Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis

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 increased risk of ICU admission (RR 1.63, 95% CI: 1.25, 2.11) and death (RR 2.36, 95% CI: 1.15, 4.81). Conclusion: we found that pregnant women with comorbidities including diabetes, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly-known risk factors, including HIV infection, pre-pregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.
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.: payments made to the institution). V.F. declares a relationship with the following entities: BMGF (payments to her 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), University of California, San Francisco Women’s Health Center of Excellence (payments to institution), and California Department of Health Care Services (payments made to institution). J.S.B. declares a relationship with Ferring Pharmaceuticals, which provided $10,000 for the expenses of the RECOGEST trial and is a part of the Colombian Federation of Perinatology. Y.A. declares a relationship with the following entities: BMGF (payments made to institution), CDC Foundation (payments made to institution), Robert Woods Johnson Foundation (payments made to institution), and University of California, Los Angeles Dean’s Office COVID-19 research (payments made to institution). M.C.N. declares a relationship with the following entities: BMGF (project grant made to institution), European and Developing Countries Clinical Trials Partnership, 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). E.S.M. declares a relationship with Pfizer (Site Principal Investigator for phase 2/3 randomized controlled trial of COVID-19 vaccine in pregnancy). O.S. declares a relationship with the following entities: NordForsk (Nordic research funding grant number 105545), the Swedish Medical Products Agency (funding for reports on COVID-19 vaccines in pregnancy), and Karolinska Institutet (funding for COVID-19 research in pregnancy, 2020-01567). E.G. declares a relationship with the following entities: Stavros Niarchos Foundation, Santander Foundation, and La Caixa Foundation (payments made to institution). S.A.M. declares a relationship with the BMGF (funded study in South Africa). This study was funded by the Bill & Melinda Gates Foundation (grant to E.R.S.; INV-022057).