Context Prader‐Willi syndrome (PWS) is characterized by hypothalamic dysfunction, hyperphagia and a typical behavioural phenotype, with characteristics of autism spectrum disorder (ASD) like stubbornness, temper tantrums and compulsivity. It has been suggested that the oxytocin system in patients with PWS is dysfunctional. In ASD, intranasal oxytocin treatment has favourable effects on behaviour. Objective To evaluate the effects of 3 months of twice daily intranasal oxytocin (dose range 16‐40 IU/day), compared to placebo, on behaviour and hyperphagia in children with PWS. Design Randomized, double‐blind, placebo‐controlled, crossover study in the Dutch PWS Reference Center. Patients Twenty‐six children with PWS aged 3‐11 years. Main outcome measures (Change in) behaviour and hyperphagia measured by Oxytocin Questionnaire and Dykens hyperphagia questionnaire. Results In the total group, no significant effects of oxytocin on social behaviour or hyperphagia were found. However, in boys, the Oxytocin Questionnaire scores improved significantly during oxytocin treatment, compared to a deterioration during placebo (4.5 (−0.8 to 15.3) vs. −4.0 (−11.3 to 0.8), P = .025). The Dykens hyperphagia questionnaire scores remained similar during oxytocin treatment, while there was a deterioration during placebo (0.0 (−0.8 to 4.3) vs. −3.5 (−6.0 to 0.0), P = .046). Patients with a deletion had significant improvements in both questionnaire scores during oxytocin treatment, but deteriorations during placebo. Oxytocin treatment was well tolerated, and there were no serious adverse events. Conclusions Intranasal oxytocin treatment has positive effects on social and eating behaviour in 3‐11 years aged boys with PWS and in children with a deletion without safety concerns. Intranasal oxytocin in children with PWS might be considered, but individual effects should be carefully evaluated and treatment discontinued if no effects are found.

Context Growth hormone (GH) has been approved for children with Prader‐Willi syndrome (PWS) and significantly improves body composition in adults with PWS. Adults with PWS are predisposed to develop impaired glucose tolerance (IGT) and diabetes mellitus type 2 (DMT2). Continuation of GH maintains body composition, but GH is known to induce insulin resistance, which might affect glucose homeostasis. Studies on long‐term effects of GH treatment in adults are very limited. Objective To investigate effects of 3 years of GH treatment on glucose homeostasis and prevalence of metabolic syndrome (MS) in adults with PWS. Design Open‐label, prospective study. Patients 43 young adults with PWS. Setting Dutch PWS Reference Center. Main outcome measures Glucose and insulin during oral glucose tolerance test. Results Estimated mean (95% CI) fasting glucose and insulin levels remained stable during 3 years of GH treatment. Glucose being 4.6 (4.4‐4.8) mmol/l at start and 4.7 (4.6‐4.9) mmol/l after 3 years (P = .07); insulin being 59.5 (45.2‐75.8) pmol/l and 56.7 (45.2‐69.6) pmol/l resp. (P = .72). Sex, ethnicity and fat mass percentage were significantly associated with fasting glucose levels, while IGF‐I or GH‐dose were not. Blood pressure, lipids and prevalence of MS remained stable during 3 years of GH. IGT prevalence was variable over time, six patients had IGT at start and eleven after 3 years of GH. One patient developed DMT2. However, prevalence of IGT or DMT2 was not significantly higher after 3 years than at study start. Conclusions Three years of GH treatment in adults with PWS does not impair glucose homeostasis and does not lead to an increased prevalence of DMT2.

Objective: Prader-Willi syndrome (PWS) is a rare genetic syndrome with a wide spectrum of clinical features in early life. Late diagnoses are still present. We characterized the perinatal and neonatal features of PWS, compared them with those of healthy newborns and assessed the prenatal and neonatal differences between the genetic subtypes. Design: A cohort study in children with PWS. The prevalence of variables was compared with healthy infants (PLUTO cohort) and to population statistics from literature. Patients: 244 infants with PWS and 365 healthy infants. Measurements: Data on prenatal and neonatal variables in both cohorts. Population statistics were collected through an extensive literature search. Results: A higher prevalence of maternal age >35 years was found in PWS compared to healthy infants and population statistics, and the highest maternal age was found in the mUPD group. Higher prevalence of polyhydramnios, caesarean section, labour induction and breech presentation, and lower birth weight SDS was found in PWS compared to healthy infants. High prevalences of decreased fetal movements (78.5%), hypotonia (100%), cryptorchism (95.9%) and poor sucking/tube feeding (93.9%) were found in PWS. Conclusions: This study presents an overview of prenatal and neonatal variables in infants with PWS compared to healthy infants. Our findings may increase clinical awareness of the early perinatal signs of PWS by obstetricians, neonatologists and all those involved in infant care, enabling early diagnosis and start of multidisciplinary treatment.