Growth Hormone Effects in Infants and Toddlers with Prader-Willi Syndrome: Does Early Intervention Make a Difference?

Barbara Y. Whitman¹, Sue Myers¹, Aaron Carrel², David Allen²

St. Louis University Department of Pediatrics¹, University of Wisconsin – Madison²

INTRODUCTION: Infants with PWS display decreased muscle mass, hypotonia, and abnormally increased fat tissue as documented by DEXA scan prior to any evidence of excess weight, or hyperphagia. Growth hormone (GH) administration to older children with PWS improves, but does not normalize, body composition, energy expenditure, and strength and agility. We investigate whether GH therapy of infants with PWS can ameliorate hypotonia and prevent deterioration in body composition, and whether GH dose impacts changes in these areas. We compare a subset of these children, now treated for four years, starting in infancy, with the youngest subset of a previous study for whom growth hormone replacement was not initiated until age four and above.

METHODS: Twenty-nine infants and toddlers with genetically confirmed PWS (ages 4-37 months) were randomized to GH treatment (1mg/m2/day) or control (no treatment) for 12 months. During months 12-24, control subjects were treated with GH (1.5mg/m2/day), while previously treated subjects continued on 1mg/m2/day. Sixteen of these children now between the ages of 48 to 72 months and having been enrolled in the study for 48 months are compared with the youngest subset of a previous study for whom GH replacement therapy was not initiated until age 4 years and above. This subset was selected on the basis of those who were between the ages of 48 and 72 months at the time of initial enrollment into the study protocol. Comparisons are made between the 48 month values of those enrolled in the infant study and the baseline values of the children starting GH replacement between 48 and 72 months.

RESULTS: Children treated since infancy had significantly improved standardized height scores (0.902 vs -1.2), had significantly better BMI’s (18.5 vs. 25); body composition by DEXA indicated that the early treated groups had significantly less total fat tissue (34.5 vs. 43.5). In addition, the early treated group talked significantly earlier (14.5 mo vs. 21.5 mo.).

DISCUSSION: This comparison of a group of infants receiving GH replacement therapy from early on to an untreated group of approximately the same age suggests that the impact of early GH hormone therapy has a broad ranging impact in this population beyond simply increased height. The positive changes in both body composition and neuro-developmental areas are intriguing and will require long term follow-up to assess both the stability and ultimate meaning of these findings.