COVID-19 pneumonia and pregnancy; a systematic review and meta-analysis

Abstract

Background: The new SARS-CoV-2 originated from Wuhan, China is spreading rapidly worldwide. A number of SARS-CoV-2 positive pregnant women have been reported. However, more information is still needed on the pregnancy outcome and the neonates regarding COVID-19 pneumonia.
Material and Methods: A systematic search was done and nine articles on COVID-19 pneumonia and SARS-CoV-2 positive pregnant women were extracted. Some maternal-fetal characteristics were extracted to be included in the meta-analysis.
Results: The present meta-analysis was conducted on 87 SARS-CoV-2 positive pregnant women. Almost 65% of the patients reported a history of exposure to an infected person, 78% suffered from mild or moderate COVID-19, 99.9% had successful termination, 86% had cough, and 68% had fever (p = .022 and p < .001). The overall proportions of vertical transmission, still birth, and neonatal death were zero, 0.002, and, 0.002, respectively (p = 1, p = .86, and p = .89, respectively). The means of the first- and fifth-minute Apgar scores were 8.86 and 9, respectively (p < .001 for both). The confounding role of history of underlying diseases with an estimated overall proportion of 33% (p = .03) resulted in further investigations due to sample size limitation. A natural history of COVID-19 pneumonia in the adult population was presented, as well.
Conclusion: Currently, no evidence of vertical transmission has been suggested at least in late pregnancy. No hazards have been detected for fetuses or neonates. Although pregnant women are at an immunosuppressive state due to the physiological changes during pregnancy, most patients suffered from mild or moderate COVID-19 pneumonia with no pregnancy loss, proposing a similar pattern of the clinical characteristics of COVID-19 pneumonia to that of other adult populations.

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COVID-19 pneumonia and pregnancy; a systematic
review and meta-analysis
Maryam Kasraeian, Marjan Zare, Homeira Vafaei, Nasrin Asadi, Azam Faraji,
Khadijeh Bazrafshan & Shohreh Roozmeh
To cite this article: Maryam Kasraeian, Marjan Zare, Homeira Vafaei, Nasrin Asadi, Azam Faraji,
Khadijeh Bazrafshan & Shohreh Roozmeh (2020): COVID-19 pneumonia and pregnancy; a
systematic review and meta-analysis, The Journal of Maternal-Fetal & Neonatal Medicine, DOI:
10.1080/14767058.2020.1763952
To link to this article: https://doi.org/10.1080/14767058.2020.1763952
Published online: 19 May 2020.
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ORIGINAL ARTICLE
COVID-19 pneumonia and pregnancy; a systematic review and meta-analysis
Maryam Kasraeian, Marjan Zare , Homeira Vafaei , Nasrin Asadi , Azam Faraji ,
Khadijeh Bazrafshan and Shohreh Roozmeh
Maternal-fetal medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
ABSTRACT
Background: The new SARS-CoV-2 originated from Wuhan, China is spreading rapidly world-
wide. A number of SARS-CoV-2 positive pregnant women have been reported. However, more
information is still needed on the pregnancy outcome and the neonates regarding COVID-
19 pneumonia.
Material and Methods: A systematic search was done and nine articles on COVID-19 pneumo-
nia and SARS-CoV-2 positive pregnant women were extracted. Some maternal-fetal characteris-
tics were extracted to be included in the meta-analysis.
Results: The present meta-analysis was conducted on 87 SARS-CoV-2 positive pregnant women.
Almost 65% of the patients reported a history of exposure to an infected person, 78% suffered
from mild or moderate COVID-19, 99.9% had successful termination, 86% had cough, and 68%
had fever (p¼.022 and p<.001). The overall proportions of vertical transmission, still birth, and
neonatal death were zero, 0.002, and, 0.002, respectively (p¼1, p¼.86, and p¼.89, respect-
ively). The means of the first- and fifth-minute Apgar scores were 8.86 and 9, respectively
(p<.001 for both). The confounding role of history of underlying diseases with an estimated
overall proportion of 33% (p¼.03) resulted in further investigations due to sample size limita-
tion. A natural history of COVID-19 pneumonia in the adult population was presented, as well.
Conclusion: Currently, no evidence of vertical transmission has been suggested at least in late
pregnancy. No hazards have been detected for fetuses or neonates. Although pregnant women
are at an immunosuppressive state due to the physiological changes during pregnancy, most
patients suffered from mild or moderate COVID-19 pneumonia with no pregnancy loss, propos-
ing a similar pattern of the clinical characteristics of COVID-19 pneumonia to that of other adult
populations.
ARTICLE HISTORY
Received 28 April 2020
Accepted 29 April 2020
KEYWORDS
COVID-19 pneumonia;
SARS-CoV-2 positive
pregnant women; maternal-
fetal outcomes; meta-
analysis; systematic review
Introduction
Among the seven zoonotic strains of coronaviruses, includ-
ing 229E, NL63, OC43, HKU1, Middle East Respiratory
Syndrome (MERS-CoV), Severe Acute Respiratory
Syndrome (SARS-CoV), and SARS-CoV-2, SARS-CoV-2 has
been responsible for the current pandemic in 2020.
Due to variation in its genetic structure in addition to
human-animal interaction, SARS-CoV infected many
people during 2002 and 2003, resulting in 774 deaths
[1]. Totally, 50% of SARS-CoV infected pregnant women
needed intensive care and about 33% of them needed
mechanical ventilation, with a death rate of almost 25%
in critical cases [2]. In 2012, another type of coronavirus;
i.e. MERS-CoV, originated from Saudi Arabia caused a
cluster of cases. SARS-CoV and MERS-CoV are both
known to be responsible for severe complications
during pregnancy, resulting in endotracheal intubation,
ICU admission, renal failure, and death [2,3].
From December 2019 onwards, SARS-Cov-2 has
caused COVID-19 pneumonia. It has been identified as
an upper and lower respiratory tract dysfunction origi-
nated from Wuhan, China. It rapidly caused epidemic
in China and was gradually spread in all continents,
except for Antarctica [4]. As the outbreak progressed,
person-to-person transmission through droplets and
fomites became the main source of transmission.
Pregnancy is a vulnerable period needing more
care and attention regarding both the mother and her
fetus. Pregnant women are particularly vulnerable to
respiratory pathogens and acute pneumonia since
they are at an immunosuppressive state because of
the physiological changes during pregnancy.
Moreover, increase in oxygen taking, diaphragm
CONTACT Marjan Zare marjan.zare@gmail.com Maternal-fetal Medicine (Perinatology) Research Center, Hafez Hospital, Chamran Ave., Mohammad
Rasoul Allah Tower, Opposite The Maaref School, Khalili Street, Shiraz, Iran
Due to the urgent and developing nature of the topic, this paper was accepted after an expedited peer review process. For more information about the
process, please refer to the instructions for authors.
ß2020 Informa UK Limited, trading as Taylor & Francis Group
THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
https://doi.org/10.1080/14767058.2020.1763952

elevation, and respiratory tract mucosa edema make
them susceptible to hypoxia [5,6].
The results of pregnancies infected with SARS-CoV-
2 are still unclear [7]. In comparison to SARS-CoV and
MERS-CoV, COVID-19 pneumonia has been supposed
be less severe with pregnant women [6,8,9].
Nonetheless, reporting of one SARS-CoV-2 positive
newborn infant in Wuhan Children’s Hospital in Hubai
Province, China on 5 February (during the epidemic)
led to the emergence of further questions regarding
the current status of SARS-Cov-2 infection among
pregnant women and neonates [10,11]. The current
meta-analysis and systematic review aims to deter-
mine the overall effects of COVID-19 pneumonia on
SARS-CoV-2 positive pregnant women and their new-
born infants.
Material and methods
A systematic literature search was performed in
English and Chinese in PubMed, Google Scholar,
MedRXiv, and UpToDate search engines up to 18
March 2020. The MeSH terms applied in PubMed
included “COVID-19 OR Wuhan coronavirus OR Wuhan
sea food market pneumonia OR COVID-19 virus OR
coronavirus disease 2019 virus OR SARS-CoV-2 OR
SARS-2 OR 2019-nCoV OR 2019 novel coronavirus”
AND “pregnancy OR gestation.”The terms used for
searching in Google Scholar, MedRXiv, and UpToDate
search engines included “Pregnancy, Pregnant,
Coronavirus, and SARS-CoV-2.”Out of the 11 eligible
records, two were review studies. Finally, nine studies
were included [5,6,12–18].
The data included COVID-19 severity (mild, moder-
ate, severe, ICU admission, and death), COVID-19 clin-
ical and lab characteristics (asymptomatic, cough,
fever, and lymphopenia), history of exposure to an
infected person, history of underlying diseases, suc-
cessful termination, rapture of membranes, and route
of termination (cesarean section and normal vaginal
delivery). Data regarding fetal distress, vertical trans-
mission, neonatal death, preterm and still birth, and
first- and fifth-minute Apgar scores, were also col-
lected for newborn babies.
A SARS-CoV-2 positive pregnant woman (mostly in
the third trimester) was defined as a patient suffering
from COVID-19 pneumonia with a positive lab test of
either oropharyngeal swab specimen or polymerase
chain reaction. To assess vertical transmission, cord
blood samples, placental tissues, and nasopharyngeal
swab samples were collected.
Defined effect size formats were generic point and
variance for dichotomous variables and mean and
standard deviation for continuous variables to com-
pute the overall effect sizes.
Forest plot with 95% Confidence Interval (CI) and
heterogeneity indices, including I
2
, Q-statistic, and p-
value, were reported. In case of heterogeneity, the
random effects model was used. In case of high het-
erogeneity of I
2
>70%, subgroup analysis was applied
to control heterogeneity.
Publication bias was evaluated using the funnel
plot. Sensitivity analysis was performed to assess the
stability of the results by removing one study each
time. All statistical analyses were performed using
Comprehensive Meta-Analysis software, version 2 and
type I error was considered to be 0.05.
Results
Accordingly, all patients, except for two who were in
the second trimester and were discharged, were in the
third trimester. The results of meta-analysis of mater-
nal, fetal, and neonatal characteristics of the 87 SARS-
CoV-2 positive pregnant women and the 86 newborn
infants in China during COVID-19 pneumonia epidemic
in 2020 have been reported in Table 1.
Maternal considerations and covid-19 pneumonia
An overall proportion of almost 65% exposure to an
infected person in SARS-CoV-2 positive pregnant
women that was significantly different from zero
(p¼.022) proved that the chain of transmission could
be curbed by following the most important and easi-
est rule of prevention; i.e. simply observing the stand-
ard distance of 190 cm in relationships. Pregnant
women have also been recommended to avoid going
out and to wear masks and sanitary gloves when
necessary. Sensitivity analysis removing one study
resulted in an overall proportion of 99% regarding the
history of exposure to an infected person (p<.001).
COVID-19 pneumonia appeared in mild or moder-
ate states in 78% of the pregnant women (p<.001).
Severe, ICU, and death cases were not statistically dif-
ferent from zero (p¼1, p¼.319, and p¼1,
respectively).
Among the two clinical characteristics and one lab
sign of COVID-19 pneumonia in pregnant women,
fever had the highest overall proportion of almost
86% and cough and lymphopenia had the overall pro-
portions of 68% and 70%, respectively (p<.001).
Moreover, asymptomatic COVID-19 pneumonia was
2 M. KASRAEIAN ET AL.

Table 1. The results of meta-analysis of maternal, fetal, and neonatal characteristics of the 87 SARS-CoV-2 positive pregnant
women and the 86 newborn infants in China during COVID-19 pneumonia epidemic in 2020.
Event (n¼number of
infected pregnant women
with COVID-19 pneumonia/
newborn babies) Study name Overall proportion pValue
ANOVA table for heterogeneity
I
2
Q-statistic pValue
History of exposure to an
infected person (n¼40)
Huijun Chen; 2020 1.000 <.001 70.375 666.939 <.001
Dehan Liu; 2020 0.600 <.001
Lei D; 2020 1.000 <.001
Weiyong Lui; 2020 0.000 1.000
Random 0.651 .022
COVID-19 severity
Severe (n¼25) Dehan Liu; 2020 0.000 1.000 0.000 0.000 .100
Xiaotong Wang; 2020 0.000 1.000
Lei D ; 2020 0.000 1.000
Fixed 0.000 1.000
ICU admission (n¼32) Huaping Zhu; 2020 0.000 1.000 0.000 2.507 .474
Lei D ; 2020 0.111 .267
Xiaotong Wang; 2020 0.000 .292
Yangli Lui; 2020 0.076 .282
Fixed 0.027 .319
Death (n¼87) Huijun Chen; 2020 0.000 1.000 0.000 1.096 .998
Dehan Liu; 2020 0.000 1.000
Huaping Zhu; 2020 0.000 1.000
Lei D ; 2020 0.000 1.000
Yu Han; 2020 0.000 1.000
Xiaotong Wang; 2020 0.000 1.000
Kenneth Mcintosh; 2020 0.000 1.000
Yangli Lui; 2020 0.000 1.000
Weiyong LIU; 2020 0.000 1.000
Fixed 0.000 1.000
Mild or moderate (n¼25) Dehan Liu; 2020 0.733 <.001 55.185 4.463 .107
Xiaotong Wang; 2020 0.000 <.001
Lei D ; 2020 0.890 <.001
Fixed 0.784 <.001
COVID-19 clinical and lab
characteristics
Asymptomatic (n¼28) Dehan Liu; 2020 0.000 1.00 95.958 74.229 <.000
Lei D ; 2020 0.890 <.001
Xiaotong Wang; 2020 0.000 .038
Yangli Lui; 2020 0.077 .276
Random 0.309 .092
Cough (n¼50) Huijun Chen; 2020 0.444 .739 85.110 33.579 <.001
Dehan Liu; 2020 0.600 .442
Huaping Zhu; 2020 0.890 .050
Xiaotong Wang; 2020 1.000 .008
Yangli Lui; 2020 0.538 .782
Weiyong LIU; 2020 0.333 .571
Random 0.680 <.001
Fever (n¼37) Huijun Chen; 2020 0.778 <.001 0.000 1.689 .891
Dehan Liu; 2020 0.867 <.001
Xiaotong Wang; 2020 1.000 <.001
Huaping Zhu; 2020 0.889 <.001
Weiyong LIU; 2020 0.667 .014
Fixed 0.865 <.001
Lymphopenia(n¼24) Huijun Chen; 2020 0.556 .001 40.800 .031 .194
Dehan Liu; 2020 0.800 <.001
Fixed 0.696 <.001
History of underlying
diseases (n¼75)
Huijun Chen; 2020 0.780 <.001 89.634 38.589 <.001
Dehan Liu; 2020 0.200 .046
Xiaotong Wang; 2020 0.000 .0100
Weiyong LIU; 2020 0.333 .221
Random 0.327 .031
Route of termination
Cesarean section(n¼69) Huijun Chen; 2020 1.000 <.001 72.396 18.615 .009
Dehan Liu; 2020 0.667 <.001
Huaping Zhu; 2020 0.778 <.001
Lei D ; 2020 1.000 <.001
Yu Han; 2020 1.000 <.001
Xiaotong Wang; 2020 1.000 <.001
Yangli Lui; 2020 0.770 .014
Weiyong LIU; 2020 0.666 <.001
Random 0.922 <.001
(continued)
THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 3

estimated to occur in 31%, which was not statistically
different from zero (p¼.09).
Successful termination was another critical aspect of
COVID-9 pneumonia in pregnancy. The overall propor-
tion of successful termination was estimated to be
99.9%, which was different from zero (p<.001). This
implies that there is no worry for SARS-CoV-2 positive
pregnant women about their termination success. The
forest and funnel plots of successful termination have
been presented in Graph 1, revealing I
2
¼0, Q-statistic ¼
4.36, and p¼.652.
Almost 92% of SARS-CoV-2 positive pregnant
women underwent cesarean section (p<.001), while
only 1% preferred to have normal vaginal deliv-
ery (p¼.47).
Maternal-fetal considerations and covid-
19 pneumonia
Pooling the results derived from these SARS-CoV-2
positive pregnant women showed that the overall pro-
portion of getting infected from an infected mother
Table 1. Continued.
Event (n¼number of
infected pregnant women
with COVID-19 pneumonia/
newborn babies) Study name Overall proportion pValue
ANOVA table for heterogeneity
I
2
Q-statistic pValue
Normal vaginal
delivery (n¼69)
Huijun Chen; 2020 0.000 1.000 4.223 7.309 .397
Dehan Liu; 2020 0.067 .274
Yu Han; 2020 0.000 1.000
Huaping Zhu; 2020 0.222 .107
Lei D ; 2020 0.000 1.000
Xiaotong Wang ; 2020 0.000 .114
Yangli Lui; 2020 0.000 1.000
Weiyong LIU; 2020 0.333 .221
Fixed 0.011 .476
Fetal distress (n¼31) Huaping Zhu; 2020 0.667 <.001 70.000 6.667 .036
Lei D ; 2020 0.222 .026
Yangli Lui; 2020 0.231 .044
Random 0.310 <.000
Rapture of
membranes (n¼31)
Huaping Zhu; 2020 0.333 .327 25.913 2.700 .259
Lei D ; 2020 0.222 .118
Yangli Lui; 2020 0.077 .017
Fixed 0.139 .017
Neonatal death (n¼86) Huijun Chen; 2020 0.000 1.000 0.000 1.215 .991
Dehan Liu; 2020 0.000 1.000
Huaping Zhu; 2020 0.111 .267
Lei D ; 2020 0.000 1.000
Yu Han; 2020 0.000 1.000
Kenneth Mcintosh; 2020 0.000 1.000
Yangli Lui; 2020 0.000 1.000
Weiyong LIU; 2020 0.000 1.000
Fixed 0.002 .895
Preterm delivery (n¼41) Huaping Zhu; 2020 0.670 <.001 34.705 4.595 .204
Lei D ; 2020 0.444 .007
Xiaotong Wang; 2020 0.800 <.001
Yangli Lui; 2020 0.461 .001
Fixed 0.612 <.000
Still birth (n¼87) Huijun Chen; 2020 0.000 1.000 0.000 1.157 .997
Dehan Liu; 2020 0.000 1.000
Huaping Zhu; 2020 0.000 1.000
Lei D ; 2020 0.000 1.000
Yu Han; 2020 0.000 1.000
Xiaotong Wang; 2020 0.000 1.000
Kenneth Mcintosh; 2020 0.000 1.000
Yangli Lui; 2020 0.077 .276
Weiyong LIU; 2020 0.000 1.000
Fixed 0.002 .865
Event Study name Overall mean pValue I
2
[N/A]
2
pValue
First-minute Apgar (n¼40) Huijun Chen; 2020 8.000 <.001 100.000 1.600 <.001
Dehan Liu; 2020 10.000 <.001
Yangli Lui; 2020 8.660 <.001
Weiyong LIU; 2020 8.000 <.001
Random 8.857 <.001
Fifth-minute Apgar (n¼25) Huijun Chen; 2020 9.000 <.001 92.744 0.000 <.001
Yangli Lui; 2020 9.770 <.001
Weiyong LIU; 2020 9.000 <.001
Random 9.000 <.001
4 M. KASRAEIAN ET AL.

was 0.000 (p¼1.000), indicating no intrauterine infec-
tion. The forest plot of vertical transmission has been
presented in Graph 2, with I
2
¼0, Q¼3.23, and p¼1.
Almost 60% of the babies were born prematurely
and 31% suffered from fetal distress (p<.001 for
both). Additionally, 14% of SARS-CoV-2 positive preg-
nant women were estimated to suffer from the rap-
ture of membranes (p¼.017). Fortunately, still birth
had an overall proportion of 0.2%, which was not dif-
ferent from zero (p¼.86).
Neonatal considerations and covid-19 pneumonia
The overall means of the first- and fifth-minute Apgar
scores were 8.86 and 9, respectively (p<.001 for
both). Furthermore, the overall neonatal death of 0.2%
(p¼.89) showed no hazards for the newborn infants
born from SARS-CoV-2 positive pregnant women.
History of underlying diseases was not shown to be
a confounder for COVID-19 pneumonia in pregnancy.
However, looking at the overall proportions of asymp-
tomatic COVID-19, cough, cesarean section, and fifth-
minute Apgar score in SARS-CoV-2 positive pregnant
women with a history of underlying diseases (I
2
¼75%,
88%, 68%, and 100%, respectively) showed that the
heterogeneity still existed at least in this subgroup
and might originate from another source that was not
included in the study.
Currently, COVID-19 pneumonia in pregnancy has
been supposed to follow the same pattern as other
adult populations. The natural history of COVID-19
pneumonia in adult populations has been
depicted below:
Discussion
The present study aimed to investigate the effects of
COVID-19 pneumonia among 87 SARS-CoV-2 positive
pregnant women with the median age of 30 years in
late pregnancy. Some effects of COVID-19 pneumonia
on the fetuses and infants born from these women
were explored, as well. The progressive COVID-19
pneumonia has been demonstrated to be highly con-
tagious. Almost 65% of the infected pregnant women
had an exposure to an infected person. Additionally,
an overall proportion of 68% had cough, 86% had
fever, and 70% had lymphopenia. An important find-
ing of this meta-analysis was that there was no evi-
dence of vertical transmission. Furthermore, 78% of
the pregnant women showed mild or moderate symp-
toms for SARS-CoV-2. In addition, the overall propor-
tions of successful termination and cesarean section
−2.0 −1.5 −1.0 −0.5 0.0 0.5 1.0 1.5 2.0
0.00
0.05
0.10
0.15
0.20
Proportion of successf ul termination
Funnel plot of standard error by proportion of successful termination
Standard
error
Study name Event Statistics for each study Point estimate and 95% CI
Proportion Lower Upper Relative
limit limit Z-value P-value weight
Huijun Chen; 2020 Successful termination 1.000 0.938 1.062 31.623 0.000 12.40
Dehan Liu; 2020 Successful termination 1.000 0.938 1.062 31.623 0.000 12.40
Huaping Zhu; 2020 Successful termination 1.000 0.938 1.062 31.623 0.000 12.40
Lei D; 2020 Successful termination 1.000 0.938 1.062 31.623 0.000 12.40
Yu Han; 2020 Successful termination 1.000 0.938 1.062 31.623 0.000 12.40
Xiaotong Wang; 2020 Successful termination 1.000 0.938 1.062 31.623 0.000 12.40
KennethMcintosh; 2020 Successful termination 1.00 0 0.938 1.062 31.623 0.000 12.40
Yangli Lui; 2020 S uccessful termination 0.900 0.652 1.148 7.115 0.000 0.78
Weiyong LIU; 2020 Successful termination 1.000 0.938 1.062 31.6 23 0.000 12.40
0.999 0.977 1.021 89.722 0.000
−1.00 −0.50 0.00 0.50 1.00
Fixed Overall proporon
Graph 1. The overall proportion of successful termination in 83 SARS-CoV-2 positive pregnant women in China during COVID-19
pneumonia epidemic in 2020.
THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 5

were 99.9% and 92%, respectively. An overall estima-
tion of 33% for the history of underlying diseases
could support the preference of cesarean section. The
overall means of the first- and fifth-minute Apgar
scores were 8.84 and 9, respectively. Furthermore,
some complications related to pregnancy namely pre-
maturity, fetal distress, and rapture of membranes
with the overall proportions of 61%, 31%, and 14%,
respectively were significantly different from zero.
However, asymptomatic COVID-19, severe COVID-19,
ICU admission, death, normal vaginal delivery, still
birth, and neonatal death were not significantly differ-
ent from zero. Since the history of underlying diseases
could influence pregnancy, its confounding role was
assessed with no clear result due to sample size limita-
tion regarding subgroups. Finally, a natural history of
COVID-19 pneumonia in adults was presented, which
could be similar to that of the pregnant women.
The overall proportion of mild or moderate COVID-
19 was 78%, which was close to its proportion in the
general adult population (81%). Severe COVID-19 and
ICU admission were not statistically different from
zero, indicating that SARS-CoV-2 could not cause
severe hazards in pregnant women during late preg-
nancy [19].
In one study comparing the clinical and laboratory
features of nine non-pregnant adults, 16 laboratory-
confirmed pregnant women, and 25 clinically diag-
nosed pregnant women, there were no differences
regarding cough (64%, 38%, and 36%, respectively;
p¼.195) and lymphopenia (79%, 56%, and 64%,
respectively; p¼.430). However, the three groups
were statistically different regarding fever (100%, 44%,
and, 36%, respectively; p<.001). The pregnant wom-
en’s lab signs like leukocytosis and elevated neutrophil
ratio were atypical, speculating that it is not wise to
delay managing the cases and to wait for confirmed
diagnosis [20]. In another study, fever and cough
respectively occurred in 88% and 67% of the cases,
which were respectively estimated to be 86% and
68% in the present study [19].
The global proportion of preterm birth has been
estimated to be 11%. This measure was found to be
4.06% in China in 2017. Both values were lower than
the overall proportion of 60% in SARS-CoV-2 positive
pregnant women in the current study, demonstrating
a higher trend of preterm birth with COVID-19 pneu-
monia [21,22].
Generally, the rate of cesarean section increases
with the population’s economic status. The global rate
of cesarean section was approximately 29.7% in 2017.
In China as a high-income country, the rate of
cesarean section was 41.1% and that of normal vaginal
delivery was 78.68% in 2015. In the present study, the
overall proportion of cesarean section was 92%
[23–25]. Some reasons for undergoing cesarean sec-
tion included having an underlying disease, obstetri-
cian’s tendency to have less complicated deliveries,
and elective cesarean sections due to intolerance
against respiratory dysfunction in the pregnancies
accompanied by SARS-CoV-2.
Premature rupture of membranes has been associ-
ated with high maternal and perinatal morbidity and
mortality risks. It has been reported to occur in 5-10%
of all pregnancies [26,27]. The present study findings
estimated the rate of rupture of membranes as 14%,
which was higher compared to healthy preg-
nant women.
The Apgar score ranges from 7 to 10 in normal
newborns [28,29]. In the current research, the overall
means of the first- and fifth-minute Apgar scores did
not deviate from the normal values, indicating no haz-
ards for the infants born from SARS-CoV-2 posi-
tive women.
The global proportion of stillbirth has been
reported to be 1.5%. This value was found to be 0.5%
in China in 2017. It was also estimated to be 0.02% in
the current investigation, presenting no difference
from zero in SARS-CoV-2 positive pregnant women
[30]. Similar results were also obtained for neonatal
death, with the global rate of 1.2% and rate of 0.4% in
China based on 2017 reports [22].
Unfortunately, the underlying diseases accompa-
nied with pregnancies were not specified in the pre-
sent study. The underlying diseases were only
identified in five SARS-CoV-2 positive pregnant
women. Accordingly, two women had gestational
hypertension since the 27th week of gestation and
one suffered from preeclampsia at week 31 [6].
Additionally, one patient had thalassemia and gesta-
tional diabetes, one had undergone mitral and tricus-
pid valve replacement 10 years ago, and one had
complete placenta previa [5]. Overall, underlying dis-
eases could aggravate the COVID-19 pneumonia sever-
ity in SARS-CoV-2 positive pregnant women.
In the current study, the clinical characteristics of
the pregnant women with COVID-19 pneumonia were
shown to be the same as those of the adult popula-
tion developing COVID-19.
The present investigation revealed no direct evi-
dence of vertical transmission. The reported newborn
infant was negative for SARS-CoV-2 in both placenta
and cord blood, but pharyngeal swab specimen was
not taken at birth. Positive swabs for SARS-CoV-2 were
6 M. KASRAEIAN ET AL.

collected 36 h after birth. Therefore, the possibility of
transmission by droplets and close contacts could not
be neglected [14,31]. Similar to pregnancies with
SARS-CoV and MERS-CoV, there were no confirmed
cases of intrauterine transmission of SARS-CoV-2 from
the mothers with COVID-19 to their fetuses .
Person-to-person transmission of SARS-CoV-2 has
been supposed to be the same as influenza and other
respiratory pathogens. These respiratory droplets are
transmitted through sneeze and cough and are
inhaled by close contact within 190 cm [32]. Hence,
initial management needs to be focused on detecting
the suspected cases and immediate isolation. Airborne
precautions are also recommended, especially in some
countries and high-risk people [17].
The most important point of the current investiga-
tion was that it was the first systematic review and
meta-analysis on COVID-19 pneumonia and pregnancy
during the current epidemic recruiting the related
studies done on the same area up to 18 March 2020.
It may offer a bright insight to the scientists and
experts controlling the tragedy of the year.
Since COVID-19 pneumonia is a new infection and
more information is required to judge its various
aspects, the present meta-analysis had several limita-
tions. Firstly, the systematic search strategy was
focused on COVID-19 pneumonia and pregnancy
MeSH terms, and no specific effect size was consid-
ered. In other words, it was tried to analyze all
reported pregnancy features affected by COVID-19
pneumonia. As a result, there was a fluctuation in
sample size regarding each event in the meta-analysis
process since not all studies had reported all events.
Another limitation impressed by sample size was
assessing the confounding role of the history of
underlying diseases, which was considered to be a
potential confounder based on the experts’opinions.
In some studies, there was an event in one con-
founder category, while there were no events in the
other category of the confounder. Therefore, its con-
founding role has remained ambiguous. Furthermore,
the indications for preterm birth, rupture of mem-
branes, neonatal death, and fetal distress were not
reported precisely in few studies.
Acknowledgements
The authors would like to thank Ms. A. Keivanshekouh at
the Research Improvement Center of Shiraz University of
Medical Sciences for improving the use of English in
the manuscript.
Disclosure statement
No potential conflict of interest was reported by
the author(s).
ORCID
Marjan Zare http://orcid.org/0000-0002-0199-3230
Homeira Vafaei http://orcid.org/0000-0002-9399-7836
Nasrin Asadi http://orcid.org/0000-0002-2089-8941
Azam Faraji http://orcid.org/0000-0001-6534-2923
Khadijeh Bazrafshan http://orcid.org/0000-0002-
6345-1277
Shohreh Roozmeh http://orcid.org/0000-0002-4254-2049
References
[1] de Wit E, van Doremalen N, Falzarano D, et al. SARS
and MERS: recent insights into emerging coronavi-
ruses. Nat Rev Microbiol. 2016;14(8):523–534.
[2] Wong SF, Chow KM, Leung TN, et al. Pregnancy and
perinatal outcomes of women with severe acute
respiratory syndrome. Am J Obstet Gynecol. 2004;
191(1):292–297.
[3] Alfaraj SH, Al-Tawfiq JA, Memish ZA. Middle East
Respiratory Syndrome Coronavirus (MERS-CoV) infec-
tion during pregnancy: report of two cases & review
of the literature. J Microbiol Immunol Infect. 2019;
52(3):501–503.
Study name Event Statistics for each study Point estimate and 95% CI
Lower Upper Relative
Proportion
limit limit Z-value P-value weight
Vertical transmission
Vertical transmission
Vertical transmission
Vertical transmission
Vertical transmission
Vertical transmission
Vertical transmission
0.062 0.000 1.000 14.29
0.062 0.000 1.000 14.29
0.062 0.000 1.000 14.29
0.062 0.000 1.000 14.29
0.062 0.000 1.000 14.29
0.062 0.000 1.000 14.29
0.000 −0.062
0.000 −0.062
0.000 −0.062
0.000 −0.062
0.000 −0.062
0.000 −0.062
0.000 −0.062
Huijun Chen; 2020
Dehan Liu; 2020
Huaping Zhu; 2020
Lei D; 2020
Yu Han; 2020
Xiaotong Wang; 2020
Weiyong LIU; 2020 0.062 0.000 1.000 14.29
0.000 0.023−0.023 0.000 1.000
−1.00 −0.50 0.00 0.50 1.00
Fixed Overall proporon
Graph 2. The overall proportion of vertical transmission in 50 newborn infants born from SARS-CoV-2 positive pregnant women
in China during epidemic in 2020.
THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 7

[4] Ong SWX, Tan YK, Chia PY, et al. Air, surface environ-
mental, and personal protective equipment contamin-
ation by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) from a symptomatic
patient. JAMA. 2020;323(16):1610.
[5] Liu D, Li L, Wu X, et al. Pregnancy and perinatal out-
comes of women with COVID-19 pneumonia: a pre-
liminary analysis. Available at SSRN 3548758, 2020.
https://www.ncbi.nlm.nih.gov/pubmed/32186894
[6] Chen H, Guo J, Wang C, et al. Clinical characteristics
and intrauterine vertical transmission potential of
COVID-19 infection in nine pregnant women: a retro-
spective review of medical records. Lancet. 2020;
395(10226):809–815.
[7] Xu X-W, Wu X-X, Jiang X-G, et al. Clinical findings in a
group of patients infected with the 2019 novel cor-
onavirus (SARS-Cov-2) outside of Wuhan, China: retro-
spective case series. BMJ. 2020;368:m606.
[8] Huang C, Wang Y, Li X, et al. Clinical features of
patients infected with 2019 novel coronavirus in
Wuhan, China. Lancet. 2020;395(10223):497–506.
[9] Li Q, Guan X, Wu P, et al. Early transmission dynamics
in Wuhan, China, of novel coronavirus–infected pneu-
monia. N Engl J Med. 2020;382(13):1199–1207.
[10] Qiao J. What are the risks of COVID-19 infection in
pregnant women? Lancet. 2020;395(10226):760–762.
[11] Schwartz DA. An analysis of 38 pregnant women with
COVID-19, their newborn infants, and maternal-fetal
transmission of SARS-CoV-2: maternal coronavirus
infections and pregnancy outcomes. Arch Pathol Lab
Med. 2020:1–20. ISSN:0003-9985. DOI:10.5858/arpa.
2020-0901-SA.
[12] Zhu H, Wang L, Fang C, et al. Clinical analysis of 10
neonates born to mothers with 2019-nCoV pneumo-
nia. Transl Pediatr. 2020;9(1):51–60.
[13] Lei D, Li C, Fang C, et al. Clinical characteristics of
pregnancy with the 2019 novel coronavirus disease
(COVID-19) infection. Chin J Perinat Med. 2020;23(3):
157–163.
[14] Han Y, Yang H. The transmission and diagnosis of
2019 novel coronavirus infection disease (COVID-19):
a Chinese perspective. J Med Virol. 2020;92(6):
639–644.
[15] Liu Y, Chen H, Tang K, et al. Clinical manifestations
and outcome of SARS-CoV-2 infection during preg-
nancy. J Infect. 2020. pii: S0163-4453(20)30109-2. DOI:
10.1016/j.jinf.2020.02.028
[16] Liu W, Wang Q, Zhang Q, et al. Coronavirus Disease
2019 (COVID-19) During Pregnancy: A Case Series.
2020. https://www.preprints.org/manuscript/202002.
0373/v1
[17] McIntosh K, Hirsch MS, Bloom A. Coronavirus disease
2019 (COVID-19). 2020. https://apps.who.int/iris/bit-
stream/handle/10665/331685/nCoVsitrep01Apr2020-
eng.pdf
[18] Wang1a X, Zhou2a Z, Zhang J, et al. A case of 2019
Novel Coronavirus in a pregnant woman with
preterm delivery. 2020. DOI:10.1093/cid/ciaa200.
[Epub ahead of print]
[19] Joseph T, Ashkan M. COVID-19. 2020. http://turkpedo.
org/wp-content/uploads/2020/04/pulmonologist.pdf
[20] Liu H, Liu F, Li J, et al. Clinical and CT imaging fea-
tures of the COVID-19 pneumonia: focus on pregnant
women and children. J Infect. 2020;80(5):e7–e13.
[21] Vogel JP, Chawanpaiboon S, Moller A-B, et al. The
global epidemiology of preterm birth. Best Pract Res
Clin Obstet Gynaecol. 2018;52:3–12.
[22] Wang H, Yue H, Sun B, et al. Birth population survey
in Huai’an in 2015: perinatal-neonatal mortality and
preterm birth rate in emerging regions in China. J
Matern Fetal Neonatal Med. 2020;33(5):838–846.
[23] Boatin AA, Schlotheuber A, Betran AP, et al. Within
country inequalities in caesarean section rates: obser-
vational study of 72 low and middle income coun-
tries. BMJ. 2018;360:k55.
[24] Boerma T, Ronsmans C, Melesse DY, et al. Global epi-
demiology of use of and disparities in caesarean sec-
tions. Lancet. 2018;392(10155):1341–1348.
[25] Zhao L, Lin Y, Jiang T-t, et al. Vaginal delivery among
women who underwent labor induction with vaginal
dinoprostone (PGE2) insert: a retrospective study of
1656 women in China. J Matern Fetal Neonatal Med.
2019;32(10):1721–1727.
[26] Gayak K, Palakodeti N. A comparitive study on induc-
tion of labour versus expectant management in term
premature rupture of membranes in tertiary care hos-
pital, Visakhapatnam. Glob J Res Anal. 2019;8(10):
28–29.
[27] Ocviyanti D, Wahono WT. Risk factors for neonatal
sepsis in pregnant women with premature rupture of
the membrane. J Pregnancy. 2018;2018:1–6.
[28] Razaz N, Cnattingius S, Joseph K. Association between
Apgar scores of 7 to 9 and neonatal mortality and
morbidity: population based cohort study of term
infants in Sweden. BMJ. 2019;365:l1656
[29] Siddiqui A, Cuttini M, Wood R, et al. Can the Apgar
score be used for international comparisons of new-
born health? Paediatr Perinat Epidemiol. 2017;31(4):
338–345.
[30] Oladimeji O. Global, regional, and national under-5
mortality, adult mortality, age-specific mortality, and
life expectancy, 1970–2016: a systematic analysis for
the Global Burden of Disease Study 2016. 2018.
http://ecommons.hsrc.ac.za/handle/20.500.11910/12052
[31] Zhang Z, Wang C, Gao C. Neonatal coronavirus expert
confirmed at 30 h of birth: vertical transmission from
mother to infant. 2020;395:809–815. https://www.sci-
encedirect.com/science/article/pii/S0140673620303603?
casa_token=tLmHTYJap8MAAAAA:b8SKT6MczLQAfhwbD
Di0ECXq8Oqo75IOvawdlsThuG3Zds9YMLuSKM7T4pcMe-
VuReGtgFVXdeQ
[32] Rasmussen SA, Smulian JC, Lednicky JA, et al.
Coronavirus disease 2019 (COVID-19) and pregnancy:
what obstetricians need to know. Am J Obstet
Gynecol. 2020;222(5):415–426.
8 M. KASRAEIAN ET AL.