Prenatal exposure to a mixture of EDCs, maternal thyroid function and child neuro

产前接触 EDC 混合物、母亲甲状腺功能和儿童神经功能

基本信息

批准号：
8913175
负责人：
Megan K Horton
金额：
$ 23.88万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8913175
关键词：
5 year old Address Animals Area Award Behavioral Biological Biological Markers Body Burden Brain Brain imaging Chemicals Child Childhood Competence Complement Complex Complex Mixtures Consent Data Development Discipline Doctor&apos s Degree Endocrine Disruptors Endocrine disruption Enrollment Environmental Exposure Environmental Health Environmental Tobacco Smoke Epidemiologic Studies Epidemiologist Epidemiology Evaluation Exposure to Functional Magnetic Resonance Imaging Goals Health Human Image Infant Development Institutes Life Cycle Stages Magnetic Resonance Imaging Manuscripts Maternal Exposure Measures Mediation Methodology Modeling Mothers New York Outcome Outcome Assessment Parents Perchlorates Pesticides Phase Postdoctoral Fellow Pregnancy Pregnancy Trimesters Pregnant Women Prospective Studies Public Health Schools Publications Research Research Personnel Research Proposals Research Training Risk Sampling Scanning Science Social Environment Solid Structure Testing Thyroid Function Tests Thyroid Gland Thyroid Hormones Toxic Environmental Substances Training Training Programs United States National Institutes of Health Universities Urine Work adverse outcome base behavior measurement bisphenol A career design early life exposure fetal follow-up imaging modality indexing interdisciplinary approach metropolitan neurobehavioral neurodevelopment neuropsychological novel offspring phenyl ether phthalates prenatal prenatal exposure prospective psychologic skill acquisition skills social tool

项目摘要

The overarching goal of the proposed research is to elucidate mechanisms relating prenatal exposure to complex mixtures of endocrine disrupting compounds (EDCs) to adverse neurodevelopment sequelae in children. Several classes of EDCs are known to interfere with thyroid function. Adequate thyroid function during pregnancy is a known determinant of successful fetal brain development and maternal thyroid hormone insufficiency is associated with adverse developmental outcomes in experimental animals and humans. Although several studies have evaluated risks associated with exposure to single classes of EDCs, these studies are limited in their evaluation of the complex mixtures within the human exposome and have not explored structural deficits in brain development leading to adverse outcomes. The proposed study attempts to address these limitations by developing a composite index of body burden to EDCs and by applying brain imaging methods to elucidate changes in brain structure and function following exposure. Specifically, we propose to evaluate whether prenatal exposure to a complex mixture of EDCs is associated with a) disrupted maternal thyroid function, b) changes in brain structure and function in children at 5 years of age and c) adverse neurobehavioral and psychological function in children at 5 years of age. The training and research will take place within the ongoing Metropolitan Study of Chemicals and Pregnancy Health (The Parent Study) (R21ES016610-01 PI. Wapner). This is a prospective study of 316 mothers enrolled during pregnancy. The parent study provides information key to the current proposal including prenatal exposure levels to polybrominated diphenyl ethers (PBDEs) and perchlorate, an assessment of maternal thyroid function during the 2nd trimester of pregnancy, and consent to contact mothers for prospective follow-up of their offspring. Additionally, stored biological samples are available for additional EDC analysis. During the initial K99 phase, Dr. Horton proposes to measure BPA and phthalates in stored maternal urine samples. In combination with the PBDE and perchlorate data, she will develop and apply sophisticated statistical methodologies to examine the impact of a complex mixture of EDCs on maternal thyroid function. Also during the K99 phase, Dr. Horton will receive intensive training in the use of brain imaging in epidemiological studies at the New York State Psychiatric Institute. During the transition to independence in the R00 phase of the award, she proposes to apply these trainings within the context of the parent study. Specifically she will follow 75 children, selected on exposure status, with brain imaging (anatomical and functional magnetic resonance imaging) and neurodevelopmental testing. Finally, Dr. Horton will apply these data to examine the complex relationships between prenatal EDC exposure, maternal thyroid function, children's brain structure and function and developmental outcomes using a meditational model. This K99/R00 proposal is a direct extension of the candidate's previous work in children's environmental health and a logical progression into a career as a life-course epidemiologist focused on environmental exposures. At the conclusion of this award, the candidate will have gained expertise in the emerging fields of chemical mixture analysis and brain imaging. The acquisition of these skills sets the candidate above other researchers by combining competence across several disciplines.

拟议研究的总体目标是阐明产前相关机制接触内分泌干扰化合物（EDC）的复杂混合物会产生不利影响儿童神经发育后遗症。已知几类 EDC 会干扰甲状腺功能。怀孕期间充足的甲状腺功能是成功的已知决定因素胎儿大脑发育和母亲甲状腺激素不足与不良反应有关实验动物和人类的发育结果。尽管多项研究表明评估了与接触单一类别 EDC 相关的风险，这些研究仅限于他们对人类暴露组内的复杂混合物进行了评估，但尚未探索大脑发育的结构性缺陷会导致不良后果。拟议的研究尝试通过制定 EDC 身体负担综合指数来解决这些局限性应用脑成像方法阐明脑结构和功能的变化接触。具体来说，我们建议评估产前是否暴露于复杂的混合物 EDC 与 a) 母体甲状腺功能紊乱、b) 大脑结构变化和 5 岁儿童的功能和 c) 不良的神经行为和心理功能 5 岁儿童。培训和研究将在正在进行的大都会化学品和化学品研究中进行怀孕健康（家长研究）（R21ES016610-01 PI. Wapner）。这是一项前瞻性研究共有 316 名怀孕期间的母亲参加。家长研究提供了当前的关键信息提案包括多溴二苯醚 (PBDE) 的产前暴露水平和高氯酸盐，妊娠第二个月期间母亲甲状腺功能的评估，以及同意联系母亲对其后代进行前瞻性随访。此外，储存的生物样品可用于额外的 EDC 分析。在最初的 K99 阶段，霍顿博士建议测量储存的母体尿液样本中的 BPA 和邻苯二甲酸盐。结合 PBDE 和高氯酸盐数据，她将开发和应用复杂的统计方法研究 EDC 的复杂混合物对母体甲状腺功能的影响。期间还 K99阶段，霍顿博士将接受脑成像在流行病学中的应用强化培训在纽约州精神病学研究所学习。在 R00 向独立过渡期间在颁奖阶段，她建议在家长研究的背景下应用这些培训。具体来说，她将跟踪 75 名儿童，这些儿童根据暴露状态进行选择，并进行脑成像（解剖学）和功能磁共振成像）和神经发育测试。最后，霍顿博士将应用这些数据来检查产前 EDC 暴露之间的复杂关系，母亲甲状腺功能、儿童大脑结构和功能以及发育结果冥想模型。该 K99/R00 提案是候选人之前在儿童领域工作的直接延伸环境健康和作为生命全程流行病学家的职业生涯的逻辑发展关于环境暴露。在该奖项结束时，候选人将获得化学混合物分析和脑成像等新兴领域的专业知识。收购这些技能通过结合多个方面的能力使候选人高于其他研究人员学科。