Matters Arising: Safety of SARS-CoV-2 vaccination during pregnancy - obstetric outcomes from a large cohort study: methodological biases in study design with potential impact on the study’s interpretation

Abstract

In the paper “Safety of SARS-CoV-2 vaccination during pregnancy - obstetric outcomes from a large cohort study”, BMC Pregnancy and Childbirth 22 [1], Dick et al. compare the retrospective maternal and neonatal outcomes of vaccinated and unvaccinated women, who delivered in a large tertiary care center in Jerusalem, Israel, during the period December 2020 throughout July 2021. Two of the main outcomes in their study are ‘Preterm birth’ (prior to gestational week 37) and ‘intrauterine fetal demise’ (stillbirth) rates.

The authors find no statistical difference between the respective rates of these two outcomes among vaccinated and unvaccinated women with singleton pregnancy and no history of prior SARS-CoV-2 infection (0.87% and 1% stillbirth rate and 5.5% and 6.2% preterm birth rate for vaccinated and unvaccinated women, respectively). They optimistically conclude that “SARS-CoV-2 appears to be safe during pregnancy” since there is no association between vaccination during pregnancy and negative maternal and neonatal outcomes. They do acknowledge however, that women who first vaccinated in the second trimester had a higher rate of preterm birth compared to unvaccinated women, and hypothesized that there could be “unmeasured confounding that may contribute to the result”. They also acknowledge the retrospective design as a limitation of the study and call for further studies to address some of the limitations.

The purpose of this Matters Arising is to highlight that the analysis by Dick et al. seems to have several inherent biases with potentially significant impact on the interpretation of the results.