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.

项目总结/摘要 由于很少有非遗传原因的自闭症谱系障碍（ASD）的研究，这项建议寻求 一种新的方法来提高我们对ASD复杂病因学的认识， 化学品全氟化合物（PFC）被选为感兴趣的化学类别，因为它们是 普遍存在于消费品中，如食品包装、纺织品和炊具上的不粘涂层， 在实验室动物实验中具有神经或神经发育毒性。另外，至少500万 美国目前，人们饮用的水中全氟化学品的污染超过了健康建议水平。整体 该项目的目标是确定在早期发育阶段（怀孕或 母乳喂养期）与ASD的风险有关。为了验证我们的假设，我们将使用两个研究 被称为“CHARGE”（遗传和环境造成的儿童自闭症风险）和“MARBLES”的人群 （婴儿自闭症风险的标志-学习早期迹象）。CHARGE是一项基于人群的病例对照研究 该中心已招收了1800多名索引儿童及其家庭，因此提供了大量病例， （ASD儿童）和对照组（通常为发育中（TD）儿童）沿着来自母亲的血液样本 当他们的孩子2到4岁的时候。MARBLES是一项前瞻性队列研究，招募符合以下条件的孕妇： 已经有一个患有ASD的孩子，因此有高风险分娩另一个患有ASD的孩子， 确定ASD的原因和早期标志物。来自CHARGE，提供大量最终诊断 (ASD或TD），我们将使用母亲血液中的直接测量值作为儿童早期暴露的替代指标 在怀孕和哺乳期间。来自MARBLES，提供更精确的特定时间曝光 测量比充电，我们将使用直接测量母亲的血液收集在怀孕期间， 哺乳期。当我们预计母亲在孩子2到4岁时血液中的水平 由于PFC在体内的消除半衰期相对较长， 此外，还利用MARBLES纵向生物标志物测量结果来重建暴露水平 在怀孕和哺乳期的参与者在充电，然后测试相同的假设 使用重建的估计。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CHARGE中332例病例（=ASD）和332例对照（=TD）的母亲的样本，以及来自 112位在怀孕期间提供至少一个MARBLES的母亲，一个在母乳喂养期间，一个在 他们的孩子两岁了因此，该项目实现了1）大样本量; 2）精确表征 在特定发育时期的全氟化碳暴露;以及3）全氟化碳与ASD病例的关联， 由训练有素、研究可靠的临床医生使用金标准仪器证实。本研究将 提高对从怀孕到产后头几年身体负担的时间变化的理解， 并提供了关于早期PFC暴露在ASD中的作用的独特的高质量数据。