A large cohort study reassures the safety of the mRNA vaccine in early pregnancies

A large cohort study reassures the safety of the mRNA vaccine in early pregnancies

A landmark German study finds that mRNA Covid-19 vaccination in the first trimester does not increase the risk of major congenital disabilities, providing crucial reassurance to expectant parents and healthcare providers.

In a recently published study inClinical Microbiology and InfectionA group of researchers evaluated the association between maternal first trimester coronavirus disease 2019 (Covid-19) messenger ribonucleic acid (MRNA) and the risk of congenital malformations.

background

Can a vaccine equipped to protect against Covid-19 risks during early pregnancy? When the pandemic hit, mRNA vaccines were deployed quickly, but vaccination for pregnant people was initially not recommended due to insufficient safety data. The first trimester is a critical window of fetal development when exposure to potential teratogens can lead to important congenital anomalies. Given the urgency of pandemic reduction and widespread uptake of vaccines, it is important to ensure their safety in vulnerable populations, including pregnant individuals. Further research is needed to evaluate potential associations between first trimester vaccination and fetal development outcomes.

About the study

This prospective observational cohort study was conducted by the Embryotox Center for Clinical Teratology and Drug Safety in Pregnancy in collaboration with the Paul Ehrlich Institute, the German Federal Institute for Vaccines and Biomedicine. Pregnant women who contacted Embryotox for individual advice between January 2021 and October 2022 were included if they had received at least one mRNA Covid-19 vaccine dose between weeks 2+0 and 12+6 of pregnancy. Their data were compared to a cohort of unvaccinated pregnant women from the same period identified using identical methods.

Information was collected through structured questionnaires during the initial contact and again eight weeks after the expected delivery date. Data included maternal demographics, medication use, pregnancy outcomes, and newborn characteristics. The presence of congenital malformations was coded using the International Classification of Diseases, 10th Revision (ICD-10) and graded by two blinded experts according to the European Surveillance of Congenital Anomalies (EUROCAT). Statistical analyzes were performed using multivariable logistic regression, with missing values ​​treated via multiple imputation. Ethics approval was granted by the Charité Ethics Committee and the study was registered in the German Clinical Trials Register and the World Health Organization International Clinical Trials Registry.

Study results

The exposed group included 1,828 pregnant women who received an mRNA Covid-19 vaccination in the first trimester, including 1,518 who received Comirnaty® (Pfizer-Biontech) and 308 who received Spikevax® (Moderna). The unexposed comparison group included 1,955 women. At follow-up, 1,762 exposed and 1,717 unexposed pregnancies had complete outcome data.

Major congenital malformations were identified in 68 infants (3.86%) from the exposed group and 53 infants (3.09%) from the comparison group, with the paper finding that both rates are within the expected range for the German population. The adjusted odds ratio for the overall rate of major congenital disabilities was 1.30 with a 95% confidence interval of 0.90–1.86, indicating no statistically significant increase in risk. Sensitivity analyzes produced similar results, with odds ratios ranging from 1.19 to 1.41, all of which remained statistically insignificant.

The most commonly affected system was the cardiovascular system. In the vaccinated cohort, 32 cases (1.82%) involved congenital heart defects, compared to 15 cases (0.87%) in the comparison cohort. Ventricular septal defects were most common with 18 cases in the exposed group and 7 cases in the unexposed group. In six of the exposed cases, vaccination occurred after the 11th week of pregnancy, beyond the period in which the fetal septum challenged causality. Patent ductus arteriosus, which is classified as a major anomaly when present in infants, was found in three vaccinated and one unvaccinated child.

Renal and urinary tract abnormalities were reported in 16 vaccinated versus 8 unvaccinated infants, driven primarily by cases of renal duplex and ureteral dilatation. No clear clustering or pattern suggesting a causal link to vaccination has been suggested.

Retrospective reports of 73 cases were also analyzed; 8 showed different major anomalies with no consistent pattern. Newborn characteristics, including birth weight, head circumference, and gestational age, were comparable between groups. Premature births occurred in 3.9% of vaccinated and 7.5% of unvaccinated cases. The rates of infants at the smallest age were 7.29% in the vaccinated group and 9.09% in the comparison group.

Potential biases, including differences in health behaviors and access to ultrasound, were considered. Vaccinated women may have undergone more detailed screening, potentially increasing abnormality detection, a factor known as detection bias. Limitations included potential selection bias due to the voluntary reporting process, incomplete education and pregnancy setting data, and unknown Covid-19 infection status during pregnancy.

Conclusions

In conclusion, this prospective cohort study found no statistically significant increase in the risk of congenital malformations after mRNA Covid-19 vaccination during the first trimester of pregnancy. While slightly higher rates of congenital cardiac and urinary tract abnormalities were observed in the vaccinated group, no consistent or biologically plausible patterns emerged. These results reassure the safety of Covid-19 vaccination during early pregnancy but highlight the need for further surveillance.

The study authors note that while their results are reassuring, possible associations with specific congenital disabilities cannot be ruled out and that if considered for women of reproductive age, it should preferably be offered before conception or after the first trimester. Future research should focus on larger cohorts, specific types of defects, and underlying risk factors to further strengthen guidance on vaccination during pregnancy.

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