Autism and Prenatal Endocrine Disruptors (A-PED)

项目摘要 自闭症和谱系障碍(ASD)是一种严重的和衰弱的神经发育障碍， 这给患者带来了巨大的痛苦，并对我们的医疗保健系统构成了重大挑战。据估计，现在 每68名儿童中就有1名患有自闭症，男女比例为4：1。遗传和环境因素都有 导致自闭症的因素，但环境因素一直研究不足。因为环境因素是 潜在的可修改他们的研究应该是研究的优先事项。因此，迫切需要了解 环境因素在ASD风险中的作用。这一努力受到了收购挑战的阻碍 在适当规模的流行病学队列中采取准确和相关的暴露措施。 我们资助的应用程序的目标是确定产前暴露于多种类别的 内分泌干扰物(EDCs)对ASD风险的影响。为了实现这一点，我们使用来自 瑞典南部的血清生物库和相应的基于人群的登记，包括可链接的， 1998年所有出生人口的个人围产期、诊断、医学和人口资料-- 2007年。我们最初建议确定600例自闭症患者和600名性别和出生年份相似的对照 检测母体血清中内皮细胞的分布和水平，并调查三种整合的特异性 目的：首先，确定ASD风险与我们的目标EDCs和产前血清浓度之间的关系 它们的混合物；第二，确定性行为是否改变了这些联系；第三，确定产前 单独和联合暴露于内皮细胞可导致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，以衡量397个自闭症病例的内分泌细胞水平和#年的对照。 此外，还有600个病例和对照，其数据收集由原始赠款提供资金。一开始， 拟议样本量反映了统计能力的估计，这些估计是根据现有的 (但不具代表性)数据。自研究开始以来获得的试点数据证实，添加请求的 学科将提供足够的统计力量来实现目标和完成特定的目标 不能满足最初提出的样本量的原始申请。 所有997例病例都已确认，并确认了其储存的产前血清的可用性。此外, 因为997例病例的扩大样本包括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所有 在十年的时间里，在大量临床特征良好的人群中诊断出ASD病例。这项研究， 包括997个有广泛暴露和注册数据的自闭症病例，将是最大和最完整的 到目前为止对产前EDCs暴露的研究，应该为未来的这方面的研究设定一个新的标准 很重要的问题。

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.