COVID-19 mRNA VACCINES

MAJOR CONGENITAL ANOMALIES
 
No association was found between first-trimester mRNA COVID-19 vaccination and the prevalence of major congenital anomalies, overall or by specific organ system, in two record-linkage studies from Canada and the United States covering a total of 41,813 infants born to vaccinated mothers (Jorgensen et al., 2024; Kharbanda et al., 2024). Similarly, a United States retrospective analysis of insurance claims data, including 12,725 women who received an mRNA COVID-19 vaccine from shortly before conception through 20 weeks of gestation, found no association with major structural malformations overall or by specific categories of birth defects among liveborn infants (Rowe et al., 2025). Furthermore, a large prospective Nordic registry study of liveborn infants identified 29,135 pregnancies with first-trimester exposure to mRNA COVID-19 vaccines and found no increased risk of major congenital anomalies overall or across EUROCAT-defined organ system categories (Magnus et al., 2024). Consistent with these findings, a nationwide French population-based cohort study including 130,338 liveborn infants with first-trimester exposure, found no increased risk of major congenital malformations overall, by organ system, or for any of 75 individual EUROCAT-defined anomalies (Bernard et al., 2025). 

The rates of major malformations overall, and of congenital heart defects specifically, were no different among liveborn infants of 2134 mothers vaccinated with an mRNA COVID-19 vaccine in the first trimester and the infants of unvaccinated pregnant women (Goldshtein et al., 2022). Negative findings were also reported in other record-linkage studies from Australia, Scotland and South Korea, encompassing a total of 15,598 women vaccinated with an mRNA COVID-19 vaccine in the first half of pregnancy (Hui et al., 2023; Calvert et al., 2023; Kim et al., 2025), and prospective cohort studies from France, Switzerland, and Germany. including 3,278 first-trimester mRNA vaccine exposures (Favre et al., 2023; Kayser et al., 2025).

In a retrospective cohort study using data from electronic medical records, the rate of major congenital anomalies identified on second trimester ultrasonography among fetuses of 1149 women who received at least one dose of a COVID-19 vaccine anytime 30 days before conception through 14 weeks of gestation was similar to that seen in the fetuses of women who were unvaccinated or vaccinated outside the first trimester (adjusted odds ratio=1.01, 95% confidence interval 0.69-1.48) (Ruderman et al., 2022). No teratogenic effect was found when the window of exposure was narrowed down to two to ten weeks gestation. Although the type of vaccine was not explicitly reported, most women were likely immunized with an mRNA COVID-19 vaccine given the study’s timing and location.  A study using data from the CDC COVID-19 Vaccine Pregnancy Registry reported major anomalies in 750 (3.8%) of 19,931 infants born to women who received any COVID-19 vaccine during or just prior to pregnancy, with no significant differences by timing of vaccination (<14 vs ≥14 weeks gestation); approximately 97% of participants received an mRNA vaccine (Sharma et al., 2025).
 
PREGNANCY AND NEONATAL OUTCOMES
 
Several systematic reviews and meta-analyses of epidemiological studies reporting on more than 127,273 pregnancies in women who were vaccinated for COVID-19 --almost exclusively with mRNA vaccines--showed no significant differences in the overall frequency of adverse pregnancy and neonatal outcomes, including spontaneous abortion, preterm birth, low birth weight, small for gestational age, neonatal intensive care unit (NICU) admission, and low Apgar scores, between vaccinated and unvaccinated pregnancies (Carbone et al., 2022; Ma et al., 2022; Prasad et al., 2022; Watanabe et al., 2022; Ding et al., 2023; Tormen et al., 2023; Zhang et al., 2023). In fact, the incidence of some of these adverse outcomes, including stillbirth, neonatal death and preterm birth, was slightly reduced among vaccinated women compared to the rates seen in the unvaccinated group in some of these studies (Carbone et al., 2022; Prasad et al., 2022; Watanabe et al., 2022; Oliveira et al., 2024; Adusei-Mensah et al., 2025). Some of the individual studies included in the meta-analyses and reviews are discussed below.
 
The cumulative risk of spontaneous abortion among pregnant women who received at least one dose of an mRNA COVID-19 vaccine before conception or early in pregnancy was similar to that expected in the general population, based on data from 2,456 exposed pregnancies in the V-Safe Pregnancy Registry (Zauche et al., 2021) and 6,840 exposed pregnancies in the Vaccines International Pregnancy Exposure Registry (C-VIPER) (Mansour et al., 2023). Similarly, using data from the Vaccine Safety Datalink, a matched case–control study of 296 spontaneous abortions and 592 live births, no association was found between mRNA COVID-19 vaccination during pregnancy and spontaneous abortion (aOR 0.85, 95% CI 0.56–1.30), including by dose number or vaccination within 6 weeks of fetal loss (Sheth et al., 2025). 

No evidence of an increased risk of spontaneous abortion following mRNA COVID-19 vaccination in early pregnancy was observed across multiple studies, including a Scottish record-linkage study of 15,935 women vaccinated shortly before conception or through 19 weeks’ gestation (Calvert et al., 2022), several additional observational reports evaluating first-trimester exposure (Magnus et al., 2021; Trostle et al., 2021; Aharon et al., 2022; Citu et al., 2022), and a European pharmacovigilance study in which the frequency of spontaneous abortion was lower among 2,612 mRNA-vaccinated pregnant women compared with 619 recipients of a COVID-19 viral vector vaccine (Mascolo et al., 2022).

   
No neonatal deaths were reported among 724 liveborn infants of mothers who received an mRNA COVID-19 vaccine in the third trimester of pregnancy, and rates for preterm birth (9.4%), small for gestational age (3.2%), and stillbirth (0.1%) were similar to background population rates (Shimabukuro et al., 2021). In other population-based studies conducted in Canada, Israel, Malaysia, Sweden, Norway, and the United Kingdom, vaccination against SARS-CoV-2 during pregnancy was not significantly associated with an increased risk of adverse pregnancy and neonatal outcomes, including stillbirth, small for gestational age, preterm delivery, low Apgar scores, or NICU admission, compared to the outcome of unvaccinated pregnant women (Goldshtein et al., 2022; Arulappen et al., 2022; Blakeway et al., 2022; Fell et al., 2022; Magnus et al., 2022; Sadarangani et al., 2022; Kugelman et al., 2023). Most of the vaccinations in those studies used mRNA COVID-19 vaccines and were given during the second and third trimesters of pregnancy. Three cohort studies from Mexico, Australia, and the United States reported significantly reduced incidences of stillbirth and preterm birth among a total of more than 46,226 pregnant women immunized with an mRNA vaccine compared to unvaccinated women (Piekos et al., 2022; Hui et al., 2023; Morgan et al., 2023).

In a Korean propensity score–matched cohort study using influenza-vaccinated pregnant women as an active comparator, mRNA COVID-19 vaccination during pregnancy was not associated with a clinically meaningful increase in adverse maternal or neonatal outcomes overall, although isolated differences were observed for specific outcomes (large-for-gestational-age birth and preterm birth) (Choi et al., 2025). In a Canadian record-linkage study, a small increase in gestational hypertension—but not placenta-mediated outcomes—was observed among vaccinated mothers; however, residual confounding may account for this finding (Regan et al., 2025).

 
ANIMAL TERATOLOGY STUDIES
 
No teratogenic or other adverse fetal effects were observed among the offspring of mice and rats injected with an mRNA  vaccine against COVID-19 during early pregnancy in doses 50-300 times greater than those used in humans (Bowman et al., 2021; Lu-Culligan et al., 2022).