Pre- and Postnatal PBDE Exposure, Thyroid Hormones, and Neurodevelopment

描述（由申请人提供）：实验证据表明，发育过程中接触多溴二苯醚会破坏甲状腺激素功能，具有神经毒性，导致学习和行为缺陷。少量的流行病学研究同样表明但并没有证实这些联系，每项研究都有很大的局限性。这些关系还有待在人类研究中进行检验，该研究可以：1）检查多溴二苯醚暴露对整个大脑发育窗口期的认知和行为结果的纵向影响（从妊娠期到青春期）; 2）确定多溴二苯醚暴露对甲状腺激素的影响，作为整个儿童期多溴二苯醚诱导神经毒性的独立效应或媒介。在本申请中要检验的中心假设是， 产前和产后接触多溴二苯醚会改变儿童时期的甲状腺激素循环，从而影响认知和行为发育指数。我们将在哥伦比亚儿童环境健康中心的纵向出生队列研究的现有基础设施内评估这一假设。本研究对居住在纽约市市中心社区的350名儿童从出生到12岁的化学和社会环境进行了表征，并对儿童认知、行为和甲状腺激素状态进行了详细的评估。通过测定三个发育时间点外周血中的多溴联苯醚含量，（出生、2-3岁和5-7岁），我们将在3-5岁、7- 9岁和10-11岁的儿童中实现以下具体目标：1）确定多溴二苯醚接触是否影响儿童认知发育（包括学习、工作记忆和空间记忆）; 2）评估多溴联苯醚暴露对儿童行为的影响（包括多动症、注意力和社会问题）; 3）评估多溴二苯醚接触是否影响甲状腺功能，以及甲状腺激素紊乱是否介导多溴二苯醚接触与儿童认知发展和行为之间的关联。这项研究是创新的，因为它填补了现有流行病学文献中的几个重要空白， 阻碍了我们描述整个儿童时期多溴二苯醚暴露对神经发育的纵向影响的能力。通过评估美国一个大型的这项基于纵向队列研究的研究将提供多溴联苯醚对人类神经毒性的“指纹”，提供证据，说明或反驳甲状腺激素紊乱的作用。虽然所有含多溴二苯醚产品的生产计划于2013年在美国逐步淘汰，但我们预计，由于其持久性，多溴二苯醚暴露将在此后通过住宅和饮食水库持续多年。了解多溴二苯醚的指纹将使我们能够很容易地将其影响与其他潜在的神经毒性环境暴露区分开来。这些信息将为关于如何最好地管理这些和其他无处不在的环境污染物的紧迫和持续的政策辩论提供信息。

DESCRIPTION (provided by applicant): Experimental evidence indicates that developmental exposure to polybrominated diphenyl ethers (PBDEs) disrupts thyroid hormone function and is neurotoxic, leading to deficits in learning and behavior. A small number of epidemiologic studies, each with significant limitations, similarly suggest but do not confirm these associations These relationships have yet to be tested in a human study that can 1) examine the longitudinal impact of PBDE exposure on cognitive and behavioral outcomes throughout the window of brain development (from gestation through adolescence); and 2) determine the impact of PBDE exposure on thyroid hormones as an independent effect or mediator of PBDE-induced neurotoxicity throughout childhood. The central hypothesis to be tested in this application is that both prenatal and postnatal exposure to PBDEs alters circulating thyroid hormones during childhood, thereby influencing cognitive and behavioral developmental indices. We will evaluate this hypothesis within the existing infrastructure of the Columbia Center for Children's Environmental Health's longitudinal birth cohort study. This study has characterized the chemical and social environments of 350 children, residing in inner-city communities of New York City, from birth through age 12 and has conducted detailed assessments of child cognition, behavior, and thyroid hormone status longitudinally throughout childhood. By measuring PBDEs in peripheral blood collected at three developmental time points (birth, ages 2-3, and 5-7 years), we will pursue the following specific aims in children at ages 3-5, 7- 9, and 10-11: 1) determine whether PBDE exposure affects child cognitive development (including learning, working memory and spatial memory); 2) evaluate whether PBDE exposure affects child behavior (including hyperactivity, attention and social problems); and 3) assess whether PBDE exposure affects thyroid function and if thyroid hormone disruption mediates associations between PBDE exposure and child cognitive development and behavior. The proposed research is innovative because it fills several important gaps in the existing epidemiologic literature that have thus far impeded our ability to characterize the longitudinal impact of PBDE exposure occurring throughout childhood on neurodevelopment over time. By evaluating the neurotoxic effects of both pre- and postnatal PBDE exposure in a large, U.S.-based longitudinal cohort study, this study will provide a "fingerprint" of PBDE-induced neurotoxicity in humans, supplying evidence that will implicate or refute the role of thyroid hormone disruption. While the production of all PBDE-containing products is slated to be phased out in the U.S. as of 2013, we anticipate that due to its persistence, PBDE exposure will continue for many years thereafter through residential and dietary reservoirs. Understanding the PBDE fingerprint will allow us to readily distinguish its effects from other potentially neurotoxic environmental exposures. This information will inform the urgent and ongoing policy debate about how best to regulate these and other ubiquitous environmental pollutants.