Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis
Authors: Allotey John , Fernandez Silvia , Bonet Mercedes , Stallings Elena , Yap Magnus , Kew Tania , Zhou Dengyi , Coomar Dyuti , Sheikh Jameela , Lawson Heidi , Ansari Kehkashan , Attarde Shruti , Littmoden Megan , Banjoko Adeolu , Barry Kathryn , Akande Oluwadamilola , Sambamoorthi Dharshini , van Wely Madelon , van Leeuwen Elisabeth , Kostova Elena , Kunst Heinke , Khalil Asma , Tiberi Simon , Brizuela Vanessa , Broutet Nathalie , Kara Edna , Kim Caron Rahn , Thorson Anna , Escuriet Ramón , Gottlieb Sami , Tong Van T , Ellington Sascha , Oladapo Olufemi T , Mofenson Lynne , Zamora Javier , Thangaratinam Shakila 
Published: September 2020

Abstract

Objective
To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19).

Design
Living systematic review and meta-analysis.

Data sources
Medline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 27 April 2021, along with preprint servers, social media, and reference lists.

Study selection
Cohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19.

Data extraction
At least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios or risk difference and proportions with 95% confidence intervals. All analyses are updated regularly.

Results

435 studies were included. Overall, 9% (95% confidence interval 7% to 10%; 149 studies, 926 232 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever and cough (both 36%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to report symptoms of fever, dyspnoea, cough, and myalgia. The odds of admission to an intensive care unit (odds ratio 2.61, 95% confidence interval 1.84 to 3.71; I
2
=85.6%), and invasive ventilation (2.41, 2.13 to 2.71; I
2
=0%) were higher in pregnant and recently pregnant than non-pregnant women of reproductive age. Overall, 970 pregnant women (0.2%, 123 studies, 179 981 women) with confirmed covid-19 died from any cause. In pregnant women with covid-19, non-white ethnicity, increased maternal age, high body mass index, any pre-existing maternal comorbidity including chronic hypertension and diabetes, and pregnancy specific complications such as gestational diabetes and pre-eclampsia, were associated with serious complications (severe covid-19, admission to an intensive care unit, invasive ventilation, and maternal death). Compared to pregnant women without covid-19, those with the disease had increased odds of maternal death (odds ratio 6.09, 95% confidence interval 1.82 to 20.38; I
2
=76.6%), of admission to the intensive care unit (5.41, 3.59 to 8.14; I
2
=57.0%), caesarean section (1.17, 1.01 to 1.36; I
2
=80.3%), and of preterm birth (1.57, 1.36 to 1.81; I
2
=49.3%). The odds of stillbirth (1.81, 1.38 to 2.37, I
2
=0%), and admission to the neonatal intensive care unit (2.18, 1.46 to 3.26, I
2
=85.4%) were higher in babies born to women with covid-19 versus those without covid-19.

Conclusion
Pregnant and recently pregnant women with covid-19 attending or admitted to the hospitals for any reason are less likely to manifest symptoms such as fever, cough, dyspnoea, and myalgia, but are more likely to be admitted to the intensive care unit or needing invasive ventilation than non-pregnant women of reproductive age. Pre-existing comorbidities, non-white ethnicity, chronic hypertension, pre-existing diabetes, high maternal age, and high body mass index are risk factors for severe covid-19 outcomes in pregnancy. Pregnant women with covid-19 versus without covid-19 are more likely to deliver preterm and have an increased risk of maternal death and of being admitted to the intensive care unit. Their babies are more likely to be admitted to the neonatal intensive care unit.

Systematic review registration
PROSPERO CRD42020178076.

Readers’ note

This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 2 of the original article published on 1 September 2020 (
BMJ
2020;370:m3320), and previous updates can be found as data supplements (
https://www.bmj.com/content/370/bmj.m3320/related#datasupp
). When citing this paper please consider adding the update number and date of access for clarity.