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）：我们提议对圣地亚哥县2300名孕妇及其新生儿的高氯酸盐暴露和甲状腺激素水平进行研究，该地区已知存在高氯酸盐饮用水污染。高氯酸盐是一种高度稳定的氧化性化学品，在许多工业应用中都有使用，美国有数百万人通过受污染的食物或水接触到高氯酸盐。高氯酸盐竞争性地抑制碘化物进入甲状腺。由于甲状腺激素的合成需要碘化物，这可能导致甲状腺激素的产生减少。这是一个公共卫生问题，因为充足的甲状腺激素供应对大脑和神经的正常发育至关重要，在发育过程中，即使这种激素的微小减少也与智商下降和其他不利的神经系统影响有关。来自几项人体研究的有趣的新证据表明，常见的高氯酸盐环境水平可能会改变某些易感亚群的甲状腺功能，包括发育中的胎儿、幼儿、孕妇或碘摄入量低或硫氰酸盐摄入量高的人。（硫氰酸盐是一种常见于食物中的化学物质，与高氯酸盐一样，也能竞争性地抑制甲状腺碘的吸收）。目前，尽管高氯酸盐广泛存在，但美国饮用水没有高氯酸盐的监管标准。但如果这些新发现是正确的，公共卫生干预可能需要保护婴儿、儿童和其他潜在的易感群体。重要的是，关于高氯酸盐的新证据主要是基于小样本量的研究、生态数据或关于潜在混杂因素或效应调节剂的有限信息。因此，这一新证据必须得到证实。我们提出的研究计划利用了从孕妇及其婴儿收集的数千份血液和尿液样本以及问卷数据，这些数据是之前在高氯酸盐暴露地区进行的研究的一部分。我们将利用这些样本测量2300名孕妇尿液中高氯酸盐、硫氰酸盐和碘化物的浓度，以及血清中甲状腺素、促甲状腺激素（TSH）、游离甲状腺素和甲状腺抗体的浓度。在这些妇女的2300名新生儿中已经测量了血斑TSH水平（TSH升高是甲状腺激素分泌减少的高度敏感标志）。857对母婴脐带血也将用于检测高氯酸盐、硫氰酸盐、碘化物和甲状腺激素。所有这些测量将用于调查高氯酸盐与孕妇及其婴儿甲状腺激素之间的关系，并检查与碘化物、硫氰酸盐和甲状腺抗体的相互作用。关于母亲年龄、教育程度、婴儿性别、出生体重、社会经济地位、种族/民族、吸烟和其他问卷信息的数据将用于调整潜在的混淆和调查效果修正。这项研究将是迄今为止对孕妇和婴儿进行的最大的高氯酸盐暴露个体数据研究。这也将是第一个包括大量在美国常见的低碘和高硫氰酸盐水平的孕妇。我们研究的一个主要优势是，我们已经从已知的高氯酸盐污染地区收集了大量孕妇和婴儿的生物样本和问卷调查数据。在一个确定的暴露群体中获得这些样本和数据，为研究重要易感群体的高氯酸盐毒性提供了独特的机会，提供了关于高氯酸盐暴露和潜在混杂因素的准确信息，并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，发现即使甲状腺激素的微小变化也可能改变神经发育，以及婴儿、胎儿和孕妇可能特别容易受到高氯酸盐影响的新证据，尽管这是初步的。我们的最终目标是提供可用于帮助确定是否需要美国饮用水监管标准来保护这些易感群体的信息，如果需要，则提供剂量反应和其他可能对制定安全有效的公共卫生标准有用的信息。