No Increased Risk of Birth Defects with First-Trimester mRNA COVID-19 Vaccination, finds study

A recent study published in the journal of Clinical Microbiology and Infection found no significant association between repeated mRNA COVID-19 vaccination during the first trimester of pregnancy and an increased risk of major structural birth defects. This research analyzed data from 47,665 infants, using national immunization and healthcare records, with follow-up for at least one year. The findings support the safety of mRNA COVID-19 vaccines in early pregnancy.

This large population-based cohort study examined whether receiving repeat doses of mRNA COVID-19 vaccines during early pregnancy increases the risk of major structural birth defects. While earlier studies had established that a single vaccine dose in the first trimester did not elevate such risks, this new analysis is among the first to specifically evaluate outcomes following revaccination.

The study included 47,665 live births to Singaporean mothers aged 18 to 50 who had previously received at least one COVID-19 vaccine dose. This research tracked pregnancies with last menstrual periods between July 1, 2021, and December 31, 2023. Using data from the national immunization registry and healthcare claims databases, this study assessed vaccination exposure and birth outcomes with a high degree of completeness and reliability.

Among the cohort, 5,327 mothers (11.2%) received repeat mRNA COVID-19 vaccination during the first trimester. Of these, nearly 10% received newer bivalent vaccine formulations, designed to target multiple virus variants.

The findings showed no statistically significant increase in the risk of major structural birth defects among infants born to mothers who received repeat vaccinations during early pregnancy. The adjusted prevalence ratio (aPR) was 0.97, with a 95% confidence interval ranging from 0.74 to 1.27 which indicated no meaningful difference when compared to mothers who were not vaccinated during the first trimester.

Further analysis by vaccine type also revealed no elevated risk. For bivalent vaccines, the aPR was 0.45 (95% CI: 0.14–1.39), while for earlier formulations, the aPR was 1.04 (95% CI: 0.79–1.36). Despite these subgroup estimates having wider confidence intervals, they did not indicate any increased risk.

Using generalized Poisson regression with robust standard errors and overlap weighting, this study ensured balanced comparisons after accounting for potential confounding factors. Overall, the findings of this study reinforce the safety profile of mRNA COVID-19 vaccines during pregnancy, even when administered as repeat doses in the first trimester.

Source:

Wee, L. E., Abdul Malek, M. I. B., Ho, R. W. L., Lim, J. T., Chiew, C., Li, R. J., Chong, C. Y., Choolani, M., Lye, D. C. B., & Tan, K. B. (2026). Risk of major-structural-birth-defects following repeat mRNA COVID-19 vaccination in the first trimester: a population-based cohort study. Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. https://doi.org/10.1016/j.cmi.2026.03.027