Objctive

To assess the safety of the respiratory syncytial virus prefusion F protein (RSVpreF) vaccine in pregnant women during the 2024–2025 French immunization campaign, with a particular focus on the risk of preterm birth.

Methods

Using the national health care database, which covers almost 99% of the population in France, we included all women who gave birth after 22 weeks of gestation between September 16 and December 31, 2024. Women vaccinated with RSVpreF were matched 1:1 with unvaccinated women on the basis of gestational age at vaccination, maternal age at pregnancy onset, region of residence, week of conception, history of preterm birth, influenza vaccination during the same pregnancy, and multiple pregnancy. Outcomes included preterm birth, delivery within 1 and 3 weeks after vaccination, stillbirth, small-for-gestational-age (SGA) birth weight, cesarean delivery, hemorrhage, preeclampsia, and major cardiovascular events, including maternal death. Time-to-event analyses were conducted with Poisson regression models with robust variance to estimate weighted incidence rate ratios (IRRs) and their 95% CIs for each outcome.

Results

Among the 29,032 women vaccinated during the study period, 24,891 (85.7%) were successfully matched to 24,891 unvaccinated women in a control group. In the matched cohort, the mean±SD maternal age was 30.9±5.0 years, 3.2% had a history of preterm birth, 0.6% had multiple pregnancies, and 21.8% had received influenza vaccination. No significant increase in the risk of the following outcomes was observed: preterm birth (weighted IRR 0.97, 95% CI, 0.89–1.06), delivery within 1 week (weighted IRR 0.81, 95% CI, 0.72–0.90) or within 3 weeks (weighted IRR 0.97, 95% CI, 0.93–1.00), stillbirth (weighted IRR 0.77, 95% CI, 0.45–1.32), cesarean delivery (weighted IRR 1.00, 95% CI, 0.96–1.03), SGA birth weight (weighted IRR 1.01, 95% CI, 0.96–1.07), postpartum hemorrhage (weighted IRR 1.03, 95% CI, 0.97–1.10), preeclampsia (weighted IRR 1.02, 95% CI, 0.85–1.22), or major adverse cardiovascular event (weighted IRR 0.60, 95% CI, 0.26–1.40) outcomes. Among women vaccinated at or before 32 weeks of gestation, no significant increase in the risk of preterm birth was observed (weighted IRR 1.13, 95% CI, 0.98–1.31).

Conclusion

This large observational study found no major safety concerns associated with RSVpreF vaccination during pregnancy. Further research, including international comparisons and evaluations of effectiveness relative to monoclonal antibodies against RSV, will be needed to fully characterize the benefit–risk balance of RSVpreF. Ongoing surveillance remains essential, particularly to monitor rare adverse events.