Neurodevelopmental effects of Perfluorinated Chemicals

全氟化学品对神经发育的影响

• 批准号: 9243107
• 负责人: Zeyan Liew
• 金额: $ 15.83万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9243107
• 关键词: 11 year old; 5 year old; Age; Animals; Anxiety; Attention; Attention deficit hyperactivity disorder; Autistic Disorder; Behavior; Birth; Blood specimen; Brain; Brain Diseases; Cerebral Palsy; Chemical Exposure; Chemicals; Child; Clinical; Clinical Psychology; Cognition; Collaborations; Complex; Congenital Abnormality; Convulsions; Country; Data; Data Collection; Denmark; Development; Diagnosis; Disease; Eating Disorders; Ecology; Education; Endocrine disruption; Environment; Epidemiologic Methods; Epidemiology; Epigenetic Process; Epilepsy; Exposure to; Febrile Convulsions; Fetal Development; Fetus; First Pregnancy Trimester; Future; Genes; Genetic; Gonadal Steroid Hormones; Growth and Development function; Hearing; Hospitals; Human; Human Genetics; Intelligence; Knowledge; Life; Link; Measures; Mediation; Medical Psychology; Memory; Mental Depression; Mental Health; Mental disorders; Mentors; Mothers; Motor; Motor Skills; Neonatal; Neurodevelopmental Disorder; Neuropsychological Tests; Neuropsychology; Obsessive-Compulsive Disorder; Online Systems; Outcome; Pathway Analysis; Performance; Phenotype; Plasma; Positioning Attribute; Pregnancy; Pregnant Women; Problem behavior; Process; Property; Psychotic Disorders; Questionnaires; Registries; Regulation; Reporting; Research; Resources; Sampling; Schools; Scientific Advances and Accomplishments; Secondary Schools; Self Perception; Social Problems; Stress; Surveys; Symptoms; Testing; Thyroid Hormones; Thyrotropin; Thyroxine; Time; Training; Universities; Vision; adverse outcome; case control; cognitive function; cohort; early childhood; executive function; fetal; follow-up; gene environment interaction; in utero; insight; instrument; interest; man; neurobehavioral; neurodevelopment; neuropsychiatric disorder; neurotoxic; novel; offspring; persistent organic pollutants; population based; prenatal; prenatal exposure; professor; repository; screening; sex; skills; social skills; statistics; toxicant; training opportunity

ABSTRACT This proposal builds on the candidate’s dissertation research that examined the associations between prenatal exposure to perfluorinated chemicals (PFCs) and three specific neurodevelopmental outcomes, including autism, attention-deficit/hyperactivity disorder, and cerebral palsy in the Danish National Birth Cohort (DNBC) that consists of ~100,000 mothers and children. PFCs are widespread persistent organic pollutants, and pregnant women and fetuses are often involuntarily and nearly ubiquitously exposed to these synthetic compounds since the 1950s. Animal studies suggest that PFCs are developmental toxicants but evidence from human studies is sparse. Decade long collaborations between UCLA and Aarhus University enabled the candidate to gain access to the unique, large-scale, nationwide Danish cohorts and registries for research. The proposed study will greatly expand the use of DNBC and various Danish registers and allow for the very first time examination of the link between prenatal PFC exposures and an array of neurodevelopmental outcomes never investigated before, including (1) extensive neuropsychological assessments of intelligence, cognition, attention, memory and motor skills in children at age 5; (2) hospital diagnosis of epilepsy; (3) the child’s social competence and mental health at age 11; and (4) intellectual capacity and school performance up to age 16. The proposed studies will capitalize upon the valuable resource of stored maternal pregnancy blood samples from DNBC, allowing a reliable and valid assessment of PFC exposure levels during fetal development. The proposal will be pursued within the context of a strong ongoing collaboration between the UCLA Department of Epidemiology and Aarhus University, adding new partners from the UCLA Medical Psychology Assessment Center (MPAC) and Department of Human Genetics. This application builds on Dr. Liew’s expertise in environmental sciences and advanced epidemiologic methods. It will allow him to newly gain the necessary training in clinical psychology, environmental statistics, and neurobehavioral epi/genetics and to build a skillset compatible with conducting future cutting-edge epi-gene/environment interactions research that optimally uses existing large bio-sample repositories in the Nordic countries. Drs. Beate Ritz and JØrn Olsen have agreed to mentor the candidate through the K99 process. Dr. Robert Asarnow will provide training in administrating/scoring complex neuropsychological instruments and clinical knowledge of neuropsychiatric disorders. Dr. Michael Jerrett will provide training opportunities in environmental statistics and exposure assessment referred to as the ‘external exposome’. Dr. Steve Horvath will provide training in advanced gene-environment and epigenetic network analysis. The contents of this application provide a strategy to position the candidate to successfully launch into a tenured professor track position and equip him with the necessary skills to move towards independence and pursue R01 proposals.

摘要 这个建议建立在候选人的论文研究的基础上，该论文研究了产前和产后的关系。 暴露于全氟化学品（PFCs）和三种特定的神经发育结果，包括 丹麦国家出生队列（DNBC）中的自闭症、注意力缺陷/多动障碍和脑瘫 由大约10万名母亲和儿童组成。PFC是广泛存在的持久性有机污染物， 孕妇和胎儿经常不自觉地和几乎无处不在地暴露于这些合成的 自20世纪50年代以来的化合物。动物研究表明，PFC是发育毒物，但证据表明， 人类研究很少。加州大学洛杉矶分校和奥胡斯大学之间长达十年的合作使 候选人可以获得独特的，大规模的，全国性的丹麦队列和登记研究。的 拟议的研究将大大扩大DNBC和各种丹麦登记册的使用， 产前PFC暴露与一系列神经发育结果之间联系的时间检查 以前从未研究过的，包括（1）对智力，认知， 注意力，记忆力和运动技能的儿童在5岁;（2）医院诊断的癫痫;（3）儿童的社会 （4）直至16岁的智力及学业表现。 拟议的研究将利用储存的孕产妇妊娠血液样本的宝贵资源 从DNBC，允许在胎儿发育过程中的PFC暴露水平的可靠和有效的评估。 该提案将在加州大学洛杉矶分校与加州大学洛杉矶分校之间进行强有力的持续合作的背景下进行。 流行病学系和奥胡斯大学，增加了来自加州大学洛杉矶分校医学心理学的新合作伙伴 评估中心（MPAC）和人类遗传学系。这个应用程序建立在刘博士的 在环境科学和先进的流行病学方法的专业知识。这将使他获得新的 在临床心理学，环境统计学和神经行为表观/遗传学方面进行必要的培训， 一套与进行未来尖端的表观基因/环境相互作用研究兼容的技能， 最佳地利用北欧国家现有的大型生物样品储存库。Beate Ritz和Jürn Olsen博士 同意通过K99流程指导候选人。Robert Asarnow博士将提供以下培训： 管理/评分复杂的神经心理学仪器和神经精神病学的临床知识 紊乱Michael Jerrett博士将提供环境统计和暴露方面的培训机会 评估被称为“外部麻烦”。史蒂夫·霍瓦特博士将提供高级培训 基因-环境和表观遗传网络分析。本应用程序的内容提供了一种策略， 定位候选人成功地发射到终身教授轨道的位置，并装备他与 必要的技能，走向独立和追求R 01提案。