Assess the Effects of Pre- and Postnatal exposure to the organophosphorus

评估产前和产后接触有机磷的影响

• 批准号: 7584733
• 负责人: Virginia A Rauh
• 金额: $ 56.7万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-11 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7584733
• 关键词: 10 year old; 3 year old; 9 year old; Adverse effects; Affect; Agriculture; Air Pollutants; Anatomy; Animal Model; Animals; Area; Attention; Attention deficit hyperactivity disorder; Behavioral; Biological Markers; Birth Weight; Brain; Brain Chemistry; Brain region; Chemicals; Child; Child Development; Chlorpyrifos; Clinical; Cognition; Cognitive; Cohort Studies; Development; Developmental Delay Disorders; Diagnosis; Diazinon; Diffusion Magnetic Resonance Imaging; Documentation; Dose; Environmental Health; Exposure to; Fetal Growth; Fiber; Head; Health; Hippocampus (Brain); Hyperactive behavior; Image; Lateral; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Memory; Metabolism; Modeling; Motor; Motor Activity; N-acetylaspartate; National Institute of Environmental Health Sciences; Neurobiology; Neurons; Neuropsychological Tests; Organophosphates; Parietal; Pattern; Performance; Pesticides; Problem behavior; Regression Analysis; Relative (related person); Safety; Sensorimotor functions; Sensory; Severities; Structure; Subgroup; Symptoms; TNFRSF5 gene; Temporal Lobe; Translational Research; Umbilical Cord Blood; United States; Work; association cortex; base; brain size; brain volume; cognitive function; cohort; depression; early childhood; inattention; indexing; inner city; neurobehavioral; neurodevelopment; neuroimaging; neuropsychological; postnatal; prenatal; prenatal exposure; prospective; psychologic; public health relevance; relating to nervous system; respiratory; response; toxic organophosphate insecticide exposure; white matter

DESCRIPTION (provided by applicant): The purpose of this study is to assess the effects of pre- and postnatal exposure to the organophosphorus (OP) pesticide chlorpyrifos (CPF) on neurobehavioral functioning in a cohort of inner-city children who have reached 9 years of age. This work builds on, and shares a cohort with, a prospective cohort study of ambient air pollutant effects on child development and respiratory health, being conducted by the Columbia Center for Children's Environmental Health (NIEHS R01 ES08977, P.I. Perera:11/01/03-10/31/08; 5 P01 ES09600/EPA RD-83214101, P.I. Perera, Co-I Rauh:11/01/03-10/31/08). Previous findings from the Children's Center study reveal adverse effects of prenatal exposure to CPF (validated with biomarkers in cord blood) on birth weight (Whyatt et al., 2004), cognitive and motor development, and neuro-behavioral problems at 3 years (Rauh et al., 2006). Affected neurobehavioral areas include attention and ADHD-- conditions with serious long-term clinical implications. Based on these findings, and evidence from the experimental literature showing long-term, possibly irreversible effects of CPF exposure on brain development and sensorimotor activity (Dam et al, 2000; Levin et al, 2002; Slotkin et al, 2005), we now propose to evaluate the longer-term neurodevelopmental effects of CPF in 300 9-year-old children. We will use Magnetic Resonance Imaging (MRI) to define the intermediary neurobiological effects of CPF exposure on the structure, metabolism, and anatomical connectivity of the brain in all 300 children. CPF was selected as a model for translational research because it is representative of the class of OP pesticides, well characterized, and well-studied in animals. Furthermore, agricultural and commercial uses continue, despite the 2001 residential ban by EPA. Specifically, we propose to: (1) assess the 9- year effects of prenatal and early childhood exposures to CPF on neurobehavioral (inattention, hyperactivity and depression) and neuropsychological functioning (attentional capacity, memory, impulse control and sensory motor functioning); and (2) assess the 9-year effects of prenatal and early childhood exposures to CPF on measures of brain structure (using anatomical MRI), brain chemistry/cellular metabolism (using magnetic resonance spectroscopy), and anatomical connectivity (using diffusion tensor imaging) in the same children. PUBLIC HEALTH RELEVANCE: This application is for a 5-year study to assess the effects of exposure to the organophosphorus pesticides, chlorpyrifos and diazinon, on neurobehavioral functioning in a cohort of inner-city children (n=400) who have reached 8-9 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 9 years of age, being conducted by the Columbia Center for Children's Environmental Health. The project has access to biomarkers of exposure, includes neuroimaging assessments on a subset of 60 children, and has potential for further informing regulatory safety standards for OP use in the United States.

描述（由申请人提供）：本研究的目的是评估出生前和出生后暴露于有机磷（OP）农药毒死蜱（CPF）对9岁以下的市中心儿童的神经行为功能的影响。这项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前瞻性队列研究的基础上，并与之共享一个队列，该研究由哥伦比亚儿童环境健康中心进行（NIEHS R 01 ES 08977，P.I. Perera：11/01/03-10/31/08; 5 P01 ES 09600/EPA RD-83214101，P.I. Perera，Co-I Rauh：11/01/03-10/31/08）。来自儿童中心研究的先前发现揭示了产前暴露于CPF（用脐带血中的生物标志物验证）对出生体重的不利影响（Whyatt等人，2004）、认知和运动发育以及3年时的神经行为问题（Rauh等人，2006年）。受影响的神经行为领域包括注意力和多动症-具有严重长期临床影响的条件。基于这些发现，以及来自实验文献的证据表明CPF暴露对大脑发育和感觉运动活动的长期、可能不可逆的影响（Dam et al，2000; Levin et al，2002; Slotkin et al，2005），我们现在建议在300名9岁儿童中评价CPF的长期神经发育影响。我们将使用磁共振成像（MRI）来确定CPF暴露对所有300名儿童大脑结构，代谢和解剖连接的中介神经生物学影响。选择CPF作为转化研究的模型，因为它是OP农药类的代表，具有良好的特性，并在动物中进行了充分的研究。此外，尽管美国环保局于2001年颁布了住宅禁令，但农业和商业用途仍在继续。具体而言，我们建议：（1）评估产前和幼儿期暴露于CPF对神经行为的9年影响，（注意力不集中、多动症和抑郁）和神经心理功能（注意力、记忆力、冲动控制和感觉运动功能）;和（2）评估产前和幼儿期暴露于CPF对脑结构测量的9年影响（使用解剖MRI），脑化学/细胞代谢（使用磁共振波谱），和解剖连接（使用扩散张量成像）在同一儿童。公共卫生相关性：这项申请是一项为期5年的研究，以评估暴露于有机磷农药，毒死蜱和二嗪农，对一个队列的内城儿童（n=400）谁达到8-9岁的神经行为功能的影响。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发育影响的纵向研究（从产前到9岁）共享一个队列。该项目可以获得暴露的生物标志物，包括对60名儿童的神经影像学评估，并有可能进一步为美国OP使用的监管安全标准提供信息。