Cognitive and adaptive advantages of growth hormone treatment in children with Prader‐Willi syndrome

Abstract

Background People with Prader-Willi syndrome (PWS) typically have mild to moderate intellectual deficits, compulsivity, hyperphagia, obesity, and growth hormone deficiencies. Growth hormone treatment (GHT) in PWS has well-established salutatory effects on linear growth and body composition, yet cognitive benefits of GHT, seen in other patient groups, have not been well studied in PWS. Methods Study 1 included 96 children and youth with PWS aged 4 to 21 years who naturalistically varied in their exposures to GHT. Controlling for socio-economic status, analyses compared cognitive and adaptive behavior test scores across age-matched treatment naïve versus growth hormone treated children. Study II assessed if age of treatment initiation or treatment duration was associated with subsequent cognition or adaptive behavior in 127, 4- to-21 year olds with PWS. Study III longitudinally examined cognitive and adaptive behavior in 168 participants who were either consistently on versus off GHT for up to 4–5 years. Results Compared to the treatment naïve group, children receiving growth hormone treatment had significantly higher Verbal and Composite IQs, and adaptive communication and daily living skills. Children who began treatment before 12 months of age had higher Nonverbal and Composite IQs than children who began treatment between 1 to 5 years of age. Longitudinally, the groups differed in their intercepts, but not slopes, with each group showing stable IQ and adaptive behavior scores over time. Conclusions Cognitive and adaptive advantages should be considered an ancillary benefit and additional justification for GHT in people with PWS. Future efforts need to target apparent socio-economic inequities in accessing GHT in the PWS population.

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

“…GH replacement therapy showed significant improvements in these variables (254,285,286,287,288,289,290,291,292). Similar observations were also made following GH treatment in patients with Prader-Willi syndrome (293). Interestingly, while considering the detrimental effect of lack of GH in GHD patients, an important point to consider is that GHD patients did not have a congenital absence of GH action, but rather had a peri-and post-natal exposure to GH, prior to development of GHD.…”

Impact of genetic subtypes of Prader–Willi syndrome with growth hormone therapy on intelligence and body mass index

“…Based on previous studies, starting GH treatment at an early age will maximize the benefits of treatment. Dykens et al () revealed a similar correlation with children who began GH treatment at <1 year of age having significantly higher nonverbal scores when compared to older age groups. The infant group had higher composite scores than children beginning GH treatment in the older age groups.…”

“…The authors suggested that a larger cohort was needed to examine for intelligence differences between the PWS deletion subtypes. More recently, Dykens, Roof, and Hunt‐Hawkins () showed that children who began GH treatment before 12 months of age had higher nonverbal and composite IQ scores than children with PWS who began treatment between 1 and 5 years of age.…”

A multidisciplinary approach to the clinical management of Prader–Willi syndrome

“…Early treatment with rGH improves growth and body composition resulting in better motor strength and function. Additional benefits include more favorable lipid profiles, positive effects on development and cognition, and improved depressive symptoms (Bakker, Kuppens, et al, ; Dykens, Roof, & Hunt‐Hawkins, ; Lo et al, ). Contraindications to use include severe obesity, untreated severe obstructive sleep apnea (OSA), uncontrolled diabetes, active malignancy, and active psychosis.…”