Maternal ethylenethiourea levels, newborn thyroid function & infant development

母体乙撑硫脲水平、新生儿甲状腺功能

• 批准号: 9988656
• 负责人: Alexis Handal
• 金额: $ 65.53万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9988656
• 关键词: Address; Adult; Adverse effects; Affect; Age-Months; Agricultural Workers; Agriculture; Area; Behavioral; Biological Markers; Birth; Blood specimen; Brain; Child; Child Development; Child Health; Cognitive; Cohort Studies; Communities; Costa Rica; Data; Demographic Factors; Development; Dietary Practices; Disease; Economic Factors; Economics; Ecuador; Employment; Enrollment; Environmental Exposure; Environmental Health; Environmental Impact; Environmental and Occupational Exposure; Ethylenethiourea; Exposure to; Farming environment; Female of child bearing age; Fetal Growth Retardation; Flowers; Food production; Functional disorder; Goals; Growth; Growth and Development function; Health; Health Policy; Home environment; Hormones; Household; Impaired cognition; Industrial fungicide; Industrialization; Industry; Infant; Infant Development; Infant Health; Intervention; Irrigation; Knowledge; Labor Forces; Language; Life; Maternal Health; Measures; Mediating; Mission; Motor; National Institute of Environmental Health Sciences; Neonatal; Neuraxis; Newborn Infant; North America; Nutritional status; Occupational; Outcome; Performance; Pesticides; Play; Population; Postpartum Period; Poverty; Pregnancy; Pregnancy loss; Pregnant Women; Premature Birth; Production; Prospective Studies; Public Health; Readiness; Research; Running; Sampling; Schools; Serum; Social support; Source; Stress; Surveys; Teratogens; Testing; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Time; Toxic effect; Toxicant exposure; Translating; United States; Urine; Vision; Visit; Visual; Water; Woman; Work; Working Women; adverse outcome; agricultural community; carcinogenicity; developmental toxicity; early childhood; epidemiology study; fetal; follow-up; improved; infancy; lifestyle factors; maternal depression; maternal stress; neurobehavioral; nutrition; prenatal; prenatal exposure; professional atmosphere; public health intervention; residence; social; socioeconomics; urinary

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.

项目概要 据估计，美国有六分之一的儿童和发展中国家有超过 2 亿的儿童未能达到这一标准 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， 全球范围内，关于杀菌剂神经发育毒性的科学知识存在重大差距。 亚乙基双二硫代氨基甲酸酯（EBDC）是农业生产和工业生产中常用的杀菌剂。 花艺和园艺。 EBDC 被代谢成毒性更强的致癌和致畸化合物， 亚乙基硫脲 (ETU)，与血清甲状腺素水平降低、甲状腺激素水平升高有关 刺激激素水平和甲状腺疾病。尽管研究表明产前 ETU 接触可能导致孕产妇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、胎儿中枢神经紊乱 系统和大脑发育以及认知和运动功能受损，迄今为止尚无流行病学研究 评估了产前暴露于 ETU 对新生儿甲状腺功能或随后的影响 婴儿的神经行为发育。这项研究建议追踪孕妇及其婴儿， 纳入 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，以及敏感的生长和神经行为发育指标。我们 假设怀孕期间较高的母体尿 ETU 水平与生长延迟有关 测量并降低出生时、6 岁、12 岁和 12 岁时的认知、视觉和精神运动发育评估分数 18 个月大，并且这种关联将通过对新生儿甲状腺功能的影响来介导。 拟议的研究利用了一个独特的机会来高度调查这个问题 厄瓜多尔的暴露人口。我们将招募 420 名妊娠 10-12 周的孕妇并对她们进行跟踪 从怀孕到产后 18 个月。我们将每月获取产前尿液样本。我们将获得 新生儿血液样本可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，柜员卡）将评估认知、运动、语言和社交行为发展，以及 婴儿的视觉功能。还将测量婴儿的生长和营养状况。每次访问时 在整个研究过程中，将收集有关工作条件、压力、家庭环境暴露的数据 和工作环境、社会支持、孕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 暴露水平，并按妊娠期分析水平。我们将评估 产前尿 ETU 代谢水平与婴儿发育结果之间的关联，并将运行 多变量路径分析来测试新生儿甲状腺功能障碍对此关联的中介作用。这 研究将进一步科学地了解接触杀菌剂的发育后果， 已成为美国和全球农业中最常用的农药。