Early-onset growth hormone treatment in Prader-Willi syndrome attenuates transition to severe obesity

Objectives Subsequent to early life feeding issues, children with Prader-Willi syndrome (PWS) develop hyperphagia and severe obesity. Growth hormone (GH) therapy has been approved in PWS to improve growth, body composition, and BMI. We aimed to clarify the role of age at GH therapy onset on growth and BMI trajectories in children with PWS. Methods We analyzed height and BMI in 114 patients (58 boys) from REPAR - Czech national GH registry. From them, 69 started GH therapy prior to 2 y/o (age 0.8 +/- 0.4 years; mean +/- SD; early-onset group [EO]), and 45 later (age 7.1 +/- 4.1 years; late-onset group [LO]). Results Height-SDS before therapy was similar in all (EO: -1.9 +/- 1.2 [mean +/- SD]; LO: -1.7 +/- 1.1). After the first year of GH therapy, height-SDS in the EO group increased to -1.0 +/- 1.2, in the LO group to -0.9 +/- 1.1. After 5 years, height fully normalized in all (-0.1 +/- 1.1 SDS). The LO children were already obese at treatment initiation (BMI-SDS: 2.9 +/- 2.2), and their BMI-SDS decreased after 1 year of GH therapy by 0.9 (p=0.003). The weight in EO children was below average before GH treatment (BMI-SDS: -0.9 +/- 1.2) and their BMI-SDS increased to the overweight range of 1.3 +/- 2.2 (p<0.001) within the oncoming 3 years. Albeit BMI-SDS was around the obesity limit in most children after 5 years on GH therapy, the highest lifetime BMI-SDS was lower in EO (2.2 +/- 2.6) than in LO (3.7 +/- 2.2; p<0.001). Conclusions GH treatment in PWS normalizes body height. After 5 years of GH therapy, BMI-SDS in EO and LO groups are similar; however, the EO group is exposed to lower maximal BMI-SDS values.