After more than 20 yr, leukemia, a major safety issue initially believed associated with GH, has not been confirmed, but other signals, including risk of second malignancies in patients previously treated with irradiation, have been detected or confirmed through the NCGS. These data further clarify the events associated with rhGH and, although confirming a favorable overall safety profile, they also highlight specific populations at potential risk.

Obesity and premature adrenarche (PA) are both associated with bone age (BA) advancement of unclear etiology, which may lead to earlier puberty, suboptimal final height and obesity in adulthood. Our objective was to understand the hormonal and anthropometric characteristics of BA advancement in a spectrum of prepubertal children with and without obesity and PA. In this cross-sectional study of 66 prepubertal children (35 PA, 31 control, 5–9 years), body mass index (BMI) z-score, hormonal values and response to an oral glucose tolerance test were the main outcome measures. Subjects were divided into tertiles by BA divided by chronological age (BA/CA), an index of BA advancement. Subjects in the top tertile for BA/CA had the highest dehydroepiandrosterone sulfate (DHEAS), free testosterone (%), hemoglobin A1C, BMI z-score and weight (P < 0.05). BMI z-score (r = 0.47), weight (r = 0.40), free testosterone (%) (r = 0.34) and DHEAS (r = 0.30) correlated with BA/CA (P<0.02). Regression analysis showed greater BA/CA in PA compared to controls after controlling for weight (0.21 ± 0.56, p<0.004). An exploratory stepwise regression model showed that weight, estradiol and DHEAS were the strongest predictors of BA/CA accounting for 24% of its variance. Obesity was highly associated with BA advancement in this study of prepubertal children. In addition, children with PA had greater BA/CA at any given weight when compared to controls. These findings suggest a possible hormonal factor, which potentiates the effect of obesity on BA advancement in children with obesity and/or PA.

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With these data and other published studies, more than 600 patients have been reported to detoxify from opiates during pregnancy with no report of fetal harm related to the process. These data highly suggest that detoxification of opiate-addicted pregnant patients is not harmful. The rate of neonatal abstinence syndrome is high but primarily when no continued long-term follow-up occurs. Once a patient is drug free, intense behavioral health follow-up is needed for continued success.

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