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: 8917642
• 负责人: Craig J Newschaffer
• 金额: $ 27.39万
• 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 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8917642
• 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; 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; Self Care; Sex Characteristics; Siblings; Soaps; Structure; Teratogens; Testosterone; Time; Toothpaste; Triclosan; Twin Multiple Birth; Umbilical Cord Blood; United States; Urine; antimicrobial drug; autism spectrum disorder; boys; cohort; disorder risk; environmental chemical; fetal; girls; interest; male; neuropathology; novel; prenatal; prenatal exposure; prospective; public health relevance; 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（由适用提供）：自闭症谱系障碍（ASD）是美国的主要公共卫生问题，在所有种族，种族和社会经济群体中都影响了该国超过1％的儿童。在ASD中，大约4：1的男性与女性患病率是一种公认​​的，但理解不佳的现象。明确关注与这种性别差异一致的潜在病因学途径，应该是阐明ASD灾难机制（包括可符合环境影响的）的优先事项。雄激素，尤其是睾丸激素，在大脑妊娠法案中产生的雄激素，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ASD是“男性大脑”的极端表现，胎儿睾丸激素是可能的决定因素。众所周知，很少有内分泌破坏化学物质对雄激素作用。然而，三氯糖类和三氯甲烷（TCS/TCC）已被证明具有雄激素潜力，现在广泛用于液体肥皂，牙膏，口冲洗和其他个人护理产品中。通过对213名ASD儿童的前瞻性群体研究中的储存生物样本的可用性，在随后的怀孕开始时，ASD儿童的儿童的可用性，我们建议评估产前TCS/TCC暴露于产产产产产产日尿液样本中的产前尿液样本和胎儿睾丸激素水平，然后在这些摩托群中，并在36个摩托中衡量了36个摩托车，并与ASD摩擦相关，并与ASD相关。进入队列。胎儿睾丸激素水平将作为TCS/TCC与早期与ASD相关结果之间关联的潜在介导和/或调节因素进行探讨。该研究将研究潜在的可避免的环境ASD风险因素，提供与与观察到的ASD性别比例相符的病因机制相关的证据，并在Meconium评估的胎儿睾丸激素水平上生成I数据。