Sleep‐disordered breathing in Australian children with Prader‐Willi syndrome following initiation of growth hormone therapy

Abstract

Aim In children with Prader‐Willi syndrome (PWS), growth hormone (GH) improves height and body composition; however, may be associated with worsening sleep‐disordered breathing (SDB). Some studies have reported less SDB after GH initiation, but follow‐up with polysomnography is still advised in most clinical guidelines. Methods This retrospective, multicentre study, included children with PWS treated with GH at seven PWS treatment centres in Australia over the last 18 years. A paired analysis comparing polysomnographic measures of central and obstructive SDB in the same child, before and after GH initiation was performed with Wilcoxon signed‐rank test. The proportion of children who developed moderate/severe obstructive sleep apnoea (OSA) was calculated with their binomial confidence intervals. Results We included 112 patients with available paired data. The median age at start of GH was 1.9 years (range 0.1–13.5 years). Median obstructive apnoea hypopnoea index (AHI) at baseline was 0.43/h (range 0–32.9); 35% had an obstructive AHI above 1.0/h. Follow‐up polysomnography within 2 years after the start of GH was available in 94 children who did not receive OSA treatment. After GH initiation, there was no change in central AHI. The median obstructive AHI did not increase significantly (P = 0.13), but 12 children (13%, CI95% 7–21%) developed moderate/severe OSA, with clinical management implications. Conclusions Our findings of a worsening of OSA severity in 13% of children with PWS support current advice to perform polysomnography after GH initiation. Early identification of worsening OSA may prevent severe sequelae in a subgroup of children.

Neurobehavioral Dimensions of Prader Willi Syndrome: Relationships Between Sleep and Psychosis-Risk Symptoms

“…We also were unable to collect information of growth hormone therapy (GHT) and body mass index (BMI). Existing data suggests a complex relationship between sleep apnea, GHT, and BMI in PWS ( 72 – 77 ) with some studies showing associations and others not. However, since our analyses studied multiple dimensions of sleep, it is unclear if inclusion of these variables would impact our results.…”

Sleep Disorders in Children with Prader Willi Syndrome: Current Perspectives

“…However, a small subset of patients (2 patients in the younger group, 1 patient in the older group) developed moderate or severe OSA 3 months after starting rhGH. Similarly, Caudri et al 41 also showed no statistically significant differences in baseline and follow up OAHI among 94 children with PWS after rhGH initiation. Yet, it is notable that 12 subjects (13%) had no or mild OSA at baseline yet progressed to moderate or severe OSA which altered their clinical management after rhGH.…”

“…Ultimately, this led authors to advocate for close OSA monitoring (eg, home pulse oximetry) in infants with PWS and respiratory illness on rhGH. Regarding central apneic events, most studies 15,[41][42][43] demonstrate improvement following rhGH initiation. In the absence of placebo-controlled trials, it is not known whether these improvements would have been seen regardless of rhGH due to natural physiologic maturation.…”

Sleep Consequences of Prader-Willi Syndrome

“…GH therapy can result in improvement in ventilatory control and inspiratory drive [39]. In an Australian multicenter retrospective study, there was no significant increase in median oAHI following initiation of GH in children with PWS [43]. One study showed worsening of sleep disturbance after initiation of GH therapy; however, on average, affected patients had higher IGF-1 levels and respiratory issues, so they may have had other causes of morbidity [28].…”