Early Life Exposure to Endocrine Disrupting Chemicals and Child Growth, Adiposity, and Neurodevelopment

生命早期接触内分泌干扰化学物质与儿童生长、肥胖和神经发育

基本信息

批准号：
10469410
负责人：
LISA A CROEN
金额：
$ 396.47万
依托单位：
KAISER FOUNDATION RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-21 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10469410
关键词：
4 year old Address Adverse effects Affect Behavioral Biological Biological Assay Body mass index California Chemicals Child Child Health Clinical Clinical Data Collection Consent DNA DNA Methylation Data Data Collection Detection Diet Disease Electronic Health Record Endocrine Disruptors Energy Intake Enrollment Environmental Exposure Environmental Health Etiology Exposure to Fatty acid glycerol esters Flame Retardants Follow-Up Studies Future Genetic Gestational Diabetes Glucose Growth Growth and Development function Health Human Individual Insulin Integrated Delivery of Health Care Intervention Knowledge Leptin Life Style Measures Mediating Mental Depression Metabolic Mothers Nature Neurodevelopmental Disorder Obesity Organophosphates Outcome Overnutrition Participant Pathway interactions Phase Phenols Physical activity Policies Poly-fluoroalkyl substances Pregnancy Pregnant Women Prevention strategy Production Protocols documentation Public Health Questionnaires Resources Role Site Stress System Testing Thyroid Hormones United States National Institutes of Health Woman Work clinical database cohort data collection site dietary early life exposure environmental chemical ethnic diversity excessive fetal growth follow-up genome wide methylation gestational weight gain in utero insight interest member methylation biomarker neurodevelopment obesity in children pilot test polybrominated diphenyl ether prenatal prenatal exposure prospective racial diversity sex

项目摘要

PROJECT SUMMARY/ABSTRACT The rapid rise in childhood obesity and neurodevelopment disorders (NDDs) in children has occurred over a period of increased manufacturing and exposure to endocrine disrupting compounds (EDCs), suggesting a possible etiologic role for these environmental exposures. EDCss of interest include perfluoroalkyl substances (PFASs), polybrominated diphenyl ethers (PBDEs), and contemporary organophosphate flame retardants (OPFRs). Despite their widespread detection, few studies have characterized the effects of in-utero exposure to these EDCs in humans, and even fewer have investigated associated mechanistic pathways. We will leverage and expand two large extant racially and ethnically diverse pregnancy cohorts to prospectively investigate the role of in-utero exposure to EDCs in relation to child obesity and NDDs. The first of these cohorts (PETALS) has enrolled 1,800 women since 2013 to investigate phenol exposure in relation to gestational diabetes and excessive fetal growth. The second (KPRB-PC) has enrolled ~22,000 women since 2010 to create a resource for studies related to women's and children's health. The NIH Environmental Influences on Child Health Outcomes (ECHO) provides an opportunity to extend follow-up and to expand the work of these two cohorts. During the UG3 phase, we will re-contact and consent study participants, pilot test our proposed data collection protocol, and work with ECHO partners to develop the multi-site protocol. During the UH3 phase, we will follow 1,600 mother-child pairs, hereafter referred to as the ELEGANT cohort. We will assess in-utero EDC exposures in biospecimens of 1,600 pregnant women and clinically evaluate their children at age 4 years for growth, adiposity, and neurodevelopment. Our hypothesis is that in-utero exposure to EDCs (i.e., PFASs, PBDEs, OPFRs), individually or in combination, have adverse effects on child growth (i.e. BMI), adiposity (i.e. fat mass), and neurodevelopment, possibly through common pathways. In our Aims, we propose to: 1. evaluate whether in-utero exposures to EDCs, individually or in combination are associated with child growth, adiposity, and neurodevelopment, and whether these associations vary by child sex; 2. evaluate whether overnutrition (high dietary energy intake, high pregravid BMI, high gestational weight gain and gestational diabetes) modifies the associations of in-utero exposure to EDCs and child growth, adiposity and neurodevelopment; 3. evaluate whether in-utero EDC exposures are associated with metabolic factors (pregnancy levels of glucose, insulin, leptin and thyroid hormones) and whether these factors mediate the association between in-utero exposure to EDCs and child growth, adiposity, and neurodevelopment; and 4. measure genome-wide methylation in child DNA, to develop sensitive and specific child DNA methylation markers of prenatal EDC exposure, and to illuminate potential mechanistic roles of child DNA methylation. Our contemporary pregnancy cohorts and follow-up of their children represent a valuable addition to the ECHO consortium and will enhance knowledge of the origins of childhood obesity and NDDs.

项目摘要/摘要儿童肥胖和神经发育障碍（NDDS）的迅速增长发生在增加制造和暴露于内分泌干扰化合物（EDC）的时期，这表明这些环境暴露可能的病因作用。感兴趣的EDCS包括全氟烷基物质（PFASS），多溴二苯基醚（PBDES）和当代有机磷酸盐阻燃剂（OPFR）。尽管它们广泛检测，但很少有研究表征了Utero暴露的影响这些EDC在人类中，甚至更少研究了相关的机械途径。我们将利用并扩大两个大型现存的种族和种族多样化的怀孕同伙调查与儿童肥胖症和NDD有关的UTERO内接触性EDC的作用。其中的第一个自2013年以来，队列（花瓣）已招募了1,800名女性妊娠糖尿病和过度的胎儿生长。自从第二个（KPRB-PC）已招收约22,000名妇女 2010年为与妇女和儿童健康有关的研究创造资源。 NIH环境对儿童健康成果的影响（ECHO）提供了扩展后续行动并扩展的机会这两个队列的工作。在UG3阶段，我们将重新接触和同意研究参与者，试点测试我们提出的数据收集协议，并与Echo Partners合作开发多站点协议。期间 UH3阶段，我们将跟随1,600对母子双子，以下称为优雅的队列。我们将评估1,600名孕妇的生物测量中UTERO内EDC暴露，并在临床上评估她们年龄4岁的儿童生长，肥胖和神经发育。我们的假设是接触向EDC（即PFASS，PBDE，OPFR）单独或组合对儿童的成长产生不利影响（即BMI），肥胖（即脂肪质量）和神经发育，可能是通过公共途径。在我们的目标中我们建议：1。评估UTERO内部对EDC的暴露是单独还是组合的随着儿童的成长，肥胖和神经发育，以及这些关联是否因儿童性别而异； 2。评估营养不良（高饮食能量摄入，高预盖型BMI，高妊娠体重增加和妊娠糖尿病）修改了utero内接触EDC和儿童生长的关联和神经发育； 3。评估UTERO内EDC暴露是否与代谢因素有关（葡萄糖，胰岛素，瘦素和甲状腺激素的怀孕水平）以及这些因素是否介导 UTERO内接触EDC与儿童生长，肥胖和神经发育之间的关联；和4。测量儿童DNA中全基因组甲基化，以发展敏感和特定的儿童DNA甲基化产前EDC暴露的标记，并阐明儿童DNA甲基化的潜在机械作用。我们的当代怀孕队列和孩子的随访代表了回声的宝贵补充财团将增强对儿童肥胖和NDD的起源的了解。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Prenatal air pollution exposure and neurodevelopment: A review and blueprint for a harmonized approach within ECHO.

DOI：
10.1016/j.envres.2020.110320
发表时间：
2021-05
期刊：
Environmental research
影响因子：
8.3
作者：
Volk HE;Perera F;Braun JM;Kingsley SL;Gray K;Buckley J;Clougherty JE;Croen LA;Eskenazi B;Herting M;Just AC;Kloog I;Margolis A;McClure LA;Miller R;Levine S;Wright R;Environmental influences on Child Health Outcomes
通讯作者：
Environmental influences on Child Health Outcomes

Erratum: "Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research".

勘误：“识别和优先考虑具有不确定暴露负担的化学品：生物监测和健康相关研究的机会”。

DOI：
10.1289/ehp6769
发表时间：
2020
期刊：
Environmental health perspectives
影响因子：
10.4
作者：
Pellizzari,EdoD;Woodruff,TraceyJ;Boyles,RebeccaR;Kannan,Kurunthachalam;Beamer,PalomaI;Buckley,JessieP;Wang,Aolin;Zhu,Yeyi;Bennett,DeborahH;(EnvironmentalinfluencesonChildHealthOutcomes)
通讯作者：
(EnvironmentalinfluencesonChildHealthOutcomes)

Household mold, pesticide use, and childhood asthma: A nationwide study in the U.S.