Journal of Obstetrics and Gynaecology

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Evaluation of pregnancy outcomes in mothers

with COVID-19 infection: a systematic review and
meta-analysis

Masoumeh Simbar, Sima Nazarpour & Ali Sheidaei

To cite this article: Masoumeh Simbar, Sima Nazarpour & Ali Sheidaei (2023) Evaluation
of pregnancy outcomes in mothers with COVID-19 infection: a systematic review
and meta-analysis, Journal of Obstetrics and Gynaecology, 43:1, 2162867, DOI:
10.1080/01443615.2022.2162867

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JOURNAL OF OBSTETRICS AND GYNAECOLOGY
2023, VOL. 43, NO. 1, 2162867
https://doi.org/10.1080/01443615.2022.2162867

REVIEW ARTICLE

Evaluation of pregnancy outcomes in mothers with COVID-19 infection:

a systematic review and meta-analysis
Masoumeh Simbara , Sima Nazarpourb and Ali Sheidaeic
a
Midwifery and Reproductive Health Research Center, Department of Midwifery and Reproductive Health, School of Nursing and Midwifery,
Shahid Beheshti University of Medical Sciences, Tehran, Iran; bDepartment of Midwifery, Varamin-Pishva Branch, Islamic Azad University,
Tehran, Iran; cDepartment of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

ABSTRACT ARTICLE HISTORY

Pregnant women are one of the endangered groups who need special attention in the COVID-19 epi­ Received 13 May 2022
demic. We conducted a systematic review and summarised the studies that reported adverse preg­ Accepted 17 December 2022
nancy outcomes in pregnant women with COVID-19 infection. A literature search was performed in
KEYWORDS
PubMed and Scopus up to 1 September 2022, for retrieving original articles published in the English
Coronavirus; COVID-19;
language assessing the association between COVID-19 infection and adverse pregnancy outcomes. pregnancy outcomes;
Finally, in this review study, of 1790 articles obtained in the initial search, 141 eligible studies including SARS-CoV-2; systematic
1,843,278 pregnant women were reviewed. We also performed a meta-analysis of a total of 74 cohort review; meta-analysis
and case-control studies. In this meta-analysis, both fixed and random effect models were used.
Publication bias was also assessed by Egger’s test and the trim and fill method was conducted in case
of a significant result, to adjust the bias. The result of the meta-analysis showed that the pooled preva­
lence of preterm delivery, maternal mortality, NICU admission and neonatal death in the group with
COVID-19 infection was significantly more than those without COVID-19 infection (p<.01). A meta-re­
gression was conducted using the income level of countries. COVID-19 infection during pregnancy may
cause adverse pregnancy outcomes including of preterm delivery, maternal mortality, NICU admission
and neonatal death. Pregnancy loss and SARS-CoV2 positive neonates in Lower middle income are
higher than in High income. Vertical transmission from mother to foetus may occur, but its immediate
and long-term effects on the newborn are unclear.

Introduction those reported in non-pregnant patients (Chen et al. 2020,

Yu et al. 2020).
Severe acute respiratory syndrome caused by COVID-19
Pregnant women are a high-risk population for infectious
(SARS-CoV-2) is an emerging and rapidly evolving situation respiratory diseases. This may be due to physiological and
and a global public health emergency and crisis that can anatomical changes, such as an increase in the transverse
cause severe lung disease and death (World Health diameter of the chest, diaphragm elevation, decreased lung
Organization 2020). The spread of this virus has caused a capacity and functional residual volumes, increased heart rate
devastating epidemic, challenged health and social services and oxygen consumption, respiratory tract mucosa oedema,
and led to high mortality rates that vary according to the and increased secretions in the upper respiratory tract follow­
epidemiological and social characteristics of each country ing vasodilation (O’Day 1997, Ramsey and Ramin 2001,
(Mascarenhas et al. 2020). Despite efforts to control the Mosby et al. 2011, Mertz et al. 2013, Chen et al. 2020, Liu
et al. 2020a, 2020c). These alterations may increase the risk
pathogen, COVID-19 was considered a pandemic by the
of more severe disease compared with no pregnant adults. In
WHO on 11 March 2020 (Silva et al. 2020).
addition to these mechanical changes, immunological adap­
Clinical manifestations of this disease range from asymp­
tation is essential to ensure maternal tolerance to the foetus,
tomatic cases and mild upper airway infection to severe and
which makes pregnant women a more vulnerable group
fatal cases with pneumonia and acute respiratory failure (Silva et al. 2020). The first and third trimesters of pregnancy
(Lopes de Sousa et al. 2020). Studies to date have shown can be considered periods of increased inflammatory activity,
that the clinical, radiological and laboratory features of while the second trimester is a period of decreased overall
COVID-19 pneumonia in pregnant women are similar to immune system activity (Mor et al. 2017, Liu et al. 2020b).

CONTACT Sima Nazarpour [email protected] Department of Midwifery, Varamin-Pishva Branch, Islamic Azad University, Tehran, Iran; Reproductive
Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, 24 Parvaneh St., Yaman Street,
Velenjak, P.O. Box 19395-4763, 1985717413 Tehran, Iran
Supplemental data for this article can be accessed online at https://doi.org/10.1080/01443615.2022.2162867
� 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
2 M. SIMBAR ET AL.

Changes in cell-mediated immunity lead to increased suscep­ ‘pregnancy-induced hypertension’ OR ‘PIH’ OR ‘gestational
tibility of pregnant women to being infected with intracellu­ diabetes’ OR ‘GDM’ OR ‘hemorrhage’ OR ‘postpartum hemor­
lar organisms such as viruses (Zaigham and Andersson 2020). rhage’ OR ‘PPH’ OR ‘Placenta abruption’ OR ‘placenta previa’
Considering the importance of pregnancy outcomes, it is OR ‘preterm’ OR ‘premature rupture of membrane’ OR
essential to obtain knowledge about pregnancy outcomes ‘PROM’ OR ‘Intrauterine growth restriction’ OR ‘IUGR’ OR
during the COVID-19 epidemic, including the severity of ‘small for gestational age’ OR ‘SGA’ OR ‘Low birth weight’
symptoms in pregnant women, possible complications during OR ‘LBW’ OR ‘oligohydramnios’ OR ‘Apgar’ OR ‘fetal distress’
pregnancy, the possibility of vertical transmission, and the OR ‘SARS-CoV-2 infection of the neonate’ OR ‘neonatal dis­
condition of infected infants. tress’ OR ‘RDS’ OR ‘neonatal death’ OR ‘neonatal mortality’
In this way, healthcare workers can be adequately OR ‘neonatal admission’ OR ‘NICU admission’ OR
equipped with knowledge about the prognoses and manage­ ‘malformation’ OR ‘anomalies’). Table S1 shows search strat­
ment of pregnant women with COVID-19. Although studies egy of the study.
on pregnancy outcomes in COVID-19 are increasing, most of
them are case reports or case series with small population
samples and conflicting results and the majority of cohort Selection criteria, study selection and data extraction
studies have focussed on evaluating the effects of COVID-19 In this systematic review and meta-analysis, all the studies
on the general population. Additionally, there is a wide vari­ with an observational design including case-series, cross-sec­
ation in the methodology and data reporting in recently pub­ tional, case-control, and prospective or retrospective cohort
lished articles, making accurate data interpretation difficult. studies were included.
The aim of this study was to conduct a systematic review Studies were included if they met the following criteria:
and meta-analysis of the published literature on pregnancy (1) the study population included pregnant women who had
with COVID-19 to evaluate the effect of this novel infection COVID-19 infection confirmed by positive viral SARS-CoV-2
on maternal, perinatal and neonatal outcomes. RNA testing; (2) the outcome of interest was at least one
adverse pregnancy outcome.
We also excluded non-original studies including guide­
Methods
lines, review articles, case reports, animal studies, studies per­
The present systematic review was conducted based on the formed in vitro, commentaries, editorials, correspondences,
Preferred Reporting Items for Systematic Reviews and letters to the editor, meeting abstracts, as well as studies
Meta-Analyses (PRISMA) (Moher et al. 2009). This study was that did not provide accurate and clear data.
approved by the Research Ethics Committees of Vice-Chancellor After removing duplicates recognised in databases and
in Research Affairs-Shahid Beheshti University of Medical reference lists, titles and abstracts were screened to evaluate
Sciences (approval code: IR.SBMU.RETECH.REC.1399.760); and the suitability of the manuscript based on the final eligibility
the study was registered in the International Prospective criteria.
Register of Systematic Reviews (PROSPERO) (code: The first assessment, carried out by three investigators
CRD42022360777). The PICO question of this study was: in (SN, MS and ASh). Disagreements were resolved through sci­
pregnant women with COVID-19 infection, what are adverse entific discussions. The general characteristics of the studies,
pregnancy outcomes, compared to those without COVID-19? including the first author’s name, article title, journal name,
country of study, publication year, study design, sample size,
population characteristics and pregnancy outcomes were
Search strategy extracted from the studies and assessed. To prevent extrac­
An electronic literature search was conducted independently tion and data entry errors, a control check between the final
by two authors, who were familiar with search methods and data used in the systematic review and the original publica­
information sources, without any restrictions, in the PubMed tions was conducted by all authors.
(including Medline) and Scopus databases for retrieving ori­
ginal articles published in English language assessing the
Quality assessment
association between COVID-19 infection and adverse preg­
nancy outcomes up to 1 September 2022. Furthermore, to All studies included in the present systematic review were
maximise the identification of eligible studies, reference lists critically appraised for the quality of their methodological
of relevant articles and reviews included were manually eval­ and the presented results. Three reviewers, blinded to study
uated as well. The following keywords, either alone or in author, journal name and institution, evaluated the quality of
combination, were used for the search: (‘coronavirus’ OR the studies independently using the Critical Appraisal
‘COVID-19’ OR ‘SARS-CoV-2’ OR ‘SARS-2’ OR ‘2019-nCoV’ OR Checklist recommended by the Joanna Briggs Institute for a
‘2019 novel coronavirus’) AND (‘pregnancy’ OR ‘pregnant variety of studies (cohort, case-control, cross-sectional and
women’ OR ‘maternal’ OR ‘gestational’) AND (‘adverse preg­ case series studies) (Munn et al. 2019), and disagreements
nancy outcomes’ OR ‘pregnancy outcomes’ OR ‘pregnancy were resolved by consensus. The Joanna Briggs Institute
complications’ OR ‘neonatal outcomes’ OR ‘abortion’ OR Critical Appraisal tools included eight questions for cross-sec­
‘miscarriage’ OR ‘pregnancy loss’ OR ‘fetal death’ OR ‘stillbirth’ tional and case series studies, nine questions for reporting
OR ‘preeclampsia’ OR ‘gestational hypertension’ OR prevalence data, 10 questions for case-control studies and 11
 JOURNAL OF OBSTETRICS AND GYNAECOLOGY 3

questions for cohort studies, that reviewers addressed for using income level of countries according to the World Bank
each study. The answer ‘yes’ to each question received one classification (Bank 2021).
point. Thus, the final scores for each study could range from All the analysis and graphical presentations were done in
0 to 8, 0 to 9, 0 to 10 and 0 to 11 for cross-sectional and R statistical software version 4.0.5 (R Foundation for
case series studies, reporting prevalence data, case-control Statistical Computing, Vienna, Austria) and the ‘meta’ library
studies and cohort studies, respectively. Table S2 shows in this environment. All the confidence intervals were
results of quality assessment of included studies. reported at 95%, and the tests were considered significant if
the p value was calculated as less than .05.

Outcome measures in meta-analysis

Maternal, neonatal and foetal outcomes of interest were cate­ Results
gorised into 10 outcomes, including five composite outcomes
Search results and study selection
including: (1) preterm delivery was defined as birth below
37 weeks of gestation (preterm <34 weeks, and <37 weeks), As the flowchart of the literature search in Figure 1 shows,
(2) pregnancy loss was defined as death of an unborn baby the search strategy yielded 1790 potentially relevant articles.
(foetus) at any time during pregnancy (abortion, foetal death, Based on selection inclusion criteria, 213 articles were identi­
foetal loss, still birth), (3) PROM was defined as rupture fied for further full-text assessment. We included 141 studies,
(breaking open) of the membranes (amniotic sac) before which included data from 1,843,278 pregnant women for this
labour begins (PROM and PPROM), (4) IUGR/SGA was systematic review.
described a foetus that has not reached its growth potential Out of 141 studies included, seven were case-control, 28
(IUGR) and/or an infant whose birth weight was below the were case series, 26 were cross-sectional and 80 were cohort
10th percentile for the appropriate gestational age (SGA), (5) studies. Finally, a total of 74 including 69 cohort and five
hypertension disorders of pregnancy (PIH, preeclampsia and case-control studies were included in this meta-analysis.
severe preeclampsia, eclampsia), (6) GDM was defined as any Table 1 shows the characteristics of cohort and case-control
degree of glucose intolerance with onset or first recognition studies included in the meta-analysis.
during pregnancy, (7) maternal mortality was defined as the The articles were published in various geographical
death of a woman from direct or indirect obstetric causes, (8) regions. Most studies were conducted in China (45 studies)
LBW defined an infant born weighing 2500 g or less, (9) or the United States (34 studies). Ten studies compared the
NICU admission was defined as the admission of a Neonatal pregnancy outcomes before and during the COVID-19 pan­
Intensive Care Unit and (10) neonatal death was defined as demic or lockdown (Ashish et al. 2020, Justman et al. 2020,
the death of a live born infant, regardless of gestational age Cauldwell et al. 2021, Du et al. 2021, Goyal et al. 2021,
at birth, within the first 28 completed days of life. Kirchengast and Hartmann 2021, Ranjbar et al. 2021,
Rotshenker-Olshinka et al. 2021, Shakespeare et al. 2021, Wilk
et al. 2021). Tables S3– S6 show the summary of the main
Statistical analysis
characteristics of the studies included in the systematic
This study was conducted to estimate the pooled prevalence review.
of pregnancy adverse outcomes in COVID-19 infected moth­
ers. In addition, we compared the prevalence of outcomes
Meta-analysis of outcomes
with the control groups in case of data availability. The
‘Meta-prop’ using the Mantel– Haenszel method was applied Figures S1– S11 illustrate the forest plots of the pooled preva­
to estimate the prevalence of outcomes in each group. The lence of pregnancy outcomes in pregnant women with and
heterogeneity was assessed using I-squared statistics consid­ without Covid infection. Results showed that the pooled
ering the threshold of 50% and the p value less than .05 for prevalence of preterm delivery, maternal mortality, NICU
the significance of the related test. In this regard, we selected admission and neonatal death in the group with COVID-19
the random effect model if the data heterogeneity was con­ infection (14.32 (95% CI: 12.07, 16.91), 0.65 (95% CI: 90.37,
firmed. For the other situations, the fixed effect model was 1.130), 14.57 (95% CI: 10.15, 20.48), 0.65 (95% CI: 0.51, 0.83),
chosen. The difference between subgroups was explored respectively) were significantly more than those without
using Chi-squared statistics at the significant level of .05. COVID-19 infection (5.57 (95% CI: 3.2, 9.52), 0.02 (95% CI:
We explored the publication bias using the graphical 0.01, 0.11), 4.53 (95% CI: 2.45, 8.22), 0.06 (95% CI: 0.05, 0.08),
approach funnel plot and Egger’s test. In case of a p value respectively).
less than .05 for the Egger test, we applied the trim and filled There was no significant difference in the pooled preva­
method. The forest plots for all outcomes pooled prevalence lence of other pregnancy outcomes including PROM, GDM,
were depicted. All these plots included the study-specific hypertensive disorders, IUGR/SGS, LBW, PPH and pregnancy
data and the random and fixed effect pooled prevalence. loss. The pooled prevalence of SARS-CoV2 positive neonates
A meta-regression approach was used to explore the was 2.04 (95% CI: 1.71; 2.45).
impact of geographical and economic variations on the out­ The meta-regression results showed that the mean preva­
comes. In this manner, the prevalence regresses on the lence of pregnancy loss in lower middle income and upper
income level of countries. The countries were classified as middle-income countries were 1.23% (p value ¼ .03) and
high income, lower middle income or upper middle income 1.27% (p value ¼ .001) higher than in high-income countries,
4 M. SIMBAR ET AL.

Records identified through Records identified through

database searches: hand searches:

Identification
(n = 1787) (n = 3)

Records after duplicates

removed:
(n = 972)
Screening

Records excluded. unrelated aim with

Records screened based on this study (n = 175):
title and abstract: o Irrelevant articles (n=61)
(n =388) o Review articles or guidelines, case
reports and letters to the editor (n= 114)
Eligibility

Full-text articles assessed for Full-text articles excluded: (n = 72)

eligibility: o Inappropriate data (n= 30)
(n = 213) o Focusing on clinical management and
treatment (n= 16)
o Focusing on pathogenesis (n=8)
o Focusing on vaccine (n=18)
Included

Total number of studies

included in this systematic
Review (n= 141):
Case series (n= 28);
Case-Control: (n= 7);
Cohort: (n= 80);
Cross Sectional: (n= 26)

Selected Article for meta-

analysis (n= 74):
Case-Control: (n= 5);
Cohort: (n= 69)

Figure 1. Flowchart of the literature search for the systematic review.

respectively. The mean prevalence of SARS-CoV2 positive show the results of the trim and fill of these pregnancy
neonates in lower middle income was 1.04% higher than in outcomes.
high-income countries (p value ¼ .009). While the mean
prevalence of PPH in lower middle-income countries was
Quality assessment
1.3% lower than high-income countries (p value ¼ .016).
Table 2 shows results of the meta-regression using income Quality assessment based on the Critical Appraisal Checklist
level of countries (according to the World Bank classification). showed that among seven case-control studies, four studies
were classified as being of high quality (8– 10 score) and
three studies had moderate quality (5– 7 score); among 28
case series, 18 studies were classified as being of high quality
Publication bias (7– 8 score) and 10 studies had moderate quality (5– 6 score);
Figures S12– S23 show the funnel plots of the results of publi­ among of 26 cross-sectional, two studies were classified as
cation biases based on Egger’s test in adverse pregnancy being of high quality (7– 8 score), 22 studies had moderate
outcomes. quality (5– 6 score) and two studies had low quality
Egger’s test shows significant publication biases among (�4 scores); among 80 cohort studies, 67 studies were classi­
studies investigating the prevalence of hypertensive disorders fied as being of high quality (9–11 score) and 13 studies had
(p value ¼ .02), LBW (p value¼.03), maternal mortality moderate quality (6– 8 score). As shown in Table S2, among
(p value < .001) and pregnancy loss (p value < .001) which the total of 141 studies, 71.5% had high quality, 44.2%
were adjusted by the trim and fill method. Figures S24– S27 medium and the rest (two articles) had low quality.
Table 1. Characteristics of cohort and case-control studies included in the meta-analysis.
Study
First author Title Country design Sample size Feto-maternal outcomes Neonatal outcomes
1. Manas Kumar Neonatal outcomes of pregnant India Cohort 162 mothers and 165 PROM: 25 (15.4%); LBW: 49 (29.7%); prematurity (<37 weeks): 27
Nayak women with COVID-19 in a neonates meconium-stained liquor: 39 (71%); RDS: 8 (21%); hypoglycaemia: 4
developing country setup (24.07%); PPH: 2 (1.2%); (10.5%); hyperbilirubinemia requiring
maternal mortality: 1 (0.6%); phototherapy: 15 (39.5%); necrotising
preterm (<37 weeks): 27 enterocolitis: 1 (2.6%); hypoxic ischemic
(16.6%); late preterm (34– Encephalopathy (grade II or III): 6 (15.8%);
36 þ 6): 17 (10.3%); very NICU admission: 38 (23%); mortality
preterm (28– 33 þ 6): 9 (5.4%); (<28 days): 5 (13.2%), SARS-CoV2 positive
extreme preterm (<28 weeks): neonates: 3/32 (9.4%)
1 (0.6%); stillbirth: 2 (5.2)
2. Madalina Timircan Exploring pregnancy outcomes Romania Cohort 101þ vs. 938– PIH: 6 (6%) vs. 28 (3%); Prematurity: 15 (15%) vs. 75 (8%), �p < .001;
associated with SARS-CoV-2 preeclampsia: 2 (2%) vs. 19 ICU admission: 6 (6%) vs. 27 (3%); foetal
infection (2%); GDM: 5 (5%) vs. 66 (7%); malformations: 2 (2%) vs. 19 (2%); neonatal
PROM: 11 (11%) vs. 55 sepsis: 5 (5%) vs. 56 (6%); neonatal death: 1
(6%), �p ¼ .049 (1%) vs. 4 (0.5%); SARS-CoV-2 infection:
2 (2%)
3. Jean Y. Ko Adverse pregnancy outcomes, USA Cohort 6550þ vs. 482,921– GDM: 706 (10.8%) vs. 44,554
maternal complications and (9.2%), �p < .0001; PIH: 350
severe illness among US (5.3%) vs. 31,787 (6.6%),
delivery hospitalisations with �p < .0001;
and without a coronavirus pre-eclampsia/eclampsia: 616
disease 2019 (COVID-19) (9.4%) 33,078 (6.8%),
diagnosis �p < .0001; preterm labour
with preterm delivery: 315
(4.8%) vs. 17,392 (3.6%), RR
(95% CI): 1.3 (1.2– 1.5);
stillbirth: 63 (1.0%) vs. 3439
(0.7%), RR (95% CI): 1.4 (1.1–
1.7); maternal mortality: 9
(0.1%) vs. 32 (0.0%), RR (95%
CI): 20.7 (9.9– 43.4)
4. Maria de Lourdes Maternal and neonatal outcomes Brazil Cohort 33þ vs. 82– Preeclampsia: 2 (6.9%) vs. 13
Benamor Teixeira of SARS-Cov-2 infection in a (17.1%); preterm delivery: 7
cohort of pregnant women (26.9%) vs. 10 (13.7%)
with comorbid disorders
5. Masoumeh Maternal and neonatal outcomes Iran Cohort 56þ vs. 94– Pre-eclampsia: 11 (19.8%) vs. 7 LBW: 11 (20%) vs. 14 (14.9%); foetal or neonatal
Abedzadeh- of pregnant patients with (7.4%), �p ¼ .037; preterm: 19 death: 2 (3.6%) vs. 0 (0%); NICU admission: 9
Kalahroudi COVID-19: a prospective (34.5%) vs. 12 (12.8%), (16.4%) vs. 20 (21.3%)
cohort study �p ¼ .003; PROM: 4 (7.3%) vs.
9 (9.6%); foetal distress: 9
(16.1%) vs. 4
(4.3%), �p ¼ .016
6. Federica Di Guardo Poor maternal– neonatal Italy Cohort 145 Preterm birth: 55 (38%); maternal Neonatal death: 9 (6%); vertical transmission:
outcomes in pregnant patients mortality: 7 (5%) 7 (5%)
with confirmed SARS-Cov-2
infection: analysis of 145 cases
7. Mikael Norman Association of maternal Sweden Cohort 2323þ vs. 84,719– GDM: 163 (7.0%) vs. 4331 (5.0%); Admission for neonatal care: 271 (11.7%) vs.
SARS-CoV-2 infection in preterm infants: 205/2323 7351 (8.4%); neonatal respiratory disorder:
pregnancy with neonatal (8.8%) vs. 4719/85,836 (5.5%); 2.8% vs. 2.0%; hyperbilirubinemia: 3.6% vs.
outcomes post term: 6/39 (15.4%) vs. 2.5%; mortality: 0.30% vs. 0.12%;
JOURNAL OF OBSTETRICS AND GYNAECOLOGY

146/2042 (7.1%) hypoxic-ischemic encephalopathy stage 2–

3 d: 3 (0.1%) vs. 82 (0.1%); neonatal
(continued)
5
 6

Table 1. Continued.
Study
First author Title Country design Sample size Feto-maternal outcomes Neonatal outcomes
convulsions: 6 (0.3%) vs. 173 (0.2%); severe
brain injury: 1/38 (2.6%) vs. 45/675 (6.7%);
RDS: 29 (1.2%) vs. 508 (0.5%); meconium
aspiration: 3 (0.1%) vs. 117 (0.1%); SGA: 54
(2.4%) vs. 1864 (2.2%) LGA: 84 (3.7%) vs.
M. SIMBAR ET AL.

3144 (3.7%); SARS-CoV-2-positive: 21 (0.90%)

8. Sara Cruz Melguizo Pregnancy outcomes and Spain Cohort 1347þ vs. 1607– GDM: 97/1309 (7.4%) vs. Apgar 5 score <7: 20/1335 (1.5%) vs. 21/1597
SARS-CoV-2 infection: the 136/1584 (8.6%); IUGR: (1.3%); NICU admission: 137 (10.2%) vs. 39
Spanish Obstetric Emergency 48/1290 (3.7%) vs. 44/1566 (2.4%), �p < .001; neonatal mortality: 6
Group Study (2.8%); PIH: 50 (3.7%) vs. 55 (0.4%) vs. 2 (0.1)
(3.4%); threatened abortion:
41/1275 (3.2%) vs. 43/1545
(2.8%); PROM: 209 (15.5%) vs.
179 (11.1%), �p < .001;
PPROM: 37 (2.8%) vs. 23
(1.4%), �p ¼ .012; preterm:
149 (11.1%) vs. 94 (5.8%),
�p < .001; abruptio placentae:
12 (0.9%) vs. 7 (0.4%); PPH: 61
(4.5%) vs. 86 (5.4%); severe
pre-eclampsia: 28/69 (40.6%)
vs. 10/64 (15.6%), �p ¼ .001;
moderate pre-eclampsia: 41/69
(59.4%) vs. 54/64 (84.4%),
�p ¼ .001; stillbirth: 10 (0.7%)
vs. 3 (0.2%), �p ¼ .023
9. Haley A. Steffen SARS-CoV-2 infection during USA_Iowa Cohort 61þ vs. 939– (neonate: Diabetes (T1DM, T2DM, Malformations: 10 (15.4%) vs. 117 (12.1%);
pregnancy in a rural Midwest 65þ/971– ) gestational): 8 (13.7%) vs. 147 absence of live birth: 3 (4.6%) vs. 12 (1.2%);
all-delivery cohort and (15.6%); PIH: 4 (6.6%) vs. 94 neonatal death: 0 vs. 10 (1%)
associated maternal and (10%); preeclampsia without
neonatal outcomes severe features: 3 (4.9%) vs. 35
(3.7%); preeclampsia with
severe features: 6 (9.8%) vs. 49
(5.2%); eclampsia: 0 vs. 1
(0.11%); PROM: 6 (9.8%) vs. 84
(8.9%); preterm labour: 3
(4.9%) vs. 74 (7.9%); antenatal
hypertensive disease: 14
(23.0%) vs. 228 (24.3%);
placental abruption: 1 (1.6%)
vs. 20 (2.1%); chorioamnionitis:
2 (6.3%) vs. 30 (5.2%);
morbidly adherent placenta: 0
vs. 1 (0.2%); pyelonephritis: 1
(1.6%) vs. 5 (0.5%); PPH: 14
(23%) vs. 153 (16.3%)
10. Asimenia Angelidou Association of maternal perinatal USA_ Cohort 250/255 neonate Preterm birth (<32 weeks) or SGA: 13 (5.1%); very preterm birth (<32 weeks)
SARS-CoV-2 infection with Massachusetts VLBW (<1500 g): 6 (2.4%); or VLBW (<1500 g): 6 (2.4%); preterm birth
neonatal outcomes during the preterm birth (<37 weeks) or (<37 weeks) or LBW (<2500 g): 62 (24.3%);
COVID-19 pandemic in LBW (<2500 g): 62 (24.3%) congenital anomalies: 12 (4.7%);
Massachusetts hypoglycaemia: 14 (5.5%); encephalopathy: 4
(1.6%); SARS-CoV-2 positive: 5 (2.0%)
(continued)
Table 1. Continued.
Study
First author Title Country design Sample size Feto-maternal outcomes Neonatal outcomes
11. Sahar H Abdulghani Consequences of SARS-CoV-2 Saudi Arabia Cohort 62 (48 asymptomatic/14 Meconium-stained amniotic LBW: 7; premature infants: 11; positive
disease on maternal, perinatal symptomatic) fluid: 10 naso-pharyngeal swab: 1
and neonatal outcomes: a
retrospective observational
cohort study
12. Qingqing Luo Characteristics and pregnancy China Cohort 42 (16 asymptomatic/25 PROM: 6; GDM: 4; PIH: 3; Positive nucleic acid testing of SARS-CoV-2: 1
outcomes of asymptomatic symptomatic) oligohydramnios: 2;
and symptomatic women with polyhydramnios: 1;
COVID-19: lessons from malpresentation: 1; placenta
hospitals in Wuhan previa: 1; intrahepatic
cholestasis of pregnancy: 1;
postpartum fever: 5;
premature delivery: 9
13. Zahra Akbarian-Rad Neonatal outcomes in pregnant Iran Cohort 8 Preterm: 3 LBW: 1; need for resuscitation at birth: 1;
women infected with respiratory distress: 2; feeding problem: 2;
COVID-19 in Babol, North of poor reflexes: 2
Iran: a retrospective study with
short-term follow-up
14. Chrissy Liu Effect of SARS-CoV-2 infection on USA Cohort 56þ vs. 279– PIH or preeclampsia: 8 (14.3%)
pregnancy outcomes in an vs. 34 (12.2%); GDM: 6 (10.7%)
inner-city Black patient vs. 41 (14.7%); preterm 34 to
population 36 þ 6 weeks: 5 (8.9%) vs. 24
(8.8%); early preterm < 34
weeks: 3 (5.4%) vs. 17 (6.2%);
PPH � 1000 cm3: 7 (13.7%)
vs. 36 (14.5%);
15. Mehmet Ozsurmeli Clinical characteristics, maternal Turkey Cohort 24 Maternal mortality: 1 NICU admission: 1; neonatal death: 1
and neonatal outcomes of
pregnant women with
SARS-CoV-2 infection in Turkey
16. Sindy C Moreno Vertical transmission of COVID-19 USA Cohort 19/21 newborn Preterm delivery: 8 (38.1%); �34 NICU admission: 13 (61.9%); TTN: 6 (28.6%);
to the neonate weeks.: 2 (25%) �37 weeks: RDS: 1 (4.8%)
6 (75%)
17. Mehmet Yekta A multicenter study on Turkey Cohort 125 GDM: 7 (5.8%); preeclampsia: 6 Prematurity: 33 (26.4%); LBW: 16 (12.8%); NICU
Oncel epidemiological and clinical (4.9%); hypertension: 2 (1.6) admission: 108 (86.4%); neonatal mortality: 1
characteristics of 125 placenta previa: 1 (0.8%); (0.8%); positive RT-PCR test: 4/12 (3.3%)
newborns born to women maternal mortality: 6 (4.8%);
infected with COVID-19 by
Turkish Neonatal Society
18. Citra NZ Mattar Pregnancy outcomes in Singapore Cohort 16 Spontaneous miscarriages: 2
COVID-19: a prospective
cohort study in Singapore
19. Monica Cruz-Lemini Obstetric outcomes of Spain Cohort 174þ vs. 430– Threatened abortion: 9 (5.2%) vs. NICU admission: 12 (6.9%) vs. 7
SARS-CoV-2 infection in 10 (2.3%); high-risk for (1.6%), �p ¼ .001
asymptomatic pregnant preeclampsia in 1st trimester:
women 6 (3.4%) vs. 24 (5.6%); foetal
anomaly in first trimester: 1
(0.6%) vs. 2 (0�5%); foetal
anomaly in anatomy scan: 1
(0.6%) vs. 8 (1.9%); preterm
JOURNAL OF OBSTETRICS AND GYNAECOLOGY

delivery: 13 (7.5%) vs. 28

(6.5%); stillbirth: 2 (1.1%) vs.
0.0 (0); PROM: 31 (17.8%) vs.
7

(continued)
Table 1. Continued.
8

Study
First author Title Country design Sample size Feto-maternal outcomes Neonatal outcomes
44 (10.2%), �p ¼ .011; PPROM:
5 (2.9%) vs. 5 (1.2%); PIH: 11
(6.4%) vs. 24 (5.8%);
preeclampsia 7 (4%) vs. 23
(5.4%); obstetric haemorrhage:
6 (3.4%) vs. 20 (4.7%)
M. SIMBAR ET AL.

20. Sourabh Verma Outcomes of maternal-newborn USA-New York Cohort 149 Premature delivery: 16 (11%); NICU admission: 18 (12%); neonatal demise: 1
dyads after maternal GDM: 10 (7%); PIH: 17 (11%); (1%); respiratory distress: 13/148 (9%); RT-PCR
SARS-CoV-2 foetal distress: 8 (5%); positive for SARS-CoV-2: 1/87 (1%)
meconium-stained amniotic
fluids: 23 (15%)
21. Najeh Hcini Maternal, foetal and neonatal France Cohort 137þ vs. 370– Preeclampsia/hypertension during SGA foetus/foetal growth restriction: 3 (2.1%)
outcomes of large series of pregnancy: 15 (10.9%) vs. 31 vs.6 (1.6%); Apgar score
SARS-CoV-2 positive (8.3%); premature labour: 7 �7 at 1 min : 14 ð11%Þ vs:
pregnancies in peripartum (5.1%) vs. 16 (4.3%); 31 ð8:5%Þ 0:5; Apgar score � 7 at 5 min 4:
period: a single-centre spontaneous preterm delivery (3.1%) 12 vs. (3.2%); RDS: 4 (3.1%) vs. 16
prospective comparative study <37 þ 0 weeks: 11 (8.7%) (4.3%); NICU admission: 3 (2.3%) vs. 12
vs.36 (10.0%); spontaneous (3.2%); SARS-CoV-2 RT PCR: 4/29 (13.8%)
preterm delivery <34 þ 0
weeks: 1 (0.8%) vs. 9 (2.6%);
GDM: 13 (9.4%) vs. 30 (8.1%);
extremely preterm infants (22–
23 þ 6WG): 0 (0.0%) vs. 6
(1.6%); IUFD (19– 35 W G): 7
(5.1%) vs. 4 (1.1%),
�p ¼ .0057; IUFD (19– 35 W
G): 7 (5.1%) vs. 4 (1.1%),
�p ¼ .0057; termination of
pregnancy for foetal
abnormalities: 3 (2.2%) vs. 1
(0.3%); meconium-stained
amniotic fluid: 8 (6.3%) vs. 30
(8.4%); PPH: 18 (14.2%) vs. 26
(7.2%), �p ¼ .0193
22. Sara C Handley Changes in preterm birth USA Cohort 3007 vs. 5907 Spontaneous preterm birth: 135
phenotypes and stillbirth at 2 prepandemic (4.7%) vs. 315 (5.7%); stillbirth:
Philadelphia hospitals during 15 (0.50%) vs. 32 (0.54%)
the SARS-CoV-2 pandemic,
March– June 2020
23. Amihai Vaginal delivery in Israel Cohort 52 Preterm <37 weeks: 17 (32.7%), 5-min Apgar score < 8: 1 (1.9%); NICU
Rottenstreich SARS-CoV-2-infected pregnant preterm <34 weeks: 9 admission: 6 (11.5%); RDS: 6 (11.5%); TTN: 1
women in Israel: a multicenter (17.3%); GDM: 6 (11.5%); (1.9%); hypoglycaemia: 4 (9.3%);
prospective analysis Gestational hypertensive hyperbilirubinemia: 5 (9.6%)
disorders: 7 (13.4%); HELLP
syndrome 1 (1.9%); PPH:
6 (11.5%)
24. Ifeoma Ogamba Initial review of pregnancy and USA Cohort 40 Preterm 34– 37 weeks: 1 (4%), Preterm delivery, apnoea of prematurity: 1;
neonatal outcomes of <34 weeks: 3 (12%); PPH: 2 hyperbilirubinemia: 1
pregnant women with (8%); second trimester foetal
COVID-19 infection loss: 2 (8%)
25. Marjolein F Husen Unique severe COVID-19 Netherlands Cohort 36 GDM: 6 (16.7%); hypertensive SGA: 9 (23.1%); Apgar <7 at 5 min: 5 (12.8%);
placental signature disorders: 2 (5.6%); pH <7.10: 2 (5.1%); neonatal SARS-CoV-2
independent of severity of spontaneous preterm delivery: positive: (1/39) 1 (2.6%)
clinical maternal symptoms 1 (2.8%); foetal distress:
7 (19.4%)
(continued)
Table 1. Continued.
Study
First author Title Country design Sample size Feto-maternal outcomes Neonatal outcomes
26. Maryam Vizheh Characteristics and outcomes of Iran Cohort 110 pregnant and 234 Spontaneous abortion: 8 (7.3%); LBW: 12 (10.9%); NICU admission: 15 (29.4%);
COVID-19 pneumonia in nonpregnant GDM: 5 (4.5%); pre-eclampsia: respiratory complications: 7 (13.7%); neonatal
pregnancy compared with 5 (4.5%); foetal distress: 9 death: 2 (3.9%); neonatal positive SARS-CoV-2
infected nonpregnant women (22.5%); preterm labour: 13 result: 8 (15.7%)
(11.8%); PROM: 5 (4.54%)
27. Abdulrahman Clinical outcomes of maternal Saudi Arabia Cohort 288 Premature or preterm delivery: LBW: 29 (14.5%); birth weight >4000 g: 1
Al-Matary and neonate with COVID-19 31 (15.5%); PROM: 16 (8%); (0.5%); 1-min Apgar score <5: 18 (9.0%);
infection – multicenter study fatal distress: 13 (6.5%); 5-min Apgar score <5: 5 (2.5%); NICU
in Saudi Arabia preeclampsia: 4 (2.0%); admission: 86 (43.0%)
maternal mortality: 1 (0.5%);
foetal death: 4 (2.0); IUGR:
3 (1.5%)
28. Itz�ıar Carrasco SARS-COV-2 infection in pregnant Spain Cohort 105/107 newborns Preterm birth: 21 (20.6%) SGA: 6 (5.61%); NICU admission: 18 (16.8%);
women and newborns in a RT-PCR at 15 days positive 1 (0.93%)
Spanish cohort
(GESNEO-COVID) during the
first wave
29. Torri D Metz Disease severity and perinatal USA Cohort 1219 Maternal mortality: 6; PPH: 108; SGA: 126; NICU admission: 254; neonatal
outcomes of pregnant patients hypertensive disorders of death: 5
with coronavirus disease 2019 pregnancy: 285; abortion: 13;
(COVID-19) foetal death: 10; spontaneous
preterm birth: 75
30. Edward Mullins Pregnancy and neonatal UK Cohort 651 Maternal mortality: 3 (0.5%); Early neonatal death: 2/614 (0.3%); positive
outcomes of COVID-19: miscarriage: 12/647 (1.9%); neonatal SARS-CoV-2: 13/131 (9.9%)
coreporting of common Intrauterine death/stillbirth:
outcomes from PAN-COVID 4/647 (0.6%); preterm delivery
and AAP-SONPM registries (live births only): 100/622
(16.1%); spontaneous onset of
preterm labour and vaginal
delivery (live births only):
22/621 (3.5%)
31. Virginia Engels Perinatal outcomes of Spain Cohort 1347 Preterm deliveries: 148; PROM: Apgar 5 score <7: 13; NICU admission: 137;
Calvo pregnancies resulting from 209; PPROM: 37; haemorrhagic neonatal mortality: 6 (0.44%)
assisted reproduction events: 71; abruptio placentae:
technology in 12; PPH: 61; DIC: 4; gestational
SARS-CoV-2-infected women: a hypertensive disorders: 69;
prospective observational moderate preeclampsia: 41;
study severe preeclampsia: 28;
stillbirth: 10; maternal
mortality: 2 (0.15%)
32. Justine Chinn Characteristics and outcomes of USA/California Cohort 18,715þ vs. 850,364– Preterm birth: 3072 (16.4%) vs.
women with COVID-19 giving 97 967 (11.5%), �p < .001;
birth at US academic centres maternal mortality: 24 (0.1%)
during the COVID-19 vs. 71 (<0.01%), �p <.001
pandemic
33. Jos�e Villar Maternal and neonatal morbidity 18 countriesa Cohort 706þ vs. 1424– Vaginal bleeding; 44 (6.2%) vs. LBW: 145 (20.5%) vs. 181 (12.7%); SGA: 97
and mortality among pregnant 87 (6.1%); PIH: 58 (8.2%) vs. (13.7%) vs. 181 (12.7%)
women with and without 80 (5.6%);
COVID-19 infection: the preeclampsia/eclampsia/HELLP:
INTERCOVID Multinational 59 (8.4%) vs. 63 (4.4%);
JOURNAL OF OBSTETRICS AND GYNAECOLOGY

Cohort Study. preterm labour: 52 (7.4%) vs.

88 (6.2%); maternal mortality:
11 (1.6%) vs. 1 (0.1%); foetal
9

(continued)
Table 1. Continued.
10

Study
First author Title Country design Sample size Feto-maternal outcomes Neonatal outcomes
distress: 87 (12.3%) vs. 120
(8.4%); PROM: 114 (16.1%) vs.
262 (18.4%); spontaneous
preterm birth: 27 (3.8%) vs.
66 (4.6%)
34. Erica M Lokken Disease severity, pregnancy USA Cohort 240 Maternal mortality: 3 (1.3%); LBW: 7 (4.6%); NICU admission: 11 (7.1%)
M. SIMBAR ET AL.

outcomes and maternal deaths stillbirth: 2 (1.3%); preterm

among pregnant patients with birth: 15 (9.7%); GDM: 16
severe acute respiratory (10.3%); new-onset
syndrome coronavirus 2 hypertensive disorder of
infection in Washington State pregnancy or postpartum:
19 (12.3%)
35. Ann-Christin Inefficient placental virus Germany Cohort 42 Preterm delivery: 10 (24%); NICU admission: 7 (17%)
Tallarek replication and absence of <34 weeks: 2 (5%)
neonatal cell-specific immunity
upon SARS-CoV-2 infection
during pregnancy
36. Daniel Katz The Society for Obstetric USA Cohort 490þ vs. 964– GDM: 33 (6.7%) vs. 67 (7.0%); Neonatal composite outcome: 97 (19.6%) vs.
Anaesthesia and Perinatology hypertensive disorders of 164 (16.5)
Coronavirus Disease 2019 pregnancy: 75 (15.3%) vs. 123
Registry: an analysis of (12.8%); preterm delivery: 72
outcomes among pregnant (14.8%) vs. 98 (10.2%),
women delivering during the �p ¼ .011; placental
initial severe acute respiratory abruption: 6 (1.2%) vs. 10
syndrome coronavirus-2 (1.0%); PPH > 500 mL for
outbreak in the United States. vaginal delivery: 35 (11.4%) vs.
66 (10.5%); PPH >1 L for
caesarean delivery: 18 (10.8%),
40 (12.2%)
37. Francesco Maternal and perinatal outcomes 25 countries in Cohort 887 Preterm birth at <37 weeks: 94; Neonatal death: 8; perinatal death: 13; NICU
D’Antonio in high compared to low risk Europe, the United preterm birth at <34 weeks: admission: 72
pregnancies complicated by States, South 41; miscarriage: 22; IUFD: 5
severe acute respiratory America, Asia and
syndrome coronavirus 2 Australia
infection (phase 2): the World
Association of Perinatal
Medicine Working Group on
Coronavirus Disease 2019
38. Fulvia Severe SARS-CoV-2 placenta Italy Cohort 21þ/16– GDM: 2 (10%) vs. 3 (19%);
Milena Cribi�
u infection can impact neonatal gestational cholestasis: 1 (5%)
outcome in the absence of vs. 0(0%); IUGR: 0 (0%) vs.
vertical transmission 1(6%); AF anomalies 2 (10%)
vs. 0(0%); PROM: 2 (10%) vs. 2
(12%); PPROM: 1 (5%) vs. 1
(6%); foetal complications: 2
(10%) vs. 0 (0%); foetal
malformation: 1 (5%) vs. 0
(0%); therapeutic miscarriage:
1 (5%) vs. 0 (0%); macrosomia:
0 (0%) vs. 1 (6%); suspected
chorioamnionitis: 0(0%) vs. 0
(0%); premature delivery: 6
(29%) vs. 3(19%); foetal
distress: 2 (10%) vs.4 (25%)
(continued)
Table 1. Continued.
Study
First author Title Country design Sample size Feto-maternal outcomes Neonatal outcomes
39. Hilde Engjom COVID-19 in pregnancy – Nordic countries Cohort 48/51 infant Preterm delivery: 12/48 (25%) NICU admission: 7/51 (13.7%)
characteristics and outcomes (Denmark, Finland,
of pregnant women admitted Iceland, Norway,
to hospital because of Sweden)
SARS-CoV-2 infection in the
Nordic countries
40. Enrico Ferrazzi Vaginal delivery in Italy Cohort 42 GDM: 6 (14%); preterm birth: 11 NICU admission: 3; positivity to SARS-Cov-2: 3
SARS-cov-2-infected pregnant (spontaneous preterm: 5;
women in Northern Italy: a elective caesarean section: 6)
retrospective analysis
41. Noelle Breslin COVID-19 infection among USA New York Cohort 43 Preterm labour (n ¼ 1); PIH: 1; NICU admission: 3
asymptomatic and foetal distress: 3
symptomatic pregnant
women: two weeks of
confirmed presentations to an
affiliated pair of New York City
hospitals
42. Ming-zhu Yin Severe acute respiratory China Cohort 31 Premature delivery: 5/17 LBW: 1/17
syndrome coronavirus 2
(SARS-CoV-2) infection during
pregnancy in China: a
retrospective cohort study
43. Marian Knight Characteristics and outcomes of United Kingdom Cohort 427 GDM: 50 (12%); maternal Neonatal death: 2 (1%); NICU admission: 67/267
pregnant women admitted to mortality: 5 (1%); pregnancy (live born infants only) (25%); positive
hospital with confirmed loss: 4 (1%); stillbirth: 3 (1%); SARS-CoV-2 test (liveborn infants only):
SARS-CoV-2 infection in UK: preterm: 70 12/256 (4.6%)
national population based
cohort study
44. Rafael San-Juan Incidence and clinical profiles of Spain Cohort 32/6 delivery Preterm: 2/6 LBW: 2 RDS: 1; intraventricular haemorrhage
COVID-19 pneumonia in grade 1: 1
pregnant women: a
single-centre cohort study
from Spain
45. AM Rebecca Clinical course of severe and USA Cohort 64 Hypertensive disorders of NICU admission: 21 (63.6%)
Pierce-Williams critical COVID-19 in pregnancy: 2 (3%); magnesium
hospitalised pregnancies: a US sulphate for preeclampsia: 1
cohort study. (2%); IUGR: 2 (3%);
oligohydramnios: 1 (2%);
presumed chorioamnionitis or
endometritis: 3 (9%); PPH: 3
(9%); preterm delivery at <37
weeks: 19 (59%); preterm
delivery at <34 weeks: 10
(31%); spontaneous preterm
labour: 2 (6%); PPROM: 1 (3%)
46. Viktoriya London The relationship between status USA Cohort 68/55 of the 68 have GDM: 7 (10.3%); cholestasis of –
at presentation and outcomes delivered pregnancy: 2 (2.9%); preterm
among pregnant women with birth <37 weeks: 9 (16.4%);
COVID-19 preterm birth <34 weeks: 3
JOURNAL OF OBSTETRICS AND GYNAECOLOGY

(5.5%); PPH: 2 (3.6%);

preeclampsia: 4 (7.3%)
(continued)
11
Table 1. Continued.
12

Study
First author Title Country design Sample size Feto-maternal outcomes Neonatal outcomes
47. Rasha Khoury Characteristics and outcomes of USA Cohort 241 Stillbirth: 2/247 (0.8%); singleton Resuscitation at delivery: 70/233 (30.0%); NICU
241 births to women with preterm birth (<37 weeks): admission: 61/237 (25.7%); NRDS: 14/241
severe acute respiratory 34/233 (14.6%); singleton early (5.8%); complications of prematurity or LBW:
syndrome coronavirus 2 preterm birth (<34 weeks): 21/241 (8.7%); sepsis: 1/241 (0.4%);
(SARS-CoV-2) infection at Five 10/233 (4.3%); congenital anomaly: 8/241 (3.3%); neonatal
New York City Medical mal-presentation: 5/100 (5%) COVID-19 test result positive 6/236 (2.5%)
M. SIMBAR ET AL.

Centres.
48. Valeria M Savasi Clinical findings and disease Italy Cohort 77 Preterm delivery: 12 (21%) NICU admission: 9 (16%); newborn COVID-19
severity in hospitalised test result, positive: 4 (7%)
pregnant women with
coronavirus disease 2019
(COVID-19)
49. Christine M Neonatal management and USA Cohort 116 Preterm (<37 weeks): 14; LBW: 12 NICU admission: 12
Salvatore outcomes during the COVID-19 PROM: 96
pandemic: an observation
cohort study
50. Kate R Woodworth Birth and infant outcomes USA Cohort 4442 PIH: 211 (7.6%); GDM: 228 (8.2%); NICU admission among term live births:
following laboratory-confirmed pregnancy loss: 32 (0.7%); 279/2995 (9.3%); birth defects among live
SARS-CoV-2 infection in pregnancy loss <20 weeks: 12 births: 28/4447 (0.6%)
pregnancy – SET-NET, 16 (0.3%): pregnancy loss �20
jurisdictions, March 29– weeks: 20 (0.4%): preterm
October 14, 2020 (<37 weeks): 506 (12.9%); late
preterm (34– 36 weeks): 357
(9.1%); late preterm (34– 36
weeks): 357 (9.1%) ; moderate
preterm (32– 33 weeks): 50
(1.3%); very preterm (28– 31
weeks): 69 (1.8%); extremely
preterm (<28 weeks):
30 (0.8%)
51. Miranda J Delahoy Characteristics and maternal and USA Cohort 598 GDM: 64/581 (11.0%); Neonatal death: 2/448 (0.4%)
birth outcomes of hospitalised hypertensive disorders of
pregnant women with pregnancy: 70/581 (12.0%);
laboratory-confirmed COVID-19 IUGR: 11/581 (1.9%);
– COVID-NET, 13 states, March pregnancy loss: 10/458 (2.2%);
1– August 22, 2020 pregnancy loss at <20 weeks’
gestation: 4/458 (0.9%);
pregnancy loss at �20 weeks’
gestation: 5/458 (1.1%);
pregnancy loss at unknown
gestational age 1/458 (0.2%);
maternal mortality:
2/598 (0.3%)
52. Claudio Fenizia Analysis of SARS-CoV-2 vertical Italy Cohort 31 Preterm delivery: 1 (3%) NICU admission: 2 (6%); APGAR score 50 <7: 1
transmission during pregnancy (3%); infected neonates, positive: 2 (6%)
53. Dilek Sahin Updated experience of a tertiary Turkey Cohort 533 Maternal mortality: 2 (0.4%); Macrosomia 5 (5.7%); NICU admission: 13 (9.9%)
pandemic centre on 533 threatened abortion: 2 (0.3%);
pregnant women with miscarriage: 12 (2.2%);
COVID-19 infection: a hyperemesis gravidarum: 2
prospective cohort study from (0.3%); cholestasis of
Turkey. pregnancy: 5 (0.9%); foetal
anomaly: 3 (0.5%); intrauterine
foetal demise: 1 (0.2%); foetal
(continued)
Table 1. Continued.
Study
First author Title Country design Sample size Feto-maternal outcomes Neonatal outcomes
growth restriction: 5 (0.9%);
GDM: 3 (0.5%); PIH: 4 (0.7%);
preterm delivery: 22 (4.1%);
pre-eclampsia: 5 (0.9%);
placental abruption: 1 (0.2%);
deep vein thrombosis: 1
(0.2%); pregnancy loss: 13
(2.4%); foetal distress:
12 (13.8%)
54. Jayasree Santhosh Clinical characteristics of Oman Cohort 60 Hypertension: 3 (5%); GDM: 15 LBW <2500 g (47/60) 15 (32%)
COVID-19 in pregnant women: (25%); preterm: 18 (30%); (late
A retrospective descriptive preterm delivery (34– 36 þ 6):
single-centre study from a 14 (24%); early preterm
tertiary hospital in delivery (24– 33 þ 6): 4
Muscat, Oman (6.8%)); amniotic fluid,
meconium stain (7/47): 7
(15%); PPROM: 1 (2.0%);
preeclampsia: 4 (6.7%);
preterm labour: 8 (16%); PPH:
2 (3.3%); pulmonary embolism:
2 (3.3%); pelvic haematoma: 1
(2.0%); miscarriage: 4 (6.7%);
macerated stillbirth (47/60):
1 (2.1%)
55. Mahtab Sattari Evaluating clinical course and risk Iran Cohort 50/26 have not given Maternal mortality: 2 (4%); Infection of the newborn according to Covid-19:
factors of infection and birth yet preterm delivery: 7 (29.2%) 7 (28%)
demographic characteristics of
pregnant women with
COVID-19 in Hamadan
Province, West of Iran.
56. Yan-Ting Wu Neonatal outcome in 29 China Cohort 29/30 newborn Gestational hypertensive disorder: COVID-19 diagnosis 2 confirmed and 3
pregnant women with 2 (6.90%); GDM: 3 (10.34%); suspected
COVID-19: a retrospective gestational anaemia: 3
study in Wuhan, China (10.34%); PPROM: 5 (17.24%);
foetal distress: 3 (10.34%);
preterm: 3 (10.34%)
57. Laura D Zambrano Update: characteristics of USA Cohort 23,434 Maternal mortality: 34 (1.5%) (a
symptomatic women of total of 5152 (22.0%) pregnant
reproductive age with women and 66,346 (17.2%)
laboratory-confirmed nonpregnant women were
SARS-CoV-2 infection by missing information on death
pregnancy status – United and were assumed to have
States, January 22– October survived)
3, 2020
58. Malavika Prabhu Pregnancy and postpartum USA Cohort 70/73 newborn Pre-eclampsia or PIH: 11; GDM: 6; NICU admission: 13 (17.8%)
outcomes in a universally preterm birth <37 weeks: 11;
tested population for malpresentation: 1;
SARS-CoV-2 in New York City: Intrapartum fever: 7; PPH
a prospective cohort study >1000 mL: 3; postpartum
fever: 8
JOURNAL OF OBSTETRICS AND GYNAECOLOGY

59. Amanda Dhuyvetter Coronavirus disease 2019 in USA Cohort 23 GDM: 1 (4.3%);PIH: 2 (8.7%); SGA: 1 (4.3%)
pregnancy: the experience at cholestasis of pregnancy:
an urban safety net hospital 2 (8.7%)
13

(continued)
Table 1. Continued.
14

Study
First author Title Country design Sample size Feto-maternal outcomes Neonatal outcomes
60. Mohsen AA Characteristics of newborns born USA Cohort 15 Preterm: 2 (13.3%) NICU admission: 10 (66.7%); nursery admission:
Farghaly to SARS-CoV-2-positive 5 (33.3%)
mothers: a retrospective
cohort study
61. M� onica R�ıos-Silva COVID-19 mortality among Mexico Cohort 448 Maternal mortality: 10 (2.2%)
(Silva et al. 2020) pregnant women in Mexico: a
M. SIMBAR ET AL.

retrospective cohort study

62. Niyazi Tug Pregnancy worsens the morbidity Turkey Cohort 188 Extremely preterm: 1/60 (1.7%),
of COVID-19 and this effect very preterm: 2/60 (3.3%),
becomes more prominent as moderate/late preterm: 11/60
pregnancy advances (18.3%); preeclampsia: 6
(3.2%); GDM: 1; placenta
previa: 1
63. Rong Yang Pregnant women with COVID-19 China Cohort 65 PIH: 3 (5%); preeclampsia: 1 (1%);
and risk of adverse birth GDM: 3 (5%); PROM: 4 (6%);
outcomes and maternal– foetal preterm birth: 9 (14%)
vertical transmission: a
population-based cohort study
in Wuhan, China
64. Wei Liu Clinical analysis of neonates born China Cohort 15 Hypertensive disorders: 2 (13.3%);
to mothers with or without GDM: 2 (13.3%);
COVID-19: a retrospective chorioamnionitis: 2 (13.3%);
analysis of 48 cases from two PPH: 1 (6.7%)
neonatal intensive care units
in Hubei Province
65. Puneet Gupta SARS-CoV-2 prevalence and India Cohort 108þ vs. 3057– Preterm: 31 (28.3%) vs. (14.6%)�; Birth weight, �p < .0001; NICU admission: 14
maternal– perinatal outcomes maternal mortality: 1 (0.9%) (12.9%) vs. 254 (8.3%); neonatal deaths: 2
among pregnant women vs. 7 (0.22%); GDM: 16 (14.8%) (1.9%) vs. 42 (1.3)
admitted for delivery: vs. 334 (10.9%); PIH: 12
experience from (11.1%) vs. 264 (7.39%);
COVID-19-dedicated maternity intrahepatic cholestasis: 10
hospital in Jammu, Jammu (9.2%) vs. 212 (6.93%);
and Kashmir (India) antepartum haemorrhage: 6
(5.55%) vs. 132 (4.3%); PPH: 5
(4.6%) vs. 110 (3.59%); foetal
distress: 24 (22.2%) vs. 334
(10.9%), �p < .001
66. Adhikari Pregnancy outcomes among USA Cohort 252 SARS-CoV-2-positive Abortion: 7 (3%) vs. 87 (3%); SGA: 31 (13%) vs. 316 (10%); 5-min Apgar score
women with and without and 3122 negatives GDM: 14 (6%) vs. 207 (7%); <4: 0 (0%) vs. 37 (1.2%); umbilical cord
severe acute respiratory severe preeclampsia: 26 (11%) blood pH <7.0 d: 1 (0.4%) vs. 9 (0.3%);
syndrome coronavirus 2 vs. 359 (12%); abruption: 0 positive infants: 6
infection (0.0%) vs. 24 (1%); clinical
chorioamnionitis: 24 (10%) vs.
345 (11%); stillbirth: 0 (0%) vs.
18 (0.6%); excessive blood loss
(haemorrhage): 17 (7%) vs.
278 (9%); meconium-stained
amniotic fluid: 53 (22%) vs.
571 (19%)
67. Milbak A prospective cohort study of Denmark Cohort 28 pregnant women with PIH: 1 (3.6%); deep venous Apgar (5 min) <7: 1 (3.6%); NICU: 3 (10.7%);
confirmed severe acute SARS-CoV-2 infection thrombosis: 1 (3.6%); neonatal death: 1 (3.6%)
respiratory syndrome pulmonary embolism: 1 (3.6%);
coronavirus 2 (SARS-CoV-2) GDM: 2 (7.1%); preterm
(continued)
Table 1. Continued.
Study
First author Title Country design Sample size Feto-maternal outcomes Neonatal outcomes
infection during pregnancy delivery (<37 þ 0 weeks):
evaluating SARS-CoV-2 2 (7.1%)
antibodies in maternal and
umbilical cord blood and
SARS-CoV-2 in vaginal swabs
68. Ward The clinical impact of maternal USA Cohort 115 mothers with PIH: 16 (13.9%); GDM: 11 (9.57%); NICU/PICU admission: 23 (20.0%); premature
COVID-19 on mothers, their SARS-CoV-2 meconium: 16 (13.9%); (<37 weeks): 14 (12.2%); LGA: 8 (6.96%);
infants, and placentas with an chorioamnionitis: 7 (6.09%); SGA: 4 (3.48%); newborns tested for
analysis of vertical transfer of PPROM/PROM: 3 (2.61%); SARS-CoV-2 positive: 1 (1.47%)
maternal SARS-CoV-2-specific IUGR: 4 (3.48%); nuchal chord:
IgG antibodies 13 (11.3%); haemorrhage: 14
(12.2%); foetal intolerance: 14
(12.2%); failure to progress: 9
(7.83%); preeclampsia/HELLP
syndrome: 15 (13.0%); preterm
labour: 1 (0.87%); abruptio
placenta: 1 (0.87%); retained
placenta: 1 (0.87%);
oligohydramnios: 1 (0.87%);
shoulder dystocia: 1 (0.87%)
69. P�eju Management and outcomes of France Cohort 187 pregnant women Abortion: 4; PIH: 10; GDM: 48; Foetal or neonatal mortality: 8; SGA: 9
pregnant women admitted to with COVID-19 preeclampsia: 8; mortality: 2;
intensive care unit for severe PPH: 11; stillbirth: 3; preterm
pneumonia related to birth (<32 weeks’ gestation):
SARS-CoV-2 infection: the 47; preterm birth (<37 weeks’
multicenter and international gestation): 79
COVIDPREG study
70. Seyed- Obstetric, maternal and neonatal Iran Case-control Case ¼ 55/control ¼ 55 GDM: 4 (7.27) vs. 2 (3.63); PIH: 2 LBW: 2/20 (10) vs. 1/20 (5); Apgar in 5 min <7:
Abdolvahab outcomes in COVID-19 (3.63) vs. 1 (1.81); abortion 3/20 (15) vs.4/20 (20); respiratory distress:
Taghavi compared to healthy pregnant <21 weeks: 3/14 (21.42) vs. 3/20 (15) vs. 1/20 (5); NICU admission: 2/20
women in Iran: a retrospective, 2/14 (14.28); IUFD: 0 vs. 1/20 (10) vs. 3/20 (15), neonatal dead: 1/20 (5)
case-control study (5); PPH: 1/20 (5) vs. 3/20 (15); vs. 0
preterm birth: 5/20 (25) vs.
2/20 (10), �p value <.05;
foetal distress: 2/20 (10) vs.
1/20 (5)
71. Justin S. Brandt Epidemiology of coronavirus USA Case-control 61 cases/122 controls Preterm delivery: <37 weeks: 7 NICU admission: 53 (86.9%) vs. 14 (11.5%); RDS:
disease 2019 in pregnancy: (11.5%) vs.10 (8.2%); <34 5 (8.2%) vs. 6 (4.9%); intraventricular
risk factors and associations weeks: 4 (6.6%) vs. 4 (3.3%); haemorrhage: 2 (3.3%) vs. 1 (0.8%); neonatal
with adverse maternal and <28 weeks: 2 (3.3%) vs. 1 death: 1 (1.6%) vs. 1 (0.8)
neonatal outcomes (0.8%); chorioamnionitis: 2
(3.3%) vs. 2 (1.6%);
preeclampsia: 6 (9.8%) vs.
10 (8.2%)
72. MP Tadas Maternal and neonatal outcomes India Case-control 181 vs. 181 Pregnancy morbidity: 100 NICU admission: 14 vs. 16; neonatal death: 1
of pregnant women with (55.24%) vs. 54, �p ¼ .000; vs. 3
covid-19: a case-control study stillbirth: 7 vs. 7
at a tertiary care centre in
India
73. Na Li Maternal and neonatal outcomes China Case-control Confirmed (n ¼ 16); Preeclampsia: 1; PIH: 3; GDM: 3; Premature birth: 4 (23.5%), 4 (21.1%) 7 vs.
JOURNAL OF OBSTETRICS AND GYNAECOLOGY

of pregnant women with suspected hypothyroidism: 2; PROM: 1; (5.8%) and 6 (5.0%); low birth weight: 3
COVID-19 pneumonia: a (n ¼ 18)/control 2020 placental abruption: 1 in 16 (17.6%), 2 (10.5%) vs. 3 (2.5%) and 3 (2.5%)
case-control study confirmed cases; preterm
15

(continued)
 16 M. SIMBAR ET AL.

Feto-maternal outcomes

membrane; PPROM: preterm premature rupture of membrane; PPH: postpartum haemorrhage; NRDS: neonatal respiratory distress syndrome; GTT: glucose tolerance test; HELLP: haemolysis elevated liver enzymes, and
GDM: gestational diabetes mellitus; PIH: pregnancy-induced hypertension (gestational hypertension); PP/PA: placenta previa/accrete; IUGR: intrauterine growth restriction; AF: amniotic fluid; PROM: premature rupture of
in confirmed case, suspected case vs. control
Comparison of outcomes in patients with or without
COVID-19 in included analytical studies showed a significant
difference in the outcomes of preterm birth (Mar�ın Gabriel
Neonatal outcomes

et al. 2020, Abedzadeh-Kalahroudi et al. 2021, Chinn et al.

2020 and 2019, respectively

low platelets; RDS: respiratory distress syndrome; TTN: transient tachypnoea of the newborn; HELLP: haemolysis elevated liver enzymes, and low platelets; DIC: disseminated intravascular coagulation.
2021, Cruz Melguizo et al. 2021, Gupta et al. 2021, Katz et al.
2021, Milln et al. 2021, Taghavi et al. 2021, Timircan et al.
2021), PROM (Cruz-Lemini et al. 2021, Cruz Melguizo et al.
2021, Du et al. 2021, Timircan et al. 2021), PPROM (Cruz
Melguizo et al. 2021), prematurity, GDM (Ko et al. 2021), ges­
tational hypertension (Ko et al. 2021), pre-eclampsia/eclamp­
sia (severe pre-eclampsia and moderate pre-eclampsia)
(Abedzadeh-Kalahroudi et al. 2021, Cruz Melguizo et al. 2021,
Ko et al. 2021, Wilk et al. 2021), foetal distress
delivery: 3 (18.8%), 3 (16.7%)

intrauterine foetal distress: 2

(11.7%), 1 (5.3%) vs.6 (5.0%)

(Abedzadeh-Kalahroudi et al. 2021, Gupta et al. 2021), still­

Feto-maternal outcomes

and 6 (5.0%) in confirmed

birth (Cruz Melguizo et al. 2021), pregnancy morbidity (Tadas

case, suspected case vs.
control 2020 and 2019,
vs. 7 (5.8%), 6 (5.0%);

et al. 2021), IUFD (Hcini et al. 2021), PPH (Hcini et al. 2021),
Argentina, Brazil, Egypt, France, Ghana, India, Indonesia, Italy, Japan, Mexico, Nigeria, North Macedonia, Pakistan, Russia, Spain, Switzerland, UK and the US.

maternal mortality (Chinn et al. 2021), and prolonged labour

Preterm: 10 (16.67)

(Wilk et al. 2021). Maternal mortality has been reported in 26

respectively

studies, but only in one analytical study there was a signifi­

cant difference between patients with and without COVID-19
infection (Chinn et al. 2021).
Some studies have compared the pregnancy outcomes
before and during the COVID-19 pandemic. The results of
these studies have also been different. Some studies showed
(n ¼ 121) Control

a significant difference in pregnancy outcomes such as high-­

Sample size

2019 (n ¼ 121)

risk pregnancies (Goyal et al. 2021), GDM, PROM (Du et al.

2021), hypertensive disorders/pre-eclampsia (Justman et al.
2020, Wilk et al. 2021), stillbirth (Ashish et al. 2020), pro­
longed labour (Wilk et al. 2021), between two periods, while
60

other studies reported no significant change in maternal

Case-control

mortality or severe maternal morbidity (such as PPH, uterine

design
Study

rupture and severe preeclampsia/eclampsia) and stillbirth

(Shakespeare et al. 2021).

Neonatal outcomes
Country

Comparison of outcomes in patients with or without

COVID-19 in included analytical studies showed a significant
difference in the outcomes of prematurity (Timircan et al.
China

2021), NICU admission (Cruz-Lemini et al. 2021, Cruz

Melguizo et al. 2021), neonatal admission (Milln et al. 2021)
COVID-19 patients: an updated

and birth weight (Gupta et al. 2021).

Blood test results of pregnant

The comparison of neonatal outcomes in the two periods

(before and during the COVID-19 pandemic) was not the
same. Some studies have reported an increase in neonatal
case-control study
Title

mortality (Du et al. 2021, Wilk et al. 2021), while some studies
�Statistically significant differences p < .05.

showed no significant change in NICU admissions or other

outcomes (Justman et al. 2020, Du et al. 2021, Shakespeare
et al. 2021, Wilk et al. 2021, Wagner et al. 2022).

Discussion
Table 1. Continued.

74. Guoqiang Sun

Since the onset of the COVID-19 epidemic in early 2020,

there has been concern that the disease in pregnant women
First author

may have adverse effects on pregnancy outcomes. In this sys­

tematic review and meta-analysis, we summarise the result of
141 studies. The clinical characteristics, radiological and
a
 JOURNAL OF OBSTETRICS AND GYNAECOLOGY 17

Table 2. Results of the meta-regression using income level of countries (according to the World Bank classification).
High income (reference) Lower middle income Upper middle income
Outcome Coefficient Coefficient (95% CI) p Value Coefficient (95% CI) p Value
GDM 1 – 0.63 (– 1.59, 0.32) .195 – 0.26 (– 0.73, 0.21) .258
Hypertensive disorders 1 – 0.91 (– 2.45, 0.63) .248 – 0.31 (– 0.74, 0.12) .163
IUGR/SGAa 1 – – – 1.42 (– 3.26, 0.41) .129
LBW 1 – 0.30 (– 1.38, 0.78) .583 0.08 (– 1.01, 1.17) .891
Maternal mortality 1 1.82 (– 0.82, 4.45) .176 1.59 (– 0.03, 3.21) .054
Neonatal death 1 1.30 (– 0.42, 3.02) .138 1.25 (– 0.49, 2.99) .160
NICU admission 1 – 0.36 (– 1.57, 0.84) .553 – 0.08 (– 1.09, 0.93) .875
PPH 1 – 1.30 (– 2.35, 0.24) .016 – 0.67 (– 1.49, 0.15) .109
Pregnancy loss 1 1.23 (0.48, 1.98) .001 1.27 (0.11, 2.41) .030
Preterm delivery 1 0.01 (– 0.88, 0.91) .974 – 0.02 (– 0.55, 0.51) .93
PROM 1 – 0.29 (– 1.98, 1.40) .736 – 0.44 (– 1.44, 0.55) .384
SARS-CoV2 positive neonates 1 1.04 (0.26, 1.81) .009 0.30 (– 0.58, 1.19) .504
a
There was no sample for the lower middle-income countries.

laboratory manifestations are similar in pregnant women outcomes (Dior et al. 2016). Jafari et al. (2021) based on a
with COVID-19 infection when compared with non-pregnant meta-analysis reported that pregnant women with COVID-19
women or the general population. The result of a meta-analy­ had similar clinical, laboratory and imaging characteristics to
sis of 74 cohort and case-control studies showed that pre­ non-pregnant adult patients in the general population (Jafari
term delivery, maternal mortality, NICU admission and et al. 2021). A systematic review and meta-analysis found
neonatal death in pregnant women with COVID-19 infection that being symptomatically varied across ethnicities, with
were significantly more than in those without COVID-19 black and Asian pregnant women more likely to be symp­
infection. tomatic, while white pregnant women were more likely to be
This result is similar to the results of some meta-analyses asymptomatic (Khan et al. 2021).
performed. Karaçam et al. (2022) based on the results of a Pregnant women are more susceptible to respiratory
meta-analysis of 54 studies, reported that morbidity, preterm pathogens and pneumonia due to the immunosuppressive
and caesarean birth rates necessitating admission to the state as well as physiological differences which often lead to
intensive care unit as well as maternal and perinatal death severe hypoxia (O’Day 1997, Ramsey and Ramin 2001, Mosby
rates were higher in pregnant women with COVID-19 and et al. 2011, Mertz et al. 2013, Chen et al. 2020, Liu et al.
their infants (Karaçam et al. 2022). As Jafari et al. (2021) 2020a, 2020c). Therefore, infection with the COVID-19 during
showed that preterm birth, caesarean delivery and LBW were pregnancy is expected to increase the risk of maternal and
more probable in women with COVID-19 compared to foetal complications, and women with severe pneumonia to
women without COVID-19 (Jafari et al. 2021). Gao et al.
be more at risk for adverse pregnancy outcomes. But the
(2020) also reported that the rate of preterm labour in
results of different studies about the adverse pregnancy out­
healthy pregnant women worldwide is lower than that in
comes in women infected with COVID-19 were very different.
pregnant women with COVID-19. They believe that the prob­
The comparison of the outcomes in patients with or with­
able reason for this higher rate is the higher rate of induction
out COVID-19 in analytical studies showed that some of the
in women with COVID-19 in the third trimester of pregnancy.
feto-maternal outcomes such as preterm birth (Mar�ın Gabriel
Most of these women also choose to give birth prematurely
et al. 2020, Abedzadeh-Kalahroudi et al. 2021, Chinn et al.
by caesarean section to prevent prolonged labour (Gao
2021, Cruz Melguizo et al. 2021, Gupta et al. 2021, Katz et al.
et al. 2020).
2021, Milln et al. 2021, Taghavi et al. 2021, Timircan
Our study showed that pregnancy loss and SARS-CoV2
positive neonates in lower middle income were higher than et al. 2021), PROM (Cruz-Lemini et al. 2021, Cruz Melguizo
in high income. Consistent with this result, a meta-analysis et al. 2021, Du et al. 2021, Timircan et al. 2021), PPROM
by Yang et al. (2022) comparing pandemic and pre-pandemic (Cruz Melguizo et al. 2021), GDM (Ko et al. 2021), gestational
periods showed that stillbirths were higher for middle-in­ hypertension (Ko et al. 2021), pre-eclampsia/eclampsia
come countries but not for high-income countries (Yang (Abedzadeh-Kalahroudi et al. 2021, Cruz Melguizo et al. 2021,
et al. 2022). Ko et al. 2021, Wilk et al. 2021), foetal distress
The current systematic review showed that the most com­ (Abedzadeh-Kalahroudi et al. 2021, Gupta et al. 2021), still­
mon signs and symptoms of pregnant women were fever, birth (Cruz Melguizo et al. 2021), pregnancy morbidity (Tadas
dry cough and fatigue. However, other less common symp­ et al. 2021), IUFD (Hcini et al. 2021), PPH (Hcini et al. 2021),
toms, including headache, myalgia, nasal congestion, sore maternal mortality (Chinn et al. 2021), and prolonged labour
throat, dyspnoea, chills, body aches, conjunctivitis, skin rash, (Wilk et al. 2021) in pregnant women with Covid-19 were sig­
diarrhoea, loss of taste or smell, and discolouration of fingers nificantly more than in those without Covid.
or toes, have been reported (Hassanipour et al. 2020, Khan The function of the immune system in pregnant women is
et al. 2020, Berghella and Hughes 2021, Saadaoui et al. 2021). very complex. Therefore, maternal and neonatal outcomes
In pregnant women, as in other adults, fever was a common will be different in each pregnant woman based on gesta­
clinical manifestation at the onset of COVID-19. Evidence has tional age, immune system, duration of infection, and sever­
shown that intrapartum fever may lead to adverse neonatal ity of infection (Banaei et al. 2020).
18 M. SIMBAR ET AL.

There are different opinions about changes in the immune but it is unclear whether COVID-19 infection in the first or
response in pregnant women. Some have suggested that the second trimester of pregnancy can carry the risk of vertical
transition to a Th2 anti-inflammatory environment during transmission or not? (Wang et al. 2020). Musa et al. (2021)
pregnancy may result in protection from a severe COVID-19 based on a review of 69 studies, reported that most of the
presentation (Dashraath et al. 2020, Saadaoui et al. 2021). It mother-to-child infection was likely due to environmental
has also been reported that COVID-19 infection during preg­ exposure, although a significant proportion was attributable
nancy was characterised by placental inflammation and to potential vertical transmission of SARS-CoV-2 (Musa
reduced antiviral antibody responses, which may impact the et al. 2021).
efficacy of COVID-19 therapeutics in pregnancy (Sherer et al. However, in the majority of studies, there was no evidence
2020). In our systematic review, maternal mortality was of vertical transmission and the findings of some systematic
uncommon. This result is consistent with the results of other reviews do not also support the possibility of vertical trans­
review studies (Allotey et al. 2020, Khalil et al. 2020, Lassi mission of COVID-19 infection (Banaei et al. 2020, Islam et al.
et al. 2021, Saadaoui et al. 2021). 2020, Mullins et al. 2020). The results of some meta-analyses
COVID-19 may be associated with some neonatal out­ also showed that the possibility of vertical transmission from
comes. Based on the comparison of the outcomes in patients mother to foetus is low (Jafari et al. 2021, Kotlyar et al. 2021).
with or without COVID-19 in analytical studies, the main Current evidence suggests that neonates and children do not
adverse neonatal outcome found is iatrogenic preterm birth develop severe COVID-19, and neonatal mortality is rare.
(Timircan et al. 2021), and neonatal or NICU admission However, we must be careful about the possibility of vertical
(Cruz-Lemini et al. 2021, Cruz Melguizo et al. 2021, Milln et al. transmission. It is important to diagnose neonatal infection
2021). There is no evidence for congenital malformations because neonates can play a role in creating community-re­
associated with maternal infection. lated infections (Saadaoui et al. 2021).
Some studies showed that women with pneumonia during The current systematic review and meta-analysis have sev­
pregnancy were more likely to have preterm deliveries, LBW eral strengths. First, we included in this systematic review
and SGA infants than women without pneumonia (B�anhidy 141 studies and conducted a meta-analysis of 74 studies with
et al. 2008, Brito and Niederman 2011, Romanyuk et al. 2011, a large number of pregnant women that contribute to a
Chen et al. 2012). Some studies have also reported that SARS more comprehensive understanding of COVID-19 in preg­
during pregnancy is associated with high incidences of spon­ nancy. Second, we followed the correct methodology for
taneous miscarriage, preterm delivery and intrauterine
conducting the present systematic review. Third, this study
growth restriction (Wong et al. 2004).
presents pregnancy outcomes of COVID-19 from different
This finding is consistent with other review studies that
countries’ perspectives. The limitation of this study was the
reported that preterm delivery, foetal distress and LBW were
high heterogeneity in methods, study designs and estimates,
the common pregnancy outcomes of women with COVID-19
which made meta-analysis difficult for all of them, so we per­
(Banaei et al. 2020, Mullins et al. 2020, Mark et al. 2021).
formed a meta-analysis on cohort and case-control studies.
A systematic review and meta-analysis to evaluate differ­
Another limitation is that we were only able to search for
ences in pregnancy and perinatal outcomes among symp­
articles in the PubMed and Scopus databases, and it was not
toms compared with asymptomatic pregnant women
possible for us to access other databases. Also, we only
infected with COVID-19 showed that the mean birth weight
included English language articles in the study.
was significantly lower, while the probability of LBW and pre­
The findings of this study, as well as recently published
term delivery was more common among symptomatic preg­
systematic reviews and meta-analysis, may help physicians
nant women (Khan et al. 2021). Another systematic study
understand the nature of the disease and make appropriate
reported that preterm delivery before 37 weeks of gestation
decisions when treating pregnant women with COVID-19.
was common in 21.8% of pregnant women with COVID-19
(Khalil et al. 2020). Certainly, early identification and intervention of patients can
The possibility of vertical transmission of COVID-19 is a reduce adverse pregnancy outcomes and improve the conse­
tremendous concern for both patients and neonatologists quences of pregnancy. However, further studies are needed
and neonatal health care providers. Information on vertical to confirm the long-term outcomes and potential vertical
transmission of COVID-19 is limited in studies and there is transmission from mother to foetus. On the other hand, with
controversial information about the vertical transmission of the identification of new strains of COVID-19, there are still
COVID-19. In our systematic review, 32 studies reported the questions as to whether each of these strains has more
number of positive newborns for COVID-19, which may indi­ severe effects on the mother, foetus and newborn.
cate vertical transmission from mother to foetus or due to
infection after birth and it is not clear whether the source of Conclusions
the reported infection in these neonates is from the mother
or from the environment. Our meta-analysis showed that COVID-19 infection during pregnancy may cause adverse
there were SARS-CoV2 positive in 2% of infected mothers pregnancy outcomes including preterm delivery, maternal
neonates. mortality, NICU admission and neonatal death. Pregnancy
Wang et al. (2020) summarised that there is currently no loss and SARS-CoV2 positive neonates in lower middle
evidence of intrauterine infection due to vertical transmission income are higher than in high income. The findings and
in women with COVID-19 in the third trimester of pregnancy, knowledge gained from our systematic review show that the
 JOURNAL OF OBSTETRICS AND GYNAECOLOGY 19

reported pregnancy outcomes for women with COVID-19 Brito, V. and Niederman, M.S., 2011. Pneumonia complicating pregnancy.
were been varied. Although studies reported some feto-ma­ Clinics in Chest Medicine, 32 (1), 121– 132.
Cauldwell, M., et al., 2021. Seasonal and SARS-CoV-2 pandemic changes
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Disclosure statement 521– 531.
Dior, U.P., et al., 2016. Very high intrapartum fever in term pregnancies
No potential conflict of interest was reported by the author(s). and adverse obstetric and neonatal outcomes. Neonatology, 109 (1),
62– 68.
Du, M., et al., 2021. Association between the COVID-19 pandemic and
Funding the risk for adverse pregnancy outcomes: a cohort study. BMJ Open,
11 (2), e047900.
The authors did not receive support from any organisation for the sub­
Gao, Y.J., et al., 2020. Clinical features and outcomes of pregnant women
mitted work.
with COVID-19: a systematic review and meta-analysis. BMC Infectious
Diseases, 20 (1), 564.
Goyal, M., et al., 2021. The effect of the COVID-19 pandemic on maternal
ORCID health due to delay in seeking health care: experience from a tertiary
Masoumeh Simbar http://orcid.org/0000-0003-2843-3150 center. International Journal of Gynaecology and Obstetrics, 152 (2),
Sima Nazarpour http://orcid.org/0000-0001-7972-2513 231– 235.
Ali Sheidaei http://orcid.org/0000-0002-0480-5768 Gupta, P., Kumar, S., and Sharma, S.S., 2021. SARS-CoV-2 prevalence and
maternal– perinatal outcomes among pregnant women admitted for
delivery: experience from COVID-19-dedicated maternity hospital in
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supplementary information. The datasets generated during and/or ana­ pregnancy and COVID-19: signs and symptoms, laboratory tests, and
lysed during the current study are available from the corresponding perinatal outcomes. International Journal of Reproductive Biomedicine,
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