In a study published in Clinical Microbiology and Infection, researchers in Singapore uncover no tie between repeated mRNA COVID-19 vaccination in the first trimester of pregnancy and a significantly increased risk of major structural birth defects.
Led by investigators with the Communicable Diseases Agency, the team used data from the national immunization registry and healthcare claims to assess rates of major structural birth defects among all 47,665 infants born to mothers in Singapore who had previously received one or more doses of mRNA COVID-19 vaccine. All infants were tracked for at least one year or until October 6, 2025.
Major structural birth defects are physical abnormalities caused by improper development in the womb. Examples include heart defects, spina bifida, and cleft lip and palate.
“Substantial evidence supports maternal COVID-19 vaccination during endemicity [continued presence of a disease], including decreased risk of severe COVID-19 in pregnancy, maternal long COVID-19, and adverse neonatal outcomes,” the researchers wrote. “However, decreasing rates of COVID-19 vaccination amongst pregnant women during endemicity remains of concern.”
1% in both groups had major abnormalities
In total, 11.2% of mothers had repeated maternal mRNA COVID-19 vaccinations in the first trimester, of which 9.9% received the bivalent (two-strain) vaccine, 6.8% were booster doses (total of at least three doses), and 23.2% were second doses.
Major structural birth defects were reported in 1.1% of live births to mothers repeatedly vaccinated in their first trimester, compared with 1.2% of those born to mothers not revaccinated. Limb abnormalities were the most common type of birth defect, followed by congenital heart disease.
Relative to no vaccination, the risk of a major structural birth defect was not significantly elevated after repeated vaccination (adjusted prevalence ratio [aPR], 0.97). Nor was there a significantly higher risk of such birth defects after revaccination with bivalent formulations (aPR, 0.45) or ancestral vaccines (aPR, 1.04), although confidence intervals were wide due to the relatively small number of mothers revaccinated with updated vaccines.
There was no significantly greater risk of major structural birth defects after revaccination in either COVID-infected (aPR, 1.02) or uninfected (aPR, 0.97) mothers.
Findings underscore safety of revaccination in pregnancy
Sensitivity analyses showed that the risk of birth defects after COVID-19 revaccination up to 20 weeks’ gestation didn’t differ significantly (aPR, 1.09), compared with the risk among unvaccinated mothers.
Our findings underline safety of repeat maternal vaccination with seasonally updated COVID-19 booster doses during endemicity.
The risk of major structural birth defects after booster vaccination in the first trimester (aPR, 1.01) or up to 20 weeks of gestation (aPR, 1.13) wasn’t significantly higher than those noted in infants of fully vaccinated mothers who didn’t receive a booster in either period.
After quantifying the potential effect of missing pregnancies ending in stillbirth, the corrected PR for major structural birth defects shifted from 0.97 to 1.14 for the most extreme scenario modelled (probability of live birth, 55% and 80% for unexposed fetuses with and without a defect, respectively, and a 20% absolute decrease in the probability of live birth among mothers receiving mRNA COVID vaccination).
When stillbirth was directly evaluated as a separate outcome, the risk of stillbirth was not significantly elevated (aPR, 0.64) after repeated vaccination with an mRNA COVID-19 vaccine dose in the first trimester.
“Our findings underline safety of repeat maternal vaccination with seasonally updated COVID-19 booster doses during endemicity,” the study authors concluded.
