PERCHLORATE AND THYROID HORMONES IN PREGNANCY AND INFANTS IN SOUTHERN CALIFORNIA

描述(申请人提供)：我们提议对圣地亚哥县2,300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，圣地亚哥县是已知的高氯酸盐饮用水污染地区。高氯酸盐是一种高度稳定的氧化化学品，用于许多工业应用，在美国，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甲状腺对碘的摄取。由于碘是合成甲状腺激素所必需的，这可能会导致甲状腺激素的生成减少。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，即使在发育过程中这种激素的轻微下降也会导致智商下降和其他不利的神经影响。来自几项人类研究的耐人寻味的新证据表明，环境中常见的高氯酸盐水平可能会改变某些易感人群的甲状腺功能，包括发育中的胎儿、幼儿、孕妇，或那些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品中的化学物质，与高氯酸盐一样，它也可以竞争性地抑制甲状腺碘的摄取)。目前，尽管高氯酸盐暴露广泛，但美国还没有针对高氯酸盐的饮用水监管标准。但如果这些新发现属实，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小样本量、生态数据或关于潜在混杂因素或效果修饰剂的有限信息的研究。正因为如此，这一新证据必须得到证实。我们建议的研究计划利用了从孕妇及其婴儿那里收集的数千份血液和尿液样本以及问卷数据，这是先前在高氯酸盐暴露地区进行的一项研究的一部分。我们将使用这些样本来测量2300名孕妇的尿中高氯酸盐、硫氰酸盐和碘的浓度，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。这些妇女的所有2300名新生儿的血斑TSH水平都已被测量(TSH升高是甲状腺激素产生减少的一个高度敏感的标志)。857对母婴的脐带血也将被用来检测高氯酸盐、硫氰酸盐、碘化物和甲状腺激素。所有这些测量都将用于研究高氯酸盐和孕妇及其婴儿的甲状腺激素之间的关系，并检查与碘、硫氰酸盐和甲状腺抗体的相互作用。关于产妇年龄、教育、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改。这项研究将是迄今为止对有高氯酸盐暴露个人数据的孕妇和婴儿进行的最大规模的研究。这也将是第一次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可以获得数以千计的生物样本和问卷数据，这些样本已经在一大群孕妇和婴儿中收集，这些样本来自已知的高氯酸盐污染地区。在明确的暴露社区中获得这些样本和数据，为调查重要易感人群中的高氯酸盐毒性提供了一个独特的机会，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。这项研究对公众健康的重要性在于高氯酸盐暴露的广泛程度，发现即使是甲状腺激素的微小变化也可能改变神经发育，以及有趣的、尽管是初步的新证据，即婴儿、胎儿和孕妇可能特别容易受到高氯酸盐的影响。我们的最终目标是提供信息，帮助确定是否需要美国饮用水监管标准来保护这些易感人群，如果需要，提供剂量反应和其他可能有助于制定安全有效的公共卫生标准的信息。

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.