Prenatal Organochlorine Metabolites, Thyroid Function and Development

描述（由申请人提供）：本项目的总体目标是评估怀孕期间暴露于内分泌干扰化合物代谢物是否与以下因素有关：a)子女出生时、幼儿期、中期和青春期的不良发育（认知功能、身高、体重、体重与身高之比，以及女性的初潮年龄）；b)母亲甲状腺功能轻度缺陷；c)是否有不良发育发现（如果有的话）；部分原因是在子宫内暴露于母体甲状腺激素不足。我们还旨在描述代谢物与母体化合物之间的关系，并检查代谢物与孕妇甲状腺功能之间的关系。这项提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年间出生的孩子进行了纵向跟踪调查，这些孩子的母亲都是加州奥克兰凯撒基金会健康计划的成员，并扩展了之前由美国国立卫生研究院资助的研究。产前血清已适当冷冻和储存，可用于评估暴露于有机氯化合物代谢物；在怀孕期间暴露于有机氯化合物和母亲的甲状腺功能已经被测量。从出生到17岁，可以对同一儿童进行一系列的生长测量，以及5岁、9-11岁和15-17岁的标准化发育检查。建议的有机氯暴露测量和暴露于母体甲状腺功能测量（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，并考虑到潜在的混杂变量。我们将区分从婴儿期到青春期产前有机氯代谢物暴露的影响。我们还将研究一个特定的机制：通过母亲的甲状腺功能。结果将充分描述产前暴露的影响，并将进一步了解亚临床母体甲状腺激素缺乏与儿童发育之间的关系。这一系列的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。我们还将研究一个特定的机制：通过母亲的甲状腺功能。结果将充分描述产前暴露的影响，并将进一步了解亚临床母体甲状腺激素缺乏与儿童发育之间的关系。这一系列的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.