Phthalate Exposure and Gender-related Development

邻苯二甲酸盐接触与性别相关发展

• 批准号: 9059714
• 负责人: Shanna H Swan
• 金额: $ 62.33万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9059714
• 关键词: 6 year old; Address; Affect; Age; Androgens; Animal Model; Anthropometry; Anxiety; Attention; Behavior; Behavior assessment; Birth; Characteristics; Child; Child Behavior; Childhood; Classification; Cohort Studies; Data; Databases; Development; Digit structure; Endocrine; Environment; Environmental Health; Environmental Policy; Event; Exposure to; Family; Feminine; Fetal Development; First Pregnancy Trimester; Future; Gender; Genital system; Goals; Head circumference; Health; Health Policy; Height; Hyperactive behavior; Infant Development; Investigation; Length; Life; Longevity; Masculine; Measurement; Measures; Mental Depression; Methodology; Methods; Modeling; Modification; Mothers; Newborn Infant; Occupations; Outcome; Outcome Measure; Play; Policies; Pregnancy; Prospective Studies; Psychosocial Stress; Public Health; Reporting; Research; Sampling; Skinfold Thickness; Social support; Stress; Time; Urine; Visit; Visuospatial; Weight; anogenital distance; behavior measurement; biobank; boys; cohort; design; early childhood; fetal; follow-up; gender behavior; global environment; improved; indexing; instrument; maternal stress; middle childhood; neurobehavioral; neurodevelopment; novel; phthalates; postnatal; prenatal; prenatal exposure; prenatal stress; prospective; reproductive; sex; social; stressor; success

 DESCRIPTION (provided by applicant): In animal models phthalates and stress can alter fetal androgens and disrupt androgen-sensitive endpoints. We will examine associations between exposure to phthalates and psychosocial stress at multiple time points in early childhood development and androgen-sensitive reproductive, anthropometric, and neurodevelopmental endpoints. In The Infant Development and the Environment Study (TIDES) we confirmed that first trimester phthalate exposure is significantly and inversely associated with boy's anogenital distance (AGD) and that prenatal stress can modify this association. These novel findings suggest hypotheses that can be addressed with further follow-up of the TIDES cohort during middle childhood. We propose to extend our methodology in several novel directions in order to achieve our overarching goal of identifying the effects of exposure to phthalates and stress on androgen-sensitive development. Children born to TIDES mothers will be invited to two study visits between 3 and 6 years of age. At the 1st visit we will measure height, weight, skin fold thickness, and head circumference, and collect a sample of the child's urine for phthalate measurement. We will assess the child's attention, hyperactivity, social responsiveness, and play behavior by parental report. At the 2nd visit we will repeat these assessments and measure the length of the 2nd and 4th digits and their ratio as well as measuring the child's verbal abilit and visuospatial reasoning by direct assessment. At each visit mothers will complete instruments designed to measure perceived stress, anxiety and depression, job stress and stressful life events. We will create a novel index that transforms the binary classification of se into a gender continuum score and examine its association with pre and postnatal exposure to phthalates and psychosocial stress. We hypothesize that physical measurements (AGD, digit ratio, head circumference) will be sensitive to prenatal exposure, while neurodevelopmental endpoints may be sensitive to both prenatal and postnatal exposure. We hypothesize that AGD will correlate with anthropometric outcomes as well as one or more neurodevelopmental endpoints such as play behavior as our preliminary data suggest. This study could have several implications for public health and environmental policy. Finding robust associations between developmental endpoints and phthalate exposure at current low levels would suggest the need for further reducing exposure. If newborn AGD predicts dimorphic development in multiple domains this would strengthen its importance as a marker of altered androgen-related development. If maternal stress modifies associations between phthalates and dimorphic development, as we have seen with AGD, this would lend support to efforts to reduce stress-related exposures during pregnancy. Any one of these findings from this large, robust, multi- center prospective study would support the hypothesis that a common androgen-dependent mechanism underlies these associations. Our findings could impact future research and policy because our study exposures are ubiquitous and many of our study endpoints, or their correlates, are early predictors of lifelong health.

 描述（由申请方提供）：在动物模型中，邻苯二甲酸酯和应激可改变胎儿雄激素并破坏雄激素敏感性终点。我们将研究在儿童早期发育的多个时间点暴露于邻苯二甲酸酯和心理社会压力之间的关联，以及雄激素敏感的生殖，人体测量和神经发育终点。在婴儿发育和环境研究（TIDES）中，我们证实，前三个月邻苯二甲酸酯暴露与男孩的肛门生殖器距离（AGD）显著负相关，产前压力可以改变这种关联。这些新的发现提出了一些假设，这些假设可以通过在儿童中期对TIDES队列进行进一步随访来解决。我们建议在几个新的方向扩展我们的方法，以实现我们的总体目标，确定暴露于邻苯二甲酸酯和压力对雄激素敏感的发展的影响。TIDES母亲所生的儿童将被邀请参加两次3至6岁的研究访问。在第一次访视时，我们将测量身高、体重、皮褶厚度和头围，并收集儿童的尿液样本用于邻苯二甲酸酯测量。我们将通过父母的报告来评估孩子的注意力、多动症、社会反应和游戏行为。在第二次访视时，我们将重复这些评估，并测量第2和第4个数字的长度及其比例，以及通过直接评估来测量儿童的语言能力和视觉空间推理。在每次访问中，母亲将完成旨在测量感知压力、焦虑和抑郁、工作压力和压力性生活事件的工具。我们将创建一个新的指数，将se的二元分类转换为性别连续体分数，并检查其与产前和产后邻苯二甲酸酯暴露和心理压力的关系。我们假设，物理测量（年龄，手指比，头围）将是敏感的产前暴露，而神经发育终点可能是敏感的产前和产后暴露。我们假设AGD与人体测量结果以及一个或多个神经发育终点（如我们的初步数据显示的游戏行为）相关。这项研究可能对公共卫生和环境政策产生一些影响。在目前的低水平下，发现发育终点与邻苯二甲酸酯暴露之间存在强有力的关联，这表明需要进一步减少暴露。如果新生儿AGD预测多个领域的二态发育，这将加强其作为雄激素相关发育改变的标志物的重要性。如果母体压力改变了邻苯二甲酸酯和二态发育之间的关联，正如我们在AGD中所看到的那样，这将为减少妊娠期间与压力相关的暴露提供支持。这项大型、稳健、多中心前瞻性研究的任何一项发现都将支持这一假设，即这些相关性的基础是一种共同的雄激素依赖机制。我们的研究结果可能会影响未来的研究和政策，因为我们的研究暴露是无处不在的，我们的许多研究终点或其相关因素是终身健康的早期预测因素。