Phthalates, BPA, Trajectories of In and Ex Utero Growth and Cardiometabolic Risks

邻苯二甲酸盐、BPA、宫内和宫外生长轨迹以及心脏代谢风险

基本信息

批准号：
9043893
负责人：
Leonardo Trasande
金额：
$ 53.81万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-02 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9043893
关键词：
19 year old Academic Medical Centers Adolescence Adolescent Age Age-Years Air Beverages Biological Biological Markers Birth Birth Weight Blood Pressure Body mass index Cardiovascular Diseases Chemical Exposure Chemicals Child Childhood Chronic Cohort Studies Cosmetics Cross-Sectional Studies Data Data Analyses Date of birth Development Diabetes Mellitus Diet Diethylhexyl Phthalate Dust Elderly Endocrine Environment Environmental Health Epidemiologist Esters Exposure to Fatty acid glycerol esters Femur Fetal Growth Food Food Processing Future Generations Gestational Age Growth Health Infant Insulin Insulin Resistance Intervention Laboratories Length Life Life Expectancy Liquid substance Measurement Metabolism Modeling Molecular Molecular Weight Mothers National Health and Nutrition Examination Survey New York Nursery Schools Obesity Overweight Perinatal Perinatal Exposure Peroxisome Proliferator-Activated Receptors Peroxisome Proliferators Physical activity Plant Resins Play Pregnancy Process Randomized Controlled Trials Reducing diet Risk Risk Factors Role Sampling Scanning School-Age Population Solid Specificity Specimen Time Urine Weight Weight maintenance regimen Woman Work base bisphenol A carbohydrate metabolism cardiometabolic risk cardiovascular risk factor clinical practice cohort energy balance environmental chemical experience fetal fetal bisphenol-A exposure fetal programming improved in utero lifestyle factors lipid metabolism medical schools mono-(2-ethylhexyl)phthalate obesity in children obesity prevention phthalates polycarbonate postnatal prenatal prospective receptor standardize measure study population urinary

项目摘要

DESCRIPTION (provided by applicant): NYU School of Medicine, Erasmus University Medical Center and New York State Department of Health respond to PA-12-185, proposing to study prenatal and childhood phthalate and bisphenol A (BPA) exposures in relationship to fetal growth, body mass, insulin resistance, fat mass and blood pressure in childhood. Di-2- ethylhexylphthalate (DEHP) is a high-molecular weight phthalate ester commonly found in processed foods, and mono-(2-ethylhexyl) phthalate increases expression of three peroxisome proliferator- , a DEHP metabolite, activated receptors which play key roles in lipid and carbohydrate metabolism, providing biological plausibility for DEHP metabolites in childhood obesity and insulin resistance. BPA, which is used to manufacture polycarbonate resin used to coat food and beverage containers, has been found to produce molecular hallmarks of obesity, and insulin resistance. Past studies of these chemical exposures and obesity have been cross-sectional and of older children and adolescents, whereas DEHP metabolites and BPA are more likely to disrupt developmental endocrine processes earlier in life and produce the chronic caloric imbalance that leads to obesity. We propose to analyze samples from three timepoints in pregnancy and two in childhood from 1431 mother-infant pairs in Generation R, a prospective, longitudinal multi-ethnic birth cohort study which has longitudinally followed 9,778 pregnancies with birth dates between 2002-2006. BPA (adjusted median 1.6 �g/g Cr) and total DEHP metabolites (adjusted median 88.4 �g/g Cr) in the study population are consistent with NHANES samples, increasing applicability of study findings to the US context. The PI, L. Trasande, is a nationally renowned expert in children's environmental health and first author on the first study to identify an association of an environmental chemical with childhood obesity in a nationally representative sample. The proposed study also benefits from strong support from Generation R, including the Director (V. Jaddoe), an experienced pediatric and perinatal epidemiologist with a strong record in studying early determinants of cardiovascular disease and A. Burdorf, who has developed standardized fetal growth curves for the study population. A major strength of this proposal is analysis of urine samples from three timepoints in pregnancy, which will permit examination of period-specific associations of phthalate metabolites and BPA with body mass, insulin resistance and cardiovascular risks. Analyses will be performed by K. Kannan at Wadsworth Laboratories of the New York State Department of Health, who has deep experience with precise measurement of phthalate and BPA biomarkers in urine. The proposed work endeavors to challenge existing clinical practice paradigms that obesity prevention should focus only on improved energy balance to an approach that also recognizes the role of chemical factors in the environment that may impart risk independently.

描述（由申请人提供）：纽约大学医学院、伊拉斯姆斯大学医学中心和纽约州卫生部对 PA-12-185 做出回应，提议研究产前和儿童期邻苯二甲酸盐和双酚 A (BPA) 暴露与胎儿生长的关系、体重、胰岛素抵抗、脂肪量和儿童血压邻苯二甲酸二-2-乙基己酯 (DEHP) 是一种高分子量邻苯二甲酸酯。常见于加工食品中，邻苯二甲酸单（2-乙基己基）酯可增加三种过氧化物酶体增殖物（一种 DEHP 代谢物）的表达，激活在脂质和碳水化合物代谢中起关键作用的受体，为 DEHP 代谢物在儿童肥胖和胰岛素中的作用提供生物学依据用于制造用于涂覆食品和饮料容器的聚碳酸酯树脂的 BPA 已被发现会产生肥胖和胰岛素抵抗的分子特征。已经针对年龄较大的儿童和青少年进行了横断面研究，而 DEHP 代谢物和 BPA 更有可能扰乱生命早期的发育内分泌过程，并产生导致肥胖的慢性热量失衡。我们建议分析怀孕和怀孕期间三个时间点的样本。 R 世代的 1431 对母婴中，有两个处于童年时期，这是一项前瞻性纵向、多种族出生队列研究，纵向跟踪了 9,778 名出生日期介于2002-2006 年，研究人群中的 BPA（调整中位数 1.6 µg/g Cr）和总 DEHP 代谢物（调整中位数 88.4 µg/g Cr）与 NHANES 样本一致，增加了研究结果在美国环境中的适用性。 L. Trasande 是全国知名的儿童环境健康专家，也是第一项确定环境化学物质与儿童期之间关系的研究的第一作者拟议的研究还得益于 R 一代的大力支持，包括主任 (V. Jaddoe)，一位经验丰富的儿科和围产期流行病学家，在研究心血管疾病的早期决定因素方面拥有丰富的记录。他为研究人群制定了标准化的胎儿生长曲线，该提案的一个主要优点是分析怀孕三个时间点的尿液样本，这将允许检查邻苯二甲酸盐代谢物和 BPA 与体重、胰岛素抵抗的特定时期的关联。分析将由纽约州卫生部沃兹沃斯实验室的 K. Kannan 进行，他在精确测量尿液中的邻苯二甲酸盐和 BPA 生物标志物方面拥有丰富的经验。肥胖预防应仅关注改善能量平衡，并采取一种方法，该方法还应认识到环境中可能独立带来风险的化学因素的作用。