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      Maternal lipids and leptin concentrations are associated with large-for-gestational-age births: a prospective cohort study

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          Abstract

          The change in maternal lipid, leptin and adiponectin concentrations during pregnancy and infant birth weight (BW) is still poorly characterized. Thus, the aim of the study was to evaluate the association of maternal lipids, leptin and adiponectin throughout pregnancy with large-for-gestational-age (LGA) births and BW z-score. A prospective cohort of 199 mothers was followed during pregnancy in Rio de Janeiro, Brazil. The statistical analyses comprised multiple logistic and linear regression. Women delivered 36 LGA and 11 small-for-gestational-age newborns. HDL-c rate of change throughout pregnancy was negatively associated with BW z-score (β = −1.99; p = 0.003) and the delivery of a LGA newborn (OR = 0.02; p = 0.043). Pregnancy baseline concentration of log leptin was positively associated (OR = 3.92; p = 0.025) with LGA births. LDL-c rate of change throughout pregnancy was positively associated with BW z-score (β = 0.31; p = 0.004). Log triglycerides and log adiponectin were not significantly associated with BW z-score or LGA birth. In conclusion, a higher log leptin pregnancy baseline concentration and a lower HDL-c rate of change during pregnancy were associated with higher odds of having a LGA newborn. These maternal biomarkers are important to foetal growth and could be used in prenatal care as an additional strategy to screen women at risk of inadequate BW.

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          Gestational diabetes and pregnancy outcomes - a systematic review of the World Health Organization (WHO) and the International Association of Diabetes in Pregnancy Study Groups (IADPSG) diagnostic criteria

          Background Two criteria based on a 2 h 75 g OGTT are being used for the diagnosis of gestational diabetes (GDM), those recommended over the years by the World Health Organization (WHO), and those recently recommended by the International Association for Diabetes in Pregnancy Study Group (IADPSG), the latter generated in the HAPO study and based on pregnancy outcomes. Our aim is to systematically review the evidence for the associations between GDM (according to these criteria) and adverse outcomes. Methods We searched relevant studies in MEDLINE, EMBASE, LILACS, the Cochrane Library, CINHAL, WHO-Afro library, IMSEAR, EMCAT, IMEMR and WPRIM. We included cohort studies permitting the evaluation of GDM diagnosed by WHO and or IADPSG criteria against adverse maternal and perinatal outcomes in untreated women. Only studies with universal application of a 75 g OGTT were included. Relative risks (RRs) and their 95% confidence intervals (CI) were obtained for each study. We combined study results using a random-effects model. Inconsistency across studies was defined by an inconsistency index (I2) > 50%. Results Data were extracted from eight studies, totaling 44,829 women. Greater risk of adverse outcomes was observed for both diagnostic criteria. When using the WHO criteria, consistent associations were seen for macrosomia (RR = 1.81; 95%CI 1.47-2.22; p < 0.001); large for gestational age (RR = 1.53; 95%CI 1.39-1.69; p < 0.001); perinatal mortality (RR = 1.55; 95% CI 0.88-2.73; p = 0.13); preeclampsia (RR = 1.69; 95%CI 1.31-2.18; p < 0.001); and cesarean delivery (RR = 1.37;95%CI 1.24-1.51; p < 0.001). Less data were available for the IADPSG criteria, and associations were inconsistent across studies (I2 ≥ 73%). Magnitudes of RRs and their 95%CIs were 1.73 (1.28-2.35; p = 0.001) for large for gestational age; 1.71 (1.38-2.13; p < 0.001) for preeclampsia; and 1.23 (1.01-1.51; p = 0.04) for cesarean delivery. Excluding either the HAPO or the EBDG studies minimally altered these associations, but the RRs seen for the IADPSG criteria were reduced after excluding HAPO. Conclusions The WHO and the IADPSG criteria for GDM identified women at a small increased risk for adverse pregnancy outcomes. Associations were of similar magnitude for both criteria. However, high inconsistency was seen for those with the IADPSG criteria. Full evaluation of the latter in settings other than HAPO requires additional studies.
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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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              Adiponectin--a key adipokine in the metabolic syndrome.

              Adiponectin is a recently described adipokine that has been recognized as a key regulator of insulin sensitivity and tissue inflammation. It is produced by adipose tissue (white and brown) and circulates in the blood at very high concentrations. It has direct actions in liver, skeletal muscle and the vasculature, with prominent roles to improve hepatic insulin sensitivity, increase fuel oxidation [via up-regulation of adenosine monophosphate-activated protein kinase (AMPK) activity] and decrease vascular inflammation. Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in the liver. In contrast to other adipokines, adiponectin secretion and circulating levels are inversely proportional to body fat content. Levels are further reduced in subjects with diabetes and coronary artery disease. Adiponectin antagonizes many effects of tumour necrosis factor-alpha(TNF-alpha) and this, in turn, suppresses adiponectin production. Furthermore, adiponectin secretion from adipocytes is enhanced by thiazolidinediones (which also act to antagonize TNF-alpha effects). Thus, adiponectin may be the common mechanism by which TNF-alpha promotes, and the thiazolidinediones suppress, insulin resistance and inflammation. Two adiponectin receptors, termed AdipoR1 and AdipoR2, have been identified and these are ubiquitously expressed. AdipoR1 is most highly expressed in skeletal muscle and has a prominent action to activate AMPK, and hence promote lipid oxidation. AdipoR2 is most highly expressed in liver, where it enhances insulin sensitivity and reduces steatosis via activation of AMPK and increased peroxisome-proliferator-activated receptor alpha ligand activity. T-cadherin, which is expressed in endothelium and smooth muscle, has been identified as an adiponectin-binding protein with preference for HMW adiponectin multimers. Given the low levels of adiponectin in subjects with the metabolic syndrome, and the beneficial effect of the adipokine in animal studies, there is exciting potential for adiponectin replacement therapy in insulin resistance and related disorders.
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                Author and article information

                Contributors
                gilberto.kac@gmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                11 April 2017
                11 April 2017
                2017
                : 7
                : 804
                Affiliations
                [1 ]GRID grid.8536.8, Nutritional Epidemiology Observatory, , Department of Social and Applied Nutrition, Institute of Nutrition Josué de Castro, Rio de Janeiro Federal University, ; Rio de Janeiro, Brazil
                [2 ]GRID grid.13097.3c, Division of Women’s Health, , King’s College London, St Thomas’ Hospital, ; London, UK
                [3 ]GRID grid.411204.2, Public Health Department, , Federal University of Maranhão, ; São Luís, Brazil
                Article
                941
                10.1038/s41598-017-00941-y
                5429770
                28400574
                79a253f8-0615-4817-86fe-755b4f9b8c6d
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 19 October 2016
                : 20 March 2017
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