Study Affirms mRNA Vaccine Safety in Early Pregnancy Amid Concerns

A significant prospective cohort study conducted in Germany has provided reassurance regarding the safety of mRNA COVID-19 vaccines during the first trimester of pregnancy. Published in *Clinical Microbiology and Infection* on June 11, 2025, the study, led by researchers from the Embryotox Centre of Clinical Teratology and Drug Safety in Pregnancy in collaboration with the Paul-Ehrlich-Institut, evaluated the potential risks associated with maternal vaccination and its impact on congenital malformations.

The urgent need for this research arose as the COVID-19 pandemic prompted a rapid rollout of vaccines, yet initial recommendations for vaccination during pregnancy were hesitant due to a lack of sufficient safety data. This study aimed to assess whether vaccination during the critical period of fetal development posed any risks of major congenital anomalies.

Approximately 1,828 pregnant women who received at least one dose of mRNA COVID-19 vaccine between gestational weeks 2+0 and 12+6 were included in the study. They were compared against a cohort of 1,955 unvaccinated pregnant women from the same timeframe. Data was collected using structured questionnaires during initial contact and follow-ups approximately eight weeks postpartum. This comprehensive approach allowed for an analysis of maternal demographics, medication use, pregnancy outcomes, and neonatal characteristics, with congenital malformations coded according to the International Classification of Diseases, 10th Revision (ICD-10).

The findings indicated that 3.86% of infants in the vaccinated group were born with major congenital malformations, compared to 3.09% in the unvaccinated cohort. The adjusted odds ratio for the overall rate of major congenital disabilities was 1.30 (95% confidence interval: 0.90–1.86), which signifies no statistically significant increase in risk. Sensitivity analyses yielded similar results, reinforcing the study's conclusions.

Notably, while the vaccinated group exhibited higher rates of congenital heart defects and urinary tract anomalies, no consistent patterns or causal links emerged that could be attributed to vaccination. For instance, the most common congenital heart defect observed was the ventricular septal defect, which occurred in 1.82% of the vaccinated group compared to 0.87% in the unvaccinated group. The authors emphasized that the timing of vaccination relative to fetal development stages argues against a causal relationship.

Potential biases were acknowledged, particularly regarding health-seeking behavior and access to medical interventions that may have led to enhanced detection of anomalies in vaccinated women. Limitations included possible selection bias due to voluntary reporting and incomplete data concerning the women's educational backgrounds and attitudes toward pregnancy. Moreover, the impact of COVID-19 infection status during pregnancy was not fully assessed, which could influence outcomes.

In conclusion, this large cohort study offers crucial reassurance regarding the safety of mRNA COVID-19 vaccines in early pregnancy. While some anomalies were observed at slightly higher rates within the vaccinated group, the absence of significant statistical correlations and the lack of biologically plausible patterns suggest that the benefits of vaccination outweigh the potential risks. The study advocates for continued monitoring and further research to explore specific congenital disabilities and underlying risk factors associated with vaccination during pregnancy. The authors recommend that vaccination for women of reproductive age should ideally occur before conception or following the first trimester to mitigate any risks associated with early pregnancy.

This study represents an essential contribution to the growing body of evidence supporting the safety of COVID-19 vaccines for pregnant individuals, providing critical information for healthcare providers and prospective parents alike.