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（由适用提供）：纽约大学医学院，伊拉斯mus大学医学中心和纽约州卫生署对PA-12-185做出了回应，建议研究邻苯二甲酸酯和邻苯二甲酸酯和双苯酚A（BPA）（BPA）与胎儿生长，体重，胰岛素抵抗，脂肪质量，脂肪质量和儿童血压的关系。 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 peroxysome proliferator- , a DEHP metabolite, activated receptors which play key roles in lipid and carbonhydrate metabolism, providing biologic plausibility for儿童肥胖和胰岛素抵抗中的DEHP代谢产物。 BPA用于制造用于涂上食物和卧室容器的聚碳酸酯树脂，已被发现产生肥胖和胰岛素抵抗的分子标志。过去对这些化学曝光和肥胖症的研究是横断面的，并且对年龄较大的儿童和青少年进行了研究，而DEHP代谢产物和BPA更有可能破坏生命早期发展的内分泌过程，并导致慢性热量失衡，从而导致肥胖。我们建议分析1431年R中的1431年母亲对的三个时间点的样本，这是一对Reation R，这是一项前瞻性的，纵向的多种族出生队列研究，在2002-2006之间纵向遵循9,778次妊娠，遵循9,778例出生日期。研究人群中的BPA（调整后的1.6'g Cr）和总DEHP代谢物（调整后的中位数88.4'g/g Cr）与NHANES样本一致，从而提高了研究结果对美国背景的适用性。 PI，L。Trasande是全国著名的儿童环境健康专家，也是第一项研究的第一作者，以确定环境化学化学物质与儿童期在全国代表性样本中的关联。拟议的研究还受益于R代的强大支持，其中包括经验丰富的儿科和围产期流行病学家，在研究早期研究心血管疾病和A. Burdorf方面具有很强的记录，他们为研究人群开发了标准化的胎儿生长曲线。该提案的主要优势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酯代谢物和BPA与体重，胰岛素抵抗和心血管风险的特定周期相关。分析将由纽约州卫生部Wadsworth Laboratories的K. Kannan进行，他在尿液中对邻苯二甲酸酯和BPA生物标志物的精确度量具有丰富的经验。拟议的工作努力挑战肥胖症预防范围的现有临床实践范式，应仅专注于改善能量平衡，从而可以认识到化学因素在环境中的作用，从而可以独立带来风险。