February 2017, VOLUME139 /ISSUE 2

Oxytocin Treatment May Improve Infant Feeding and Social Skills in Prader-Willi Syndrome

  1. Nancie J. MacIver, MD, PhD
  1. Division of Pediatric Endocrinology, Duke University School of Medicine, Durham, North Carolina
  • Abbreviation:
    Prader-Willi syndrome
  • Prader-Willi syndrome (PWS) is a common neurogenetic obesity syndrome that is complicated by hypotonia, poor feeding, and failure to thrive in early infancy, followed by hyperphagia, obesity, and profound social defects later in life.1 Autopsy studies have shown a significant reduction in the number and volume of oxytocin-producing neurons in the paraventricular nucleus of the hypothalamus in individuals with PWS.2 Given the importance of oxytocin in regulating social interactions and mother-infant bonding, it has been postulated that treatment of PWS with oxytocin may improve poor feeding and social behaviors in infants. This was tested in the study presented by Tauber et al3 in this issue of Pediatrics.

    PWS results from lack of expression of paternally inherited genes on chromosome 15q11-q13, due to deletion of the paternally inherited region, to maternal uniparental disomy (ie, both copies inherited from the mother), or to an imprinting defect. Magel2 is one of the affected genes located on 15q11-q13, and Magel2 mutations have been found in individuals with autism spectrum disorder, intellectual disability, and some features of PWS.4 Magel2-deficient mice have been shown to reproduce some of the phenotype of PWS, and have 50% mortality from impaired suckling activity.5 Interestingly, the hypothalamus of Magel2-deficient newborns shows reduced oxytocin, and administration of a single dose of oxytocin within the first 5 hours of life rescued abnormal feeding behaviors by restoring normal suckling and preventing early death.5 In a separate study, Magel2-deficient mice displayed abnormal social recognition and social interactions that improved after 1 week of oxytocin treatment in the first week of life.6

    In the phase 2 study presented by Tauber et al3 in this issue of Pediatrics, 18 human infants <6 months old were treated with intranasal oxytocin for 7 days in 1 of 3 treatment groups: group 1 received oxytocin every other day, group 2 received oxytocin once daily, and group 3 received oxytocin twice daily. Importantly, there were no adverse events, and there were no differences in outcomes among the 3 treatment groups. Overall, the authors observed 88% of subjects (16 of 18 studied) had normalization of sucking and improved swallowing studies immediately after treatment. Treated infants also had increased alertness, less fatigability, increased facial expressions, and less social withdrawal. One very interesting finding of this study was in the long-term observational data, in which it was reported that 81% of oxytocin-treated subjects with PWS were able to crawl as toddlers, compared with 13% of untreated age-matched controls with PWS. This improvement in gross motor skills was presumed secondary to improved muscle tone and motor coordination. As the treatment was given for only 1 week during infancy, this finding implies that a short course of oxytocin during infancy may have potential long-term benefits. The authors suggest a positive feedback loop may explain these interesting results, whereby exogenous oxytocin promotes the continued secretion of endogenous hormones, leading to long-term benefits. Moreover, the authors observed increased connectivity of the right superior orbitofrontal network after treatment with oxytocin and suggest that this increased connectivity may also mediate long-term effects. Increased circulating acyl-ghrelin (the active form of ghrelin) was observed at day 2 and day 4 after treatment with oxytocin. As ghrelin is a well-described “hunger” hormone, the influence of oxytocin on acyl-ghrelin levels may explain, in part, the improvement in feeding behavior seen in this study.

    Other studies also have examined the use of oxytocin in humans with PWS. In an earlier study by Tauber et al,7 adults with PWS were treated with intranasal oxytocin or placebo. Subjects who received oxytocin had improved behaviors, including increased trust in others, decreased sadness, and less disruptive behavior shortly after receiving the medication.7 This study did not, however, discern any difference in social skills between the treated and untreated groups.7 A more recent double-blind randomized placebo-controlled crossover study of subjects with PWS age 12 to 30 years examined intranasal oxytocin on behavioral outcomes and found little effect.8 In yet another double-blind, placebo-controlled crossover study, intranasal oxytocin given to 25 children with PWS aged 6 to 14 years resulted in no significant effect of oxytocin on social behaviors overall; however, children younger than 11 experienced less anger, sadness, conflict, and food-related behavior, along with a generalized improvement in social behavior.9 Altogether, these results suggest that oxytocin may have a greater benefit in PWS when given earlier in life. In that regard, this new study by Tauber et al3 is important, as it is the first to examine the effect of oxytocin on human infants with PWS.

    In summary, early administration of oxytocin to infants with PWS shows promise as potential treatment of poor social behavior and feeding in infancy. Larger clinical trials are needed to confirm this result and determine long-term effects and safety. These findings are important, as the results of this study may be applicable to autism spectrum disorder and to other disorders in which early feeding dysfunction, abnormal musculoskeletal function, or depressed social interactions threaten well-being.


      • Accepted November 17, 2016.
    • Address correspondence to Nancie J. MacIver, MD, PhD, Department of Pediatrics, Duke University School of Medicine, 3000 Erwin Rd, Ste 200, DUMC Box 102820, Durham, NC 27710. E-mail: nancie.maciver{at}
    • FINANCIAL DISCLOSURE: The author has indicated she has no financial relationships relevant to this article to disclose.

    • FUNDING: This work was supported by National Institutes of Health grant R01-DK106090. Funded by the National Institutes of Health (NIH).

    • POTENTIAL CONFLICT OF INTEREST: The author has indicated she has no potential conflicts of interest to disclose.

    • COMPANION PAPER: A companion to this paper can be found online at