Assess the Effects of ETS on Neurodevelopment

描述(申请人提供)：这项研究的目的是评估出生前和儿童早期暴露于环境烟草烟雾(ETS)对9-10岁市中心儿童大脑结构和功能的影响。拟议的工作建立在环境空气污染物对儿童发育和呼吸健康影响的预期队列研究的基础上，并与之共享，该研究目前由哥伦比亚儿童环境健康中心(P.I.Perera，RO1 ES08977 NIEHS：8/01/07-5/31/12；NIEHS P50 ES09066，EPA R827027：11/1/03-10/31/08)进行。CCCEH队列研究以前的研究结果表明，产前暴露于ETS与2岁时认知障碍的风险增加(Rauh等人，2004年)和2-3岁时ADHD样症状的风险增加(Rauh等人，2006年)相关。这些发现表明，认知障碍、注意力不集中、多动症和 与早期接触ETS相关的冲动控制。与这些行为发现一致的是，我们的初步MRI数据比较了15名产前暴露于ETS的儿童和15名未暴露的儿童的大脑，结果显示，在5-7岁时，无论他们出生后暴露的程度如何，大脑的局部体积和解剖连接都会受到显著影响。基于这些初步发现，我们建议评估产前和儿童早期暴露于ETS对250名9-10岁儿童大脑发育和认知功能的影响。我们将使用磁共振成像(MRI)来研究这些儿童的详细大脑解剖、纤维束和代谢物，我们将使用一系列神经心理学任务来评估认知和注意力功能。ETS被选为翻译研究的模型代理，因为它具有很好的特性，在动物中得到了很好的研究，并且仍然是一种高度流行的暴露。具体地说，我们建议：(1)评估产前和儿童早期接触ETS对神经行为(注意力不集中、多动)和神经心理功能(注意力、记忆、冲动控制和感觉运动功能)的9-10年影响；以及(2)评估产前和儿童早期接触ETS对大脑结构(使用解剖MRI)、脑化学(使用 磁共振波谱)和解剖连接性(使用扩散张量成像)，以及 相同儿童的功能活动(使用功能磁共振成像)。 公共卫生相关性：这项应用是一项为期5年的研究，旨在评估暴露在环境烟草烟雾中对大脑发育(通过MRI和fMRI评估)和神经行为功能(通过标准化的临床和发育测试评估)的影响，队列中有250名9-10岁的市中心儿童。这项工作与哥伦比亚儿童环境健康中心正在进行的一项关于环境空气污染物对儿童从产前到11岁的发展影响的纵向研究是相同的。该项目可以获得以前收集的暴露生物标志物和整个童年时期丰富的社会人口数据。

DESCRIPTION (provided by applicant): The purpose of this study is to assess the effects of prenatal and early childhood exposure to environmental tobacco smoke (ETS) on brain structure and function in a cohort of inner-city children who are 9-10 years of age. The proposed work builds on, and shares a cohort with, a prospective cohort study of ambient air pollutant effects on child development and respiratory health, currently being conducted by the Columbia Center for Children's Environmental Health (CCCEH) (P.I. Perera, RO1 ES08977 NIEHS: 8/01/07-5/31/12; NIEHS P50 ES09066, EPA R827027:11/1/03-10/31/08). Previous findings from the CCCEH cohort study have shown that prenatal exposure to ETS was associated with an increased risk of cognitive disturbances at age 2 years (Rauh et al., 2004) and increased risk of ADHD-like symptoms at age 2-3 years (Rauh et al., 2006). These findings suggest the concerning presence of disturbances of cognition, inattention, hyperactivity, and impulse control associated with early exposure to ETS. Consistent with these behavioral findings, our pilot MRI data comparing the brains of 15 children prenatally exposed to ETS with 15 unexposed children showed significant effects on regional brain volumes and anatomical connectivity at 5-7 years of age, regardless of their degree of postnatal exposure. Based on these preliminary findings, we propose to evaluate the effects of prenatal and early childhood exposure to ETS on brain development and cognitive functioning in 250 children at 9-10 years of age. We will use Magnetic Resonance Imaging (MRI) to study detailed brain anatomy, fiber tracts, and metabolites in these children, and we will assess cognitive and attentional functioning using an array of neuropsychological tasks. ETS was selected as a model agent for translational research because it is well characterized, well-studied in animals, and continues to be a highly prevalent exposure. Specifically, we propose to: (1) assess the 9-10-year effects of prenatal and early childhood exposures to ETS on neurobehavioral (inattention, hyperactivity) and neuropsychological functioning (attentional capacity, memory, impulse control and sensory motor functioning); and (2) assess the 9-10-year effects of prenatal and early childhood exposures to ETS on measures of brain structure (using anatomical MRI), brain chemistry (using magnetic resonance spectroscopy), and anatomical connectivity (using diffusion tensor imaging), and functional activity (using fMRI) in the same children. PUBLIC HEALTH RELEVANCE: This application is for a 5-year study to assess the effects of exposure to environmental tobacco smoke on brain development (assessed by MRI and fMRI) and neurobehavioral functioning (assessed by standardized clinical and developmental testing) in a cohort of 250 inner-city children who have reached 9-10 years of age. This work shares a cohort with a longitudinal study of ambient air pollutant effects on child development, from the prenatal period to 11 years of age, being conducted by the Columbia Center for Children's Environmental Health. The project has access to previously collected biomarkers of exposure and rich socio-demographic data throughout childhood.