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

• 批准号: 8696589
• 负责人: Leonardo Trasande
• 金额: $ 60.89万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 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/8696589
• 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; Population Study; 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; cardiovascular risk factor; clinical practice; cohort; energy balance; environmental chemical; experience; fetal; 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; public health relevance; receptor; standardize measure; urinary

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.

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 对PA-12-185的反应，建议研究产前和儿童期邻苯二甲酸盐和双酚A(BPA)的暴露 儿童时期体重、胰岛素抵抗、脂肪质量、血压与胎儿生长发育的关系。迪-2- 邻苯二甲酸乙基己酯(DEHP)是一种高分子质量的邻苯二甲酸酯，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体增殖物的表达。 ，DEHP代谢物， 激活的受体在脂肪和碳水化合物代谢中发挥关键作用，提供了生物学上的可能性 用于儿童肥胖和胰岛素抵抗的DEHP代谢物。双酚A，用于制造 用于食品和饮料容器涂层的聚碳酸酯树脂已被发现可产生分子 肥胖和胰岛素抵抗的特征。过去对这些化学物质暴露与肥胖的研究一直是 横断面和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，并产生慢性热量失衡，从而导致 为了肥胖。我们建议分析孕期三个时间点和儿童时期两个时间点的样本 R世代1431对母婴，这是一项前瞻性的、纵向的多种族出生队列研究， 对2002-2006年间出生日期为9778例的孕妇进行了纵向跟踪调查。双酚A(调整中位数1.6g/g 铬)和总DEHP代谢物(调整后的中位数为88.4g/g铬)符合 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 全国著名的儿童环境健康专家和第一位作者，第一次研究发现 具有全国代表性的样本中环境化学物质与儿童肥胖的关系。这个 拟议的研究还得益于R世代的大力支持，包括主任(V.Jaddoe)和 经验丰富的儿科和围产期流行病学家，在研究糖尿病早期决定因素方面有很强的记录 心血管疾病和A.Burdorf，他为这项研究开发了标准化的胎儿生长曲线 人口。这项提议的一个主要优势是对怀孕期间三个时间点的尿样进行了分析， 这将允许检查特定时期的邻苯二甲酸酯代谢物和双酚A与身体的联系 体重、胰岛素抵抗和心血管风险。Wadsworth的K.Kannan将进行分析 纽约州卫生局的实验室，他对Precision有丰富的经验 尿液中邻苯二甲酸盐和双酚A生物标志物的测定。拟议的工作致力于挑战现有的 临床实践范例认为，肥胖预防只应侧重于改善能量平衡，而不是 一种也认识到环境中可能传递风险的化学因素的作用的方法 独立的。