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: 10745230
• 负责人: LISA A CROEN
• 金额: $ 311.29万
• 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 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10745230
• 关键词: Address; Adverse effects; Affect; Age; Appetite Regulation; Behavior; Behavioral; Body fat; Body mass index; Breast Feeding; Child; Child Health; Childhood; Clinical Research; Conceptions; DNA Methylation; Data; Development; Diabetes Mellitus; Diet and Nutrition; Disease; Emotional; Endocrine Disruptors; Energy Intake; Enrollment; Environmental Impact; Equity; Esters; Ethnic Population; Exposure to; Flame Retardants; Future; Geographic Locations; Gestational Diabetes; Growth; Growth and Development function; Health; Health behavior; Human; Individual; Institution; Intervention; Joints; Lead; Leptin; Life Style; Longevity; Mediating; Mental Depression; Mothers; Obesity; Organophosphates; Outcome; Overnutrition; Participant; Pathway interactions; Phase; Physical activity; Policies; Poly-fluoroalkyl substances; Prevention strategy; Process; Protocols documentation; Psychosocial Factor; Quality Control; Race; Recommendation; Research; Research Personnel; Role; Science; Serum; Sleep; Stress; Unhealthy Diet; autism spectrum disorder; career; cohort; cost; dietary; disadvantaged background; early life exposure; environmental chemical; epigenetic marker; ethnic diversity; evidence base; experience; follow-up; gestational weight gain; member; metabolomics; neurodevelopment; obesity in children; perceived discrimination; personalized intervention; postnatal; prenatal; prenatal exposure; prenatal health; racial diversity; racial population; residential segregation; response; sex assigned at birth; social health determinants; trait

PROJECT SUMMARY/ABSTRACT We propose continued follow-up of our large, racially/ethnically diverse ECHO ELEGANT cohort (n=2130) and to lead collaborative ECHO Cohort science. Our scientific aims focus on child obesity and adverse neurodevelopment, two common and increasingly prevalent conditions. Our comprehensive planned analyses take advantage of the core longitudinal data collected via the ECHO Cohort Protocol during the initial phase and the new phase. In Aim 1, we will assess the role of in-utero exposure to endocrine disrupting compounds (EDC) on child growth (growth trajectory), adiposity (body fat mass), obesity (body mass index [BMI]) and neurodevelopment (autism, autism-related traits, and emotional-behavioral development [ND]), by addressing solution oriented scientific questions that may promote precision interventions, practice recommendations and policies. We will clarify the effects of two understudied classes of EDCs (perfluoroalkyl substances (PFAS) and contemporary organophosphate ester flame retardants (OPE)) and increase understanding of real-world exposure scenarios by examining individual and joint effects. In Aim 2, we will clarify the joint effects of multiple maternal prenatal overnutrition factors (high dietary energy intake/poor diet quality, high pre- conception BMI, excessive gestational weight gain, gestational diabetes/diabetes) on child growth, adiposity, obesity, and ND. While likely to co-occur, human studies on their joint effects on childhood obesity and ND are sparse. Since child growth and development are dynamic processes, we will address the proposed associations at different ages of the child. Our hypotheses are that prenatal exposure to EDCs and maternal overnutrition factors adversely affect child growth, adiposity, obesity and ND by mechanistic pathways (metabolomics, DNA methylation), and that maternal prenatal and child lifestyle behaviors, psychosocial factors, social determinants of health, and sex assigned at birth may moderate these effects. In Aim 3 we will maximize retention of our existing ECHO participants by implementing evidence-based strategies focused on engaging diverse groups in clinical research and implementing the ECHO Cohort Protocol applying systematic quality control approaches and best practices. Our experienced research team is very diverse, including investigators from historically underrepresented racial and ethnic groups, disadvantaged backgrounds, different career stages, multiple scientific fields, geographic locations, and institutions. We are committed to providing equitable opportunities for all members of our research team to contribute to all aspects of our proposed project and assure that they will have equal opportunity to be involved in the new ECHO phase. Our continued involvement in ECHO provides an unparalleled opportunity to further understanding of the developmental origins of child obesity and neurodevelopment and inform future interventions, prevention strategies and policies to reduce the burden of these common and costly childhood disorders and possibly their long-term impact on health across the lifespan.

项目总结/摘要 我们建议继续随访我们的大型、种族/民族多样化的ECHO ELEGANT队列（n=2130） 并领导ECHO队列科学合作。我们的科学目标集中在儿童肥胖和不良 神经发育，两种常见且日益普遍的情况。我们全面的计划分析 利用初始阶段通过ECHO队列方案收集的核心纵向数据 新的阶段。在目标1中，我们将评估子宫内暴露于内分泌干扰化合物的作用 (EDC)对儿童生长（生长轨迹）、肥胖（体脂量）、肥胖（体重指数[BMI]）和 神经发育（自闭症，自闭症相关特征和情感行为发育[ND]），通过解决 以解决问题为导向的科学问题，可以促进精确的干预，实践建议， 施政纲要而我们将阐明两类未充分研究的内分泌干扰物（全氟烷基物质（PFAS）和 现代有机磷酸酯阻燃剂（OPE）），并增加对现实世界的了解 通过检查个体和联合效应来确定暴露情景。在目标2中，我们将阐明以下方面的联合影响： 多种母亲产前营养过剩因素（高膳食能量摄入/饮食质量差，高产前 怀孕BMI，妊娠期体重增加过多，妊娠期糖尿病/糖尿病）对儿童生长，肥胖， 肥胖和ND。虽然可能同时发生，但关于它们对儿童肥胖和ND的联合影响的人类研究仍在继续。 稀疏。由于儿童的成长和发展是一个动态的过程，我们将讨论建议的 不同年龄段的孩子。我们的假设是，产前暴露于内分泌干扰物和母亲 营养过剩因素通过机械途径对儿童生长发育、肥胖、肥胖和ND产生不利影响 （代谢组学，DNA甲基化），母亲产前和儿童的生活方式行为，心理社会 健康的社会决定因素和出生时的性别分配可能会缓和这些影响。在目标3中， 通过实施以证据为基础的战略，最大限度地保留我们现有的ECHO参与者，重点是 让不同的群体参与临床研究，并实施ECHO队列方案， 质量控制方法和最佳做法。我们经验丰富的研究团队非常多样化，包括 来自历史上代表性不足的种族和民族群体，弱势背景， 不同的职业阶段，多个科学领域，地理位置和机构。我们致力于 为我们研究团队的所有成员提供公平的机会，为我们的各个方面做出贡献。 他们将有平等的机会参与新的ECHO阶段。我们 继续参与欧共体人道处提供了一个无与伦比的机会，以进一步了解 儿童肥胖和神经发育的发展起源，并为未来的干预措施，预防 战略和政策，以减少这些常见的和昂贵的儿童疾病的负担， 它们对整个生命周期健康的长期影响。