Prenatal Exposure to Phthalates in a High-Risk ASD Pregnancy Cohort

高风险自闭症谱系障碍 (ASD) 妊娠群体的产前邻苯二甲酸盐暴露情况

• 批准号: 9406896
• 负责人: Hyeong-Moo Shin
• 金额: $ 11.78万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9406896
• 关键词: Prenatal; Exposure; Phthalates; Risk; ASD

 DESCRIPTION (provided by applicant): Because little is known about non-genetic causes of autism spectrum disorders (ASD), this proposal seeks a novel approach to advance our knowledge of the complex etiology of autism due to environmental chemical exposures from the use of common consumer products. Phthalates are selected as a chemical class of interest because they are ubiquitous in personal care products (e.g., cosmetics, fragrances, shampoos) and indoor residential environments (e.g., polyvinyl chloride (PVC) flooring and plastics, children's toys, vinyl tiles, shower curtains), have been shown to influence sex steroids critical n early brain development, and have neuro- developmental toxicity in infants and children. A recent epidemiologic study also found that having PVC flooring material (a source of airborne phthalates) in a parent's or child's room was associated with an increased risk of ASD. The overall goal of this project is to determine whether exposure to phthalates during pregnancy is associated with an increased risk of ASD. To estimate prenatal exposure to phthalates, this study will leverage existing resources from a unique longitudinal study initiated under the NIEHS-funded UC Davis Center for Children's Environmental Health known as "MARBLES" (Markers of Autism Risk in Babies - Learning Early Signs). MARBLES is a prospective investigation, enrolling pregnant women who already have a child with ASD and are therefore at high risk for delivering another child with autism, designed to identify causes and early markers of autism. From this study, we have available multiple urine samples collected from the mother throughout pregnancy, a key feature for improving the exposure estimates for each infant and mother due to the fact that phthalates are metabolized and excreted quickly, with elimination half-lives on the order of hours. Moreover, two hundred fifteen of the children from this pregnancy cohort will have been assessed for autism at the age of 36 months during the time of this R21, enriching the value of these prenatal biological samples. Close to one in five of the firt 147 children to reach 36 months has been confirmed with a diagnosis of ASD. Other developmental diagnoses, including adaptive function and cognitive development, are also available for these children. Therefore, multiple gestational urine samples collected from mothers and confirmed diagnoses of autism in MARBLES are invaluable resources that will enable rigorous analyses of the association between prenatal exposure to phthalates and the risk for ASD or other developmental concerns. Up to four urine samples were collected each trimester for each woman. To reduce analytical costs while maintaining some information about variability, we will analyze the first sample collected each trimester as an individual sample and pool all remaining samples for that trimester. To assess variability of maternal exposures during pregnancy, longitudinal individual urine samples collected approximately one week apart from 9 mothers will be analyzed for phthalate metabolite levels. This study will markedly advance understanding of the role of a class of endocrine disrupting compounds common in consumer products on ASD.

 描述（由申请人提供）：由于对自闭症谱系障碍（ASD）的非遗传原因知之甚少，该提案寻求一种新的方法来推进我们对自闭症复杂病因学的认识，这是由于使用普通消费品导致的环境化学暴露。邻苯二甲酸酯被选作感兴趣的化学类别，因为它们普遍存在于个人护理产品中（例如，化妆品、芳香剂、洗发剂）和室内居住环境（例如，聚氯乙烯（PVC）地板和塑料、儿童玩具、乙烯基瓷砖、浴帘）已被证明会影响对早期大脑发育至关重要的性类固醇，并对婴儿和儿童的神经发育具有毒性。最近的一项流行病学研究还发现，在父母或孩子的房间里使用PVC地板材料（空气中邻苯二甲酸盐的来源）与ASD的风险增加有关。该项目的总体目标是确定妊娠期间暴露于邻苯二甲酸酯是否与ASD风险增加相关。为了估计产前邻苯二甲酸酯的暴露量，本研究将利用NIEHS资助的加州大学戴维斯分校儿童环境健康中心发起的一项独特纵向研究的现有资源，该研究被称为“MARBLES”（婴儿自闭症风险标志物-学习早期迹象）。MARBLES是一项前瞻性研究，招募已经有一个患有ASD的孩子的孕妇，因此有高风险分娩另一个患有自闭症的孩子，旨在确定自闭症的原因和早期标志物。从本研究中，我们获得了整个妊娠期间从母亲采集的多份尿液样本，这是改善每名婴儿和母亲暴露估计值的一个关键特征，因为邻苯二甲酸酯代谢和排泄迅速，消除半衰期约为小时。此外，来自该妊娠队列的215名儿童将在R21期间在36个月时接受自闭症评估，丰富了这些产前生物样本的价值。在首批147名36个月大的儿童中，近五分之一的儿童被确诊为ASD。其他发育诊断，包括适应功能和认知发展，也适用于这些儿童。因此，从母亲那里收集的多个妊娠尿液样本和确诊的MARBLES自闭症是非常宝贵的资源，将能够严格分析产前暴露于邻苯二甲酸酯与ASD或其他发育问题风险之间的关联。每名妇女每三个月最多采集四份尿样。为了降低分析成本，同时保持一些关于变异性的信息，我们将分析每个三个月收集的第一个样本作为一个单独的样本，并合并该三个月的所有剩余样本。为了评估妊娠期间母体暴露量的变异性，将分析9位母亲间隔约1周采集的纵向个体尿液样本的邻苯二甲酸酯代谢物水平。这项研究将显着推进对消费品中常见的一类内分泌干扰化合物对ASD的作用的理解。