First trimester mRNA COVID-19 vaccination and risk of congenital malformation: a prospective observational Embryotox cohort study.

Objectives: This observational cohort study evaluates the risk of major birth defects after maternal mRNA COVID-19 vaccination in the first trimester of pregnancy.

Methods: Outcomes of prospectively ascertained pregnancies with at least one mRNA COVID-19 vaccination in the first trimester (gestational week 2 + 0 to 12 + 6) were compared with a cohort of unvaccinated pregnant women of the same period, whose data were collected using the same approach. The enrolment of study cases was conducted over a period of 21 months. For inclusion in the study, a structured pregnancy follow-up had to be completed afterwards. The reported congenital anomalies were classified according to EUROCAT. Relevant maternal characteristics were considered and adjusted ORs were calculated using logistic regression.

Results: The exposed study cohort included 1828 pregnant women who were vaccinated with an mRNA vaccine in the first trimester. The unexposed comparison cohort consisted of 1955 pregnant women. Sixty-eight major congenital malformations have been observed in the vaccinated and 53 in the unexposed cohort (3.86% vs. 3.09%). The analysis resulted in an adjusted OR of 1.30 (95% CI: 0.90-1.86). A wide range of performed sensitivity analyses was in line with this finding.

Conclusions: We did not detect a statistically significant increase in the overall birth defect rate after maternal mRNA COVID-19 vaccination in the first trimester.