Prenatal Organochlorine Metabolites, Thyroid Function and Development

描述（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化合物的代谢物是否与a）不良发育有关（认知功能、身高、体重、身高体重，以及对于女性，初潮年龄），B）母体甲状腺功能的轻度缺陷，以及c）如果有的话，是否部分归因于在子宫内暴露于母体甲状腺激素的不足。我们还旨在描述代谢产物和母体化合物之间的关系，并检查代谢产物和孕妇甲状腺功能之间的关联。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年至1966年出生的儿童进行了纵向随访，这些儿童的母亲参加了凯泽基金会健康计划的加州奥克兰成员，并扩展了以前NIH资助的研究。产前血清已被适当冷冻和储存，可用于评估有机氯化合物代谢物的接触情况;已对妊娠期间有机氯化合物的接触情况和母体甲状腺功能进行了测量。从出生到17岁，这些儿童都有一系列的生长指标，5岁、9-11岁和15-17岁的标准化发育检查也是如此。拟议的有机氯接触措施和接触母亲甲状腺功能的措施（促甲状腺激素、游离甲状腺素和甲状腺过氧化物酶抗体）。统计分析将利用数据的重复测量结构来估计关联。分析将采用广义估计方程（GEE）方法进行重复测量，同时考虑潜在的混杂变量。我们将区分从婴儿期到青春期的产前有机氯代谢物暴露的影响。我们还将研究一种特定的机制：通过母体甲状腺功能。结果将充分描述产前暴露的影响，也将进一步了解亚临床母亲甲状腺激素缺乏症和儿童发育之间的关系。这一系列研究可能会导致产前干预。公共卫生相关性：我们将区分从婴儿期到青春期的产前有机氯代谢物暴露的影响。我们还将研究一种特定的机制：通过母体甲状腺功能。结果将充分描述产前暴露的影响，也将进一步了解亚临床母亲甲状腺激素缺乏症和儿童发育之间的关系。这一系列研究可能会导致产前干预。

DESCRIPTION (provided by applicant): The overall goal of this project is to assess whether exposure to metabolites of 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. We also aim to describe the relationships between the metabolites and parent compounds and to examine the associations between the metabolites and thyroid function in the pregnant women. 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 and expands upon previous NIH funded research. Prenatal sera has been appropriately frozen and stored, and are available to assess exposure to the metabolites of organochlorine compounds; exposure to organochlorine compounds and maternal thyroid function during pregnancy has already been measured. 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, and thyroid peroxidase antibodies). 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 metabolite 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. PUBLIC HEALTH RELEVANCE: We will distinguish effects of prenatal organochlorine metabolite 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.