Exposure to Perfluorinated Compounds and Risk for Autism Spectrum Disorders

接触全氟化合物和患自闭症谱系障碍的风险

• 批准号: 9339029
• 负责人: Hyeong-Moo Shin
• 金额: $ 31.93万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9339029
• 关键词: 2 year old; 4 year old; Address; Autistic Disorder; Biological Markers; Blood; Blood specimen; Body Burden; Breast Feeding; Case-Control Studies; Chemicals; Child; Childhood Autism Risks from Genetics and the Environment; Complex; Data Quality; Development; Diagnosis; Diagnostic; Drug Kinetics; Enrollment; Environmental Health; Epidemiology; Etiology; Exposure to; Family; Food Packaging; Funding; Goals; Gold; Half-Life; Health; Household; Household Products; Human; Individual; Infant; Investigation; Knowledge; Laboratory Animals; Learning; Life; Measurement; Measures; Medical Records; Metabolic; Modeling; Mothers; National Institute of Environmental Health Sciences; Neurologic; Participant; Physiological; Postpartum Period; Pregnancy; Pregnant Women; Privatization; Prospective cohort; Proxy; Public Health; Questionnaires; Recurrence; Research; Risk; Risk Factors; Role; Sample Size; Serum; Source; Testing; Textiles; Time; Toxic effect; Training; autism spectrum disorder; base; case control; cohort; consumer product; contaminated drinking water; design; disorder risk; drinking water; environmental chemical; environmental chemical exposure; experimental study; high risk; improved; in utero; indexing; instrument; interest; non-genetic; novel strategies; pharmacokinetic model; placental transfer; pollutant; population based; postnatal; prenatal; prospective; public health relevance; study population

Project Summary/Abstract Because few non-genetic causes of autism spectrum disorders (ASD) have been studied, this proposal seeks a novel approach to advance our knowledge of the complex etiology of ASD due to exposure to environmental chemicals. Perfluorinated compounds (PFCs) are selected as a chemical class of interest because they are ubiquitous in consumer products such as food packaging, textiles and non-stick coatings on cookware, and have neurologic or neuro-developmental toxicity in experiments with laboratory animals. Also, at least 5 million U.S. people are currently drinking water contaminated with PFCs above a health advisory level. The overall goal of this project is to determine whether exposure to PFCs at an early developmental stage (pregnancy or breastfeeding periods) is associated with risk for ASD. To test our hypothesis, we will utilize two study populations known as “CHARGE” (CHildhood Autism Risk from Genetics and Environment) and “MARBLES” (Markers of Autism Risk in Babies – Learning Early Signs). CHARGE is a population-based case-control study that has enrolled over 1800 index children and their families and thus provides a large number of cases (children with ASD) and controls (typically developing (TD) children) along with blood samples from mothers when their child was 2 to 4 years old. MARBLES is a prospective cohort, enrolling pregnant women who already have a child with ASD and are therefore at high risk for delivering another child with ASD, designed to identify causes and early markers of ASD. From CHARGE that provides a large number of final diagnoses (ASD or TD), we will use direct measures in the mother's blood as a proxy for early life children's exposure during pregnancy and breastfeeding. From MARBLES that provides more accurate time-specific exposure measurements than CHARGE, we will use direct measures in mother's blood collected during pregnancy and breastfeeding periods. While we anticipate that the mother's level in blood when their child was 2 to 4 years old would be a good marker of exposure due to the relatively long elimination half-life of PFCs in the body, we will additionally capitalize on the MARBLES longitudinal biomarker measurements to reconstruct exposure levels during pregnancy and breastfeeding periods for participants in CHARGE and then test the same hypothesis using reconstructed estimates. To achieve our goals, we propose PFC analysis of randomly selected blood samples from mothers of 332 cases (=ASD) and 332 controls (=TD) in CHARGE and 336 blood samples from 112 MARBLES mothers who provided at least one during pregnancy, one during breastfeeding, and one when their child was 2 years old. This project thereby achieves 1) large sample size; 2) precise characterization of PFC exposures during specific developmental periods; and 3) associations of PFCs with cases of ASD that were confirmed by highly trained, research reliable clinicians using gold standard instruments. This study will improve understanding of temporal changes in body burden from pregnancy through the first few years post- partum and provide uniquely high quality data on the role of early PFC exposures in ASD.

项目摘要/摘要 因为很少有自闭症谱系障碍的非遗传原因（ASD）是研究的，所以该提案寻求 通过暴露于环境而导致的ASD复杂病因的一种新颖的方法，以提高我们对ASD复杂的病因的了解 化学物质。全氟化化合物（PFC）被选为化学兴趣类别，因为它们是 无处不在的消费产品，例如食品包装，纺织品和炊具上的不粘涂料，以及 在实验动物的实验中，具有神经系统或神经发展毒性。另外，至少有500万 目前，美国人民饮用水受到健康咨询水平以上的PFC污染。总体 该项目的目标是确定是否在早期发育阶段（怀孕或 母乳喂养期）与ASD的风险有关。为了检验我们的假设，我们将利用两项研究 人口被称为“指控”（遗传学和环境的儿童自闭症风险）和“大理石” （婴儿自闭症风险标记 - 学习早期迹象）。电荷是一项基于人群的病例对照研究 这已经招募了1800多名指数儿童及其家人，因此提供了大量案件 （患有ASD的儿童）和对照（通常是发育（TD）儿童）以及母亲的血液样本 当他们的孩子2至4岁时。大理石是一个潜在的队列，招募了孕妇 已经有一个患有ASD的孩子，因此有高风险，可以送另一个ASD的孩子，旨在 确定ASD的原因和早期标记。从充电提供大量最终诊断 （ASD或TD），我们将在母亲的血液中使用直接措施作为早期生活的代理 在怀孕和母乳喂养期间。从大理石提供更准确的特定时间曝光 测量值大于收费，我们将在怀孕期间收集的母亲血液中的直接措施 母乳喂养期。虽然我们预计母亲在孩子2至4岁时的血液水平 由于体内PFC的相对长发射半衰期，将是接触的好标志，我们将 另外将大理石的纵向生物标志物测量值大写以重建暴露水平 在怀孕和母乳喂养期间，负责参与者，然后检验相同的假设 使用重建的估计值。为了实现我们的目标，我们建议对随机选择的血液进行PFC分析 来自332例（= ASD）和332例对照（= TD）的母亲的样本，负责的336个血液样本 112个大理石母亲，在怀孕期间至少提供一个，在母乳喂养期间提供一个 他们的孩子2岁。因此，这个项目实现了1）大型样本量； 2）精确表征 PFC在特定发育期间暴露； 3）PFC与ASD案例的关联 使用金标准仪器，经过高度培训的可靠临床医生证实了我们。这项研究会 提高对从怀孕到最初几年的身体燃烧暂时变化的理解 - Partum并提供有关PFC早期暴露在ASD中的作用的独特高质量数据。