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

项目摘要 纽约大学医学院、伊拉斯谟大学医学中心和纽约州卫生部 回应PA-12-185，建议研究产前和儿童邻苯二甲酸酯和双酚A（BPA）暴露 与胎儿生长、体重、胰岛素抵抗、脂肪量和儿童期血压的关系。地-2- 邻苯二甲酸乙基己酯（DEHP）是一种常见于加工食品中的高分子量邻苯二甲酸酯， 和单-（2-乙基己基）邻苯二甲酸酯增加三种过氧化物酶体增殖物的表达， ，一种DEHP代谢物， 激活受体，在脂质和碳水化合物代谢中发挥关键作用，提供生物相容性 儿童肥胖和胰岛素抵抗中的DEHP代谢物。BPA，用于制造 已发现用于涂覆食品和饮料容器的聚碳酸酯树脂产生分子 肥胖和胰岛素抵抗的标志。过去对这些化学物质暴露和肥胖的研究一直是 年龄较大的儿童和青少年，而DEHP代谢物和BPA更有可能 在生命早期破坏发育的内分泌过程，并产生慢性热量不平衡， 到肥胖。我们建议分析来自妊娠期三个时间点和儿童期两个时间点的样本， R世代的1431对母婴对，这是一项前瞻性、纵向多种族出生队列研究， 在2002年至2006年期间，纵向跟踪了9，778例出生日期的妊娠。BPA（调整后的中位数为1.6 μ g/g Cr）和总DEHP代谢物（校正中位数88.4 μ g/g Cr）与以下结果一致： NHANES样本，增加了研究结果对美国背景的适用性。PI，L。Trasande是一个 全国知名的儿童环境健康专家和第一位研究报告的作者， 在全国代表性样本中，环境化学物质与儿童肥胖症的关联。的 拟议的研究也受益于R世代的大力支持，包括主任（V. Jaddoe）， 经验丰富的儿科和围产期流行病学家，在研究早期决定因素方面有很好的记录。 心血管疾病和A. Burdorf博士为这项研究开发了标准化的胎儿生长曲线 人口该建议的一个主要优点是分析怀孕三个时间点的尿样， 这将允许检查邻苯二甲酸酯代谢物和BPA与身体的特定时期的关联 体重、胰岛素抵抗和心血管风险。分析将由K进行。坎南在沃兹沃斯 纽约州卫生部的实验室，他对精确的 测量尿液中的邻苯二甲酸酯和BPA生物标志物。拟议的工作努力挑战现有的 临床实践范例，肥胖预防应该只关注改善能量平衡， 也认识到环境中可能带来风险的化学因素的作用的方法 独立地。

Project Summary 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.