ABSTRACT. Objective. The pathophysiological mechanisms of growth impairment frequently associated with the obstructive sleep apnea syndrome (OSAS) in children are poorly defined. The main objective of this study was to evaluate whether nighttime upper airway obstruction attributable to adenotonsillar hypertrophy and subsequent surgical treatment affect the circulating concentrations of insulin-like growth factor-I (IGF-I) and IGFbinding protein 3 (IGFBP-3) along with other growth parameters in children.Patients and Methods. We initially studied 70 children (mean age: 5.8 years; range: 2.4 -10.5 years) admitted to a university hospital because of clinical symptoms of OSAS. Their sleep was monitored with a 6-channel computerized polygraph. Data on anthropometry and circulating concentrations of IGF-I and IGFBP-3 were generated and compared with corresponding characteristics in control children (N ‫؍‬ 35). Thirty children with an obstructive apnea-hypopnea index (OAHI) of 1 or more were categorized as children with OSAS (mean OAHI: 5.4 [95% confidence interval for mean (CI): 3.8 -6.9]), whereas 40 children with an OAHI of <1 were considered as primary snorers (PS) (mean OAHI 0.13 [95% CI: 0.05-0.21]). Nineteen children with OAHI >2 underwent adenotonsillectomy attributable to OSAS and were reassessed 6 months later together with 34 nonoperated children with OAHI <2.Results. There were no initial differences in relative height and weight for height between the 3 groups of children. No differences were observed in peripheral IGF-I concentrations, but both OSAS and PS children had reduced peripheral IGFBP-3 levels. The operated children with initial OSAS experienced a highly significant reduction in their OAHI from 7.1 (95% CI: 5.1-9.1) to 0.37 (95% CI: 0.2-0.95). Weight-for-height, body mass index, body fat mass, and fat-free mass increased during the follow-up in the operated children with OSAS, whereas only fat-free mass and relative height increased in the PS children. Both the IGF-I and the IGFBP-3 concentrations increased significantly in the operated children, whereas no significant changes were seen in the PS children.Conclusions. These observations indicate that growth hormone secretion is impaired in children with OSAS and PS. Respiratory improvement after adenotonsillectomy in children with OSAS results in weight gain and restored growth hormone secretion. Pediatrics 2002;109(4). URL: http://www.pediatrics.org/cgi/content/full/109/4/e55; snoring, obstructive sleep apnea, growth hormone, insulinlike growth factor-I, insulin-like growth factor-binding protein 3.ABBREVIATIONS. OSAS, obstructive sleep apnea syndrome; GH, growth hormone; IGF-I, insulin-like growth factor-I; IGFBP-3, insulin-like growth factor-binding protein 3; PS, primary snorer; EMG, electromyogram; OAHI, obstructive sleep apnea-hypopnea index; SDS, standard deviation score; BMI, body mass index; SWS, slow-wave sleep. S noring is relatively common in children, with the prevalence of regular snoring about 10% in preschool-aged subjects. 1-3 Obs...

Valproate is effective for treatment of a variety of seizure types both in adults and in children with epilepsy, but it induces obesity and polycystic ovaries in a considerable proportion of adult women, particularly when the medication is started before the age of 20. In the present study we evaluated reproductive endocrine function in 41 girls, 8 to 18 years old, taking valproate for epilepsy and in 54 healthy control girls. Among the girls taking valproate, 16 were prepubertal, 11 were pubertal, and 14 were postpubertal, and the corresponding numbers were 20, 13, and 21 in the control group. The mean serum testosterone concentrations of prepubertal, pubertal, and postpubertal girls taking valproate were significantly higher than those of the control girls at the same pubertal stage. Hyperandrogenism, defined as serum testosterone levels higher than the mean + 2SD in the control girls at the same pubertal stage, was seen in 38% of prepubertal, 36% of pubertal, and 57% of postpubertal girls taking valproate. In addition, postpubertal girls taking valproate were more obese than the controls and the mean serum insulin‐like growth factor binding protein‐1 concentration of pubertal and postpubertal hyperandrogenic girls taking valproate was lower than in valproate‐treated girls without hyperandrogenism. Valproate may induce hyperandrogenism in girls with epilepsy during the sensitive period of pubertal maturation, and the frequency of hyperandrogenism increases with pubertal development. This emphasizes the importance of careful endocrine observation of girls taking valproate for epilepsy. Ann Neurol 1999;45:444–450

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AEDs do not seem to have any adverse effects on linear growth or sexual maturation in girls with epilepsy. VPA-related weight gain can be seen already in prepuberty and it is not associated with hyperinsulinemia in these young patients. The clinical significance of high circulating concentrations of IGF-I in patients taking CBZ or OXC remains to be defined.

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