Nirsevimab vs RSVpreF Vaccine for Respiratory Syncytial Virus-Related Hospitalization in Newborns.

Importance: Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants. The comparative effectiveness of 2 recently introduced preventive strategies (infant immunization through placental antibody transfer after maternal vaccination with the RSV prefusion F protein [RSVpreF] vaccine and passive infant immunization with nirsevimab) remains unknown. Objective: To compare the associations of maternal vaccination with the RSVpreF vaccine vs passive infant immunization with nirsevimab for the prevention of RSV-related hospitalization. Design, Setting, and Participants: This population-based cohort study used data from the French National Health Data System. Maternal vaccination with the RSVpreF vaccine occurred during 32 to 36 weeks' gestation among infants born in mainland France between September 1 and December 31, 2024. Passive infant immunization with nirsevimab occurred prior to hospital discharge. Infants were matched 1:1 by maternity ward discharge date, sex, gestational age, and region. Follow-up ended at the time of RSV hospitalization or death or on February 28, 2025. Exposures: Maternal immunization with the RSVpreF vaccine and passive infant immunization with nirsevimab. Main Outcomes and Measures: The primary outcome was hospitalization for RSV-associated lower respiratory tract infection. The secondary outcomes included admission to the pediatric intensive care unit (PICU), admission to high-dependency unit, ventilator support, and oxygen therapy. The hazard ratios (HRs) were estimated using conditional Cox proportional hazards models with inverse probability of treatment weighting. Results: A total of 42 560 infants (mean age, 3.7 [SD, 1.4] days; 51.7% male) were included in the study (21 280 per group) with a median follow-up of 84 days (IQR, 70-99 days). Of the 481 hospitalizations for RSV-associated lower respiratory tract infection, 212 (44.1%) occurred in the nirsevimab group vs 269 (55.9%) in the RSVpreF vaccine group (between-group difference, -11.8% [95% CI, -18.1% to -5.5%]). Compared with the RSVpreF vaccine, passive infant immunization with nirsevimab was associated with a lower risk of hospitalization for RSV-associated lower respiratory tract infection (adjusted HR, 0.74 [95% CI, 0.61 to 0.88]). Compared with the RSVpreF vaccine, passive infant immunization with nirsevimab was associated with a lower risk of severe outcomes, including PICU admission (adjusted HR, 0.58 [95% CI, 0.42 to 0.80]), requiring ventilator support (adjusted HR, 0.57 [95% CI, 0.40 to 0.81]), or requiring oxygen therapy (adjusted HR, 0.56 [95% CI, 0.38 to 0.81]). The results were consistent across subgroups and in the sensitivity analyses. Conclusions and Relevance: Compared with maternal vaccination with the RSVpreF vaccine, passive infant immunization with nirsevimab was associated with lower risks of RSV-related hospitalization and severe outcomes. These findings reflect the first RSV season with use of these immunization strategies in mainland France; their use should be reevaluated in future studies.