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      Pre-Pubertal Children Born Post-Term Have Reduced Insulin Sensitivity and Other Markers of the Metabolic Syndrome

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          Abstract

          Background

          There are no data on the metabolic consequences of post-term birth (≥42 weeks gestation). We hypothesized that post-term birth would adversely affect insulin sensitivity, as well as other metabolic parameters and body composition in childhood.

          Methods

          77 healthy pre-pubertal children, born appropriate-for-gestational-age were studied in Auckland, New Zealand: 36 born post-term (18 boys) and 41 (27 boys) born at term (38–40 weeks gestation). Primary outcome was insulin sensitivity measured using intravenous glucose tolerance tests and Bergman’s minimal model. Other assessments included fasting hormone concentrations and lipid profiles, body composition from whole-body dual-energy X-ray absorptiometry, 24-hour ambulatory blood pressure monitoring, and inflammatory markers.

          Results

          Insulin sensitivity was 34% lower in post-term than in term children (7.7 vs. 11.6 x10 -4·min -1·(mU/l); p<0.0001). There was a compensatory increase in acute insulin response among post-term children (418 vs 304 mU/l; p=0.037), who also displayed lower glucose effectiveness than those born at term (2.25 vs 3.11 x10 -2·min -1; p=0.047). Post-term children not only had more body fat (p=0.014) and less fat-free mass (p=0.014), but also had increased central adiposity with more truncal fat (p=0.017) and greater android to gynoid fat ratio (p=0.007) compared to term controls. Further, post-term children displayed other markers of the metabolic syndrome: lower normal nocturnal systolic blood pressure dipping (p=0.027), lower adiponectin concentrations (p=0.005), as well as higher leptin (p=0.008) and uric acid (p=0.033) concentrations. Post-term boys (but not girls) also displayed a less favourable lipid profile, with higher total cholesterol (p=0.018) and LDL-C (p=0.006) concentrations, and total cholesterol to HDL-C ratio (p=0.048).

          Conclusions

          Post-term children have reduced insulin sensitivity and display a number of early markers of the metabolic syndrome. These findings could have important implications for the management of prolonged pregnancies. Future studies need to examine potential impacts later in life, as well as possible underlying mechanisms.

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          Most cited references 34

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          Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition.

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            Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty.

            New charts for height, weight, height velocity, and weight velocity are presented for clinical (as opposed to population survey) use. They are based on longitudinal-type growth curves, using the same data as in the British 1965 growth standards. In the velocity standards centiles are given for children who are early- and late-maturing as well as for those who mature at the average age (thus extending the use of the previous charts). Limits of normality for the age of occurrence of the adolescent growth spurt are given and also for the successive stages of penis, testes, and pubic hair development in boys, and for stages of breast and pubic hair development in girls.
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              Body mass index reference curves for the UK, 1990.

              Reference curves for stature and weight in British children have been available for the past 30 years, and have recently been updated. However weight by itself is a poor indicator of fatness or obesity, and there has never been a corresponding set of reference curves to assess weight for height. Body mass index (BMI) or weight/height has been popular for assessing obesity in adults for many years, but its use in children has developed only recently. Here centile curves for BMI in British children are presented, from birth to 23 years, based on the same large representative sample as used to update the stature and weight references. The charts were derived using Cole's LMS method, which adjusts the BMI distribution for skewness and allows BMI in individual subjects to be expressed as an exact centile or SD score. Use of the charts in clinical practice is aided by the provision of nine centiles, where the two extremes identify the fattest and thinnest four per 1000 of the population.
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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
                2013
                1 July 2013
                : 8
                : 7
                Affiliations
                [1 ]Liggins Institute, University of Auckland, Auckland, New Zealand
                [2 ]Gravida: National Centre for Growth and Development, Auckland, New Zealand
                [3 ]Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
                [4 ]National Women’s Health, Auckland District Health Board, Auckland, New Zealand
                Virgen Macarena University Hospital, School of Medicine, Spain
                Author notes

                Competing Interests: The authors have no financial or non-financial conflicts of interest to disclose that may be relevant to this work.

                Conceived and designed the experiments: AA WSC PLH PS. Performed the experiments: AA JB. Analyzed the data: JGBD . Wrote the manuscript: AA JGBD WSC . Other: Compiled the data: AA JGBD LS SM.

                Article
                PONE-D-13-14174
                10.1371/journal.pone.0067966
                3698136
                23840881

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Funding
                This study was funded by Gravida: National Centre for Growth and Development, the Australasian Paediatric Endocrine Group (APEG), and Maureen Trotter. The funders had any role in study design, data collection and analysis, decision to publish, or preparation of this manuscript.
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                Research Article

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