Oxytocin in infants with Prader-Willi syndrome to improve dysphagia and disease trajectory

Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder with a characteristic trajectory. Infants display hypotonia, poor social and feeding skills, and high risk of choking, which have been shown to improve after oxytocin (OT) treatment. Our aim is to demonstrate the efficacy of intranasal OT treatment administered in the postnatal critical period on infant feeding skills and document its long-term effects. We enrolled 52 infants with PWS (median age 2.2 months) in a European double-blind randomized placebo-controlled study. Infants were randomly assigned in a 1:1 ratio to either 4 IU/day of OT or placebo for a 4-week evaluation of efficacy. A second randomization in each group was performed. Infants in the placebo group were randomized into 4 weeks of OT followed by 4 weeks of placebo or 8 consecutive weeks of OT. Those in the OT group were randomized into additional 4 weeks of OT followed by 4 weeks of placebo or 8 consecutive weeks of placebo. Infants were followed-up to 26 weeks from baseline. Feeding skills were evaluated using Neonatal Oral-Motor Scale (NOMAS) as primary endpoint and videofluoroscopy of swallowing study (VFSS) as key secondary endpoint. Subsequently, 40 infants included in France (OT-exposed cohort) participated in a new study to document long term safety of OT treatment and to compare them with an unexposed cohort (n = 24) at about 3 years of age. Prevalence and severity of comorbidities of the disorder were compared between the two cohorts. OT was well tolerated. At 4 weeks, NOMAS normalization rates were similar between OT and placebo, but OT yielded a higher VFSS responder rate (53.3% vs 16.7%, p = 0.05) and a greater reduction in VFSS total score (LS mean difference −1.55; 95% CI −2.9 to −0.2; p = 0.03). At 3 years, the OT-exposed cohort demonstrated consistently better motor, adaptive and behavioral outcomes than unexposed controls. The primary endpoint did not show significant difference between OT and placebo groups. However, using VFSS we showed for the first time a positive effect of 4 weeks intranasal OT treatment on swallowing. We also document long-term effect on disease trajectory, with less severe comorbidities.