Prenatal Antimicrobial Agent Exposure, Fetal Androgens and ASD Risk

 描述(由申请人提供)：自闭症谱系障碍(ASD)是美国一个主要的公共卫生问题，影响着全国所有种族、民族和社会经济群体中超过1%的儿童。在自闭症患者中，男性与女性的患病率约为4：1，这是一个广为人知但却鲜为人知的现象。明确关注与性别差异相一致的潜在致病途径应该是试图阐明ASD病因机制的优先事项，包括那些受环境影响的机制。怀孕期间产生的雄激素，特别是睾丸素，作用于大脑，在结构和功能上产生永久性的性别差异。一些研究人员假设，自闭症是“男性大脑”的极端表现，胎儿睾丸素可能是决定因素。已知的对雄激素起作用的内分泌干扰物很少；然而，三氯生和三氯碳酸酯(TCS/TCC)已被证明具有促雄激素的潜力，现在被广泛用于液体肥皂、牙膏、漱口水和其他个人护理产品。利用一项前瞻性队列研究中储存的生物样本的可用性，我们建议评估母亲产前尿样中的TCS/TCC暴露以及脐带血和胎粪中的胎儿睾酮水平，然后将这些测量与队列中出生的儿童在12个月和36个月时评估的ASD相关结果相关联。将探讨胎儿睾酮水平作为TCS/TCC和ASD相关早期结局之间的潜在中介和/或调节因素。这项研究将调查一个潜在的可避免的环境ASD风险因素，提供与ASD的病因机制相关的证据，符合观察到的ASD性别比，并产生胎粪中评估的胎儿睾酮水平的I数据。

 DESCRIPTION (provided by applicant): Autism spectrum disorders (ASDs) are a major public health concern in the United States affecting more than 1% of the nation's children in all racial, ethnic, and socioeconomic groups. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized, but poorly-understood, phenomenon. An explicit focus on potential etiologic pathways consistent with this gender difference should be a priority in attempts to elucidate ASD causal mechanisms, including those amenable to environmental influence. Androgens, in particular testosterone, produced during pregnancy act on the brain to produce permanent gender differences in structure and function. Some researchers have hypothesized that ASD is an extreme presentation of "male brain," with fetal testosterone as the possible determining factor. Few endocrine disrupting chemicals are known to act on androgens; however, triclosans and triclocarbans (TCS/TCC) have been shown to have androgenic potential and are now widely used in liquid soap, toothpaste, mouth rinse, and other personal care products. Capitalizing on the availability of stored biosamples from a prospective cohort study of 213 mothers of children with ASD at the start of a subsequent pregnancy, we propose to assess prenatal TCS/TCC exposure in maternal prenatal urine samples and fetal testosterone levels in both cord blood and meconium and then and correlate these measures with ASD-related outcomes evaluated at 12 mos and 36 mos of age in the children born into the cohort. Fetal testosterone level will be explored as a potential mediating and/or moderating factor in associations between TCS/TCC and early ASD-related outcomes. The study will investigate a potentially avoidable environmental ASD risk factor, provide evidence related to an etiologic mechanism that comports with the observed ASD gender ratio, and generate i data on a fetal testosterone levels as assessed in meconium.