Bisphenol A and Children's Growth & Development

描述（由申请人提供）：双酚A （BPA）是世界上产量最高的化学品之一。用于聚碳酸酯饮料容器、食品包装、食品罐头衬里、牙齿密封剂等。由于最近的研究表明：1)BPA是一种内分泌干扰物，在低剂量下具有雌激素的作用；2)从消费品中渗透到食物和水中；3)人类几乎无处不在。动物研究表明，双酚a会改变性和生殖发育，包括大脑结构和行为的性别二态改变；体重增加；青春期提前。由于这些健康问题，一些国家和美国正在考虑立法禁止双酚a。然而，迄今为止几乎没有研究检验过BPA对人体健康的影响。本提案试图通过研究一组生活在加州的儿童在发育过程中暴露于BPA对健康的影响来解决这一数据缺口。CHAMACOS研究是一项纵向出生队列研究，跟踪了大约500名生活在以墨西哥裔美国人为主的农场工人社区的低收入儿童，从出生前到9岁。在出生和6个月、1岁、2岁、3岁半、5岁和7岁时对儿童的生长、健康、神经发育和行为进行评估，并在每个时间点收集尿液和/或血液样本。在这个丰富的数据集中，目的是研究子宫内和儿童时期BPA暴露与儿童生长发育的关系。具体的目的是：1)测量约400名怀孕期间的母亲和她们6个月、5岁和9岁的孩子尿液中的BPA浓度。除9岁儿童外，所有样本都已收集：2)确定母体双酚a浓度是否与母体（TSH, T3, T4）和儿童（TSH）甲状腺激素水平有关。3)确定母亲和儿童双酚a浓度是否与5岁时的认知功能和行为有关；4)确定母亲和儿童BPA暴露是否与5岁或9岁时的体重有关；5)确定母亲和儿童BPA暴露是否与9岁时代谢综合征有关。关于母亲和儿童的甲状腺水平以及5岁时的神经行为发育和体重的数据已经收集。代谢综合征的诊断将根据9岁时收集的新数据（血压、腰围、血脂和空腹血糖）来确定。该项目特别适合“大机遇”RFA，因为它使用现有的数据集和样本库，重点关注发展风险，可以立即开始，并在2年内完成。这是一个潜在的高影响项目，可以为立法者和政策制定者提供关于BPA暴露对人类健康影响的直接答案，并为未来的调查奠定基础。

DESCRIPTION (provided by applicant): Bisphenol A (BPA) is one of the highest production chemicals in the world. It is used in polycarbonate beverage containers, food packaging, linings of food cans, and sealants for teeth. Public health concerns have been raised about BPA because recent studies demonstrate: 1) that it is an endocrine disruptor that acts as an estrogen at low doses; 2) that it leaches from consumer products into food and water; 3) and that human exposure is nearly ubiquitous. Animal studies suggest that BPA alters sexual and reproductive development, including sexually-dimorphic alterations in brain structure and behavior; increased weight gain; and earlier puberty. Because of these health concerns, several countries and U.S. states are considering legislation to ban BPA. However, almost no studies to date have examined the health effects of BPA in humans. This proposal seeks to address this data gap by examining the health effects of developmental BPA exposure in a cohort of children living in California. The CHAMACOS Study is a longitudinal birth cohort study that has followed ~500 low-income children living in a predominantly Mexican-American, farmworker community from before birth to age 9. Children's growth, health, neurodevelopment, and behavior have been assessed at birth and age 6 months, 1, 2, 3 1/2, 5, and 7 years of age and urine and/or blood samples were collected at each time point. In this rich dataset, the intent is to examine the association of BPA exposure in utero and in childhood with child growth and development. The specific aims are: 1) to measure BPA concentrations in urine collected from ~400 mothers during pregnancy and from their children at 6 months, 5 years, and 9 years of age. All samples, except those at age 9, have already been collected: 2) to determine whether maternal BPA concentrations are associated with maternal (TSH, T3, T4) and child (TSH) thyroid hormone levels. 3) to determine whether maternal and childhood BPA concentrations are associated with cognitive functioning and behavior at age 5 years.; 4) To determine whether maternal and childhood BPA exposure is associated with body mass at age 5 or age 9 years; and 5) To determine whether maternal and childhood BPA exposure is associated with metabolic syndrome at age 9 years. Data has already been collected on thyroid levels in mother and child and neurobehavioral development and body mass at age 5 years. Metabolic syndrome diagnosis will be determined from new data gathered at age 9 (blood pressure, waist circumference, lipids and glucose in fasting blood). This project is uniquely suited for this Grand Opportunities RFA because it uses an extant dataset and banked samples, it focuses on developmental exposures, and it can be begun immediately and completed in 2 years. This is a potentially high-impact project that can provide immediate answers about the human health effects of BPA exposure to legislators and policy makers and lays the groundwork for future investigations. PUBLIC HEALTH RELEVANCE: The proposed research will provide some of the first data on the human health effects of BPA exposure and address key data gaps identified by advisory and regulatory bodies. By relying mainly on existing data and banked samples, we will accelerate the science by completing the research in just two years. In addition, measurement of BPA in this cohort will lay the foundation for future examination of multiple other outcomes, such as asthma (including spirometry), immune function (Th1 and Th2 cytokines), and pubertal onset, in this rich and unique dataset.