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 由于很少研究自闭症谱系障碍的非遗传原因（ASD），因此该提案寻求 一种新的方法，可以提高由于暴露于环境而对ASD复杂病因的了解 化学物质。 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， 在实验动物的经验中，具有神经系统或神经发展的二氧性毒性毒性。 目前，美国的Peple被PFC污染了以上咨询水平。 该项目的目标是在早期发育阶段（怀孕或或 母乳喂养期与ASD的风险有关。 被称为“电荷”（遗传学和环境的儿童自闭症风险）和“大理石” （在婴儿学习早期迹象中自闭症风险的标记）。 Thas招收了1800多名指数儿童和家庭，因此提供了大量的casess （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。 因此 确定ASD的原因和早期标记。 （ASD或TD），我们将在母亲的血液中使用直接措施作为血腥的早期曝光 在怀孕和母乳喂养期间。 测量托汉（Tohan）收费，我们将在前提期间收集母亲的血液中的直接措施 母乳喂养时期。 由于PFC在体内的半衰期相对较长的消除，我们将是一个很好的曝光标记，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，负责参与者和相同的假设 使用重建的估计来实现我们的目标 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个大理石母亲在预先喂食期间至少提供了一个，在母乳喂养期间提供了一个 他们的孩子2岁。 PFC在特定发育期间的暴露； 3）PFC与ASD的案例 通过训练有素的可靠临床医生使用金标准仪器确认 在最初几年的头几年中，提高对身体负担的时间变化的理解 - 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。