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      Newborn Body Fat: Associations with Maternal Metabolic State and Placental Size

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          Abstract

          Background

          Neonatal body composition has implications for the health of the newborn both in short and long term perspective. The objective of the current study was first to explore the association between maternal BMI and metabolic parameters associated with BMI and neonatal percentage body fat and to determine to which extent any associations were modified if adjusting for placental weight. Secondly, we examined the relations between maternal metabolic parameters associated with BMI and placental weight.

          Methods

          The present work was performed in a subcohort (n = 207) of the STORK study, an observational, prospective study on the determinants of fetal growth and birthweight in healthy pregnancies at Oslo University Hospital, Norway. Fasting glucose, insulin, triglycerides, free fatty acids, HDL- and total cholesterol were measured at week 30–32. Newborn body composition was determined by Dual-Energy X-Ray Absorptiometry (DXA). Placenta was weighed at birth. Linear regression models were used with newborn fat percentage and placental weight as main outcomes.

          Results

          Maternal BMI, fasting glucose and gestational age were independently associated with neonatal fat percentage. However, if placental weight was introduced as a covariate, only placental weight and gestational age remained significant. In the univariate model, the determinants of placenta weight included BMI, insulin, triglycerides, total- and HDL-cholesterol (negatively), gestational weight gain and parity. In the multivariable model, BMI, total cholesterol HDL-cholesterol, gestational weight gain and parity remained independent covariates.

          Conclusion

          Maternal BMI and fasting glucose were independently associated with newborn percentage fat. This effect disappeared by introducing placental weight as a covariate. Several metabolic factors associated with maternal BMI were associated with placental weight, but not with neonatal body fat. Our findings are consistent with a concept that the effects of maternal BMI and a number of BMI-related metabolic factors on fetal fat accretion to a significant extent act by modifying placental weight.

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          Most cited references31

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          Role of the placenta in fetal programming: underlying mechanisms and potential interventional approaches.

          Adverse influences during fetal life alter the structure and function of distinct cells, organ systems or homoeostatic pathways, thereby 'programming' the individual for an increased risk of developing cardiovascular disease and diabetes in adult life. Fetal programming can be caused by a number of different perturbations in the maternal compartment, such as altered maternal nutrition and reduced utero-placental blood flow; however, the underlying mechanisms remain to be fully established. Perturbations in the maternal environment must be transmitted across the placenta in order to affect the fetus. Here, we review recent insights into how the placenta responds to changes in the maternal environment and discuss possible mechanisms by which the placenta mediates fetal programming. In IUGR (intrauterine growth restriction) pregnancies, the increased placental vascular resistance subjects the fetal heart to increased work load, representing a possible direct link between altered placental structure and fetal programming of cardiovascular disease. A decreased activity of placental 11beta-HSD-2 (type 2 isoform of 11beta-hydroxysteroid dehydrogenase) activity can increase fetal exposure to maternal cortisol, which programmes the fetus for later hypertension and metabolic disease. The placenta appears to function as a nutrient sensor regulating nutrient transport according to the ability of the maternal supply line to deliver nutrients. By directly regulating fetal nutrient supply and fetal growth, the placenta plays a central role in fetal programming. Furthermore, perturbations in the maternal compartment may affect the methylation status of placental genes and increase placental oxidative/nitrative stress, resulting in changes in placental function. Intervention strategies targeting the placenta in order to prevent or alleviate altered fetal growth and/or fetal programming include altering placental growth and nutrient transport by maternally administered IGFs (insulin-like growth factors) and altering maternal levels of methyl donors.
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            Increased fetal adiposity: a very sensitive marker of abnormal in utero development.

            Because offspring of women with gestational diabetes mellitus have an increased risk of obesity and diabetes mellitus as young adults, our purpose was to characterize body composition at birth in infants of women with gestational diabetes mellitus and normal glucose tolerance. One hundred ninety-five infants of women with gestational diabetes mellitus and 220 infants of women with normal glucose tolerance had anthropometric measurements and total body electrical conductivity body composition evaluations at birth. Parental demographic, anthropometric, medical and family history data, and diagnostic glucose values were used to develop a stepwise regression model that related to fetal growth and body composition. There was no significant difference in birth weight (gestational diabetes mellitus [3398+/-550 g] vs normal glucose tolerance [3337+/-549 g], P=.26) or fat-free mass (gestational diabetes mellitus [2962+/-405 g] vs normal glucose tolerance [2975+/-408 g], P=.74) between groups. However, infants of women with gestational diabetes mellitus had significantly greater skinfold measures (P=.0001) and fat mass (gestational diabetes mellitus [436+/-206 g] vs normal glucose tolerance [362+/-198 g], P=.0002) compared with infants of women with normal glucose tolerance. In the gestational diabetes mellitus group, although gestational age had the strongest correlation with birth weight and fat-free mass, fasting glucose level had the strongest correlation with neonatal adiposity. Infants of women with gestational diabetes mellitus, even when they are average weight for gestational age, have increased body fat compared with infants of women with normal glucose tolerance. Maternal fasting glucose level was the strongest predictor of fat mass in infants of women with gestational diabetes mellitus. This increase in body fat may be a significant risk factor for obesity in early childhood and possibly in later life.
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              Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic?

              The Pedersen hypothesis was formulated more than 50 years ago. Jorgen Pedersen primarily cared for women with type 1 diabetes. He suggested that fetal overgrowth was related to increased transplacental transfer of glucose, stimulating the release of insulin by the fetal beta cell and subsequent macrosomia. Optimal maternal glucose control decreased perinatal mortality and morbidity. However, over the ensuing decades, there have been increases in maternal obesity and subsequently gestational diabetes mellitus (GDM) and type 2 diabetes. The underlying pathophysiology of type 1 and GDM/type 2 diabetes are fundamentally different, type 1 diabetes being primarily a disorder of beta cell failure and type 2 diabetes/GDM including both insulin resistance and beta cell dysfunction. As such the metabolic milieu in which the developing fetus is exposed may be quite different in type 1 diabetes and obesity. In this review we examine the metabolic environment of obese diabetic women and lipid metabolism affecting fetal adiposity. The importance of understanding these issues relates to the increasing trends of obesity worldwide with perinatal programming of metabolic dysfunction in the offspring. Copyright © 2011 Mosby, Inc. All rights reserved.
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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
                27 February 2013
                : 8
                : 2
                : e57467
                Affiliations
                [1 ]Section for Obstetrics, Women and Children’s Division, Rikshospitalet, Oslo University Hospital, Oslo, Norway
                [2 ]Outpatient Clinic for Specialized Endocrinology, Division of Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway
                [3 ]Faculty of Medicine, University of Oslo, Oslo, Norway
                VU University Medical Center, The Netherlands
                Author notes

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

                Conceived and designed the experiments: CMF TH EQ MCPR JB NV KG. Performed the experiments: KG NV. Analyzed the data: CMF MCPR. Contributed reagents/materials/analysis tools: NV KG JB. Wrote the paper: CMF TH EQ MCPR.

                Article
                PONE-D-12-30237
                10.1371/journal.pone.0057467
                3583865
                23460863
                f36f3f14-84ed-4dfa-9784-2f186f6b7cb8
                Copyright @ 2013

                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.

                History
                : 4 October 2012
                : 22 January 2013
                Page count
                Pages: 7
                Funding
                The project has been financially supported by South-Eastern Norway Regional Health Authority, The National Resource Centre for Women's Health, Division of Obstetrics and Gynaecology, Oslo University Hospital, Rikshospitalet; The Department of Obstetrics, Women and Children's Division, Oslo University Hospital, Rikshospitalet, Oslo, Norway; The Faculty of Medicine, Thematic Research Area, University of Oslo. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Biochemistry
                Metabolism
                Carbohydrate Metabolism
                Lipid Metabolism
                Proteins
                Lipoproteins
                Medicine
                Anatomy and Physiology
                Physiological Processes
                Energy Metabolism
                Nutrition
                Obesity
                Obstetrics and Gynecology
                Pregnancy
                Pregnancy Complications

                Uncategorized
                Uncategorized

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