Maternal ethylenethiourea levels, newborn thyroid function & infant development

项目摘要 据估计，美国每6名儿童中就有1名儿童和发展中国家超过2亿儿童没有达到 他们的全部发展潜力。尽管杀菌剂的使用在美国呈指数级增长， 在全球范围内，关于杀菌剂的神经发育毒性的科学知识存在着重大差距。 乙二硫代氨基甲酸酯，或EBDC，是农业生产中常用的杀菌剂，也是 花卉栽培和园艺。EBDC被代谢成一种毒性更强的致癌和致畸化合物， 乙硫脲(ETU)与血清甲状腺激素水平降低有关，它增加了甲状腺 刺激荷尔蒙水平和甲状腺功能紊乱。尽管研究表明，产前ETU 暴露可能导致产妇和新生儿甲状腺功能障碍，有可能导致不良后果 包括妊娠丢失、早产、宫内生长受限、胎儿中枢神经系统紊乱 系统和大脑发育以及认知和运动功能受损，迄今没有流行病学研究 评估了产前暴露于ETU对新生儿甲状腺功能或随后的 婴儿的神经行为发育。这项研究建议跟踪孕妇和她们的婴儿， 结合ETU暴露的产前尿液生物标志物、环境ETU暴露的调查数据和 关键的社会和经济因素，以及敏感的成长和神经行为发育措施。我们 假设孕期母体尿液ETU水平较高与生长迟缓有关 测量和降低出生时、6岁、12岁和12岁的认知、视觉和精神运动发育评估分数 这一关联将通过对新生儿甲状腺功能的影响来调节。 拟议的研究利用了一个独特的机会来高度地研究这个问题 厄瓜多尔的受感染人口。我们将招募420名怀孕10-12周的孕妇并对她们进行跟踪 从怀孕到产后18个月。我们将每月采集产前尿样。我们将获得 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)，将评估认知、运动、语言和社会行为发展，以及 婴儿的视觉功能。还将对婴儿的生长和营养状况进行测量。每次探访 在整个研究过程中，将收集有关工作条件、压力和家庭环境暴露的数据 和工作环境、社会支持、产妇健康和生活方式因素、社会经济和人口因素 各种因素。我们将量化产前ETU暴露的水平，并将按孕期分析水平。我们将评估 产前尿液ETU代谢产物水平与婴儿发育结局的关系 多变量通径分析，以检验新生儿甲状腺功能障碍对这种联系的中介作用。这 研究将进一步科学地理解接触杀菌剂的发育后果， 已经成为美国和全球农业行业最常用的杀虫剂。

Project Summary 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 has 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 agricultural industry in the U.S. and globally.