RSV-Pre-F Vaccination During Pregnancy and Neonatal Outcomes-A Systematic Review and Meta-Analysis.

Respiratory syncytial virus (RSV) is a major cause of infant morbidity and mortality worldwide. Recent preventive strategies include maternal vaccination and monoclonal antibodies. However, maternal RSV vaccination has raised safety concerns due to possible associations with preterm birth. This systematic review and meta-analysis evaluated whether maternal RSV vaccination increases the risk of preterm birth and neonatal intensive care unit (NICU) admission. A systematic search of PubMed, Scopus, and Web of Science was conducted on August 1st, 2025. We used the following keywords in the search: RSV, vaccine, preterm, and neonate. Eligible studies included randomized controlled trials (RCTs) and observational studies assessing currently approved RSV-PreF vaccines in pregnancy and reporting preterm birth (< 37 weeks) or NICU admission. Data extraction and risk of bias assessments (RoB 2.0, ROBINS-I) were performed independently by two reviewers. Meta-analyses were conducted using random-effects models with risk ratios (RRs) as effect measures, and the certainty of evidence was graded using the GRADE framework. Seven studies met inclusion criteria: three RCTs (n = 12,833 births) and four observational studies (n = 4245 births). In RCTs, RSV vaccination was associated with an increased risk of preterm birth (RR 1.26, 95% CI 1.08-1.46), while observational studies showed no association (RR 0.78, 95% CI 0.46-1.32). Pooled analysis revealed no overall association (RR 0.96, 95% CI 0.68-1.38). NICU admission risk was not significantly affected (RR 0.74, 95% CI 0.34-1.61). Certainty of evidence was rated low to very low. This meta-analysis found no overall evidence linking maternal RSV vaccination to preterm birth, though RCT subgroup findings suggest a potential increased risk. Continued surveillance and long-term safety monitoring are essential as global implementation expands. Open Science Framework (https://osf.io/3tfkn/).