Who is at risk of a respiratory syncytial virus hospitalisation? A linked, population-based birth cohort analysis in children aged less than 5 years

Background: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections globally in children under five years. With the development of RSV prevention strategies, understanding risk factors and relation to age and population is useful for deciding the type of program implemented. Methods: We used a probabilistically-linked population cohort of children born in Western Australia from 2010 to 2020 and hospitalised before age five years from 2010 to 2021. The primary outcome was the first laboratory-confirmed RSV-hospitalisation. Risk factor exposures included perinatal, socio-demographic, household, environmental, congenital, and comorbid conditions antecedent to RSV-hospitalisation. Adjusted hazard ratios (aHR) and population attributable fractions (PAF) were calculated using survival analysis techniques and Cox regression. Findings: Risk factors for RSV-hospitalisation in 365,582 children included demographic (male sex, Aboriginal ethnicity), perinatal (younger maternal age, maternal asthma, prematurity, maternal prenatal smoking) household/environmental (household size, season of birth), and comorbid and congenital conditions (cardiovascular defects, Trisomy 21 and cerebral palsy). Aboriginal and preterm children had an excess risk of hospitalisation at every age group. Larger households and being born moderate-late preterm had the highest PAFs (36.90% 95% CI: 35.01%, 38.74% and 7.40% 95% CI: 6.75%, 8.04%). While the risk of hospitalisation for children with some comorbid and congenital conditions was high (immunological conditions, aHR: 3.94 95% CI: 2.98, 5.23, respiratory system defects, aHR: 3.13 95% CI: 1.87, 5.25), the PAFs were relatively small (1.70% 95% CI: 1.53%, 1.86% and 0.40% 95% CI: 0.30%, 0.49%). Interpretation: While children with comorbid conditions were at higher risk of RSV-hospitalisation, the importance of socio-demographic risk factors, particularly modifiable factors such as maternal prenatal smoking and household transmission, should not be undervalued. Our analysis provides information for funders, vaccine policy makers, parents/carers, and immunisation providers. Funding: This work was supported by a Wesfarmers Centre for Vaccines and Infectious Diseases Seed grant and a Stan Perron Charitable Foundation grant (00046ProgPart).