This is a summary, written by members of the CITF Secretariat, of:

Fell DB, Dimitris MC, Hutcheon JA, Ortiz JR, Platt RW, Regan AK, Savitz DA. Guidance for design and analysis of observational studies of fetal and newborn outcomes following COVID-19 vaccination during pregnancy. Vaccine. 2021 Apr 1;39(14):1882-1886. doi: 10.1016/j.vaccine.2021.02.070.

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

Studies exploring COVID-19 vaccination among pregnant women are likely to face unique methodological challenges. In this Short Communication in Vaccine, Dr. Deshayne Fell, a member of the Vaccine Surveillance Reference Group’s Vaccine Safety Working Group, and her colleagues discuss critical study design, data collection, and analytical issues for observational epidemiologic studies of pregnancy outcomes following COVID-19 vaccination during pregnancy. They provide some guidance for optimal design and analysis of these studies to ensure high quality evidence to inform public health decision-making.

First, the variability of the timing of vaccination in observational studies of vaccination during pregnancy is critical, both in order to characterize gestational-age specific exposure and also to avoid bias from other strongly temporal issues such as for vaccination (based on vaccine availability/distribution/recommendations), exposure to background pandemic factors, and potential for immortal time bias.

Research has shown that uptake of vaccination in pregnancy tends to be strongly influenced by sociodemographic and geographic factors, which may introduce bias in the analysis, if not accounted for. The authors suggest that studies should aim to incorporate as much information as possible on variables known to be associated with vaccination and with pregnancy outcomes. These variables can then be used in statistical analyses to reduce bias.

The authors also provide several recommendations to optimize the quality of vaccine safety studies tailored to pregnant individuals. They recommend that measurement of several variables be prioritized, such as: (i) those related to vaccination (vaccine product, dates of vaccination for all doses received, number of doses, and gestational age when each dose was received); (ii) those necessary for measuring pregnancy outcomes; and (iii) those required to account for confounding factors.

Due to the unique population, a final recommendation from the authors to ensure optimal study design and execution is that studies of COVID-19 vaccination in pregnancy should involve researchers experienced in both vaccine evaluation and perinatal epidemiology.