Autism and Prenatal Endocrine Disruptors (A-PED)

自闭症和产前内分泌干扰物 (A-PED)

• 批准号: 10251532
• 负责人: ABRAHAM REICHENBERG
• 金额: $ 7.4万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-04 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10251532
• 关键词: Affect; Birth; Chemical Exposure; Child; Clinical; Communities; Data; Data Collection; Diagnosis; Diagnostic; Endocrine Disruptors; Environment; Environmental Risk Factor; Epidemiology; Exposure to; Female; Funding; Future; Genetic; Goals; Grant; Healthcare Systems; Individual; Individual Differences; Measures; Medical; Neurodevelopmental Disorder; Patients; Perinatal; Phenotype; Population; Population-Based Registry; Pregnancy; Research; Research Priority; Resources; Risk; Role; Sample Size; Sampling; Serum; Severities; Sweden; Time; autism spectrum disorder; biobank; case control; cohort; data registry; disorder risk; male; maternal serum; population based; prenatal; prenatal exposure; sex

Project Summary Autism and spectrum disorders (ASD) are serious and debilitating neurodevelopmental disorders that incur substantial suffering for patients and pose major challenges to our health care system. It is now estimated that ASD affects about 1 in 68 children, with a male:female ratio of 4:1. Both genetic and environmental factors contribute to ASD, but environmental factors have been understudied. Because environmental factors are potentially modifiable their study should be a research priority. Thus, there is an urgent need to understand the role of environmental factors in ASD risk. This effort has been hampered by the challenge of acquiring accurate and relevant exposure measures in epidemiologic cohorts of adequate size. The goal of our funded application is to determine the impact of prenatal exposure to multiple classes of endocrine disrupting chemicals (EDCs) on ASD risk. To achieve this, we are using stored samples from a serum biobank in South Sweden and corresponding population-based registries that include linkable, individual-level perinatal, diagnostic, medical, and demographic information for all births in the years 1998- 2007. We originally proposed to ascertain 600 ASD cases and 600 controls with similar sex and birth year distributions, measure levels of EDCs in maternal serum samples, and investigate three integrated specific aims: first, determine associations between ASD risk and prenatal serum concentration of our target EDCs and their mixtures; second, determine whether sex modifies these associations; third, determine whether prenatal exposure to EDCs, singly and combined, contributes to individual differences in ASD phenotype and severity. The current request is for supplemental funds to measure levels of EDCs in 397 ASD cases and controls in addition to the 600 cases and controls whose data collection is funded by the original grant. That initially proposed sample size reflects estimates of statistical power which were calculated on the basis of available (but non-representative) data. Pilot data obtained since study onset confirms that adding the requested subjects will provide sufficient statistical power to achieve the goals and accomplish the specific aims of the original application which cannot be met with the originally proposed sample size. All 997 cases have been identified, and the availability of their stored prenatal serum confirmed. In addition, because the expanded sample of 997 cases include all diagnosed ASD cases in the study region and time period, this study will provide the research community with the first-ever complete case ascertainment of all ASD cases diagnosed in a large clinically well-characterized population over a ten-year period. This study, including 997 ASD cases with extensive exposure and registry data, will then be the largest and most complete study of prenatal EDCs exposure undertaken to date and should set a new standard for future studies of this important question.

项目摘要 自闭症和频谱障碍（ASD）是严重的，令人衰弱的神经发育障碍 对患者的巨大痛苦，并对我们的医疗保健系统构成重大挑战。现在估计 ASD影响68名儿童中约1个，男性：女性比例为4：1。遗传和环境因素 有助于ASD，但已经研究了环境因素。因为环境因素是 他们的研究可能会成为研究的重点。因此，迫切需要了解 环境因素在ASD风险中的作用。收购的挑战阻碍了这一努力 足够大小的流行病学人群中的准确且相关的暴露措施。 我们资助的应用的目的是确定产前暴露于多个类别的影响 内分泌破坏化学物质（EDC）在ASD风险上。为了实现这一目标，我们正在使用来自 瑞典南部的血清生物库，以及相应的基于人群的注册表，包括可连接的， 1998年所有出生的个人级别围产期，诊断，医学和人口统计信息 2007年。我们最初建议确定600例ASD案例和600个性别和出生年份的对照 分布，孕妇血清样品中EDC的度量水平，并研究了三个集成的特定特异性 目的：首先，确定目标EDC的ASD风险与产前血清浓度之间的关联 他们的混合物；其次，确定性别是否改变了这些关联；第三，确定是否产前 单独和合并的EDC暴露会导致ASD表型和严重程度的个体差异。 当前的要求是补充资金，以测量397例ASD案件中的EDC水平和控制 除了原始赠款资助其数据收集的600个案例和控件。最初 建议的样本量反映了统计功率的估计值，根据可用 （但非代表性）数据。自从研究开始以来获得的试验数据证实，添加了请求的 受试者将提供足够的统计能力来实现目标并实现特定目标 最初建议的样本量无法满足的原始应用程序。 所有997例病例均已确定，并确认其储存的产前血清的可用性。此外， 因为扩大的997例病例的样本包括研究区域和时间中所有已诊断的ASD病例 时期，这项研究将为研究界提供有史以来第一个完整的案例确定 在十年期间，在大量临床表征的人群中诊断出的ASD病例。这项研究， 包括997个ASD案件，具有广泛的曝光和注册表数据，然后将是最大，最完整的 迄今为止进行的产前EDCS暴露的研究应为将来的研究设定新的标准 重要的问题。