First-trimester messenger RNA (mRNA)-based COVID-19 vaccine exposure does not increase major congenital malformation (MCM) risk, according to a recent study published in JAMA Network Open.1
Data has indicated significantly increased severe COVID-19 risk in pregnant vs nonpregnant women, leading to recommendations for utilizing mRNA-based COVID-19 vaccination in pregnancy to ensure protection. While data has indicated no significant increases in complication risk from vaccinations, only 2 studies have evaluated associated MCM risk.
Key takeaways:
- A large French cohort study found no increased risk of major congenital malformations (MCMs) after first-trimester exposure to mRNA-based COVID-19 vaccines.
- Among more than 527,000 infants analyzed, MCM rates were similar between vaccinated and unvaccinated mothers.
- No significant differences were observed across 13 organ system categories or any of the 75 individual malformations evaluated.
- Stillbirth rates were identical between groups, further supporting vaccine safety in early pregnancy.
- Experts emphasize the importance of clinician communication to counter vaccine hesitancy amid declining support for COVID-19 vaccination during pregnancy.
“Furthermore, neither study estimated the association with the risk of individual MCMs following first-trimester exposure to mRNA COVID-19 vaccines, which is crucial to the evaluation of the dilution of risks that could potentially be masking other factors associated with specific MCMs,” wrote investigators.
Assessing COVID vaccine outcomes
The nationwide cohort study was conducted to determine MCM risks in pregnant women with first-trimester mRNA-based COVID-19 vaccination. Data was obtained from the Mother-Child EPI-MERES Register, which includes over 99% of patients residing in France.
Live-born infants from pregnancies between April 1, 2021, and January 31, 2022, were included in the analysis. Mothers were aged 15 to 49 years at conception, which was determined based on the pregnancy outcome date and gestational age.
Exclusion criteria included same-sex twins, maternal teratogenic infection, and prenatal teratogenic drug exposure. First-trimester mRNA-based COVID-19 vaccination was defined as receiving at least 1 dose of an mRNA COVID-19 vaccine from day 0 to day 91 of pregnancy.
Major congenital malformations by category
MCMs were determined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes within 1 year following delivery for 72 MCMs and 2 years after delivery for 3.In total 75 MCMs were assessed.
There were 13 categories of MCMs, including cardiovascular, nervous system, respiratory system, orofacial clefts, abdominal wall, digestive system, genital, urinary system, chromosomal, limb, other, and eye, ear, face, and neck. Nonexposed infants were included as controls.
Of the 527,564 infants included in the analysis, 24.7% were exposed to a first-trimester mRNA-based COVID-19 vaccination. Mothers of these infants were slightly older, less socially deprived, and more often presented with comorbidities vs those unexposed. However, these differences did not remain after weighting.
No association between vaccination and MCMs
MCMs were reported in 2302 exposed infants, indicating a rate of 176.6 MCMs per 10,000 infants. In comparison, the rate among unexposed controls was 179.4 MCMs per 10,000 infants, highlighting a nonsignificant weighted odds ratio (OR) of 0.98.
There were also no significant differences when evaluating MCMs by organ system, with the lowest OR of 0.84 for digestive system malformations and the highest of 1.20 for abdominal wall defects. Weighted ORs below 1.10 were reported for 10 of the 13 system-specific risk estimates.
Additionally, none of the individual 75 MCMs had elevated links associated with first-trimester mRNA COVID-19 vaccine exposure. Weighted ORs included:
- 1.00 for ventricular septal defect,
- 1.00 for atrial septal defect
- And 0.91 for hydronephrosis
Both groups had a stillbirth rate of 0.4%, with a non-statistically significant risk ratio of 0.96. Overall, the results highlighted no association between first-trimester mRNA-based COVID-19 exposure and MCM risk in infants.
“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,” wrote investigators.
Expert perspective on vaccine hesitancy
Despite this data, declining support for COVID-19 vaccination during pregnancy has been highlighted by Kathleen Hall Jamieson, PhD, Annenberg Public Policy Center director, in an interview with Contemporary OB/GYN.2
Jamieson highlighted the role of the CDC withdrawing its formal recommendations for COVID-19 vaccination during pregnancy toward the increase in hesitance. While other vaccines such as influenza, RSV, and Tdap remain recommended by the CDC, the absence of the COVID-19 vaccine may be interpreted by patients as a sign of risk.
To counter the decline in support, Jamieson recommended clinicians engage their patients about their concerns and highlight the evidence about safety and efficacy. According to Jamieson, health care providers remain the most trusted source of information, making them a key factor toward increasing acceptance.
“When [providers] make these recommendations, they potentially are saving individuals from serious health consequences, which can in some cases include dying,” said Jamieson.
