Background: The original Pfizer-BioNTech monovalent COVID-19 vaccine (BNT162b2) was authorized from December 2020 until April 2023, during which pregnant women were eligible for vaccination. We present a final analysis of post-vaccination pregnancy outcomes from a US post-approval safety study of BNT162b2 [EUPAS43468].
Objective: To evaluate the risk of spontaneous abortion (SAB), stillbirth, and preterm birth (PTB) among pregnant women vaccinated with BNT162b2 during pregnancy versus those unexposed to any COVID-19 vaccines during pregnancy.
Methods: Women aged 12-55 years with end of pregnancy events from December 2020-March 2024 were identified using data from 5 research partners participating in the Sentinel System. Insurance claims were supplemented with immunization registry data, where available. Pregnant women receiving at least 1 BNT162b2 dose (1, 2, and/or 3 [if received ≤60 days from dose 2]) during 28-days before the estimated last menstrual period (LMP) through pregnancy end, irrespective of doses received prior to pregnancy, were matched 1:1 to unexposed pregnant women by age, US geographic region, and calendar month of LMP date. Confounding bias was addressed via stabilized inverse probability treatment weighting, which included demographics, maternal and obstetric comorbidities, prior medication use, other vaccinations, and healthcare utilization. Separately, initial booster dose recipients (dose 3 received >60 days after dose 2) were compared to those who received 2 BNT162b2 doses without a 3rd dose.
SAB was assessed until <20 weeks gestation, stillbirth from ≥20 weeks until pregnancy end, and PTB until <37 weeks. Fine-Gray subdistribution models estimated hazard ratios (HR) and 95% confidence intervals (CI), for dose 1, 2, or 3 combined and booster dose separately.
Results: Of 561,567 eligible pregnancies, the matched outcome-specific cohorts included 45,675 SAB, 85,921 stillbirth, and 81,299 PTB pregnancies exposed to BNT162b2 doses 1-3. Baseline characteristics were balanced prior to weighting except for influenza vaccination which was higher in vaccinated than matched unvaccinated pregnancies (13-27% vs. 7-17%; standardized mean difference = 0.22-0.23), but this imbalance resolved after weighting. The risk of SAB (HR 0.83 [CI 0.73-0.93]), stillbirth (HR 0.66 [CI 0.53-0.82]) or PTB (HR 0.87 [CI 0.81-0.94]) was not elevated for those receiving BNT162b2 doses 1-3. As few women were eligible in the booster dose analysis (N=10 to 1,900, depending on the outcome), these HRs were not estimated.
Conclusions: Consistent with published studies, these analyses did not suggest an increased risk of SAB, stillbirth, or PTB after receipt of original monovalent Pfizer-BioNTech COVID-19 vaccine during pregnancy.
Shinde MU, Kawai A, Cosgrove A, Koram N, Hawrusik R, Rajbhandari R, Kempner ME, Avula R, Barrett K, Daniels K, DeFor T, DeVries A, Diessner B, Djibo DA, Ezzy S, Cai B, Layton JB, Mayer SE, Messenger-Jones E, Michaelidis M, Love S-AM, Ma Q, Nolan MB, Selvan M, Taggert E, McMahill-Walraven CN, Wang X, Wideman K, Ziyadeh NJ, Platt R, Bell EJ, Fuller CC, Gilsenan A. Pregnancy Outcomes after Pfizer-BioNTech Monovalent COVID-19 Vaccination during Pregnancy in the United States. 42nd Annual International Society for Pharmacoepidemiology Conference; 2026 Aug 31; Milan, Italy.
