Neurodevelopmental Effects of Perfluorinated Chemicals

全氟化学品对神经发育的影响

基本信息

批准号：
9789884
负责人：
Zeyan Liew
金额：
$ 24.74万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-22 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9789884
关键词：
11 year old 5 year old Age Animals Anxiety Attention Attention deficit hyperactivity disorder Behavior Biological 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 Developmental Toxicant 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 autism spectrum disorder case control cognitive function cohort developmental disease early childhood early pregnancy 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 training opportunity

项目摘要

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.

抽象的该提案以候选人的论文研究为基础，该研究检查了产前检查之间的关联接触全氟化学品 (PFC) 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/多动障碍和脑瘫由约 100,000 名母亲和儿童组成的 PFC 是广泛存在的持久性有机污染物，并且孕妇和胎儿常常不自觉地且几乎无处不在地接触这些合成物质自 20 世纪 50 年代以来，动物研究表明 PFC 是发育毒物，但证据来自加州大学洛杉矶分校和奥尔胡斯大学之间长达十年的合作使得人类研究稀少。候选人可以获得独特的、大规模的、全国性的丹麦队列和研究登记。拟议的研究将极大地扩大 DNBC 和各种丹麦登记册的使用，并允许第一个产前 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，包括（1）对智力、认知、 5 岁儿童的注意力、记忆力和运动能力；(2) 医院诊断的癫痫；(3) 孩子的社交能力； 11 岁时的能力和心理健康；以及 (4) 16 岁之前的智力和学业表现。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来自 DNBC，可以对胎儿发育期间的 PFC 暴露水平进行可靠且有效的评估。该提案将在加州大学洛杉矶分校之间持续的强有力合作的背景下进行。流行病学系和奥尔胡斯大学增加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) 和人类遗传学系该应用程序基于 Liew 博士的应用程序。环境科学方面的专业知识和先进的流行病学方法将使他获得新的知识。临床心理学、环境统计学和神经行为表观/遗传学方面的必要培训，并建立与进行未来尖端表观基因/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本库。已同意通过 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工具和神经精神病学的临床知识 Michael Jerrett 博士将提供环境统计和暴露方面的培训机会。被称为“外部暴露组”的评估 Steve Horvath 博士将提供高级培训。该应用程序的内容提供了基因环境和表观遗传网络分析的策略。使候选人能够成功进入终身教授职位，并为他配备走向独立和追求 R01 提案的必要技能。