PERCHLORATE AND THYROID HORMONES IN PREGNANCY AND INFANTS IN SOUTHERN CALIFORNIA

描述（由申请人提供）： 我们提出了一项研究，高氯酸盐暴露和甲状腺激素水平在2,300名孕妇和他们的新生儿在圣地亚哥县，一个已知的高氯酸盐饮用水污染的地区。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，美国有数百万人通过受污染的食物或水接触高氯酸盐。高氯酸盐竞争性抑制碘摄入甲状腺。由于碘是甲状腺激素合成所必需的，这可能会导致甲状腺激素产生减少。这是一个公共卫生问题，因为甲状腺激素的充足供应对大脑和神经发育至关重要，即使在发育过程中这种激素的少量减少也与智商下降和其他不良神经影响有关。几项人类研究的有趣新证据表明，常见的高氯酸盐环境水平可能会改变某些易感亚组的甲状腺功能，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，也可以竞争性地抑制甲状腺碘的吸收）。目前，尽管广泛暴露，但美国没有高氯酸盐的饮用水监管标准。但如果这些新发现是真的，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，这一新的证据必须得到证实。 我们提出的研究计划利用了数千份血液和尿液样本以及已经从孕妇及其婴儿中收集的问卷数据，这些数据是以前在高氯酸盐暴露地区进行的研究的一部分。我们将使用这些样本来测量2,300名孕妇的高氯酸盐、硫氰酸盐和碘化物的尿液浓度，以及甲状腺素、促甲状腺激素（TSH）、游离甲状腺素和甲状腺抗体的血清浓度。已经在这些妇女的所有2,300名新生儿中测量了血斑TSH水平（TSH增加是甲状腺激素产生减少的高度敏感标志物）。857对母婴的脐带血也将用于测量高氯酸盐、硫氰酸盐、碘化物和甲状腺激素。所有这些测量将用于调查孕妇及其婴儿中高氯酸盐和甲状腺激素之间的关联，并检查与碘化物，硫氰酸盐和甲状腺抗体的相互作用。将使用关于母亲年龄、教育程度、婴儿性别、出生体重、社会经济地位、人种/种族、吸烟和其他问卷信息的数据来调整潜在混杂因素并研究效应修正。 这项研究将是迄今为止在孕妇和婴儿中进行的最大规模的关于高氯酸盐暴露的个体数据的研究。它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，从已知高氯酸盐污染的地区收集了大量孕妇和婴儿的数千份生物样本和问卷数据。这些样品和数据在一个定义的暴露社区的可用性提供了一个独特的机会，调查高氯酸盐毒性在重要的易感群体，准确的信息高氯酸盐暴露和潜在的混杂因素，并具有良好的统计能力。这项研究的公共卫生重要性在于广泛的高氯酸盐暴露，发现即使甲状腺激素的微小变化也可能改变神经发育，以及有趣的，尽管是初步的，新的证据表明婴儿，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，则提供可能有助于制定安全有效的公共卫生标准的剂量反应和其他信息。

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.