Association Between BNT162b2 Vaccination and Incidence of SARS-CoV-2 Infection in Pregnant Women

Abstract

Importance: Data on BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech) effectiveness and safety in pregnancy are currently lacking because pregnant women were excluded from the phase 3 trial.

Objective: To assess the association between receipt of BNT162b2 mRNA vaccine and risk of SARS-CoV-2 infection among pregnant women.

Design, setting, and participants: This was a retrospective cohort study within the pregnancy registry of a large state-mandated health care organization in Israel. Pregnant women vaccinated with a first dose from December 19, 2020, through February 28, 2021, were 1:1 matched to unvaccinated women by age, gestational age, residential area, population subgroup, parity, and influenza immunization status. Follow-up ended on April 11, 2021.

Exposures: Exposure was defined by receipt of the BNT162b2 mRNA vaccine. To maintain comparability, nonexposed women who were subsequently vaccinated were censored 10 days after their exposure, along with their matched pair.

Main outcomes and measures: The primary outcome was polymerase chain reaction-validated SARS-CoV-2 infection at 28 days or more after the first vaccine dose.

Results: The cohort included 7530 vaccinated and 7530 matched unvaccinated women, 46% and 33% in the second and third trimester, respectively, with a mean age of 31.1 years (SD, 4.9 years). The median follow-up for the primary outcome was 37 days (interquartile range, 21-54 days; range, 0-70). There were 118 SARS-CoV-2 infections in the vaccinated group and 202 in the unvaccinated group. Among infected women, 88 of 105 (83.8%) were symptomatic in the vaccinated group vs 149 of 179 (83.2%) in the unvaccinated group (P ≥ .99). During 28 to 70 days of follow-up, there were 10 infections in the vaccinated group and 46 in the unvaccinated group. The hazards of infection were 0.33% vs 1.64% in the vaccinated and unvaccinated groups, respectively, representing an absolute difference of 1.31% (95% CI, 0.89%-1.74%), with an adjusted hazard ratio of 0.22 (95% CI, 0.11-0.43). Vaccine-related adverse events were reported by 68 patients; none was severe. The most commonly reported symptoms were headache (n = 10, 0.1%), general weakness (n = 8, 0.1%), nonspecified pain (n = 6, <0.1%), and stomachache (n = 5, <0.1%).

Conclusions and relevance: In this retrospective cohort study of pregnant women, BNT162b2 mRNA vaccination compared with no vaccination was associated with a significantly lower risk of SARS-CoV-2 infection. Interpretation of study findings is limited by the observational design.

Figure 1.. Flow of Eligible and Matched Vaccinated and Unvaccinated Pregnant Women

Figure 2.. Cumulative Incidence of SARS-CoV-2 in Vaccinated vs Matched Unvaccinated Pregnant Women

Kaplan-Meier curves were used for cumulative probability of SARS-CoV-2 infection. Follow-up for each matched pair was initiated simultaneously on the same calendar date for both the vaccinated woman and her control according to the date of the vaccinated woman’s first dose and was censored simultaneously 10 days after vaccination of the matched control to maintain groups' exchangeability over time and avoid selection bias. Median follow-up time in both groups was 37 days (interquartile range, 21-54 days). P value for statistical comparison was estimated by log-rank test using robust variance estimator to account for matching: P < .001. Shading illustrates 95% CIs. There were no further events from day 70 to end of observation at 110 days.