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      Childhood Environment Influences Adrenarcheal Timing among First-Generation Bangladeshi Migrant Girls to the UK

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          Abstract

          Background

          Adrenarche is a key early life event that marks middle childhood at approximately 7 years of age. Earlier work with British-Bangladeshi migrant women suggested that environmental conditions experienced before adrenarche influence adult reproductive function. We therefore investigated whether Bangladeshi children who migrate to the United Kingdom (UK) reach adrenarche earlier than non-migrants in Bangladesh or the United Kingdom.

          Methods and Findings

          Healthy girls, aged 5–16 years, were recruited from schools in Sylhet, Bangladesh and London, England comprising four groups: Sylhetis (n = 165), first-generation migrants to the United Kingdom (n = 42), second-generation girls (n = 162), and British girls of European origin (n = 50). Anthropometric measurements were collected together with questionnaire data for migration and socioeconomic characteristics. Saliva samples were assayed for dehydroepiandrosterone (DHEAS) using enzyme-linked immunosorbent assays. Multiple linear regressions tested for group differences in anthropometric and socioeconomic variables and DHEAS levels. Median ages at adrenarche (DHEAS>400 pg/ml) were estimated using Weibull regression models for parametric survival analysis. Hazard ratios for reaching adrenarche earlier and 95% confidence intervals (CI), both unadjusted and adjusted for anthropometric variables, were estimated from the survival analyses. First-generation migrants had a median age at adrenarche (5.3 years) that was significantly earlier than Sylheti (7.2), second-generation (7.4), and European (7.1) girls. In univariate analyses, first-generation girls reached adrenarche significantly earlier than Sylhetis [HR (CI): 2.8 (1.4–5.5]. In multivariate models, first generation girls still reached adrenarche earlier than Sylhetis after adjusting for height [HR(CI): 1.9 (0.9–4.1)] and weight [HR(CI):1.7 (0.8–3.8)], but these results were attenuated.

          Conclusions

          We suggest that rapid catch-up growth experienced by first generation girls during early childhood may explain their advanced adrenarche. The environmental conditions leading to an earlier adrenarche, as well as the health implications of this early transition, merit further exploration.

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          Most cited references55

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          Clinical manifestations and insulin resistance (IR) in polycystic ovary syndrome (PCOS) among South Asians and Caucasians: is there a difference?

          Polycystic ovary syndrome (PCOS) is more prevalent in South Asian women residing in the UK than in Caucasians. Insulin resistance (IR) is central to the pathogenesis of PCOS, while type 2 diabetes is commoner in South Asians. We aimed to determine a possible ethnic difference in the clinical and biochemical characteristics of South Asian vs. Caucasian women with PCOS. A case-control cross-sectional observational study of consecutive women with anovular PCOS (47 South Asians, 40 Caucasians) and their age-matched controls (11 South Asians and 22 Caucasians). Index subjects: a questionnaire-based interview on clinical symptoms and family history; anthropometric measurements, clinical observations of the presence and degree of acne, hirsutism and acanthosis nigricans; transvaginal pelvic ultrasound; biochemical analyses of fasting blood sugar, fasting plasma insulin, fasting lipids, testosterone, and SHBG concentrations. age- and weight-matched unrelated women from the same ethnic backgrounds without PCOS seeking treatment for male infertility were studied by similar methods to those used with the index subjects. South Asians with PCOS presented at a younger age (age 26 +/- 4 vs. 30.1 +/- 5 years, P = 0.005). Body mass index (BMI) and waist : hip ratios were similar in the two affected cohorts. More South Asians had oligomenorrhoea commencing at a younger age. Hirsutism (Ferriman Gallwey score 18 vs. 7.5, P = 0.0001), acne, acanthosis nigricans and secondary infertility were significantly more prevalent in South Asians. The fasting glucose was similar (4.52 +/- 0.08 vs. 4.62 +/- 0.09 mmol/l, P = 0.25), the fasting insulin higher (89.4 +/- 8.9 vs. 48.6 +/- 4.8 pmol/l, P = 0.0001) and insulin sensitivity (IS) lower (0.335 +/- 0.005 vs. 0.357 +/- 0.002, P = 0.0001) among South Asians. Serum SHBG was significantly less in South Asians (35 +/- 3.3 vs. 55 +/- 9.4 nmol/l, P = 0.02), while serum testosterone was similar (2.69 +/- 0.11 vs. 2.64 +/- 0.13 nmol/l, P = 0.37). We conclude that South Asians with anovular PCOS seek treatment at a younger age, have more severe symptoms, and have higher fasting insulin concentrations and lower insulin sensitivity than Caucasians.
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            Adiposity rebound in children: a simple indicator for predicting obesity.

            To follow and predict the evolution of adiposity during growth, individual adiposity curves, assessed by the weight/height2 index, were drawn for 151 children from the age of 1 month to 16 yr. Adiposity increases during the 1st yr and then decreases. A renewed rise, termed here the adiposity rebound, occurs at about 6 yr. Individual weight/height2 curves may differ regarding their percentile range level and age at adiposity rebound. The present study shows a relationship between the age at adiposity rebound and final adiposity. An early rebound (before 5.5 yr) is followed by a significantly higher adiposity level than a later rebound (after 7 yr). This phenomenon is observed whatever the subject's adiposity at 1 yr. The present observations might be connected with the cellularity of adipose tissue.
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              Role of obesity and leptin in the pubertal process and pubertal growth--a review.

              The prevalence of obesity is increasing alarmingly to epidemic proportions in children and adolescents, especially in industrialized countries. The finding that overweight children, especially girls, tend to mature earlier than lean children has led to the hypothesis that the degree of body fatness may trigger the neuroendocrine events that lead to the onset of puberty. Obese children have high leptin levels, and these may play a role in their earlier onset of puberty. Leptin receptors have been identified in the hypothalamus, gonadotrope cells of the anterior pituitary, and ovarian follicular cells, as well as Leydig cells. Leptin accelerates gonadotropin-releasing hormone (GnRH) pulsatility in hypothalamic neurons, and it has a direct effect on the anterior pituitary. Leptin administration at low doses may have a permissive, threshold effect on the central networks that regulate gonadotropin secretion. However, at high levels, such as those in obese people, it can have an inhibitory effect on the gonads. Children with obesity also have increased adrenal androgen levels, which may be involved in the accelerated growth of these children before puberty. Recent data indicate that leptin has a specific role in stimulating the activity of enzymes essential for the synthesis of adrenal androgens. Children with exogenous obesity frequently show an increase in height velocity with tall stature for age despite low growth hormone levels. Our group has shown that leptin acts as a skeletal growth factor, with a direct effect on skeletal growth centers, in the mice mandibular condyle, a model of endochondral ossification. In summary, obesity is associated with early puberty. Elevated leptin levels might have a permissive effect on the pubertal process and pubertal growth.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                13 October 2014
                : 9
                : 10
                : e109200
                Affiliations
                [1 ]Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
                [2 ]Department of Anthropology and Wolfson Research Institute for Health and Wellbeing, Durham University, Durham, United Kingdom
                [3 ]School for Medicine, Pharmacy and Health, Durham University, Durham, United Kingdom
                [4 ]Sylhet MAG Osmani Medical College, Sylhet, Bangladesh
                London School of Hygiene and Tropical Medicine, United Kingdom
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LCH GRB. Performed the experiments: LCH GDC. Analyzed the data: LCH HAK. Contributed reagents/materials/analysis tools: HAK OAC. Wrote the paper: LCH GB MB RGZ HAK RNH RT. Field work: LCH OAC.

                Article
                PONE-D-14-14425
                10.1371/journal.pone.0109200
                4195659
                25309977
                1e810dce-bad0-4dec-b571-58509846fe22
                Copyright @ 2014

                This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 31 March 2014
                : 1 September 2014
                Page count
                Pages: 12
                Funding
                This work was supported by the intramural division of the U.S. National Cancer Institute (NCI) at the National Institutes of Health and the Wellcome Trust. Intramural investigators at the NCI designed and assisted in the analysis of the study. The Wellcome Trust had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Developmental Biology
                Ecology
                Medicine and Health Sciences
                Endocrinology
                Epidemiology
                Pediatrics
                Women's Health
                People and places
                Geographical locations
                Asia
                Bangladesh
                Europe
                United Kingdom
                Population Groupings
                Age Groups
                Children
                Ethnicities
                Bengali People
                Social Sciences
                Anthropology
                Custom metadata
                The authors confirm that, for approved reasons, some access restrictions apply to the data underlying the findings. Data will be made available upon request. This study involved human subjects and to protect the privacy of study participants, data requests will be reviewed by the NCI DCEG Data Repository Committee. Requests should be directed to NCIDCEGDataAccessRequests@ 123456mail.nih.gov .

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