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

项目摘要/摘要 我们建议继续对我们庞大的、不同种族/民族的ECHO优雅队列(n=2130)进行随访。 并领导合作的回声队列科学。我们的科学目标是关注儿童肥胖和不良反应 神经发育，两种常见且日益普遍的疾病。我们全面的计划分析 利用在初始阶段通过回声队列协议收集的核心纵向数据 和新的阶段。在目标1中，我们将评估宫内暴露于内分泌干扰物的作用。 (EDC)关于儿童生长(生长轨迹)、肥胖(身体脂肪质量)、肥胖(身体质量指数[BMI])和 神经发育(自闭症、自闭症相关特征和情绪行为发育[ND])，通过解决 以解决方案为导向的科学问题，可促进精确干预、实践建议和 政策。我们将阐明两类未被研究的EDCs(全氟烷基物质(PFAS)和 当代有机磷酸酯阻燃剂(OPE))和增加对现实世界的理解 通过检查单独的和联合的影响来确定暴露场景。在目标2中，我们将阐明 多种孕产妇产前营养过剩因素(饮食能量摄入量高/饮食质量差，产前营养过剩) 怀孕体重指数、妊娠期体重过度增加、妊娠期糖尿病/糖尿病)对儿童生长发育、肥胖症、 肥胖和ND。虽然很可能同时发生，但关于它们对儿童肥胖症和ND的联合影响的人类研究是 稀疏。由于儿童的成长和发展是动态的过程，我们将讨论拟议的 在不同年龄的孩子之间的联系。我们的假设是产前接触内分泌细胞和母体 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)，以及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分配的性别可能会缓和这些影响。在《目标3》中，我们将 通过实施注重以下方面的循证战略，最大限度地留住我们现有的ECO参与者 动员不同群体参与临床研究并应用系统实施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 调查人员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 建议的项目，并确保他们将有平等的机会参与新的回应阶段。我们的 继续参与ECHO提供了一个无与伦比的机会来进一步了解 儿童肥胖和神经发育的发育起源，并为未来的干预和预防提供信息 减轻这些常见且代价高昂的儿童疾病负担的战略和政策，并可能 它们对人一生中健康的长期影响。

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.