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Meta-Analysis
. 2023 Jan;8(1):e009495.
doi: 10.1136/bmjgh-2022-009495.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis

Emily R Smith  1 , Erin Oakley  2 , Gargi Wable Grandner  2 , Kacey Ferguson  2 , Fouzia Farooq  2 , Yalda Afshar  3 , Mia Ahlberg  4 , Homa Ahmadzia  5 , Victor Akelo  6 , Grace Aldrovandi  7 , Beth A Tippett Barr  6 , Elisa Bevilacqua  8 , Justin S Brandt  9 , Nathalie Broutet  10 , Irene Fernández Buhigas  11 , Jorge Carrillo  12 , Rebecca Clifton  13 , Jeanne Conry  14 , Erich Cosmi  15 , Fatima Crispi  16 , Francesca Crovetto  16 , Camille Delgado-López  17 , Hema Divakar  18 , Amanda J Driscoll  19 , Guillaume Favre  20 , Valerie J Flaherman  21 , Chris Gale  22 , Maria M Gil  11 , Sami L Gottlieb  10 , Eduard Gratacós  16 , Olivia Hernandez  23 , Stephanie Jones  24 , Erkan Kalafat  25 , Sammy Khagayi  26 , Marian Knight  27 , Karen Kotloff  28 , Antonio Lanzone  8 , Kirsty Le Doare  29   30 , Christoph Lees  31 , Ethan Litman  5 , Erica M Lokken  32 , Valentina Laurita Longo  33 , Shabir A Madhi  24 , Laura A Magee  34 , Raigam Jafet Martinez-Portilla  35 , Elizabeth M McClure  36 , Tori D Metz  37 , Emily S Miller  38 , Deborah Money  39 , Sakita Moungmaithong  40 , Edward Mullins  31 , Jean B Nachega  41 , Marta C Nunes  24 , Dickens Onyango  42 , Alice Panchaud  43 , Liona C Poon  40 , Daniel Raiten  44 , Lesley Regan  14 , Gordon Rukundo  29 , Daljit Sahota  40 , Allie Sakowicz  38 , Jose Sanin-Blair  45 , Jonas Söderling  4 , Olof Stephansson  4 , Marleen Temmerman  46 , Anna Thorson  10 , Jorge E Tolosa  47 , Julia Townson  48 , Miguel Valencia-Prado  49 , Silvia Visentin  15 , Peter von Dadelszen  50 , Kristina Adams Waldorf  32 , Clare Whitehead  51 , Murat Yassa  52 , Jim M Tielsch  2 ; Perinatal COVID PMA Study Collaborators; Perinatal COVID PMA Study Collaborators
Collaborators, Affiliations
Meta-Analysis

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis

Emily R Smith et al. BMJ Glob Health. 2023 Jan.

Abstract

Introduction: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies.

Methods: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale.

Results: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias.

Conclusions: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Keywords: COVID-19; Epidemiology; Maternal health.

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Conflict of interest statement

Competing interests: CW declares a relationship with Ferring Pharmaceuticals COVID-19 Investigational Grant and NHMRC Fellowship (salary support). AP declares the following research grants to her institution: ‘H2020-Grant—Consortium member of Innovative medicine initiative call 13 topic 9 «ConcePTION», Efficacy and safety studies on Medicines EMA/2017/09/PE/11, Lot 4, WP 2 lead, Safety monitoring of COVID-19 vaccines in the EU—Reopening of competition no. 20 under a framework contract following procurement procedure EMA/2017/09/PE (Lot 3) (Euro 110,000), Federal Office of Public Health (207,000 CHF)’. EM declares a relationship with the National Institute for Health Research (project grant for PAN COVID study). DM declares a relationship with the Canadian Institutes of Health Research (payments to institution only), Public Health Agency of Canada (payments to institution only), BC Women’s Foundation (payments to institution only) and is a member of the COVID-19 Immunity Task Force sponsored by the Canadian government. TDM declares a relationship with Pfizer (site principal investigator for SARS-CoV-2 vaccination in pregnancy study, money paid to institution and member of Medical Advisory Board for SARS-CoV-2 vaccination in pregnancy study, money paid to TDM), NICHD (subcommittee chair for the NICHD Maternal-Fetal Medicine Units Network Gestational Research Assessments of COVID-19 (GRAVID) study) and Society for Maternal-Fetal Medicine (board member). EL declares a relationship with the US NIH (paid institution) and is an employee of AbbVie, but was employed at the University of Washington at the time of the study. KK declares a relationship with the Bill & Melinda Gates Foundation. VJF declares a relationship with the Bill & Melinda Gates Foundation (payments to institution), Yellow Chair Foundation (payments to institution), Robert Woods Johnson Foundation (payments to institution), CDC Foundation, California Health Care Foundation (payments to institution), Tara Health Foundation (payments to institution), UCSF Women’s Health Center of Excellence (payments to institution) and California Department of Health Care Services (payments made to institution). JS-B declares a relationship with the Ferring Pharmaceuticals, which gave a grant ($10 000) for the expenses of RECOGEST trial and is a part of the Columbian Federation of Perinatology. YA declares a relationship with the Bill & Melinda Gates Foundation (payments made to institution), CDC Foundation (payments made to institution), Robert Woods Johnson Foundation (payments made to institution) and UCLA Dean’s Office COVID-19 research (payments made to institution). RC declares a relationship with the NIH HD36801 (MFMU Network DCC). MCN declares a relationship with the BMGF (project grant made to institution), EDCTP, Sanofi, AstraZeneca, Pfizer (research grants made to institution), Sanofi Pasteur (payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events) and Sanofi Pasteur and Pfizer (payment for expert testimony). ESM declares a relationship with Pfizer (site principal investigator for phase 2/3 RCT of COVID vaccine during pregnancy). OS declares a relationship with the NordForsk Funding (Nordic research funding grant number: 105545), the Swedish Medical Products Agency (funding for reports on COVID-19 vaccines and pregnancy) and Karolinska Institutet (funding for COVID research and pregnancy: 2020-01567). EG declares a relationship with the Stavros Niarchos Foundation, Santander Foundation and ‘La Caixa’ Foundation (payments made to institution). SAM declares a relationship with BMGF (funded study in South Africa).

Figures

Figure 1
Figure 1
PRISMA-IPD flow diagram documenting study identification, screening and analysis. IPD, individual participant data; PI, principal investigator; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
See this image and copyright information in PMC

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