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.

项目概要 自闭症和谱系障碍 (ASD) 是严重且使人衰弱的神经发育障碍，会导致 给患者带来巨大痛苦，并对我们的医疗保健系统构成重大挑战。现在估计 自闭症谱系障碍 (ASD) 影响大约六分之一的儿童，男女比例为 4:1。遗传和环境因素都有 有助于自闭症谱系障碍（ASD），但环境因素尚未得到充分研究。因为环境因素是 潜在的可修改的研究应该是研究的重点。因此，迫切需要了解 环境因素在 ASD 风险中的作用。这项努力因收购的挑战而受到阻碍 在足够规模的流行病学队列中进行准确且相关的暴露测量。 我们资助申请的目标是确定产前接触多种类别的影响 内分泌干​​扰物 (EDC) 对 ASD 风险的影响。为了实现这一目标，我们使用来自 瑞典南部的血清生物库和相应的基于人群的登记处，包括可链接的、 1998-1998年间所有出生的个体层面的围产期、诊断、医疗和人口统计信息 2007年，我们最初提议确定600个自闭症谱系障碍病例和600个性别和出生年份相似的对照 分布，测量母体血清样本中 EDC 的水平，并研究三个综合的特定 目标：首先，确定 ASD 风险与我们的目标 EDC 的产前血清浓度之间的关联， 它们的混合物；其次，确定性别是否会改变这些关联；三、判断是否产前 单独或联合接触 EDC 会导致 ASD 表型和严重程度的个体差异。 目前的请求是提供补充资金来衡量 397 个 ASD 病例中的 EDC 水平以及控制措施 除了由原始赠款资助的 600 个病例和对照数据收集之外。那最初 拟议的样本量反映了统计功效的估计，该统计功效是根据现有数据计算得出的 （但不具有代表性）数据。自研究开始以来获得的试点数据证实，添加所要求的 受试者将提供足够的统计能力来实现目标和完成特定目标 最初提出的样本量无法满足原始申请的要求。 所有 997 例病例均已被确认，并已确认其储存的产前血清的可用性。此外， 因为997例的扩展样本包括了研究地区和时间段内所有确诊的自闭症谱系障碍病例 在此期间，这项研究将为研究界提供有史以来第一个完整的案例查明 十年间在大量临床特征明确的人群中诊断出的自闭症谱系障碍 (ASD) 病例。这项研究， 包括997个自闭症谱系障碍案例，具有广泛的曝光和登记数据，届时将是最大、最完整的 迄今为止对产前 EDC 暴露进行的研究应该为未来的研究制定新的标准 重要的问题。