Maternal vaccination with RSVpreF and risk of hypertensive disorders of pregnancy: a systematic review and meta-analysis

Background A bivalent respiratory syncytial virus (RSV) prefusion F protein–based vaccine (RSVpreF) was approved in the United States in August 2023 for use during pregnancy to prevent infant RSV-associated lower respiratory tract disease. The pivotal phase 3 trial identified a numerical imbalance in hypertensive disorders of pregnancy (HDP) that did not reach statistical significance; postmarketing observational studies have since reported inconsistent findings. We conducted a systematic review and meta-analysis to assess this association. Methods We searched MEDLINE, Embase, CENTRAL, Scopus, ClinicalTrials.gov , and WHO ICTRP from inception to Jan 26, 2026, for randomized controlled trials (RCTs) and observational studies comparing HDP outcomes in RSVpreF-vaccinated versus unvaccinated or placebo-receiving pregnant individuals. Unadjusted risk ratios (RRs) were pooled using a random-effects model; adjusted estimates from observational studies were pooled separately by inverse variance methods. This study is registered with PROSPERO (CRD420251026835). Results Nine studies were included (3 RCTs, 6 retrospective cohort studies; n = 148,267). RSVpreF vaccination was associated with a small but statistically significant increase in overall HDP risk (RR 1·08, 95% CI 1·02–1·13; p = 0·004; I 2 = 44%), driven by the observational studies group (1·08, 1·02–1·14; I 2 = 61%); RCTs showed a directionally consistent but non-significant RR (1·12, 0·87–1·43; I 2 = 0%). The association was attributable to gestational hypertension, with no significant association for preeclampsia/eclampsia. Conclusion Maternal RSVpreF vaccination was associated with a small increase in HDP attributable to gestational hypertension and driven primarily by observational studies, in which residual confounding remains possible. The benefits of infant RSV prevention remain substantial, and these findings support continued postmarketing surveillance and informed shared decision-making.