Large French study clears mRNA-based COVID-19 vaccines of teratogenic risk

Receipt of messenger RNA (mRNA)-based COVID-19 vaccine during pregnancy does not appear to be associated with an increased risk of any major congenital malformations, according to new research from France.

Analysis of large data from the Mother-Child EPI-MERES Register showed that the prevalence rate of major congenital malformations did not significantly differ between infants exposed to at least one vaccine dose in utero and nonexposed infants, at 176.6 vs 179.4 per 10,000, respectively. [JAMA Netw Open 2025;8:e2538039]

mRNA COVID-19 vaccine showed no association with major congenital malformations overall (weighted odds ratio [OR], 0.98, 95 percent confidence interval [CI], 0.93–1.04), when grouped by organ system (weighted ORs ranging from 0.84 [95 percent CI, 0.68–1.04] for digestive system congenital malformations to 1.20 [95 percent CI, 0.75–1.91] for abdominal wall defects), or when examined individually.

Sensitivity analyses excluding infants exposed to a COVID-19 infection during the first trimester of pregnancy and comparing vaccination at different pregnancy stages yielded consistent findings.

“To our knowledge, this is the only study to date to have estimated the risk of 75 individual major congenital malformations following a first-trimester exposure to these vaccines, essential for evaluating their teratogenicity as each malformation is associated with specific developmental mechanisms and critical periods of vulnerability,” researchers said.

The present data align with those from previous studies showing no association between in utero exposure to mRNA-based COVID-19 vaccines and the risk of major congenital anomalies in any specific organ system groups. [BMJ 2024;386:e079364; BMJ Med 2024;3:e000743]

“Our study confirms the foetal safety of mRNA COVID-19 vaccines during pregnancy, showing no increased risk of major congenital malformations and reassuring the millions of women worldwide who received these vaccines early in pregnancy,” the researchers noted.

“Policymakers and healthcare practitioners should update vaccination guidelines to ensure that pregnant women are adequately informed about the safety of these vaccines,” they added.

The analysis included a total of 527,564 infants, of whom 130,338 (24.7 percent) were born to mothers exposed to an mRNA COVID-19 vaccine dose during the first trimester of pregnancy. Baseline characteristics showed that the mothers of exposed vs unexposed infants were slightly older (mean age 30.4 vs 30.1 years) and were less socially deprived (18.3 percent vs 20.3 percent lived in fifth-quintile cities). Exposed mothers also presented slightly more often with comorbidities including hypertension (1.3 percent vs 1.1 percent), antidepressant use (3.4 percent vs 2.7 percent), and anxiolytic or hypnotic use (2.5 percent vs 2 percent).

The researchers acknowledged several study limitations such as the inclusion of only live-born infants and the underestimation of some comorbidities such as obesity.