Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.
Competing Interests: Clare Whitehead declares a a relationship with the following entities, Ferring Pharmaceuticals COVID19 Investigational, Grant, NHMRC Fellowship (salary support). Edward Mullins declares a relationship with the following entities National Institute for Health Research (Project grant for PAN COVID study). Deborah Money declares a relationship with the following entities, Canadian Institutes of Health Research (payments to my 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. Torri D. Metz declares a relationship with the following entities, 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 me), 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). Erica Lokken declares a relationship with the following entity, US NIH (paid institution). Karen L. Kotloff declares a relationship with the following entity, Bill and Melinda Gates Foundation. Siran He declares a relationship with the following entity, Bill and Melinda Gates Foundtion (payments made to institution). Valerie Flaherman declares a relationship with the following entities, Bill and 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). Jose Sanin-Blair declares a relationship with the following entity, Ferring Pharmaceuticals which gave a grant ($10,000) for the expenses of RECOGEST trial and is a part of the Columbian Federation of Perinatology. Yalda Afshar declares a relationship with the following entities, Bill and Melinda Gates Foundation (payments made to institution), CDC Foundation (payments made to my institution), Robert Woods Johnson Foundation (payments made to institution), and UCLA Dean’s Office COVID-19 research (payments made to institution). Rebecca Clifton declares a relationship with the following entity, NIH HD36801 (MFMU Network DCC). Alice Panchaud declared a relationship with the European Medicines Agency (research grant to institution) and the Federal Office of Public Health Switzerland (research grant to institution).