Autism and Prenatal Endocrine Disruptors (A-PED)

项目总结 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， 给病人带来了巨大的痛苦，对我们的医疗保健系统构成了重大挑战。据估计，ASD 每68名儿童中就有1名患病，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 它们可能是可修改的，应该成为研究的优先事项。这一努力受到了以下挑战的阻碍 在大规模、不偏不倚的流行病学队列中获得准确和相关的暴露措施。 在人类暴露在许多环境中的环境中，内分泌干扰物 (EDS)可能对儿科人群的神经发育有最广为人知的影响。其中的几个 化学物质，特别是在产前暴露的情况下，已经被认为与自闭症相关的表型有关，而性- 这些关联之间的差异已被记录在案。EDS已被证明影响GABA和 谷氨酸的神经传递，在ASD中起着重要作用。因此，EDS很有希望成为候选人 环境因素是ASD的诱因。据我们所知，没有一项先前的研究能够有力地将产前教育联系起来 暴露于自闭症。 该应用程序的目标是确定产前暴露于五类ED是否会影响ASD风险。 为了实现这一点，我们将使用瑞典南部一个血清生物库的存储样本，并将这些样本链接到 基于人口的登记，包括个人级别的围产期、诊断、医疗和人口统计 资料(1998-2007年出生117,318人)。我们将随机选择并验证600例ASD病例 (过度抽样女性，包括200名女性，400名男性)和600名性别和出生年份相似的对照组 分配。通过检测母体血清样本中五种化学成分中的38种内分泌物质的浓度，我们 将解决以下三个综合具体目标：第一，确定自闭症风险之间的关联 和我们的目标EDS及其混合物的产前血清浓度；第二，确定性别 改变对产前ED暴露的敏感性，导致性别二型性ED-ASD关联；第三，确定 单独或联合使用内分泌激素浓度是否会导致ASD表型和 他们的严肃性。

PROJECT SUMMARY Autism and spectrum disorders (ASD) are serious and debilitating neurodevelopmental disorders that incur substantial suffering for patients and 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 they should be a research priority. This effort has been hampered by the challenges of acquiring accurate and relevant exposure measures in large, unbiased, epidemiologic cohorts. Among the many environmental exposures to which humans are exposed, endocrine disrupting chemicals (EDs) have perhaps the best-known effects on neurodevelopment in pediatric populations. Several of these chemicals, particularly when exposure is prenatal, have been linked to autism-related phenotypes, and sex- differences in these associations have been documented. EDs have been shown to affect GABA and glutamate neurotransmission, which have prominent roles in ASD. Therefore, EDs are promising candidates as environmental triggers for ASD. To our knowledge, no prior study has been able to robustly link prenatal ED exposure to ASD. The goal of this application is to determine whether prenatal exposure to five classes of EDs impacts ASD risk. To achieve this, we will use stored samples from a serum biobank in southern Sweden and link these to population-based registries that include individual-level perinatal, diagnostic, medical, and demographic information (117,318 births in the years 1998-2007). We will randomly select and validate 600 ASD cases (oversampling females to include 200 females, 400 males) and 600 controls with similar sex and birth year distributions. By measuring concentrations of 38 EDs in five chemical classes in maternal serum samples we will address the following three integrated specific aims: First, determine the associations between ASD risk and prenatal serum concentration of our target EDs and their mixtures; Second, determine whether gender modifies sensitivity to prenatal ED exposure resulting in sex-dimorphic ED-ASD associations; Third, determine whether concentrations of EDs, singly and in combination, contribute to differences in ASD phenotype and their severity.