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IntroductionDespite 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.MethodsWe 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.ResultsWe 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.ConclusionsThis 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.

Additional file 2. Amendments to the pre-registered protocol.

Additional file 1. Supporting methods documents. PRISMA-P and PRISMA-IPD checklists, database search strategies, manuscript screening form, risk of bias instrument, and strength of evidence tool.

Background Hormonal changes during the menstrual cycle appear to play a key role in shaping immunity in the cervicovaginal tract and may influence the risk of sexually transmitted infections. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle but have often shown conflicting results. Thus, our understanding of the immunological correlates of the menstrual cycle remains vague and could be improved by a meta-analysis of all available data sets. Results We present a protocol for a systematic review and meta-analysis of individual participant data of cervicovaginal immune mediators during the menstrual cycle. Our primary objective is to estimate the differences in concentrations of immune mediators between the follicular and luteal phases of the menstrual cycle. Our secondary objectives are to compare how four technical factors (sample type, assay type, method of determining menstrual cycle phase, and normalization of immune mediator concentrations to total protein) affect the estimated differences across the menstrual cycle phases. In addition to summarizing previous studies, we will perform a new study, measuring select immune mediators in 200 paired cervicovaginal lavage samples. This additional study will strengthen the evidence and test the validity of the meta-analysis. Conclusions Our systematic review and meta-analysis will provide precise estimates of immune mediator concentrations throughout the menstrual cycle. This improved understanding of cervicovaginal immunity across the menstrual cycle will provide important baseline knowledge for the design of clinical trials of vaginal interventions, including hormonal contraception and prevention tools for sexually transmitted infections.