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

• 批准号: 8327189
• 负责人: Megan K Horton
• 金额: $ 12.31万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8327189
• 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' 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; Nervous System Physiology; New York; Outcome; Outcome Assessment; Parents; Perchlorates; Pesticides; Phase; Postdoctoral Fellow; Pregnancy; Pregnant Women; Principal Investigator; Prospective Studies; Public Health Schools; Publications; Research; Research Personnel; Research Proposals; Research Training; Risk; Risk Assessment; Sampling; Scanning; Science; Second Pregnancy Trimester; 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; public health relevance; skill acquisition; skills; social; tool

DESCRIPTION (provided by applicant) 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, the investigators 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, principal investigators-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 second 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. Public Health Relevance: This proposal aims to understand the relationship between prenatal exposure to thyroid disrupting compounds, maternal thyroid function, and neurologic function in offspring. Information generated through this research effort is essential to fill research gaps and inform human risk assessment.

描述（由申请人提供） 该研究的总体目标是阐明产前接触内分泌干扰化合物（EDC）的复杂混合物与儿童不良神经发育后遗症的相关机制。已知有几类 EDC 会干扰甲状腺功能。 怀孕期间充足的甲状腺功能是胎儿大脑成功发育的已知决定因素，而母体甲状腺激素不足与实验动物和人类的不良发育结果相关。 尽管有几项研究评估了与单一类别 EDC 暴露相关的风险，但这些研究仅限于对人类暴露组内复杂混合物的评估，并且没有探讨导致不良后果的大脑发育结构缺陷。拟议的研究试图通过开发 EDC 身体负担的综合指数并应用脑成像方法来阐明暴露后大脑结构和功能的变化来解决这些局限性。 具体来说，研究人员建议评估产前接触复杂的 EDC 混合物是否与 a) 母亲甲状腺功能紊乱、b) 5 岁儿童大脑结构和功能变化以及 c) 不良神经行为和心理功能有关。 5岁儿童。 培训和研究将在正在进行的大都会化学品与妊娠健康研究（家长研究）（R21ES016610-01，主要研究者 - Wapner）内进行。这是一项针对 316 名怀孕期间母亲的前瞻性研究。母体研究提供了当前提案的关键信息，包括多溴二苯醚 (PBDE) 和高氯酸盐的产前暴露水平、妊娠中期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，存储的生物样本可用于额外的 EDC 分析。在最初的 K99 阶段，Horton 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，她将开发并应用复杂的统计方法来检查 EDC 的复杂混合物对母亲甲状腺功能的影响。 同样在 K99 阶段，霍顿博士还将在纽约州精神病学研究所接受关于在流行病学研究中使用脑成像的强化培训。 在该奖项的 R00 阶段向独立过渡期间，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（解剖和功能磁共振成像）和神经发育测试。最后，Horton 博士将应用这些数据，使用冥想模型来检查产前 EDC 暴露、母亲甲状腺功能、儿童大脑结构和功能以及发育结果之间的复杂关系。 这项 K99/R00 提案是候选人之前在儿童环境健康方面工作的直接延伸，也是成为专注于环境暴露的生命全程流行病学家职业的合理发展。获得该奖项后，候选人将获得化学混合物分析和脑成像新兴领域的专业知识。通过结合多个学科的能力，获得这些技能使候选人高于其他研究人员。 公共健康相关性：该提案旨在了解产前暴露于甲状腺干扰化合物、母亲甲状腺功能和后代神经功能之间的关系。 通过这项研究工作产生的信息对于填补研究空白​​和为人类风险评估提供信息至关重要。