Growth hormone improves mobility and body composition in infants and toddlers with Prader–Willi Syndrome
To determine the effect of growth hormone (GH) on body composition and motor development in infants and toddlers with Prader-Willi syndrome (PWS). Twenty-nine subjects with PWS (4-37 months of age) were randomized to GH treatment (1mg/m 2 /day) or observation for 12 months. Percent body fat, lean body mass, and bone mineral density were measured by dual x-ray absorptiometry; energy expenditure was measured by deuterium dilution; and motor constructs of mobility (M) and stability (S) were assessed using the Toddler Infant Motor Evaluation (TIME). GH-treated subjects, compared with controls, demonstrated decreased percent body fat (mean, 22.6% +/- 8.9% vs 28.5% +/- 7.9%; P < .001), increased lean body mass (mean, 9.82 +/- 1.9 kg vs 6.3 +/- 1.9 kg; P < .001), and increased height velocity Z scores (mean, 5. 0 +/- 1.8 vs 1.4 +/- 1.0; P < .001). Patients who began GH before 18 months of age showed higher mobility skill acquisition compared with controls within the same age range (mean increase in raw score, 284 +/- 105 vs 206 +/- 63; P < .05). GH treatment of infants and toddlers with PWS for 12 months significantly improves body composition and when begun before 18 months of age increases mobility skill acquisition. These results suggest that GH therapy instituted early in life may lessen deterioration of body composition in PWS while also accelerating motor development.
[Show abstract] [Hide abstract] ABSTRACT: Prader-Willi syndrome (PWS) is a rare genetic disorder associated with distinct abnormal behaviors including hyperphagia, profound social deficits, and obsessive-compulsive tendencies. PWS males showed reduced oxytocin receptor (OTR) gene expression and density in the hypothalamic paraventricular nucleus that may play a role in PWS psychopathology. Oxytocin is an anorexigenic neuropeptide similar to vasopressin that is associated with social cognition and obsessive-compulsive behavior. To evaluate oxytocin biology in PWS, we examined overnight fasting plasma oxytocin levels in 23 children with PWS (mean ± SD age: 8.2 ± 2.0 year) having genetic confirmation and 18 age matched healthy unrelated siblings without PWS (mean ± SD age: 8.2 ± 2.3 year) and a similar gender ratio under the same clinical assessments, specimen processing and laboratory conditions. Multiplex immune assays were carried out using the Milliplex Human Neuropeptide Magnetic panel and the Luminex system. Natural log-transformed oxytocin levels were analyzed using general linear model adjusting for diagnosis, gender, age and body mass index (BMI). Oxytocin plasma levels were significantly elevated in children with PWS (168 ± 121 pg/ml) compared with unrelated and unaffected siblings without the diagnosis of PWS (64.8 ± 83.8 pg/ml, F = 8.8, P < 0.01) and the diagnosis of PWS predicted oxytocin level (F = 9.5, P < 0.003) in controlled regression analysis with an overall model fit R(2 ) = 0.33 (P < 0.01). The symptoms of hyperphagia, anxiety and repetitive behaviors classically seen in PWS may be related to the disruption of oxytocin responsivity or feedback in the hypothalamic paraventricular nucleus possibly influencing vasopressin signaling. Further study is needed to characterize oxytocin function in PWS. © 2015 Wiley Periodicals, Inc.0Comments 0Citations
- "Early morbid obesity, short stature, and small hands and feet are associated with growth hormone (GH) deficiency. When individuals with PWS are given GH treatment, improvements are seen with increased muscle size and decreased fat mass [Carrel et al., 2004; Butler et al., 2006; Sode-Carlsen et al., 2010; Cadoudal et al., 2014]. In addition to their characteristic physical features, individuals with PWS also have dysfunctional behavioral patterns. "
- "Назначение ГР до 2-летнего возраста имеет положительное влияние на физическое и моторное раз- витие  . При более раннем начале терапии в 6–12 месяцев получено улучшение показателей моторного развития, мышечной силы, окружности головы и, возможно, когнитивной функции . Интересно, что назначение ГР в столь ранние сроки сталкивается с проблемами даже в США, где, в отличие от стран Европы, задержка роста является необходимым условием для начала терапии ГР у детей с СПВ . "
[Show abstract] [Hide abstract] ABSTRACT: BackgroundSleep related disordered breathing (SDB) in pediatric Prader-Willi Syndrome is gaining increased attention due to the possible association of growth hormone therapy, SDB and sudden death. However data on the patterns of SDB and their management, particularly in infants in this population, is lacking.ObjectiveThe aim of this study was to 1) describe patterns of SDB in growth hormone naive infants with PWS and the management of these disorders in our institution 2) Compare the patterns of sleep disorders between infants and children with PWS.Methods and DesignPolysomnograms of infants and children (0–18 years of age) with Prader-Willi Syndrome were reviewed. Age, sex, anthropometrics, sleep architecture, obstructive and central apnea indices and oxygen saturations were recorded. Data of infants with central sleep apnea treated with oxygen were analyzed to evaluate the efficacy of this treatment. The main outcome measures were obstructive and central apnea indices on a polysomnogram.ResultsData of 44 patients, 23 under 2 years of age and 21 older children were included. Infants when compared with older children were more likely to experience central sleep apnea (43% vs. 5%; p = 0.003). In older children obstructive was significantly more prevalent than central sleep apnea. Supplemental oxygen was used to treat 9/23 infants with central sleep apnea. Oxygen therapy resulted in a significant decrease in the median central apnea index from 14 (5,68) to 1 (0,6; p = 0.008) events/hour and an improvement in the oxygen saturation nadir from 70% (52, 92) to 81% (64, 95; p = 0.080).ConclusionsCentral sleep apnea with associated oxygen desaturations is more prevalent in infants compared with older children with Prader-Willi Syndrome. Supplemental oxygen was efficacious in treating central sleep apnea in infants. Routine sleep surveillance for all children with Prader-Willi Syndrome and treatment with oxygen for central sleep apnea should be considered.0Comments 6Citations
- "Infants with PWS are increasingly referred for GH treatment, prior to which PSG screening is recommended. The early use of GH is likely related to the early diagnosis of PWS and to recent studies suggesting benefits for treatment in infancy . Obesity related OSA remains the major focus when discussing SDB in pediatric PWS  and routine and follow-up PSG screening is recommended in consensus guidelines and expert reviews mostly in the context of GH treatment , , . "