Assess the Effects of ETS on Neurodevelopment

评估 ETS 对神经发育的影响

• 批准号: 8239884
• 负责人: Virginia A Rauh
• 金额: $ 65.71万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8239884
• 关键词: 10 year old; 11 year old; 2 year old; 7 year old; Age; Air Pollutants; Anatomy; Animal Model; Animals; Attention; Attention deficit hyperactivity disorder; Basal Ganglia; Behavioral; Biological Markers; Brain; Brain Chemistry; Brain region; Child; Child Development; Childhood; Clinical; Cognition; Cognitive; Cohort Studies; Data; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Dose; Environmental Health; Environmental Tobacco Smoke; Exposure to; Fiber; Functional Magnetic Resonance Imaging; Health; Hippocampus (Brain); Hyperactive behavior; Image; Impaired cognition; Lateral; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Memory; Metabolism; Modeling; Motor; N-acetylaspartate; National Institute of Environmental Health Sciences; Neurons; Neuropsychological Tests; Parietal; Parietal Lobe; Performance; Regression Analysis; Relative (related person); Risk; Sensorimotor functions; Sensory; Severities; Structure; Subgroup; Symptoms; TNFRSF5 gene; Temporal Lobe; Testing; Translational Research; Work; association cortex; base; brain size; brain volume; cognitive function; cohort; early childhood; frontal lobe; inattention; indexing; inner city; neurobehavioral; neurodevelopment; neuropsychological; postnatal; prenatal; prenatal exposure; prospective; psychologic; public health relevance; relating to nervous system; respiratory; response; white matter

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.

描述（由申请人提供）：本研究的目的是评估产前和幼儿期暴露于环境烟草烟雾（ETS）对9-10岁内城市中心儿童中大脑结构和功能的影响。拟议的工作基于并与一项前瞻性队列研究，并与周围空气污染物对儿童发育和呼吸健康的影响进行了前瞻性研究，目前由哥伦比亚儿童环境健康中心（CCCEH）（P.I. Perera）（P.I. Perera，RO1 ES08977 NIEHS：8/01/01/07-5/07-5/31/12; Nie Hehs，p.i. Perera）进行。 R827027：11/1/03-10/31/08）。 CCCEH队列研究的先前发现表明，产前暴露于ETS与2岁时认知障碍的风险增加有关（Rauh等，2004）以及2-3岁时ADHD样症状的风险增加（Rauh等，2006）。这些发现表明存在认知，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，我们的试点MRI数据比较了15名与15个未暴露儿童的ETS的儿童的大脑相比，对区域脑体积和5-7岁年龄段的解剖连通性的影响都显着影响，无论他们的生后暴露程度如何。基于这些初步发现，我们建议评估9-10岁儿童的产前和儿童早期暴露于ETS对脑发育和认知功能的影响。我们将使用磁共振成像（MRI）研究这些儿童的详细脑解剖结构，纤维区和代谢产物，我们将使用一系列神经心理学任务评估认知和注意力功能。 ET被选择为转化研究的模型剂，因为它的特征很好，在动物中进行了充分研究，并且仍然是高度普遍的暴露。具体而言，我们建议：（1）评估产前和儿童早期对ETS对ETS的9-10年影响，对神经行为（注意力不集中，多动症）和神经心理学功能（注意力，记忆力，记忆力，冲动，冲动控制和感觉运动功能）； （2）评估产前和儿童早期暴露于ETS对脑结构测量（使用解剖学MRI），脑化学（使用）的9-10年影响（使用 磁共振光谱）和解剖连通性（使用扩散张量成像），然后 同一儿童的功能活动（使用fMRI）。 公共卫生相关性：此应用是为期5年的研究，以评估环境烟烟烟雾对脑发育的影响（由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）在250名内城患者中，患有9-10岁的内城中心儿童。这项工作与哥伦比亚儿童环境健康中心进行了对环境空气污染对儿童发育的影响的纵向研究，对环境空气污染物对儿童发育的影响，从产前期到11岁。该项目可以访问以前收集的在整个儿童期的接触和丰富的社会人口统计数据的生物标志物。