Guidance for design and analysis of observational studies of fetal and newborn outcomes following COVID-19 vaccination during pregnancy

Fell, Deshayne B.; Dimitris, Michelle C.; Hutcheon, Jennifer A.; Ortiz, Justin R.; Platt, Robert W.; Regan, Annette K.; Savitz, David A.

COVID-19 vaccines are now being deployed as essential tools in the public health response to the global SARS-CoV-2 pandemic. Pregnant individuals are a unique subgroup of the population with distinctive considerations regarding risk and benefit that extend beyond themselves to their fetus/newborn. As a compliment to traditional pharmacovigilance and clinical studies, evidence to comprehensively assess COVID- 19 vaccine safety in pregnancy will need to be generated through observational epidemiologic studies in large populations. However, there are several unique methodological challenges that face observational assessments of vaccination during pregnancy, some of which may be more pronounced for COVID-19 studies. In this contribution, we discuss the most critical study design, data collection, and analytical issues likely to arise. We offer brief guidance to optimize the quality of such studies to ensure their maximum value for informing public health decision-making.