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      Gender Bias in U.S. Pediatric Growth Hormone Treatment

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          Abstract

          Growth hormone (GH) treatment of idiopathic short stature (ISS), defined as height <−2.25 standard deviations (SD), is approved by U.S. FDA. This study determined the gender-specific prevalence of height <−2.25 SD in a pediatric primary care population, and compared it to demographics of U.S. pediatric GH recipients. Data were extracted from health records of all patients age 0.5–20 years with ≥ 1 recorded height measurement in 28 regional primary care practices and from the four U.S. GH registries. Height <−2.25 SD was modeled by multivariable logistic regression against gender and other characteristics. Of the 189,280 subjects, 2073 (1.1%) had height <−2.25 SD. No gender differences in prevalence of height <−2.25 SD or distribution of height Z-scores were found. In contrast, males comprised 74% of GH recipients for ISS and 66% for all indications. Short stature was associated (P < 0.0001) with history of prematurity, race/ethnicity, age and Medicaid insurance, and inversely related (P < 0.0001) with BMI Z-score. In conclusion, males outnumbered females almost 3:1 for ISS and 2:1 for all indications in U.S. pediatric GH registries despite no gender difference in height <−2.25 SD in a large primary care population. Treatment and/or referral bias was the likely cause of male predominance among GH recipients.

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          Most cited references28

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          National estimates of the timing of sexual maturation and racial differences among US children.

          To provide clinically meaningful, normative reference data that describe the timing of sexual maturity indicators among a national sample of US children and to determine the degree of racial/ethnic differences in these estimates for each maturity indicator. Tanner staging assessment of sexual maturity indicators was recorded from 4263 non-Hispanic white, black, and Mexican American girls and boys aged 8.00 to 19.00 years as part of the Third National Health and Nutrition Examination Survey (NHANES III) conducted between 1988 and 1994. NHANES III followed a complex, stratified, multistage probability cluster design. SUDAAN was used to calculate the mean age and standard error for each maturity stage and the proportion of entry into a maturity stage and to incorporate the sampling weight and design effects of the NHANES III complex sampling design. Probit analysis and median age at entry into a maturity stage and its fiducial limits were calculated using SAS 8.2. Reference data for age at entry for maturity stages are presented in tabular and graphical format. Non-Hispanic black girls had an earlier sexual development for pubic hair and breast development either by median age at entry for a stage or for the mean age for a stage than Mexican American or non-Hispanic white girls. There were few to no significant differences between the Mexican American and non-Hispanic white girls. Non-Hispanic black boys also had earlier median and mean ages for sexual maturity stages than the non-Hispanic white and Mexican American boys. Non-Hispanic black girls and boys mature early, but US children completed their sexual development at approximately the same ages. The present reference data for the timing of sexual maturation are recommended for the interpretation of assessments of sexual maturity in US children.
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            Utah Growth Study: growth standards and the prevalence of growth hormone deficiency.

            Serial measurements of elementary-school children were conducted for 2 consecutive years to assess height and growth velocity and to determine the prevalence of growth hormone deficiency (GHD) in American children. Trained volunteers measured 114,881 children the first year; 79,495 growth rates were calculated after the second measurements. The height and growth velocity curves generated were very similar to the currently used charts. We examined 555 children with short stature (< 3rd percentile) and poor growth rates (< 5 cm/yr). Five percent had an endocrine disorder. The presence of GHD (peak level, < 10 ng/dl with two provocative tests) was found in 16 previously unrecognized children; 17 children from this school population were already known to have GHD. Boys outnumbered girls 2.7:1 (p = 0.006). Six girls with Turner syndrome also were identified. We conclude that (1) the growth curves generated in the 1960s and 1970s are valid for children of the 1990s; (2) most children growing < 5 cm/yr (a commonly used threshold rate) will not have an endocrine disorder; (3) many children (48% in this study) with GHD and others with Turner syndrome may currently be unrecognized and untreated; (4) GHD appears to be more common in boys; and (5) the prevalence of GHD in the United States is at least 1:3480.
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              Effects of obesity on growth and puberty.

              Nutrition is an important regulator of the tempo of human growth. Infancy may represent a critical "window" where variations in nutrition have longer-term consequences for growth and development. Rapid weight gain during infancy is associated with accelerated growth and early pubertal development. Rapid weight gain in infancy is also associated with the development of insulin resistance and an exaggerated adrenarche. Such circulating hormonal changes, together with elevated leptin levels and integral effects of fat cells on hormone action through local 11beta-steroid dehydrogenase and aromatase activity could effect rate of progression of pubertal development in obese subjects. The secular trends in growth and maturation are partly attributed to changing nutrition. Recent data suggest that age at menarche may be static, but there is a debate as to whether the first signs of puberty are being seen much earlier in obese girls. Rapid early weight gain, obesity and early development may have implications for later health through the development of PCOS and overall association with cancer risk.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                09 June 2015
                2015
                : 5
                : 11099
                Affiliations
                [1 ]Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA
                [2 ]Division of Endocrinology and Diabetes, The Children’s Hospital of Philadelphia , Philadelphia, PA
                [3 ]Leonard Davis Institute of Health Economics, University of Pennsylvania , Philadelphia, PA
                [4 ]Department of Pediatrics, Albert Einstein Medical Center , Philadelphia, PA
                [5 ]Center for Biomedical Informatics, The Children’s Hospital of Philadelphia , Philadelphia, PA
                [6 ]Clinical and Translational Research Center and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA
                [7 ]Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia.
                Author notes
                [*]

                Current address: Department of Pediatric Endocrinology and Diabetes, Children’s Mercy Hospital – Wichita Specialty Clinic, Wichita, KS;

                [†]

                Current address: Department of Pediatrics, Stony Brook University School of Medicine and Stony Brook Children’s Hospital, Stony Brook, NY.

                Article
                srep11099
                10.1038/srep11099
                4650610
                26057697
                34fe2eee-90e5-403b-93f6-8f746b294cf1
                Copyright © 2015, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 06 January 2015
                : 23 April 2015
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