Early oxytocin treatment in infants with Prader-Willi is safe and is associated with better endocrine metabolic and behavior outcomes.

Abstract

Background: Oxytocin (OT) plays an important role in modulating behavior social interactions and feeding. Prader-Willi syndrome (PWS), a rare genetic neurodevelopmental disorder, is a model of hypothalamic disorder including OT dysfunction. We previously showed that infants with PWS who received an early short course (7 days) of intranasal OT treatment improved their oral and social skills. We aim to document long-term tolerance and effects of early intranasal OT treatment on the disease trajectory. We then performed a comparative clinical trial including the 17 children who received OT as infants in our previous study and compared them to 17 PWS non-exposed children at 3 to 4 years old. Primary endpoint was the total communication score on the Vineland adaptive behavior scale version II (VABS-II). Secondary endpoints were the other domains of VABS-II, behavior scored by Childhood Behavior Check-list, feeding skills, endocrine and metabolic issues, and brain connectivity on functional magnetic resonance imaging. Results: We documented long-term safety of early OT treatment. The VABS-II communication score was not different between the two groups defined as OT-exposed and non-exposed groups while a trend towards higher socialization score was found in the OT-exposed children (p=0.06). Circulating IGF-1 and HDL cholesterol were significantly higher in the OT-exposed group (p<0.05). OT-exposed children had normal acylated ghrelin levels which are lower than those observed in non-exposed children (p=0.06) and display higher connectivity of the orbitofrontal cortex brain region. Conclusion: Early OT treatment in infants with PWS is safe up to 3 to 4 years age. OT-exposed children display better social, endocrine and metabolic outcomes. This study documents for the first time in human the biological window of opportunity of early OT treatment that may change the trajectories of PWS condition. Trial Registration: Clinical trial NCT03081832 Retrospectively registered https://clinicaltrials.gov/search?cond=NCT03081832