PERCHLORATE AND THYROID HORMONES IN PREGNANCY AND INFANTS IN SOUTHERN CALIFORNIA

南加州孕妇和婴儿中的高氯酸盐和甲状腺激素

• 批准号: 8162504
• 负责人: Craig M Steinmaus
• 金额: $ 53.55万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-19 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8162504
• 关键词: Address; Adult; Adverse effects; Antibodies; Area; Birth; Birth Weight; Blood; Blood specimen; Brain; California; Cardiovascular Diseases; Cesarean section; Chemical Exposure; Chemicals; Child; Communities; Consumption; County; Data; Data Collection; Development; Dose; Education; Elements; Epidemiologic Studies; Ethnic Origin; Fetus; Food; Future; Gender; General Population; Goals; Health; Hormones; Human; Individual; Infant; Intake; Intervention; Iodide Peroxidase; Iodides; Iodine; Link; Masks; Maternal Age; Measurement; Measures; Methods; Modification; Mothers; Neonatal; Neurologic; Neurological outcome; Newborn Infant; Nitrates; Perchlorates; Physiological; Play; Population; Predisposition; Pregnancy; Pregnant Women; Production; Public Health; Questionnaires; Race; Regulation; Research; Research Design; Sample Size; Sampling; Screening procedure; Serum; Smoking; Socioeconomic Status; Source; Spottings; Subgroup; Techniques; Testing; Thiocyanates; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Time; Toxic effect; Umbilical Cord Blood; Urine; Water; Water Pollution; Woman; base; cost; drinking water; fetal; healthy volunteer; inhibitor/antagonist; neonate; neurodevelopment; novel; population based; pregnant; prenatal; programs; prospective; response; sodium-iodide symporter; uptake; urinary

DESCRIPTION (provided by applicant): We propose a study of perchlorate exposure and thyroid hormone levels in 2,300 pregnant women and their newborns in San Diego County, an area with known perchlorate drinking water contamination. Perchlorate is a highly stable oxidizing chemical used in many industrial applications, and millions of people in the US are exposed to perchlorate through contaminated food or water. Perchlorate competitively inhibits iodide uptake into the thyroid gland. Since iodide is required for thyroid hormone synthesis, this can cause a decrease in thyroid hormone production. This is a public health concern since adequate supplies of thyroid hormone are vital for proper brain and neurodevelopment, and even small decreases in this hormone during development have been linked to decreased IQ and other adverse neurological effects. Intriguing new evidence from several human studies suggests that common environmental levels of perchlorate could alter thyroid function in certain susceptible subgroups, including the developing fetus, young children, pregnant women, or those with low intake of iodine or high intake of thiocyanate. (Thiocyanate is a chemical commonly found in food which, like perchlorate, can also competitively inhibit thyroid iodide uptake). Currently, despite widespread exposure, there is no US drinking water regulatory standard for perchlorate. But if these new findings are true, public health intervention might be needed to protect infants, children, and other potential susceptibility groups. Importantly, the new evidence on perchlorate is mostly based on studies with small sample sizes, ecologic data, or limited information on potential confounders or effect modifiers. Because of this, this new evidence must be confirmed. Our proposed study plan takes advantage of thousands of blood and urine samples and questionnaire data already collected from pregnant women and their infants as part of a previous study in a perchlorate exposed area. We will use these samples to measure urine concentrations of perchlorate, thiocyanate, and iodide, and serum concentrations of thyroxine, thyroid stimulating hormone (TSH), free-thyroxine, and thyroid antibodies in 2,300 pregnant women. Bloodspot TSH levels have already been measured in all 2,300 of the newborns of these women (increased TSH is a highly sensitive marker of decreased thyroid hormone production). Umbilical cord blood in 857 mother-infant pairs will also be used to measure perchlorate, thiocyanate, iodide, and thyroid hormones. All of these measurements will be used to investigate associations between perchlorate and thyroid hormones in pregnant women and their infants and examine interactions with iodide, thiocyanate, and thyroid antibodies. Data on maternal age, education, infant gender, birth weight, socioeconomic status, race/ethnicity, smoking, and other questionnaire information will be used to adjust for potential confounding and to investigate effect modification. This study will be the largest to date in pregnant women and infants with individual data on perchlorate exposure. It will also be the first to include large numbers of pregnant women with low iodine and high thiocyanate levels commonly found in the US. A major advantage of our study is the availability of thousands of biologic samples and questionnaire data that have already been collected in a large group of pregnant women and infants, from an area with known perchlorate contamination. The availability of these samples and data in a defined exposed community offers a unique opportunity to investigate perchlorate toxicity in important susceptibility groups, with accurate information on perchlorate exposure and potential confounding factors, and with good statistical power. The public health importance of this research lies in the widespread extent of perchlorate exposure, the finding that even small changes in thyroid hormones may alter neurodevelopment, and the intriguing, albeit preliminary, new evidence that infants, fetuses, and pregnant women may be particularly susceptible to perchlorate. Our ultimate goal is to provide information that can be used to help determine whether a US drinking water regulatory standard is needed protect these susceptible groups, and if one is needed, provide dose-response and other information that might be useful in developing a safe and effective public health standard. PUBLIC HEALTH RELEVANCE: The public health importance of this project lies in the fact that millions of people are exposed to perchlorate. Perchlorate might reduce thyroid hormone levels in susceptible populations, and adequate supplies of thyroid hormone are vital in the fetus and child for proper brain and neurologic development. Despite millions of people being exposed, there is currently no U.S. regulatory standard for perchlorate in drinking water. Our goal is to provide new information that might be useful in determining whether a U.S. drinking water regulatory standard is needed to help protect infants and young children from the toxic effects of perchlorate.

描述（由申请人提供）：我们建议对2300名孕妇及其新生儿在圣地亚哥县的高氯酸盐暴露和甲状腺激素水平进行研究，这是一个已知的高氯酸盐饮用水污染的地区。高氯酸盐是一种用于许多工业应用中的高度稳定的氧化化学物质，美国数以百万计的人通过受污染的食物或水暴露于高氯酸盐。高氯酸盐有竞争力抑制碘化物吸收到甲状腺中。由于碘化物需要甲状腺激素合成，因此这可能导致甲状腺激素产生的降低。这是一个公共卫生问题，因为甲状腺激素的足够供应对于适当的大脑和神经发育至关重要，而且在发育过程中这种激素的少量减少也与智商和其他不良神经系统作用有关。来自几项人类研究的有趣新证据表明，普通环境水平可以改变某些易感亚组的甲状腺功能，包括发育中的胎儿，幼儿，孕妇，或患有低摄入碘或高摄入硫氰酸盐的甲状腺。 （硫氰酸酯是食品中常见的一种化学物质，与高氯酸盐一样，也可以竞争性抑制甲状腺碘化物的摄取）。目前，尽管暴露了广泛的曝光，但没有美国饮用水调节标准的高氯酸盐标准。但是，如果这些新发现是真实的，则可能需要公共卫生干预来保护婴儿，儿童和其他潜在的易感人群。重要的是，关于高氯酸盐的新证据主要是基于样本量，生态数据或潜在混杂因子或效应修饰符的有限信息的研究。因此，必须确认这一新证据。 我们提出的研究计划利用了已经从孕妇及其婴儿那里收集的成千上万的血液和尿液样本和问卷数据，这是先前在高氯酸盐暴露区域进行的研究的一部分。我们将使用这些样品测量甲状腺素，甲状腺素，甲状腺刺激激素（TSH），自由甲状腺素和甲状腺素抗体的尿液浓度，以及2,300名孕妇的甲状腺刺激性激素（TSH），甲状腺素和甲状腺抗体。在这些女性的所有2300名新生儿中，已经测量了血液点TSH水平（增加的TSH是甲状腺激素产生降低的高度敏感标志物）。 857对母亲的脐带血也将用于测量高氯酸盐，硫氰酸酯，碘化物和甲状腺激素。所有这些测量结果将用于研究孕妇五氯酸盐和甲状腺激素之间的关联，并检查与碘化物，硫氰酸酯和甲状腺抗体的相互作用。有关产妇年龄，教育，婴儿性别，出生体重，社会经济地位，种族/种族，吸烟和其他问卷信息的数据，将用于调整潜在的混杂并调查效果修改。 这项研究将是迄今为止最大的孕妇和婴儿，并具有有关高氯酸盐暴露的个人数据。这也将是第一个包括在美国常见的碘低和高硫氰酸酯水平的大量孕妇。我们研究的一个主要优点是，从具有已知高氯酸盐污染的地区，已经收集了数千种生物样品和问卷数据，这些数据已经收集到了一大批孕妇和婴儿中。这些样品和数据在定义的暴露社区中的可用性为研究重要易感组的高氯酸盐毒性提供了独特的机会，并具有有关高氯酸盐暴露和潜在混杂因素的准确信息，并且具有良好的统计能力。这项研究的公共卫生重要性在于高氯酸盐暴露的广泛程度，即使甲状腺激素的微小变化也可能改变神经发育，而有趣的，即初步的新证据，即婴儿，胎儿和孕妇可能特别容易过多地进行过多过多。我们的最终目标是提供可用于帮助确定美国饮用水调节标准是否需要保护这些易感群体的信息，如果需要一个易感群体，并且提供剂量反应和其他信息，这些剂量和其他信息可能对开发安全有效的公共卫生标准有用。 公共卫生相关性：该项目的公共卫生重要性在于，数以百万计的人暴露于高氯酸盐。高氯酸盐可能会降低易感人群中的甲状腺激素水平，甲状腺激素的足够供应在胎儿和儿童中至关重要，以便适当的大脑和神经系统发育。尽管有数百万的人被暴露，但目前尚无美国高级饮用水中高级监管标准。我们的目标是提供新信息，这些信息可能在确定是否需要美国饮用水调节标准以帮助保护婴儿和幼儿免受高氯酸盐毒性影响。