Context: Children with Prader-Willi syndrome (PWS) generally have mild to moderate cognitive impairment with an IQ between 60 and 70. Growth hormone (GH) treatment is a registered treatment for children with PWS and has been associated with cognitive benefits, attributed to the effects of GH and insulin-like growth factor on brain growth and development. Short-term data suggest positive effects of GH treatment on cognitive functioning in children with PWS. There are, however, no long-term studies about the effects of GH on cognitive functioning.
Objective: To investigate the long-term effects of GH on cognitive functioning in children with PWS. Secondly, to investigate whether starting GH before the age of 2 years, results in higher cognitive functioning after 8 years of GH.
Design: Prospective cohort study during 8 years of GH.
Setting: Dutch PWS Reference Center
Intervention: All children were treated with GH 1 mg/m2/day (~0.035 mg/kg/day).
Main outcome measures: Cognitive functioning assessed by the Wechsler Intelligence Scale for Children-Revised (WISC-R). Vocabulary, Similarities and Block Design subtests were used and expressed as standard deviation scores. Total IQ (TIQ) was estimated.
Results: Forty-three children with PWS (29 girls), started GH at a median (IQR) age of 8.1 (6.6; 11.5) years. Estimated mean Block Design SDS increased from -2.2 at baseline to -1.8 after 8 years of GH (P=0.18), showing that visuospatial skills tended to improve compared to healthy controls. Estimated mean Similarities SDS increased from -1.5 to -1.3 (P=0.66) and Vocabulary SDS remained similar, being -1.9 SDS at baseline and after 8 years (P=0.85), demonstrating that children with PWS develop abstract verbal reasoning and vocabulary at the same pace as healthy references. Mean estimated TIQ improved from 66 points at baseline to 69 points after 8 years of GH (P=0.57).
Another group of 20 children started GH before the age of 2 and had a significantly higher Vocabulary SDS and estimated TIQ after 8 years of GH (P<0.01 and P=0.04, resp.) than the children who participated in the current study. Scores on the Block Design and Similarities subtest were similar between the two groups (P=0.53 and P=0.19, resp.).
Conclusions: Our results demonstrate that cognitive skills in children with PWS are maintained during 8 years of GH, indicating that GH-treated PWS children develop at the same pace as healthy references.We also conclude that starting GH treatment before the age of 2 years might lead to higher cognitive functioning on the long-term.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology