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

• 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
• 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

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.

项目概要/摘要 儿童肥胖和神经发育障碍 (NDD) 的发病率在过去一段时间里迅速上升 内分泌干​​扰物 (EDC) 的生产和接触增加的时期，表明 这些环境暴露的可能病因作用。感兴趣的 EDCs 包括全氟烷基物质 (PFAS)、多溴二苯醚 (PBDE) 和当代有机磷酸酯阻燃剂 （OPFR）。尽管它们被广泛检测，但很少有研究描述子宫内暴露的影响 人类中这些 EDC 的研究较少，而研究相关机制途径的人就更少了。我们将 利用并扩大现有的两个大型种族和族裔多样化怀孕队列，以前瞻性地 研究子宫内 EDC 暴露与儿童肥胖和 NDD 的关系。其中第一个 自 2013 年以来，PETALS 队列已招募了 1,800 名女性，以调查苯酚暴露与 妊娠糖尿病和胎儿过度生长。第二个项目 (KPRB-PC) 已招募约 22,000 名女性 2010 年创建与妇女和儿童健康相关的研究资源。美国国立卫生研究院环境 对儿童健康结果的影响 (ECHO) 提供了延长随访和扩大研究范围的机会 这两个群体的工作。在UG3阶段，我们将重新联系并同意研究参与者、试点测试 我们提出的数据收集协议，并与 ECHO 合作伙伴合作开发多站点协议。期间 在 UH3 阶段，我们将跟踪 1,600 对母子，以下称为 ELEGANT 队列。我们将 评估 1,600 名孕妇生物样本的宫内 EDC 暴露，并对其进行临床评估 4 岁儿童的生长、肥胖和神经发育。我们的假设是子宫内暴露 EDC（即 PFAS、PBDE、OPFR）单独或组合使用会对儿童生长产生不利影响 （即 BMI）、肥胖（即脂肪量）和神经发育，可能通过共同途径。在我们的目标中， 我们建议： 1. 评估宫内单独或组合接触 EDC 是否相关 与儿童生长、肥胖和神经发育的关系，以及这些关联是否因儿童性别而异； 2. 评估是否营养过剩（膳食能量摄入高、孕前BMI高、妊娠期体重增加高） 和妊娠糖尿病）改变了子宫内 EDC 暴露与儿童生长、肥胖的关系 和神经发育； 3.评估宫内EDC暴露是否与代谢因素相关 （妊娠期的葡萄糖、胰岛素、瘦素和甲状腺激素水平）以及这些因素是否介导 子宫内 EDC 暴露与儿童生长、肥胖和神经发育之间的关联；和 4. 测量儿童 DNA 中的全基因组甲基化，以开发敏感且特异的儿童 DNA 甲基化 产前 EDC 暴露的标记，并阐明儿童 DNA 甲基化的潜在机制作用。我们的 当代妊娠队列及其子女的随访是对 ECHO 的宝贵补充 联盟将加强对儿童肥胖和 NDD 起源的了解。

项目成果

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.

• DOI: 10.1016/j.ijheh.2021.113694
• 发表时间: 2021-04
• 期刊: International journal of hygiene and environmental health
• 影响因子: 6
• 作者: Xiao S;Ngo AL;Mendola P;Bates MN;Barcellos AL;Ferrara A;Zhu Y
• 通讯作者: Zhu Y