Identifying the target population for primary Respiratory Syncytial Virus two-step prevention in infants: Normative Outcome of Hospitalisation Assessment for Newborns (NOHAN)
Authors: Jourdain Marine , Benchaib Mehdi , Ploin Dominique , Gillet Yves , Javouhey Etienne , Horvat Côme , Massoud Mona , Butin Marine , Claris Olivier , Lina Bruno , Casalegno Jean-Sebastien 
Published: February 2022

SummaryBackgroundRespiratory syncytial virus (RSV) is the leading cause of acute respiratory infection related hospitalisations in infants (RSVh). Most of these infants are younger than 6 months old with no known risk factors. An efficient RSVh prevention program should address both mothers and infants, relying on Non-Pharmaceutical (NPI) and Pharmaceutical Interventions (PI). This study aimed at identifying the target population for these two interventions.MethodsLaboratory-confirmed RSV-infected infants hospitalised during the first 6 months of life were enrolled from the Hospices Civils de Lyon birth cohort (2014 to 2018). Clinical variables related to pregnancy and birth (sex, month of birth, birth weight, gestational age, parity) were used for descriptive epidemiology, multivariate logistic regression, and predictive score development.FindingsOverall, 616 cases of RSVh in 45 648 infants were identified. Being born before the epidemic season, prematurity, and multiparity were independent predictors of RSVh. Infants born in January or June to August with prematurity and multiparity, and those born in September or December with only one other risk factor (prematurity or multiparity) were identified as moderate-risk, identifying the mothers as candidates for a first level NPI prevention program. Infants born in September or December with prematurity and multiparity, and those born in October or November were identified as high-risk, identifying the mothers and infants as candidates for a second level (NPI and PI) intervention.InterpretationIt is possible to determine predictors of RSVh at birth, allowing to enrol early the target population in a two-level RSV prevention intervention.FundingNone.Research in contextEvidence before this studyIn infants, the global burden of disease caused by the respiratory syncytial virus (RSV) is increasingly recognised. Nowadays the prevention programs are limited to the only licensed drug, Palivizumab, a humanised monoclonal antibody that shows some benefit in preventing RSV in high-risk infants. With the recent encouraging progress obtained using a maternal vaccine candidate and long half-life monoclonal antibodies administered to newborns, as well as the impact of Covid-19 non-pharmaceutical interventions on the RSV epidemic, there is an urgent need to revisit this prevention paradigm from a much broader perspective.Added value of this studyUsing a hospital birth cohort (NOHAN strategy) split into a training and a testing dataset, we were able to determine strong maternal and newborn predictors for the risk of RSV hospitalisation. Month of birth, multiparity, and prematurity were sufficient to accurately identify low-, moderate-, and high-risk groups in the validating cohort.Implications of all the available evidenceUsing the NOHAN strategy, future parents could be enrolled early during pregnancy follow-up in a health-related behaviour change program and then be proposed a vaccine boost for the pregnant women or neutralizing monoclonal antibodies for the newborns. The thresholds for triggering each intervention can be adjusted to the local epidemiology, the resources available, and the evolving evidence concerning the cost-efficiency of the future interventions. Stakeholders, healthcare professionals and policy makers must acknowledge this opportunity when designing the future of RSV prevention programs.