Endocrine Disrupting Chemicals, Thyroid Hormones, and Child Neurobehavior

 描述(由申请人提供)：神经发育依赖于甲状腺激素的作用，在发育的敏感时期，这一荷尔蒙轴的中断可能会增加临床疾病的风险，如注意力缺陷/多动障碍或学习障碍。邻苯二甲酸盐、三氯生和双酚A(BPA)暴露在孕妇和儿童中几乎是普遍的，可能会对甲状腺激素和大脑发育产生不利影响。没有研究前瞻性地将这些暴露与甲状腺激素和神经发育联系起来，以确定发育中的胎儿或儿童的大脑是否以及何时对这些早期生活暴露更敏感。我们将利用现有的356对母子对进行前瞻性队列来解决这一差距，这些母子对从怀孕中期开始跟踪调查，直到他们的孩子~8岁。我们将综合评估出生前和出生后邻苯二甲酸酯、三氯生和双酚A的暴露，使用婴儿粪便样本、两个妊娠尿样和最多六个婴幼儿/儿童尿样。从1-8岁开始反复评估儿童的认知能力和行为，并在怀孕期间、出生时以及1、3、5和~8岁测量甲状腺激素水平。将对这些数据进行系统调查，以：1)确定早期邻苯二甲酸酯、三氯生和双酚A暴露是否以及何时对1-8岁儿童的认知能力和行为产生不利影响；2)调查早期邻苯二甲酸酯、三氯生和双酚A暴露与母婴甲状腺激素浓度之间的关联，以确定甲状腺激素是否介导化学暴露和神经行为结果之间的关联。该项目的创新特征包括使用胎粪生物标记物进行详细的前瞻性暴露评估，以直接评估胎儿暴露和妊娠和儿童期间多达8个尿样，重复神经行为评估，对神经发育至关重要并可能对这些化学暴露敏感的荷尔蒙中间体，以及精确确定对这些化学物质最敏感的时期的复杂统计方法。这些数据将使公共卫生机构了解高度流行和潜在可改变的环境化学品暴露的毒性，并帮助针对旨在减少大脑发育最敏感时期暴露的有效公共卫生干预措施。

 DESCRIPTION (provided by applicant): Neurodevelopment is dependent on the action of thyroid hormones, and disruption of this hormonal axis during sensitive periods of development could increase the risk of clinical disorders like attention- deficit/hyperactivity disorder or learning disabilities. Phthalate, triclosan, and bisphenol A (BPA) exposures are nearly universal in pregnant women and children, and could adversely affect thyroid hormones and brain development. No studies have prospectively linked these exposures to both thyroid hormones and neurodevelopment to determine if and when the developing fetal or child brain is more sensitive to these early life exposures. We will address this gap using an existing prospective cohort of 356 mother-child pairs who have been followed from the 2nd trimester of pregnancy until their child is ~8 years old. We will comprehensively assess pre- and postnatal phthalate, triclosan, and BPA exposure using infant meconium samples, two pregnancy urine samples, and up to six urine samples from infancy/childhood. Child cognitive abilities and behavior have been repeatedly assessed from 1-8 years of age and thyroid hormone levels will be measured during pregnancy, at birth, and 1, 3, 5, and ~8 years of age. These data will be systematically investigated to: 1) determine if and when early life phthalate, triclosan, and BPA exposures have an adverse effect on children's cognitive abilities and behavior between 1-8 years of age and 2) investigate the association between early life phthalate, triclosan, and BPA exposure and maternal/child thyroid hormone concentrations to determine if thyroid hormones mediate the associations between chemical exposures and neurobehavioral outcomes. Innovative features of this project include detailed prospective exposure assessment using meconium biomarkers to directly assess fetal exposure and up to 8 urine samples during gestation and childhood, repeated neurobehavioral assessments, hormonal intermediates that are essential for neurodevelopment and potentially sensitive to these chemical exposures, and sophisticated statistical methods to pinpoint the period of maximum sensitivity to these chemicals. These data will inform public health agencies about the toxicity of highly prevalent and potentially modifiabl environmental chemical exposures and help target effective public health interventions aimed at reducing exposure during the most sensitive periods of brain development.