Prenatal organochlorines, thyroid, and development

描述(由申请人提供)：该项目的总体目标是评估怀孕期间接触内分泌干扰物是否与a)出生时、幼儿早期、童年中期和青春期的后代发育不良(认知功能、身高、体重、身高体重以及女性的月经初潮年龄)有关，b)母亲甲状腺功能轻度缺陷，以及c)不良发育结果是否部分归因于在子宫内接触母亲甲状腺激素的不足。 这项拟议的研究利用了儿童健康与发展研究的数据，该研究对1959至1966年间出生的儿童进行了纵向跟踪，这些儿童的母亲在加利福尼亚州奥克兰参加了凯撒基金会健康计划。产前血清已适当冷冻和储存，可用于评估怀孕期间有机氯化合物的暴露情况和母亲的甲状腺功能。从出生到17岁的同一批儿童可以进行一系列的发育测量，5岁、9-11岁和15-17岁的标准化发育检查也是如此。有机氯暴露的拟议措施和母亲甲状腺功能的暴露措施(促甲状腺激素、游离甲状腺素、甲状腺过氧化物酶抗体和转甲状腺素--一种负责运输甲状腺激素的蛋白质)。统计分析将利用数据的重复测量结构来估计关联。分析将使用广义估计方程(GEE)方法进行重复测量，并考虑潜在的混杂变量。 我们将区分产前有机氯暴露的影响，从婴儿期到青春期。我们还将研究一种特定的机制：通过母体甲状腺功能。结果将全面描述产前暴露的影响，并将进一步了解亚临床母亲甲状腺激素缺乏与儿童发育之间的关系。这一系列研究可能导致产前干预。

DESCRIPTION (provided by applicant): The overall goal of this project is to assess whether exposure to endocrine disrupting compounds during pregnancy is associated with a) adverse development (cognitive function, height, weight, weight for height, and for females, age at menarche) in the offspring at birth, early childhood, middle childhood, and adolescence, b) mild deficiencies in maternal thyroid function, and c) whether adverse developmental findings, if any, are attributed in part to deficiencies in exposure to maternal thyroid hormone in utero. The proposed study draws on data from the Child Health and Development Study, a longitudinal follow up of children born between 1959 and 1966 to mothers enrolled in the Oakland, California membership of the Kaiser Foundation Health Plan. Prenatal sera has been appropriately frozen and stored, and are available to assess both exposure to organochlorine compounds and maternal thyroid function during pregnancy. Serial measures of growth are available in the same children from birth to age 17 years, as are standardized developmental examinations at ages 5, 9-11, and 15-17. The proposed measures of organochlorine exposure and exposure to measures of maternal thyroid function (thyroid stimulating hormone, free thyroxine, thyroid peroxidase antibodies and transthyretin - a protein responsible for the transport of thyroid hormone). Statistical analyses will estimate associations taking advantage of the repeated measures structure of the data. The analyses will employ generalized estimating equations (GEE) methods for repeated measures, taking account of potentially confounding variables. We will distinguish effects of prenatal organochlorine exposures from infancy through adolescence. We will also investigate a specific mechanism: via maternal thyroid function. Results will fully describe the effects of prenatal exposure and will also further knowledge about the relation between subclinical maternal thyroid hormone deficiency and childhood development. This line of research could lead to prenatal interventions.