The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader–Willi Syndrome

Author:

Tauber Maïthé123,Boulanouar Kader4,Diene Gwenaelle15,Çabal-Berthoumieu Sophie16,Ehlinger Virginie5,Fichaux-Bourin Pascale1,Molinas Catherine123,Faye Sandy12,Valette Marion12,Pourrinet Jeanne1,Cessans Catie1,Viaux-Sauvelon Sylvie7,Bascoul Céline6,Guedeney Antoine8,Delhanty Patric9,Geenen Vincent10,Martens Henri10,Muscatelli Françoise11,Cohen David712,Consoli Angèle713,Payoux Pierre4,Arnaud Catherine514,Salles Jean-Pierre123

Affiliation:

1. Unité d’Endocrinologie, Obésité, Maladies Osseuses, Génétique et Gynécologie Médicale. Centre de Référence du Syndrome de Prader-Willi,

2. Axe Pédiatrique du Centre d'Investigation Clinique 9302/Intitut National de la Santé Et de la Recherche Médicale, and

3. Institut National de la Santé Et de la Recherche Médicale Unité 1043, Centre de Physiopathologie de Toulouse Purpan, Université Paul Sabatier, Toulouse, France;

4. Toulouse NeuroImaging Center, Université de Toulouse, Institut National de la Santé Et de la Recherche Médicale, Université Paul Sabatier, Toulouse, France;

5. Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche 1027, Université Toulouse III, Hôpital Paule de Viguier, Toulouse, France;

6. Service de Psychiatrie de l'Enfant et de l'Adolescent, Hôpital des Enfants, Toulouse, France;

7. Service de Psychiatrie de l'Enfant et de l'Adolescent, la Pitié Salpêtrière, Paris, France;

8. Service de Psychiatrie de l’Enfant et de l’Adolescent, Hôpital Bichat-Claude Bernard, Paris, France;

9. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands;

10. Grappe Interdisciplinaire de Génoprotéomique Appliquée-I3-Immunoendocrinologie, Université de Liège, Sart Tilman, Liege, Belgium;

11. Institut de Neurobiologie de la Méditerranée, Institut de la Santé Et de la Recherche Médicale Unité 901, Marseille, France;

12. Centre National de la Recherche Sscientifique, Unité Mixte de Recherche 7222, Institut des Systèmes Intelligents et de Robotiques, and

13. Groupe de Recherches Cliniques Abord dimensionnel des épisodes psychotiques de l’enfant et de l’adolescent, Université Pierre et Marie Curie, Paris France; and

14. Unité de Soutien méthodologique à la recherche, CHU Toulouse, Toulouse, France

Abstract

BACKGROUND AND OBJECTIVES: Patients with Prader–Willi syndrome (PWS) display poor feeding and social skills as infants and fewer hypothalamic oxytocin (OXT)-producing neurons were documented in adults. Animal data demonstrated that early treatment with OXT restores sucking after birth. Our aim is to reproduce these data in infants with PWS. METHODS: We conducted a phase 2 escalating dose study of a short course (7 days) of intranasal OXT administration. We enrolled 18 infants with PWS under 6 months old (6 infants in each step) who received 4 IU of OXT either every other day, daily, or twice daily. We investigated the tolerance and the effects on feeding and social skills and changes in circulating ghrelin and brain connectivity by functional MRI. RESULTS: No adverse events were reported. No dose effect was observed. Sucking assessed by the Neonatal Oral-Motor Scale was abnormal in all infants at baseline and normalized in 88% after treatment. The scores of Neonatal Oral-Motor Scale and videofluoroscopy of swallowing significantly decreased from 16 to 9 (P < .001) and from 18 to 12.5 (P < .001), respectively. Significant improvements in Clinical Global Impression scale scores, social withdrawal behavior, and mother–infant interactions were observed. We documented a significant increase in acylated ghrelin and connectivity of the right superior orbitofrontal network that correlated with changes in sucking and behavior. CONCLUSIONS: OXT is well tolerated in infants with PWS and improves feeding and social skills. These results open perspectives for early treatment in neurodevelopment diseases with feeding problems.

Publisher

American Academy of Pediatrics (AAP)

Subject

Pediatrics, Perinatology and Child Health

Reference28 articles.

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4. Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: a study of five cases.;Swaab;J Clin Endocrinol Metab,1995

5. A single postnatal injection of oxytocin rescues the lethal feeding behaviour in mouse newborns deficient for the imprinted Magel2 gene.;Schaller;Hum Mol Genet,2010

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