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 自闭症和谱系障碍（ASD）是严重的和衰弱的神经发育障碍， 病人的痛苦，并对我们的医疗体系构成重大挑战。现在估计 ASD影响68名儿童中的1名，男女比例为4：1。遗传和环境因素 导致ASD，但环境因素尚未得到充分研究。因为环境因素是 他们的研究应该是优先研究的。因此，迫切需要了解 环境因素在ASD风险中的作用这一努力受到了获得 在适当规模的流行病学队列中进行准确和相关的暴露测量。 我们资助申请的目标是确定产前暴露于多种类型的 内分泌干扰物（EDCs）对ASD风险的影响。为了实现这一点，我们使用存储的样本， 瑞典南部的血清生物库和相应的基于人群的登记处， 1998年所有新生儿的围产期、诊断、医疗和人口统计资料， 2007.我们原本建议确定600名自闭症患者和600名性别和出生年份相似的对照 分布，测量母体血清样品中的内分泌干扰物水平，并研究三种综合特异性 目的：首先，确定ASD风险和我们的目标EDCs的产前血清浓度之间的关联， 第二，确定性别是否改变这些关联;第三，确定产前是否 单独和联合暴露于内分泌干扰物会导致ASD表型和严重程度的个体差异。 目前的要求是提供补充资金，以测量397例ASD病例中的EDCs水平， 除了600个病例和对照组，其数据收集由原始赠款资助。最初 建议的样本量反映了根据现有数据计算的统计功效估计值 (but非代表性）数据。自研究开始以来获得的初步数据证实， 受试者将提供足够的统计能力来实现目标并完成特定目标 原申请的样本量无法满足要求。 所有997例病例均已查明，其储存的产前血清已得到确认。此外，本发明还提供了一种方法， 因为997例病例的扩大样本包括了研究地区和时间内所有确诊的ASD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件查明所有 在一个大型临床特征良好的人群中诊断出的ASD病例超过10年。这项研究， 包括997例ASD病例，有广泛的暴露和登记数据，将是最大和最完整的 迄今为止进行的产前内分泌干扰物暴露的研究，应该为今后的研究建立一个新的标准。 重要的问题。