 (3) 0/13 (0) NR 0 (0) 0 (0) 1 (9) 0 (0) 1 (20) 0 (0)

Data are given as median (range), n (%) or n/N (%). a No reported cases of first-trimester COVID-19 infection identified. b Including two
ongoing pregnancies diagnosed with COVID-19 in second trimester and one ongoing and one twin pregnancy diagnosed in third trimester,
giving total of 30 babies delivered. c Incomplete data from Liu et al.5 . d Incomplete data from Zhu et al.4 . e Fetuses in ongoing pregnancies
were assumed to survive. f Ongoing pregnancies were assumed to deliver at term, based on clinical prognosis. g Not all infants were tested
and some pregnancies were ongoing. h Including one twin pregnancy diagnosed with SARS in third trimester. i Data (n = 5) on timing of
delivery not reported by Zhang et al.19 but all were assumed to deliver at term. j Occurred in twin pregnancy. k One woman declined
radiography because of concerns about effect on pregnancy and one woman was asymptomatic in first trimester. CT, computed tomo-
graphy; FGR, fetal growth restriction; ICU, intensive care unit; IUD, intrauterine death; MERS, Middle East respiratory syndrome; NR, not
reported; SARS, severe acute respiratory syndrome; trim, trimester.

MERS. A single case of a woman with MERS in to have had an intrauterine death; this woman delivered
the first trimester has been reported. This woman was vaginally and recovered after ICU admission without
asymptomatic and went on to have a term delivery18 . ventilatory support14 .

Second/third-trimester pregnancy loss

COVID-19. One woman affected by COVID-19 pre- Prematurity
sented at 34 weeks with a fever and sore throat; her
COVID-19. Fifteen of the 32 (47%) women affected by
condition deteriorated during admission and she required
COVID-19 delivered preterm. In the study of Chen et al.,
admission to the ICU and ECMO5 . The woman had a
stillbirth, delivered by Cesarean section. No information all (n = 9) mothers were delivered electively by Cesarean
on chronology or fetal monitoring was reported. section, two of which were at 36 weeks’ gestation2 . In the
SARS. In cases of SARS reported after the first trimester, study of Zhu et al., seven women delivered by Cesarean
Zhang et al. reported a series of five women affected by section and two by vaginal delivery4 ; 5/9 women (6/10
SARS (two in the second trimester, three in third trimester) babies) delivered preterm. The indication for delivery is
in which there was loss of one fetus in a twin pregnancy not reported; however, six babies were affected by fetal
with the other surviving to delivery. It is not clear if the distress prior to delivery and it seems reasonable to assume
loss occurred in the second or third trimester; this has been that fetal condition contributed. Wang et al. reported on
recorded arbitrarily as occurring in the third trimester19 . one woman who delivered at 30 weeks for fetal distress3 .
MERS. Two pregnancy losses were reported in Liu et al. reported on 13 women, of whom seven delivered
pregnancies affected by MERS. In the first case, the preterm by Cesarean section; indication for delivery was
woman became ill at 19 weeks gestation and experienced not reported5 .
vaginal bleeding resulting in late fetal loss at 20 weeks17 . SARS. Four of the 16 SARS pregnancies that were not
It should be noted that this woman declined chest affected by miscarriage resulted in preterm delivery at 26,
radiography and medication because of her concerns 28, 32 and 33 weeks’ gestation, respectively18 . Data on
about their effect on pregnancy. The second case presented timing of delivery were not reported in the series of five
at 34 weeks with pre-eclampsia and MERS and was found women from Zhang et al.19 .

© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd Ultrasound Obstet Gynecol 2020; 55: 586–592.
on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
Rapid review: coronavirus in pregnancy 589

Table 2 Details of women affected by coronavirus in pregnancy who died, as of 6 March 2020

Delivery and
Corona- MA GA Clinical neonatal Cause of
virus (years) (weeks) presentation Comorbidity Chest imaging Progression outcome maternal death

SARS8 44 5 Cough, NR Pneumonia Secondary Miscarriage Respiratory

headache, bacterial failure
SOB, chills pneumonia,
DIC, renal
failure, ARDS
34 32 Myalgia, NR Pneumonia Sepsis, ARDS, CS, neonatal Respiratory
cough, shock, survival failure
chills abdominal
wound
dehiscence
34 27 Myalgia, NR Pneumonia Secondary CS, ARDS, MRSA
cough, bacterial NEC, pneumonia
headache, pneumonia, neonatal
SOB, sore DIC, ARDS, survival
throat abdominal
wound
dehiscence
MERS20 32 38 Fever, cough, None Bilateral Worsening Spontaneous Multiorgan
SOB infiltrates pneumonia, vaginal failure
(chest renal failure, delivery,
X-ray) ARDS neonatal
survival
31 24 Cough, Asthma, Right lower Worsening Emergency CS Severe refractory
myalgia pulmonary lobe opacity pneumonia, for maternal hypoxia,
fibrosis, ARDS hypoxemia, cardiac arrest
spontaneous neonatal
pneumotho- death
races
32 32 Fever, back None Bilateral con- Septic shock Emergency CS Septic shock
pain solidation for maternal
(CT) hypoxemia,
neonatal
death

There were no maternal deaths in COVID-19 cases. ARDS, acute respiratory distress syndrome; CS, Cesarean section; CT, computed
tomography; DIC, disseminated intravascular coagulation; GA, gestational age; MA, maternal age; MERS, Middle East respiratory
syndrome; MRSA, methicillin-resistant Staphylococcus aureus; NEC, necrotizing enterocolitis; NR, not reported; SARS, severe acute
respiratory syndrome; SOB, shortness of breath.

MERS. Three of the 11 pregnancies with MERS were MERS. Four of the 11 women with MERS went
delivered preterm by Cesarean section (one at 24 weeks on to deliver a healthy baby at term, although birth
and two at 32 weeks for maternal hypoxemia)12,18 . weight was not reported in 3/4 of these cases. In one
case, vaginal bleeding was reported at 37 weeks, causing
Fetal growth and placental effects fetal compromise and necessitating emergency Cesarean
section resulting in the delivery of a male infant weighing
COVID-19. Women affected by COVID-19 who deliv-
3140 g and in good condition. Abruption was apparent
ered did so within 13 days of onset of illness2–5 ; fetal
on placental examination13 .
growth is unlikely to be affected in this time period.
There were no data on fetal growth in the three ongo-
ing pregnancies at the time of publication5 . No placental Delivery and postnatal
pathology is available to date.
SARS. Placentas from pregnancies affected by SARS COVID-19. Chen et al. reported on nine women with
showed early changes (fibrin deposition), that are seen in COVID-19 delivering by Cesarean section from 36 weeks
pregnancies with fetal growth restriction, when delivery onwards, of which two were preterm. In two women
occurred ≤ 1 week after onset of illness; birth weight at term, fetal distress was reported. In six women
was normal in these pregnancies20 . When delivery was with COVID-19 who delivered by Cesarean section and
5–7 weeks after onset of illness, there was fetal growth subsequently underwent testing, there was no evidence of
restriction in 2/3 pregnancies8 and their placentas showed COVID-19 in the amniotic fluid, umbilical cord blood,
more severe changes (areas with loss of blood supply, neonatal throat swab or breast milk samples2 . A news
avascular villi, bleeding behind the placenta, placental report of a baby of a COVID-19-infected mother testing
abruption)20 . positive at 30 h after delivery has not been reported in a

© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd Ultrasound Obstet Gynecol 2020; 55: 586–592.
on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
590 Mullins et al.

scientific journal. Zhu et al. reported COVID-19 in nine DISCUSSION

women delivering 10 infants (seven by Cesarean section
and two by vaginal delivery), of whom only three mothers There are limited data on the impact of the current
became symptomatic after delivery. The indication for COVID-19 outbreak on women affected in pregnancy and
delivery was not reported. This cohort had COVID-19 their babies. All studies included in this review were case
from 31 weeks onwards, 6/9 pregnancies showed fetal reports or series of low quality. Reported outcomes varied,
distress and 5/9 women (6/10 babies) delivered preterm4 . with one series on COVID-19 not reporting maternal
outcome.
Wang et al. reported on one woman who underwent
Of the 23/32 women with COVID-19 in pregnancy
Cesarean section for fetal distress at 30 weeks’ gestation.
for whom maternal outcomes were reported, two had
The infant was born in good condition and samples of
serious morbidity, one of whom was still on ECMO
amniotic fluid, neonatal gastric samples, placenta and
following stillbirth, at the time her care was reported.
infant throat swabs were negative for COVID-193 . Liu
Compared with SARS and MERS, COVID-19 appears to
et al. reported on 10 women, all of whom delivered by
be less lethal, although acknowledging the limited number
Cesarean section. Vertical transmission was reported as
of cases reported to date and that one woman remains
negative in all 10 neonates. The samples and method of
in a critical condition. Preterm delivery affected 47%
testing is not stated5 .
of women hospitalized with COVID-19, which may put
SARS and MERS. No vertical transmission was
considerable pressure on neonatal services if the UK’s
reported for cases of SARS or MERS in pregnancies
reasonable worst-case scenario of 80% of the population
delivered by Cesarean section or vaginal delivery.
being affected is realized.
Other coronaviruses. A single case series reported
RCOG, in consultation with the RCPCH, have pro-
on neonates born to mothers who were positive for
vided guidance for delivery and neonatal care, which rec-
HCoV-229E; gastric samples in three out of seven cases
ommends that delivery mode be determined primarily by
were positive for HCoV-229E on reverse transcription
obstetric indication, and recommends against routine sep-
polymerase chain reaction (RT-PCR); seroconversion was
aration of COVID-19-affected mothers and their babies1 .
not assessed. No signs of infant infection were seen in
From the currently available data, an increase in the risk
those with positive gastric samples21 .
of miscarriage in women affected by COVID-19 cannot
be ruled out at this stage, given the SARS data. Data from
Neonatal outcome early pregnancy units are needed on affected women and
matched controls.
COVID-19. In the study of Chen et al., all (n = 9) babies In women affected by COVID-19 with ongoing
were delivered ≥ 36 weeks’ gestation and were well at pregnancy, surveillance for fetal growth restriction would
discharge2 . Zhu et al. reported on a cohort delivered at an be reasonable, given the acute and chronic placental
earlier gestational age (from 31 weeks); 6/10 babies were changes observed in SARS pregnancies and with 2/3
admitted to the neonatal unit for respiratory support, of those that were ongoing being affected by fetal
two developed disseminated intravascular coagulation growth restriction after SARS infection, and that placental
(DIC) and one had multiple organ failure4 . Neonatal abruption was noted in a case affected by MERS.
morbidity was more marked in this series, probably due The need for provision of fetal monitoring, including
to greater prematurity. One baby died after being born at serial ultrasound examination, of women with COVID-19
34 weeks. The neonate required admission at 30 min after will be challenging for maternity services. Women
delivery with respiratory difficulties. The baby’s condition will need to be monitored locally in their booking
deteriorated, and it developed shock, DIC and multiple maternity units, with transfer to centers with appropriate
organ failure, and died at 8 days postpartum. Nine of neonatal intensive care facilities for delivery. COVID-19 is
the 10 infants were tested for COVID-19, all of which associated with preterm delivery in 47% of reported cases.
tested negative. Wang et al. reported on a baby born at In SARS and MERS-affected cases, delivery was most
30 weeks in good condition with an uneventful neonatal often indicated by maternal hypoxemia. In COVID-19, if
course3 . Liu et al. reported on one stillborn and nine maternal illness is not as severe, the considerations will be
liveborn neonates, all of which had an Apgar score (time based more on obstetric indications for delivery.
unspecified) of 105 . Information on vertical transmission of COVID-19
SARS. Among pregnancies affected by SARS, a baby is limited, although testing of 15 neonates born to
born at 26 weeks had respiratory distress syndrome (RDS) mothers with COVID-19 was negative in all cases.
and a bowel perforation. In another case, a baby born at Guidance on mode of delivery requires expert consensus
28 weeks had RDS, necrotizing enterocolitis and a patent until further information emerges. RCOG advises that
ductus arteriosus8,11 . decisions regarding mode of delivery should be on
MERS. Among the three MERS pregnancies that were obstetric indication and not on presumed protection of
not affected by stillbirth or intrauterine death and that the baby against infection. There is evidence for vertical
were delivered preterm by Cesarean section, one delivered transmission of HCoV-229E; however, seroconversion
at 24 weeks and resulted in neonatal death (birth weight, was not investigated and all infants remained well21 .
240 g) and the other two delivered at 32 weeks for There is no evidence for vertical transmission for any
maternal hypoxemia and have no outcomes reported12,20 . other coronavirus.

© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd Ultrasound Obstet Gynecol 2020; 55: 586–592.
on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
Rapid review: coronavirus in pregnancy 591

We acknowledge the limitations of this review, given There is a need for systematic data reporting on women
that a full and comprehensive search of all medical affected by COVID-19 and their pregnancies to provide an
literature would have taken more time and personnel than evidence base for management, treatment and prevention,
were available. We used a single reviewer and a limited and to target limited resources during the outbreak.
database search in order to conduct this rapid review.
There is discrepancy between guidance for delayed cord
clamping, which is a function of a lack of evidence. DISCLOSURE
Consensus guidance from China advises that ‘delayed E.M. is seconded to the Department of Health and Social
cord clamping is not recommended’, in order to reduce Care (DHSC), England. The views in this manuscript are
the risk of vertical transmission, and that infants should be those of the authors and do not necessarily represent the
separated from mothers affected by COVID-1925 . Interim official views of DHSC or HM Government. E.M. has
guidance from ISUOG advises clinicians to consider not applied for a UKRI/MRC grant to study COVID-19 in
undertaking delayed cord clamping26 . RCOG guidance pregnancy. No other authors have conflicts of interest to
does not concur, advising that delayed cord clamping declare. E.M. received a salary from the NIHR.
should be practiced as normal. If vaginal delivery is
permitted, with exposure to maternal secretions and
blood, it could be argued that 1 min of further perfusion
REFERENCES
via the placenta is unlikely to alter the risk of vertical
1. Royal College of Obstetricians and Gynaecologists. Coronavirus (COVID-19)
transmission. Infants may acquire COVID-19 from their infection and pregnancy, 2020. https://www.rcog.org.uk/globalassets/documents/
mothers after delivery via normal routes of transmission. guidelines/coronavirus-covid-19-infection-in-pregnancy-v3-20-03-18.pdf
2. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, Li J, Zhao D, Xu D,
Guidance from China states that ‘Infants should not Gong Q, Liao J, Yang H, Hou W, Zhang Y. Clinical characteristics and intrauterine
be fed with the breast milk from mothers with confirmed vertical transmission potential of COVID-19 infection in nine pregnant women: a
retrospective review of medical records. Lancet 2020; 6736: 1–7.
or suspected 2019-nCoV’. Guidance from the Centers 3. Wang X, Zhou Z, Jianping Z, Zhu F, Tang Y, Shen X. A case of 2019 Novel
for Disease Control and Prevention is less clear but Coronavirus in a pregnant woman with preterm delivery. Clin Infect Dis 2020.
DOI: 10.1093/cid/ciaa200.
is still precautionary27 . RCOG advises against routine 4. Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, Xia S, Zhou W. Clinical
separation of mother and baby and gives guidance on analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl Pediatr
2020; 9: 51–60.
individualized care. 5. Liu Y, Chen H, Tang K, Guo Y. Clinical manifestations and outcome of SARS-CoV-2
If the UK’s reasonable worst-case scenario of 80% of infection during pregnancy. J Infect 2020. DOI: 10.1016/j.jinf.2020.02.028.
6. Robertson CA, Lowther SA, Birch T, Tan C, Sorhage F, Stockman L, McDonald C,
the population being affected by COVID-19 is realized Lingappa JR, Bresnitz E. SARS and Pregnancy: A Case Report. Emerg Infect Dis
and 4% require hospitalization, thousands of pregnant 2004; 10: 345–348.
7. Li AM, Ng PC. Severe acute respiratory syndrome (SARS) in neonates and children.
women will potentially be affected at a time at which Arch Dis Child Fetal Neonatal Ed 2005; 90: 461–465.
staff are likely themselves to be unwell. In previous 8. Wong SF, Chow KM, Leung TN, Ng WF, Ng TK, Shek CC, Ng PC, Lam PW,
Ho LC, To WW, Lai ST, Yan WW, Tan PY. Pregnancy and perinatal outcomes of
coronavirus epidemics, there has anecdotally been a women with severe acute respiratory syndrome. Am J Obstet Gynecol 2004; 191:
292–297.
tendency towards admitting any symptomatic pregnant
9. Lam CM, Wong F, Leung N, Chow M. A case-controlled study comparing clinical
woman with proven infection. course and outcomes of pregnant and non-pregnant women with severe acute
respiratory syndrome. BJOG; 2004; 111: 771–774.
A surge in workload will likely be seen in healthcare 10. Schwartz D, Graham A. Potential Maternal and Infant Outcomes from Coronavirus
services across the world at a time at which staffing is 2019-nCoV (SARS-CoV-2) Infecting Pregnant Women: Lessons from SARS, MERS,
and Other Human Coronavirus Infections. Viruses 2020; 20: 1–16.
well below optimal levels. Pragmatic choices will need to 11. Shek CC, Ng PC, Fung GPG, Cheng FWT, Chan PKS, Peiris MJS, Lee KH, Wong
be made about achievable and acceptable levels of care SF, Cheung HM, Li AM, Hon EK, Yeung CK, Chow CB, Tam JS, Chiu MC, Fok TF.
Infants Born to Mothers With Severe Acute Respiratory Syndrome. Pediatrics 2020;
according to national guidance and local adaptation. 112: e254.
Chest imaging should be undertaken in pregnant women 12. Alserehi H, Wali G, Alshukairi A, Alraddadi B. Impact of Middle East Respiratory
Syndrome coronavirus (MERS-CoV) on pregnancy and perinatal outcome. BMC
as clinically indicated. Infect Dis 2016; 16: 1–4.
Therapeutics announced as being under consideration 13. Jeong SY, Sung SI, Sung J, Ahn SY, Kang E, Chang YS, Park WS, Kim JH. MERS-CoV
Infection in a Pregnant Woman in Korea. J Korean Med Sci 2017; 3: 5–8.
and trial during the outbreak include Kaletra (lopinavir 14. Assiri A, Abedi G, Malak M, Abdulaziz B, Gerber S, Watson JT. Pregnancy: A
and ritonavir), remdesivir and chloroquine. Kaletra28 is Report of 5 Cases From Saudi Arabia. Clin Infect Dis 2016; 63: 951–953.
15. Park MH, Kim HR, Choi DH, Sung JH, Kim JH. Emergency cesarean section in an
used in the UK during pregnancy for treatment of HIV, epidemic of the middle east respiratory syndrome. Korean J Anesthesiol 2016; 69:
in which the benefits of treatment outweigh the risks 287–291.
16. Malik A, Medhat K, Masry E, Ravi M, Sayed F. Middle East Respiratory Syndrome
of toxicity seen in animal studies. The benefits of using Coronavirus during Pregnancy, Abu Dhabi, United Arab Emirates, 2013. Emerg
chloroquine outweigh the risks in the prevention and Infect Dis 2016; 22: 515–517.
17. Payne D, Ibrahim I, Sultan A. Stillbirth During Infection With Middle East
treatment of malaria during pregnancy29 . Remdesivir Respiratory Syndrome Coronavirus. J Infect Dis 2014; 209: 1870–1872.
has been used for the treatment of Ebola in pregnant 18. Alfaraj S, Al-Twfiq J, Memish Z. Middle East Respiratory Syndrome Coronavirus
(MERS-CoV) infection during pregnancy: Report of two cases & review of the
women30 . However, it should be acknowledged that literature. J Microbiol 2019; 52: 501–503.
Ebola is a condition with a CFR of 50%, and for which 19. Zhang J, Wang Y, Chen L, Zhang R, Xie Y. Clinical analysis of pregnancy in second
and third trimesters complicated severe acute respiratory syndrome. Zhonghua Fu
there would be higher tolerance for adverse effects of a Chan Ke Za Zhi 2003; 38: 516–520.
20. Ng WF, Wong SF, Lam A, Mak YF, Yao H, Lee KC, Chow KM, Yu WC, Ho LC. The
potentially beneficial treatment than would be the case placentas of patients with severe acute respiratory syndrome: A pathophysiological
for COVID-19, in which the CFR is around 1%. It would evaluation. Pathology 2006; 38: 210–218.
21. Gagneur A, Dirson E, Audebert S, Vallet S. Materno-fetal transmission of human
seem reasonable not to exclude seriously ill pregnant coronaviruses: a prospective pilot study. Eur J Clin Microbiol Infect Dis 2008; 2005:
women from trials of these therapies for COVID-19. 863–866.

© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd Ultrasound Obstet Gynecol 2020; 55: 586–592.
on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
592 Mullins et al.

22. Yudin M, Steele D, Sgro M, Read S, Kopplin P, Gough K. Severe acute respiratory 26. Poon LC, Yang H, Lee JCS, Copel JA, Leung TY, Zhang Y, Chen D, Prefumo F.
syndrome in pregnancy. Obstet Gynecol 2005; 105: 124–127. ISUOG Interim Guidance on 2019 novel coronavirus infection during pregnancy and
23. Bottomley C, Van Belle V, Pexsters A, Papageorghiou AT, Mukri F, Kirk E, Van puerperium: information for healthcare professionals. Ultrasound Obstet Gynecol
Huffel S, Timmerman D, Bourne T. A model and scoring system to predict outcome 2020; 55: 700–708.
of intrauterine pregnancies of uncertain viability. Ultrasound Obstet Gynecol 2011; 27. Centers for Disease Control and Prevention. Interim Considerations for Infection
37: 588–595. Prevention and Control of Coronavirus Disease 2019 (COVID-19) in Inpatient
24. Bignardi T, Condous G, Kirk E, Van Calsters B, Van Huffel S, Timmerman D, Obstetric Healthcare Settings, 2020. https://www.cdc.gov/coronavirus/2019-ncov/
Bourne T. Viability of intrauterine pregnancy in women with pregnancy of unknown hcp/inpatient-obstetric-healthcare-guidance.html
location: prediction using human chorionic gonadotropin ratio vs. progesterone. 28. British National Formulary. Kaletra. https://bnf.nice.org.uk/medicinal-forms/
Ultrasound Obstet Gynecol 2010; 35: 656–661. lopinavir-with-ritonavir.html
25. Wang L, Shi Y, Xiao T, Fu J, Feng X, Mu D, Feng Q, Hei M, Hu X, Li Z, 29. British National Formulary. Chloroquine. https://bnf.nice.org.uk/drug/chloroquine
Lu G, Tang Z, Wang Y, Wang C, Xia S, et al.; Working Committee on Perinatal .html#indicationsAndDoses
and Neonatal Management for the Prevention and Control of the 2019 Novel 30. Mulangu S, Dodd L, Davey R, Mbaya O, Proschan M, Mukadi D, Lusakibanza
Coronavirus Infection. Chinese expert consensus on the perinatal and neonatal Manzo M, Nzolo D, Tshomba Oloma A, Ibanda A, Ali R, Coulibaly S, Levine AC,
management for the prevention and control of the 2019 novel coronavirus infection Grais R, Diaz J, Lane HC, et al.; PALM Consortium Study Team. A Randomized,
(First edition). Ann Transl Med 2020; 8: 1–8. Controlled Trial of Ebola Virus Disease Therapeutics. NEJM 2019; 381: 2293–2203.

SUPPORTING INFORMATION ON THE INTERNET

The following supporting information may be found in the online version of this article:
Appendix S1 Search strategy

© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd Ultrasound Obstet Gynecol 2020; 55: 586–592.
on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.