Background: Prior studies have not observed increased risks of adverse pregnancy and birth outcomes following receipt of COVID-19 vaccines during pregnancy. As part of a US post-approval study [EUPAS43468], the safety of original monovalent Pfizer-BioNTech COVID-19 (BNT162b2) vaccination was assessed in pregnant women and infants.
Objectives: To assess the association of BNT162b2 receipt during pregnancy with major congenital malformations (MCM) and small for gestational age (SGA) in infants.
Methods: In data from 4 insurers participating in the Sentinel System, we identified pregnant women with ≥12 months of enrollment before last menstrual period date (LMP) who had a singleton live delivery linked to an infant. Pregnant women who received a primary series or initial booster dose of BNT162b2 during the exposure window were 1:1 matched on maternal age, US geographic region, and LMP to pregnant women who did not receive any COVID-19 vaccine during the same exposure window. The exposure window for MCM was 28 days before LMP through the end of first trimester and for SGA was 28 days before LMP through delivery.
Vaccines were identified in claims data and, when available, in immunization registry data. SGA and MCM were identified using diagnosis codes. Confounding was addressed via inverse probability treatment weighting, with comorbidities, teratogenic medications, and other vaccines included in the propensity score. Poisson regression was used to estimate prevalence ratios (PR). A secondary analysis used a historical comparator identified before COVID-19 vaccines were authorized.
Results: After matching, there were 13,201 mother-infant pairs in each exposure cohort for MCM, and 34,683 mother-infant pairs in each exposure cohort for SGA. Covariates were balanced in the matched, weighted cohorts.
The prevalence of MCM was 2.7% in the exposed cohort and 2.6% in the unexposed cohort (PR, 1.02; 95% confidence interval [CI], 0.88-1.18). The prevalence of SGA was 10.3% in the exposed cohort and 9.3% in the unexposed cohort (PR, 1.12; 95% CI, 1.07-1.17). The secondary historical comparator design yielded similar results for MCM (PR, 1.01; 95% CI, 0.87-1.18) and SGA (PR, 1.20; 95% CI, 1.14-1.26).
Conclusions: A slightly higher prevalence of SGA (but not MCM) was observed in infants born to pregnant women who had received BNT162b2 during pregnancy. No such association was reported in prior studies that have identified SGA with clinical data on birthweight and gestational age. Findings should be interpreted in the context of limitations, including use of diagnosis codes to identify outcomes, and lack of or incomplete information on some confounding variables (i.e., race/ethnicity, socioeconomic status, obesity).
Kawai A, Bell EJ, Cosgrove A, Koram N, Avula R, Barrett K, Cai B, Daniels K, Dea K, DeFor T, DeVries A, Diessner B, Djibo DA, Ezzy S, Hawrusik R, Kempner ME, Layton B, Love SAM, Ma Q, McMahill-Walraven CN, Messenger-Jones E, Michaelidis M, Nolan MB, Platt R, Shinde MU, Taggert E, Tetreault-Langlois P, Wang X, Wideman K, Ziyadeh NJ, Gilsenan A, Fuller CC. Associations of Pfizer-BioNTech COVID-19 Vaccine with Birth Outcomes: Results from a Post-approval Safety Study in the US. 42nd Annual International Society for Pharmacoepidemiology Conference; 2026 Sep 1; Milan, Italy.
