Prenatal Antimicrobial Agent Exposure, Fetal Androgens and ASD Risk

产前抗菌药物暴露、胎儿雄激素和自闭症谱系障碍 (ASD) 风险

• 批准号: 9116852
• 负责人: Craig J Newschaffer
• 金额: $ 15.65万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9116852
• 关键词: Address; Affect; Age; Androgens; Autistic Disorder; Automobile Driving; Behavior; Biological Markers; Birth; Brain; Centers for Disease Control and Prevention (U.S.); Child; Clinical Data; Cohort Studies; Complex; Data; Data Collection; Endocrine Disruptors; Enrollment; Environmental Risk Factor; Etiology; Exposure to; Female; Fetus; Gender; Gene Expression; Genetic; Genomics; Gonadal Steroid Hormones; Health; Investigation; Life; Liquid substance; Measures; Meconium; Mediating; Mediator of activation protein; Mothers; Neonatal; Oral cavity; Outcome; Pathway interactions; Perinatal Exposure; Pregnancy; Prevalence; Public Health; Recurrence; Research; Research Personnel; Risk; Risk Factors; Sampling; Siblings; Soaps; Structure; Teratogens; Testosterone; Time; Toothpaste; Triclosan; Twin Multiple Birth; Umbilical Cord Blood; United States; Urine; androgenic; antimicrobial drug; autism spectrum disorder; boys; cohort; disorder risk; environmental chemical; fetal; gender difference; gender disparity; girls; interest; male; neuropathology; novel; personal care products; prenatal; prenatal exposure; prospective; racial and ethnic; relating to nervous system; socioeconomics; triclocarban

 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.

 描述（由申请人提供）：自闭症谱系障碍（ASD）是美国的一个主要公共卫生问题，影响了所有种族，民族和社会经济群体中超过1%的儿童。ASD的男女患病率比例约为4：1，这是一个公认的现象，但人们对其了解甚少。明确关注与这种性别差异相一致的潜在病因学途径应该是试图阐明ASD因果机制的优先事项，包括那些易受环境影响的因素。怀孕期间产生的雄激素，特别是睾酮，作用于大脑，在结构和功能上产生永久的性别差异。一些研究人员假设ASD是“男性大脑”的极端表现，胎儿睾丸激素可能是决定因素。已知很少有干扰内分泌的化学物质作用于雄激素;然而，三氯生和三氯卡班（TCS/TCC）已被证明具有雄激素潜力，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。利用一项对213名ASD儿童母亲在随后怀孕开始时进行的前瞻性队列研究中储存的生物样本的可用性，我们建议评估孕妇产前尿样中的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ASD相关联。在12个月和36个月时对队列中出生的儿童的相关结局进行评价。胎儿睾酮水平将作为TCS/TCC和早期ASD相关结局之间相关性的潜在中介和/或调节因素进行探讨。该研究将调查一种潜在的可避免的环境ASD风险因素，提供与观察到的ASD性别比相符的病因机制相关的证据，并生成胎粪中评估的胎儿睾酮水平的数据。