Respiratory syncytial virus (RSV) is a leading cause of infant hospitalisation, particularly in infants younger than 6 months. On Aug 12, 2024, Scotland introduced a maternal vaccination programme with bivalent RSV prefusion F (RSVpreF) vaccine, offered from 28 weeks’ gestation. Although clinical trials have shown high efficacy of maternal RSVpreF vaccination, this study assessed RSVpreF vaccine effectiveness in a real-world setting, to inform policy and programme delivery.

We did a retrospective, nested case–control study with a cohort sensitivity analysis. The source population comprised all singleton livebirths in Scotland between Aug 12, 2024, and March 31, 2025, as recorded in the Scottish Linked Pregnancy and Baby Dataset (SLiPBD). Within this population, cases were defined as infants aged 90 days or younger with an RSV-related hospital admission for lower respiratory tract infection (LRTI; first event only) and an RSV-positive PCR test within 14 days before or 2 days after hospital admission, within the study period up to March 31, 2025. At the time of hospital admission, cases were matched to ten controls each (1:10 case:control ratio) from the source population by ISO week of birth and gestational age at birth, with controls defined as infants with no previous RSV-positive test or RSV-related hospital admission at the time of matching. Linked datasets on maternal RSV vaccination and RSV-related hospital admissions were accessed through the recently established Scottish Infectious Respiratory Surveillance Platform. Infants were classified as vaccinated if the RSV vaccine was received more than 14 days before delivery, suboptimally immunised if received 0–14 days before delivery, and unvaccinated if not received during pregnancy. The study outcome was RSV-related LRTI hospital admissions among infants aged 90 days or younger. Vaccine effectiveness against RSV-related LRTI hospital admissions was estimated with adjusted conditional logistic regression comparing vaccination status among cases and controls, adjusting for infant sex and birthweight, maternal ethnicity, maternal age and Scottish Index of Multiple Deprivation at infant birth, maternal smoking status at the first antenatal appointment, and parity. From this model, adjusted vaccine effectiveness was calculated as 100 × (1 – adjusted odds ratio).

During the study period, 27 565 singleton livebirths were recorded in the SLiPBD. 13 842 (50·2%) of the 27 565 pregnant women received the RSVpreF vaccine, 12 747 (92·1%) of whom were vaccinated more than 14 days before delivery. 354 infants aged 90 days or younger had an RSV-related LRTI hospital admission during the study period (cases), with 3511 matched controls. 33 controls later became cases. Among the 354 cases, 43 (12·1%) were vaccinated (>14 days before delivery) against RSV, compared with 1518 (43·2%) of the 3511 controls. Suboptimal immunisation (≤14 days before delivery) occurred in 18 (5·1%) cases and 205 (5·8%) controls. Median gestational age at vaccination was 31 weeks (IQR 28–34) among cases and 30 weeks (28–33) among controls. Adjusted vaccine effectiveness against RSV-associated LRTI hospital admission was 82·2% (95% CI 75·1–87·3; p<0·0001) in vaccinated infants compared with unvaccinated infants, which translated to 219 (95% CI 189–243) RSV-related LRTI hospital admissions averted during the study period. Adjusted vaccine effectiveness remained high among infants born preterm (<37 weeks’ gestation; 89·9% [55·3–97·7]; p=0·0025), as well as for term-born infants (≥37 weeks’ gestation; 81·5% [73·9–87·0]; p<0·0001). In a sensitivity analysis using a matched cohort approach in the same source population, adjusted vaccine effectiveness against RSV-associated LRTI hospital admission was 81·0% (68·6 to 88·5; p<0·0001).

This national population-based study provides evidence that maternal RSV vaccination substantially reduces the risk of RSV-related LRTI hospital admission in infants aged 90 days or younger, including in preterm infants. Maternal RSV vaccination programmes should be scaled up globally, with high coverage, to offer the potential to avert many RSV-associated infant hospitalisations.

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