ESPE Yearbook of Paediatric Endocrinology

BMJ Paediatrics Open 2020;4:e000630. doi: 10.1136/bmjpo-2019-000630. PMID: 32411831

This systematic review and meta-analysis provides an up to date report on rhGH in patients with Prader–Willi syndrome (PWS). The review included 463 papers published until September 2019. 16 randomized (RCTs) and 20 not randomized (NRCTs) trials were selected for the meta-analysis. The findings support the efficacy and safety of rhGH in patients with PWS.

PWS is the most frequent genetic cause of obesity, occurring in approximately 1:10,000–1:30,000 live births (1). PWS is a complex multisystem disorder, characterized by neonatal hypotonia, feeding difficulties in early infancy, short stature, behavioral disturbances, cognitive impairment, psychiatric illness, dysmorphic features, multiple endocrine abnormalities, early development of hyperphagia and progressive development of severe obesity (2). Reduced GH response has been documented in 58%–100% of PWS children and the efficacy of rhGH treatment on growth, body composition, resting energy expenditure, motor development, muscle strength, exercise tolerance, bone health, and lipid profiles has been reported in several studies. rhGH was approved for treatment of PWS children, without need of GH stimulation tests in 2000 (1,3,4). It has been suggested that rhGH therapy in PWS patients would also improve their cognitive function (5). This review followed the recommended Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

The key findngs were: rhGH treatment improves height (by +1.67 SD scores (SDS) in RCTs and +1.52 SDS in NRCTs); body mass index z-scores (−0.67 SDS only in RCTs) and fat mass proportion (−6.5% SDS in RCTs and –7.0% in NRCTs). RCTs also found improvements in lean mass (+2.0%) and head circumference (+0.55 SDS). It was not possible to draw a conclusion on the impact of rhGH therapy on cognitive function and behavior. The number of reported adverse events (mainly sleep apnea) was negligible. Twelve deaths were reported across all these studies.

This is the first systematic review and meta-analysis on rhGH therapy in children with PWS. The findings support the use such therapy in children with PWS and provide reassurance on the potential risk of obstructive sleep apnea syndrome associated to therapy.

Reference: 1. Cassidy SB, Schwartz S, Miller JL, Driscoll DJ. Prader-Willi syndrome. Genet Med. 2012; 14:10-262. Angulo MA, Butler MG, Cataletto ME. Prader-Willi syndrome: a review of clinical, genetic and endocrine finding. J Endocrinol Invest. 2015;38(12):1249-1263.3. Goldstone AP, Holland AJ, Hauffa BP, Hokken-Koelega AC, Tauber M; speakers contributors at the Second Expert Meeting of the Comprehensive Care of Patients with PWS. Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metab. 2008;93(11):4183-4197.4. Grugni G. Diagnoses and treatment of GH deficiency in prader-Willi syndrome. Best Pract Res Clin Endocrinol Metab 2016;30(6):785-794.5. Donze SH, Damen L, Mahabier EF, Hokken-Koelega ACS. Cognitive functioning in children with Prader-Willi syndrome during 8 years of growth hormone treatment. Eur J Endocrinol. 2020 Apr;182(4):405-411. doi: 10.1530/EJE-19-0479 PMID: 31961800