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后接触有机磷（OP）农药毒死蜱（CPF）对一组9岁以上城市儿童神经行为功能的影响。这项工作建立在哥伦比亚儿童环境健康中心（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）进行的环境空气污染物对儿童发育和呼吸系统健康影响的前瞻性队列研究的基础上，并与之共享队列研究。儿童中心先前的研究结果显示，产前暴露于CPF（通过脐带血中的生物标志物验证）对出生体重（Whyatt等人，2004年）、认知和运动发育以及3岁时的神经行为问题有不利影响（Rauh等人，2006年）。受影响的神经行为领域包括注意力和注意力缺陷多动症——这些疾病具有严重的长期临床影响。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有长期的、可能不可逆的影响（Dam et al ., 2000; Levin et al ., 2002; Slotkin et al ., 2005），我们现在提议评估300名9岁儿童CPF对神经发育的长期影响。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、代谢和解剖连通性的中间神经生物学效应。选择CPF作为转化研究的模型，是因为它是OP农药类别的代表，具有良好的特征，并且在动物中得到了充分的研究。此外，农业和商业用途仍在继续，尽管2001年美国环保署禁止住宅使用。具体而言，我们建议：(1)评估产前和儿童早期暴露于CPF对9年神经行为（注意力不集中、多动和抑郁）和神经心理功能（注意能力、记忆、冲动控制和感觉运动功能）的影响；(2)评估9年产前和儿童早期暴露于CPF对同一儿童脑结构（使用解剖MRI），脑化学/细胞代谢（使用磁共振波谱）和解剖连通性（使用弥散张量成像）测量的影响。公共卫生相关性：本申请是一项为期5年的研究，旨在评估接触有机磷农药、毒死蜱和二嗪农对一组8-9岁的市中心儿童（n=400）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）相同。该项目获得了暴露的生物标志物，包括对60名儿童子集的神经成像评估，并有可能进一步告知美国使用OP的监管安全标准。