Skip to main content
2025 ISPE Annual Meeting Main banner

Pregnancy and Lactation

1D-06 - Preterm birth and small for gestational age following RSVpreF vaccination during pregnancy

Sunday, August 24, 2025
11:45 AM - 12:00 PM ET
Background: On September 22, 2023, the U.S. Advisory Committee on Immunization Practices (ACIP) recommended seasonal RSVpreF vaccination from September through January for pregnant patients at 32 to 36 weeks gestation. During the RSVpreF clinical trial, an imbalance in preterm births and low birth weight were observed, with a higher incidence in the vaccinated compared with placebo group.

Objectives: We emulated a target trial to examine associations between RSVpreF vaccination and preterm and small for gestational age (SGA) births using an observational analog of a per-protocol effect.

Methods: We identified a retrospective matched cohort of pregnant patients using data from 8 integrated healthcare organizations (sites) in the Vaccine Safety Datalink. Eligible persons were 16–49 years, with singleton pregnancies at 30 to < 37 weeks of gestation during the first RSV vaccination season, September 22, 2023, through January 31, 2024 (or February 29, 2024, for 2 sites). Preterm birth was defined as a live birth occurring before 37 weeks gestation, and SGA as a birthweight below the 10th percentile for gestational age and sex. A series of 5 sequential target trials were emulated where persons exposed to RSVpreF vaccine were matched to unexposed pregnant patients at the same gestational age. Matching was 1:1 on site and propensity to be vaccinated during the gestational week; if an unvaccinated patient was later vaccinated, matched pairs were censored on the date of vaccination. Only the unvaccinated patient was then rematched as vaccinated. For SGA, matched pairs were excluded if the infant weight was unavailable for either infant in the matched pair. Log-binomial regression models with robust variance were used to estimate risk ratios (RR) and 95% confidence intervals (CI).

Results: RSVpreF vaccine uptake was 26.4% among eligible patients. In total, 14,099 matched pairs with index dates between 30- < 37 weeks gestation were included in the analysis from 25,092 unique pregnancies due to censoring and rematching. There were 571 (4.0%) pregnancies with a preterm birth following vaccination and 637 (4.5%) following the unvaccinated index date (RR: 0.90, 95% CI: 0.80–1.00). Among 11,920 matched pairs analyzed for the SGA outcome, 800 (6.7%) SGA births occurred among vaccinated and 781 (6.6%) among unvaccinated after the matched index date (RR: 1.02, 95% CI: 0.93–1.13). Results were unchanged when restricting the sample to index dates between the ACIP recommended 32– < 37 weeks (n = 13,965 matched pairs).

Conclusions: RSVpreF vaccine was not associated with increased risk for preterm or SGA birth. These results may inform clinical discussions and education about the safety of RSVpreF vaccine administered during pregnancy.