mRNA COVID-19 Vaccines Not Associated With Major Congenital Malformations During Pregnancy

mRNA COVID-19 vaccines are safe for women to receive in early pregnancy, according to a new study in JAMA Network Open.¹ Women who received the vaccine in their first trimester did not have an increased risk of their child having a major congenital malformation (MCM), either overall or by organ group.

Immunological and physiological changes in women while they are pregnant put them at increased risk of getting a severe case of COVID-19, which could leave them with more severe complications that affect their unborn child.² Although studies have confirmed the safety of the mRNA vaccine for use in pregnant women, the risk of MCMs has not been assessed in studies with more statistical power. This study aimed to assess the risk of MCMs in unborn fetuses exposed to the mRNA COVID-19 vaccine in the first trimester by organ system, overall, and by individual MCM.¹

The Mother-Child EPI-MERES Register was used for this study, which is a part of the French National Health Data System and covers more than 99% of the French population. The data includes a database for COVID-19 vaccination, which was used for this study. The researchers specifically used data between April 1, 2021, and January 31, 2022, on live-born infants born to women aged 15 to 49 years. Infants were excluded if they were same-sex twins, had mothers who had a teratogenic infection, or had consumed teratogenic drugs during the pregnancy. Those who received non-mRNA vaccines were also excluded.

Those who received at least 1 dose of the mRNA vaccine between the day of conception and the last day of the first trimester were considered the exposure group. Any infant who did not meet this criterion was used for the control. Diagnostic codes were used to identify MCMs, which were grouped into 13 organ systems for evaluation in the study.

There were 527,564 infants included in the study, of whom 130,338 had received an mRNA COVID-19 vaccine in the first trimester. Mothers of the infants who were exposed were slightly older and had slightly more comorbidities compared with the mothers of infants who were not exposed.

There were 2302 infants in the exposed group who were diagnosed with MCMs, equating to 176.6 MCMs per 10,000 infants. The control group contained a total of 7128 infants with MCMs, equating to 179.4 MCMs per 10,000. The OR of an MCM for the exposed group was 0.98 (95% CI, 0.93-1.04) for organ systems, which was not significant.

There were no increased risks for the 75 individual MCMs. There were 4 weighted ORs that had a 2-fold increased risk but were not statistically significant, including 3 cardiovascular system MCMs (weighted OR, 2.63; 95% CI, 0.64-10.81). Risk estimation was not possible to assess for 5 MCMs, as they were not reported in either group. No risk estimations were found to be statistically significant, even after adjusting for age, folic acid consumption, and social deprivation. The associations were not altered when excluding any infant that was exposed to COVID-19 in the first trimester.

There were some limitations to this study. MCMs in stillbirths and terminated pregnancies were not considered due to trouble identifying these cases in data. Comorbidities may be underestimated in the database. The rate of MCMs in this study was lower than previously measured. Extremely rare MCMs could not be reported on due to their not occurring in either group. There were only 6 statistically significant associations, which could be attributed to type I errors.

The researchers concluded that mRNA COVID-19 vaccines were not associated with an increased risk of MCMs in infants exposed in the first trimester of pregnancy. “Although associations with extremely rare outcomes cannot be ruled out, these findings provide reassuring evidence regarding the safety of mRNA COVID-19 vaccination during early pregnancy,” the authors wrote.

Reference

1. Bernard C, Duchemin T, Marty L, et al. First-trimester mRNA COVID-19 vaccination and risk of major congenital anomalies. JAMA Netw Open. 2025;8(10):e2538039. doi:10.1001/jamanetworkopen.2025.38039

2. COVID while pregnant. Cleveland Clinic. Updated December 20, 2024. Accessed October 16, 2025. https://my.clevelandclinic.org/health/diseases/covid-while-pregnant