Risk of major structural birth defects following repeat mRNA COVID-19 vaccination in the first trimester: a population-based cohort study.

OBJECTIVES

Vaccine safety concerns (e.g. foetal health) underpin maternal vaccine hesitancy during COVID-19 endemicity; although substantial real-world evidence highlights absence of increased risk for foetal abnormalities following one dose of COVID-19 vaccination during the first trimester, risk following repeat vaccination was not explicitly assessed. Risk of major structural birth defects following revaccination of previously vaccinated mothers with mRNA COVID-19 vaccine doses in the first trimester was assessed using national vaccination registers and healthcare claims databases.

METHODS

A population-based cohort study was performed including all infants born to Singaporean mothers (citizens/permanent residents) aged 18-50 years who had previously received ≥1 vaccine dose, with a last menstrual period from 1 July 2021 to 31 December 2023. Exposure (vaccination) was determined using the National Immunisation Registry; outcomes (birth defects) were determined using national healthcare claims data. Risk of major structural birth defects following repeat vaccination (first trimester) was estimated using generalized Poisson regression with robust standard errors and overlap weights applied.

RESULTS

A total of 47 665 live births were included in the final cohort. One-tenth (11.2%, 5327 of 47 665) had repeat maternal COVID-19 vaccination (mRNA vaccine doses) during the first trimester, of which 9.9% (527 of 5327) comprised bivalent formulations. Risk of a major structural birth defect was not significantly increased (adjusted prevalence ratio [aPR], 0.97; 95% CI, 0.74-1.27) following repeat vaccination in the first trimester, versus no vaccination (first trimester). No significantly elevated risk of major structural birth defect was observed following repeat vaccination with bivalent formulations (aPR, 0.45; 95% CI, 0.14-1.39) or ancestral vaccines (aPR, 1.04; 95% CI, 0.79-1.36), although CIs were wide.

CONCLUSIONS

Repeat vaccination with mRNA COVID-19 vaccines in the first trimester was not significantly associated with increased risk for major structural birth defects, underlining safety of maternal revaccination with seasonally updated COVID-19 booster doses during endemicity.