Long-Term Growth Hormone Treatment of Children with PWS: The Earlier the Start, the Better the Outcomes?

Abstract

Long-term effects of growth hormone (GH) treatment in young children with Prader-Willi syndrome (PWS) have never been compared with untreated age-matched controls with PWS, and it is unclear if starting GH in the first year of life is safe and more effective than starting GH in early childhood. We investigated the effects of long-term GH on body composition, anthropometrics and cognition in young children with PWS compared to untreated controls and assessed whether starting GH in the first year of life is optimal and safe. An open-label, prospective study was performed, comparing GH-treated children with untreated controls, and comparing children who started GH in the first year of life (subgroup A) with children who started between 2-5 years (subgroup C). A total of 82 GH-treated children with PWS and 22 age-matched controls with PWS were included. The main outcome measures were body composition, anthropometrics, IQ, and safety parameters. After 8 years, GH-treated children had significantly better body composition and were taller than age-matched controls. Subgroup A had a lower FM% trajectory during treatment than subgroup C and showed a greater and longer-term increase in the LBM index. After 8 years, subgroup A had a lower trunk/peripheral fat ratio (p = 0.043) and higher IQ (p = 0.043). No adverse effects of starting GH in the first year were found. Children with PWS who received long-term GH had a better body composition and growth than untreated age-matched controls and starting GH in the first year of life was optimal and safe.

Keywords: Prader-Willi syndrome; body composition; children; cognition; growth hormone.

Figure 1

Longitudinal changes in Estimated Marginal Means with SEM in FM% (A) and LBM index (B) in group A (27 children with PWS, age start GH treatment < 1.05 years) and group C (27 children with PWS, age start GH treatment between 2.27–5.00 years) during 8 years of GH treatment. FM% and LBMI are corrected for sex and pubertal stage. * p-value < 0.001, ^# p-value < 0.01, ** p-value < 0.05. All these p-values are compared to baseline, p-values indicated by the brackets are referring to the difference between the subgroups after 8 years.