(SLC-023) In utero exposure to mRNA COVID-19 vaccines during the first trimester of pregnancy and risk of congenital anomalies: a national cohort study

Background: Despite widespread recommendations, data on the fetal safety of mRNA COVID-19 vaccines – based on exposition during the teratogenic window – remains limited, especially regarding specific congenital anomalies.

Objectives: To assess the association between first-trimester exposure to mRNA COVID-19 vaccines and the risk of major congenital malformations (MCMs) across 13 organ systems and 75 specific subtypes.

Methods: We conducted a nationwide cohort study using data from the Mother-Child EPI-MERES Register, nested within the French Health Data System (SNDS). The study included all liveborn infants from pregnancies that began between April 1, 2021, and January 31, 2022. Exposure was defined as receiving at least one dose of an mRNA COVID-19 vaccine during the first trimester. All other live-born infants were considered non-exposed. In the main analysis, the non-exposed group served as the control. In sensitivity analyses, we successively restricted the control group to infants whose mothers received at least one dose during the second or third trimester, infants whose mothers received at least one dose before pregnancy, and infants whose mothers did not receive any dose before or during pregnancy. To control for potential confounders—including maternal sociodemographic characteristics and medical history—we applied a propensity score-based standardized mortality ratio (SMR) weighting approach. An overlap weighting method was used as an alternative method in an additional sensitivity analyses. Adjusted odds ratios (aORs) were estimated using logistic regression models.

Results: Among 527,564 eligible live-born infants, 130,338 (25%) were exposed to at least one vaccine dose during the first trimester. Mothers in the exposed group were slightly older, less socially deprived, more likely to have taken folic acid, and had a slightly higher prevalence of comorbidities. The prevalence of MCMs was 176.6 per 10,000 among exposed infants (n = 2,302) and 179.4 per 10,000 among non-exposed infants (n = 7,128). We found no increased risk in the overall rate of MCMs (aOR [95%CI]: 0.98 [0.93; 1.04]). Similarly, we observed no increased risk for any specific organ system (for example: 1.01 [0.91; 1.12] and 1.03 [0.83; 1.29] for the risk of any cardiac system and any nervous system MCM, respectively) or individual MCM subtype. Stratified analyses based on maternal age, social deprivation, and folic acid supplementation did not reveal any associations. Sensitivity analyses yielded consistent results.

Conclusions: Our findings suggest that first-trimester exposure to mRNA COVID-19 vaccines is not associated with an increased risk of MCMs, providing reassuring evidence regarding the safety of COVID-19 mRNA vaccination during early pregnancy.