Endocrine Disrupting Chemicals, Thyroid Hormones, and Child Neurobehavior

 描述（由申请方提供）：神经发育依赖于甲状腺激素的作用，在发育的敏感期破坏该激素轴可能会增加临床疾病（如注意力缺陷/多动障碍或学习障碍）的风险。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，并可能对甲状腺激素和大脑发育产生不利影响。没有研究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大脑是否以及何时对这些早期生活暴露更敏感。我们将使用现有的356对母子的前瞻性队列来解决这个差距，这些母子从怀孕的第二个三个月一直跟踪到他们的孩子大约8岁。我们将使用婴儿胎粪样本、两份妊娠尿液样本和婴儿/儿童期多达六份尿液样本，全面评估产前和产后邻苯二甲酸酯、三氯生和BPA暴露。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岁、3岁、5岁和8岁时测量甲状腺激素水平。将对这些数据进行系统调查，以便：1）确定早期邻苯二甲酸酯、三氯生和BPA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、BPA暴露和母亲/儿童甲状腺激素浓度，以确定甲状腺激素是否介导化学品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志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期和儿童期多达8个尿液样本，重复的神经行为评估，对神经发育至关重要且对这些化学品暴露可能敏感的激素中间体，以及精确确定对这些化学品最敏感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普遍和可能改变的环境化学品暴露的毒性，并帮助制定有效的公共卫生干预措施，旨在减少大脑发育最敏感时期的暴露。

 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.