Res Div Suppl (Lisbeth Iglesias-Rios): Maternal ethylenethiourea levels, newborn thyroid function & infant development

资助父母奖摘要 R01ES026603：母亲乙硫脲水平、新生儿甲状腺功能和婴儿 发展 据估计，美国每6名儿童中就有1名儿童，发展中国家有超过2亿儿童 没有充分发挥他们的发展潜力。尽管杀菌剂的使用在年呈指数级增长 美国和全球在科学知识方面存在着巨大的差距 杀菌剂的神经发育毒性。乙二硫代氨基甲酸酯，或EBDC，是 农业生产以及花卉和园艺中常用的杀菌剂。 EBDC被代谢成一种毒性更强的致癌和致畸化合物， 乙硫脲(ETU)，这与血清甲状腺激素水平下降有关， 甲状腺刺激激素水平升高，以及甲状腺功能紊乱。虽然研究 表明产前接触ETU可能会导致母亲和新生儿甲状腺功能障碍， 可能导致不良后果，包括流产、早产、宫内 生长受限、胎儿中枢神经系统和脑发育障碍及受损 认知和运动功能，到目前为止还没有流行病学研究评估 产前暴露ETU对新生儿甲状腺功能或随后神经行为的影响 婴儿的发育。这项研究建议跟踪孕妇和她们的婴儿， 结合ETU暴露产前尿液生物标志物、环境ETU调查资料 暴露和关键的社会和经济因素，以及敏感的成长和神经行为 发展措施。我们假设母体尿液ETU水平在 怀孕将与发育测量延迟以及认知、视觉和 在出生时、6个月、12个月和18个月时的精神运动发育评估得分 这种联系将通过对新生儿甲状腺功能的影响来调节。建议数 研究利用一个独特的机会在高度曝光的情况下调查这个问题 厄瓜多尔的人口。我们将招募420名怀孕10-12周的孕妇并进行后续 从怀孕到产后18个月。我们将每月采集产前尿液。 样本。我们将采集新生儿血液样本，以评估出生时的甲状腺激素水平。我们 将进行高度敏感的测试(BSID-III，出纳卡)，以评估认知，运动， 婴儿的语言、社会行为发育和视觉功能。婴儿也将是 测量生长和营养状况。在整个研究期间的每一次访问中，数据将 收集关于工作条件、压力、家庭和工作环境暴露的信息 环境、社会支持、产妇健康和生活方式因素、社会经济和 人口因素。我们将量化产前ETU暴露的水平，并将通过以下方式分析水平 三个月。我们将评估产前尿液ETU代谢产物水平与婴儿的关系 并将运行多变量通径分析来测试 新生儿甲状腺功能障碍与此相关。这项研究将进一步科学地理解 接触杀菌剂的发育后果，已经成为最严重的 美国和全球农业行业常用的杀虫剂。 总而言之，环境有毒暴露、营养不良、贫困、产妇抑郁和压力， 以及其他社会和经济因素导致青少年发展潜力的丧失 孩子们。拟议的研究将提供关键数据，帮助我们了解这些 影响儿童发展的因素。这些数据对于开发和启动适当的 在受影响社区采取可持续的干预措施，促进最佳儿童健康和 发展，减少与环境相关的社区暴露，并改善工人 健康政策。

Abstract of funded parent award R01ES026603: Maternal ethylenethiourea levels, newborn thyroid function & infant development An estimated 1 in 6 children in the U.S. and over 200 million children in the developing world are not reaching their full developmental potential. Although fungicide use is growing exponentially in the United States and globally, a significant gap exists in scientific knowledge about the neurodevelopmental toxicity of fungicides. Ethylenebisdithiocarbamates, or EBDCs, are commonly-used fungicides in agricultural production as well as in floriculture and horticulture. EBDCs are metabolized into a more toxic carcinogenic and teratogenic compound, ethylenethiourea (ETU), which has been associated with decreased serum thyroxine levels, increased thyroid stimulation hormone levels, and thyroid gland disorders. Although research indicates that prenatal ETU exposure may cause maternal and neonatal thyroid dysfunction, potentially leading to adverse outcomes including pregnancy loss, preterm delivery, intrauterine growth restriction, disruptions in fetal central nervous system and brain development and impaired cognitive and motor function, no epidemiological studies to date have evaluated the effects of prenatal exposure to ETU on newborn thyroid function or the subsequent neurobehavioral development of infants. This study proposes to follow pregnant women and their infants, incorporating prenatal urinary biomarkers of ETU exposure, survey data of environmental ETU exposure and key social and economic factors, and sensitive growth and neurobehavioral developmental measures. We hypothesize that higher maternal urinary ETU levels during pregnancy will be associated with delayed growth measures and lower cognitive, visual, and psychomotor developmental assessment scores at birth, 6, 12, and 18 months of age and that this association will be mediated through an impact on newborn thyroid function. The proposed research takes advantage of a unique opportunity to investigate this question in a highly exposed population in Ecuador. We will enroll 420 pregnant women at 10-12 weeks gestation and follow them through pregnancy up to 18 months post-partum. We will obtain monthly prenatal urine samples. We will obtain neonatal blood samples to assess thyroid hormone levels at birth. We will administer highly sensitive tests (BSID-III, Teller cards) that will assess cognitive, motor, language, and social-behavioral development, and visual function in infants. Infants will also be measured for growth and nutritional status. At each visit throughout the study, data will be collected on working conditions, stress, environmental exposures in home and work environments, social support, maternal health and lifestyle factors, socio-economic and demographic factors. We will quantify levels of prenatal ETU exposure and will analyze levels by trimester. We will assess associations between prenatal urinary ETU metabolite levels and infant developmental outcomes and will run a multivariate path analysis to test for a mediating effect of newborn thyroid dysfunction on this association. This study will further scientific understanding of the developmental consequences of exposure to fungicides, which have become the most commonly used pesticides in the agricultural industry in the U.S. and globally. In sum, environmental toxic exposure, poor nutrition, poverty, maternal depression and stress, and other social and economic factors contribute to the loss of developmental potential in young children. The proposed study will contribute key data to inform our understanding of how these factors impact child development. This data will be critical for developing and initiating appropriate and sustainable interventions in affected communities that promote optimal child health and development, reduce environmentally-associated community exposures, and improve worker health policies.