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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, Funded by the Bill & Melinda Gates Foundation grant to ERS (INV- 022057).

Objective: this sequential, prospective meta-analysis (sPMA) sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, adverse birth outcomes. Data sources: we prospectively invited study investigators to join the sPMA via professional research networks beginning in March 2020. Study eligibility criteria: eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. Study appraisal and synthesis methods: we included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a two-stage meta-analysis. Results: we collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (pre-existing diabetes, hypertension, cardiovascular disease) versus those without were at higher risk for COVID-19 severity and pregnancy health outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% CI: 1.12, 2.71) more likely to be admitted to the ICU. Pregnant women who were underweight before pregnancy were at higher risk of ICU admission (RR 5.53, 95% CI: 2.27, 13.44), ventilation (RR 9.36, 95% CI: 3.87, 22.63), and pregnancy-related death (RR 14.10, 95% CI: 2.83, 70.36). Pre-pregnancy obesity was also a risk factor for severe COVID-19 outcomes including ICU admission (RR 1.81, 95% CI: 1.26,2.60), ventilation (RR 2.05, 95% CI: 1.20,3.51), any critical care (RR 1.89, 95% CI: 1.28,2.77), and pneumonia (RR 1.66, 95% CI: 1.18,2.33). Anemic pregnant women with COVID-19 also had inc, C.W. declares a relationship with the following entities: Ferring Pharmaceuticals (COVID19 Investigational Grant) and National Health and Medical Research Council Fellowship (salary support). A.P. declares the following research grants: ”1) H2020-Grant - Consortium member of Innovative medicine initiative call 13 topic 9, ConcePTION; and 2) 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).” E.M. and C.L. declare a relationship with the National Institute for Health and Care Research (project grant for PAN-COVID study). D.M. declares a relationship with the following entities: Canadian Institutes of Health Research (payments to institution only), Public Health Agency of Canada (payments to institution only), and BC Women’s Health Foundation (payments to institution only). She is also a member of the COVID-19 Immunity Task Force sponsored by the Canadian government. T.D.M. declares a relationship with the following entities: Pfizer (site Principal Investigator for SARS-CoV-2 vaccination in pregnancy study—payment received by the institution; member of Medical Advisory Board for SARS-CoV-2 vaccination in pregnancy studyepayment received by the author), Eunice Kennedy Shriver National Institute of Child Health and Human Development (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). E.M.L. declares a relationship with the National Institutes of Health (paid institution) and is an employee of AbbVie, Inc, but was employed at the University of Washington at the time of the study. K.L.K. and S.H. declare a relationship with the Bill & Melinda Gates Foundation (BMGF) (S.H.: pa