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      Biomarkers for Macrosomia Prediction in Pregnancies Affected by Diabetes

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          Abstract

          Large birthweight, or macrosomia, is one of the commonest complications for pregnancies affected by diabetes. As macrosomia is associated with an increased risk of a number of adverse outcomes for both the mother and offspring, accurate antenatal prediction of fetal macrosomia could be beneficial in guiding appropriate models of care and interventions that may avoid or reduce these associated risks. However, current prediction strategies which include physical examination and ultrasound assessment, are imprecise. Biomarkers are proving useful in various specialties and may offer a new avenue for improved prediction of macrosomia. Prime biomarker candidates in pregnancies with diabetes include maternal glycaemic markers (glucose, 1,5-anhydroglucitol, glycosylated hemoglobin) and hormones proposed implicated in placental nutrient transfer (adiponectin and insulin-like growth factor-1). There is some support for an association of these biomarkers with birthweight and/or macrosomia, although current evidence in this emerging field is still limited. Thus, although biomarkers hold promise, further investigation is needed to elucidate the potential clinical utility of biomarkers for macrosomia prediction for pregnancies affected by diabetes.

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          Most cited references269

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          Birth weight and subsequent risk of type 2 diabetes: a meta-analysis.

          The "small baby syndrome hypothesis" suggests that an inverse linear relation exists between birth weight and risk of type 2 diabetes. The authors conducted a meta-analysis to examine this association. They included studies that reported odds ratios and 95% confidence intervals (or data with which to calculate them) for the association of type 2 diabetes with birth weight. Fourteen studies involving a total of 132,180 persons were identified. Low birth weight ( /=2,500 g, was associated with increased risk of type 2 diabetes (odds ratio (OR) = 1.32, 95% confidence interval (CI): 1.06, 1.64). High birth weight (>4,000 g), as compared with a birth weight of
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            The developmental origins of adult disease (Barker) hypothesis.

            Many studies have provided evidence for the hypothesis that size at birth is related to the risk of developing disease in later life. In particular, links are well established between reduced birthweight and increased risk of coronary heart disease, diabetes, hypertension and stroke in adulthood. These relationships are modified by patterns of postnatal growth. The most widely accepted mechanisms thought to underlie these relationships are those of fetal programming by nutritional stimuli or excess fetal glucocorticoid exposure. It is suggested that the fetus makes physiological adaptations in response to changes in its environment to prepare itself for postnatal life. These changes may include epigenetic modification of gene expression. Less clear at this time are the relevance of fetal programming phenomena to twins and preterm babies, and whether any of these effects can be reversed after birth. Much current active research in this field will be of direct relevance to future obstetric practice.
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              Maternal Lipids as Strong Determinants of Fetal Environment and Growth in Pregnancies With Gestational Diabetes Mellitus

              OBJECTIVE—To determine the contribution of maternal glucose and lipids to intrauterine metabolic environment and fetal growth in pregnancies with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS—In 150 pregnancies, serum triglycerides (TGs), cholesterol, free fatty acids (FFAs), glycerol, insulin, and glucose were determined in maternal serum and cord blood during the 3rd trimester. Maternal glucose values came from oral glucose tolerance testing and glucose profiles. Measurements of fetal abdominal circumference (AC) were performed simultaneously with maternal blood sampling and birth weight, and BMI and neonatal fat mass were obtained following delivery. RESULTS—Maternal TGs and FFAs correlated with fetal AC size (at 28 weeks: triglycerides, P = 0.001; FFAs, P = 0.02), and at delivery they correlated with all neonatal anthropometric measures (FFA: birth weight, P = 0.002; BMI, P = 0.001; fat mass, P = 0.01). After adjustment for confounding variables, maternal FFAs and TGs at delivery remained the only parameters independently related to newborns large for gestational age (LGA) (P = 0.008 and P = 0.04, respectively). Maternal FFA levels were higher in mothers with LGA newborns than in those with appropriate for gestational age (AGA) newborns (362.8 ± 101.7 vs. 252.4 ± 10.1, P = 0.002). Maternal levels of TGs, FFAs, and glycerol at delivery correlated with those in cord blood (P = 0.003, P = 0.004, and P = 0.005, respectively). Fetal triglyceride and cholesterol levels were negatively correlated with newborn birth weight (P = 0.001), BMI (P = 0.004), and fat mass (P = 0.001). TGs were significantly higher in small for gestational age (SGA) newborns compared with AGA or LGA newborns, while insulin-to-glucose ratio and FFAs were the highest in LGA newborns. CONCLUSIONS—In well-controlled GDM pregnancies, maternal lipids are strong predictors for fetal lipids and fetal growth. Infants with abnormal growth seem to be exposed to a distinct intrauterine environment compared with those with appropriate growth.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                31 July 2018
                2018
                : 9
                : 407
                Affiliations
                [1] 1Department of Medicine, The University of Melbourne , Melbourne, VIC, Australia
                [2] 2Department of Endocrinology, Austin Health , Melbourne, VIC, Australia
                [3] 3Mercy Hospital for Women, Mercy Health , Melbourne, VIC, Australia
                Author notes

                Edited by: Wei Bao, University of Iowa, United States

                Reviewed by: Melissa Irene March, University Hospitals Cleveland Medical Center, United States; Julianne Toohey, University of California, Irvine, United States

                *Correspondence: Elif I. Ekinci elif.ekinci@ 123456unimelb.edu.au

                This article was submitted to Diabetes, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2018.00407
                6079223
                30108547
                709792bf-6457-4813-a64f-4be1ed75ecb6
                Copyright © 2018 Nahavandi, Seah, Shub, Houlihan and Ekinci.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 March 2018
                : 29 June 2018
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 292, Pages: 25, Words: 17694
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                diabetes,pregnancy,macrosomia,birthweight,biomarkers
                Endocrinology & Diabetes
                diabetes, pregnancy, macrosomia, birthweight, biomarkers

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