Environment, Epigenetics, Neurodevelopment & Health of Extremely Preterm Children

环境、表观遗传学、神经发育

• 批准号: 10240623
• 负责人: Rebecca Fry
• 金额: $ 411.07万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10240623
• 关键词: 10 year old; 15 year old; 18 year old; Address; Adolescence; Adolescent; Age; Anxiety Disorders; Archives; Attention; Attentional deficit; Behavioral; Biological; Biological Assay; Biological Markers; Birth; Blood; Brain; Brain scan; Cellularity; Cerebral Palsy; Child; Childhood; Cognitive deficits; DNA analysis; Data; Development; Environment; Environmental Exposure; Environmental Risk Factor; Epigenetic Process; Epilepsy; Evaluation; Exposure to; Extremely low gestational age newborn; Fetal Growth Retardation; Freezing; Gene Expression; Genes; Gestational Age; Goals; Health; Impaired cognition; Individual; Inflammation; Inflammatory; Inflammatory Response; Life; Link; Magnetic Resonance Imaging; Manuals; Measures; Mental disorders; Methylation; NF-kappa B; Natural Immunity; Neonatal; Neurodevelopmental Impairment; Outcome; Outcome Study; Participant; Pathway interactions; Perinatal; Phase; Placenta; Population; Pregnancy; Premature Birth; Prevention strategy; Procedures; Process; Proteins; Protocols documentation; Public Health; Quality of life; Research; Research Personnel; Resources; Risk; Signal Transduction; Site; Specific qualifier value; Specimen; Standardization; Structure; Time; Tobacco smoke; Toxic Environmental Substances; United States; Water; Work; autism spectrum disorder; brain tissue; brain volume; cognitive disability; cohort; data harmonization; design; early detection biomarkers; epidemiology study; epigenetic marker; epigenetic variation; fetal; follow-up; gray matter; high risk population; improved; inflammatory marker; innovation; maternal obesity; member; microorganism; neonate; neurodevelopment; peripheral blood; postnatal period; premature; prenatal; prenatal environmental exposure; prenatal exposure; prevent; prospective; response; success; systemic inflammatory response; targeted treatment; therapy development; water diffusion; white matter

Project Summary/Abstract The goal of the ECHO Consortium is to identify exposures and mechanisms that link the environment in early life to childhood development and health outcomes. This proposal commits to the ECHO Consortium numerous resources from the Extremely Low Gestation Age Newborn (ELGAN) Study. Since its initiation in 2001, the broad goal of the ELGAN Study is to evaluate the relationship between perinatal inflammation and neurodevelopmental impairments among individuals born extremely premature (i.e., before 28 weeks of gestation). In the proposed project we will build on the success of the ELGAN Study by adding new information about: 1) environment exposures, 2) neurodevelopmental outcomes of study participants at 15 and 18 years of age, and 3) placental epigenetic variation, a mechanism that could link inflammation early in life to neurodevelopmental impairments. In the first two years of the project (the UG3 phase) investigators from the ELGAN team will participate in the design of studies that can be implemented across the ECHO Consortium and in efforts to harmonize data across cohorts comprising the consortium. In the second year of the proposal, we will begin to evaluate members of the ELGAN cohort, as they reach 15 years of age, using standardized neurodevelopmental assessments and brain magnetic resonance imaging (MRI). We also will complete preliminary studies of relationships between prenatal environmental exposures, early life inflammation, and neurodevelopmental impairments, using extant data from the ELGAN cohort. In addition, we will complete analysis of epigenetic markers in placenta specimens collected around the time of the births of ELGAN Study participants. These data will be utilized in the last 5 years of the proposed project (the UH3 phase). If pre-specified milestones are met, the project will transition into the UH3 phase. Standardized neurodevelopmental assessments and brain magnetic resonance imaging (MRI) will be completed as study participants reach 15 years. As participants reach 18 years of age neurodevelopmental assessments will again be completed. At the assessment at 18 years we will obtain blood for study of epigenetic markers of activation of innate immunity, which we can then relate to our extant data about systemic inflammation early in life. Specific aims in the UH3 phase of the project are examine relationships between biomarkers of early life inflammation (extant data on neonatal systemic inflammation and new data on placenta epigenetics) and neurodevelopmental impairments through age 18 years. The over-arching hypothesis to be addressed is that prenatal exposures can initiate early life inflammation, thus increasing the risk of neurodevelopmental impairments. Innovative aspects of this project include its longitudinal perspective, consideration of placenta epigenetics as a mechanism linking prenatal exposures to childhood outcomes, and evaluation of a wide range of neurodevelopmental outcome. This research has the potential to inform the development of therapies targeting epigenetic processes to prevent or ameliorate cognitive disability, thereby improving the quality of life for 16,000 individuals who survive extremely premature birth each year in the United States.

项目摘要/摘要 回声财团的目标是确定较早将环境联系起来的暴露和机制 童年发展和健康成果的生活。该提议提交回声联盟 来自极低妊娠年龄新生儿（Elgan）研究的大量资源。自从它开始 2001年，伊尔根研究的广泛目标是评估围产期炎症与 出生的个体之间的神经发育障碍极为早（即，在28周之前 妊娠）。在拟议的项目中，我们将通过添加新信息来基于Elgan研究的成功 大约：1）环境暴露，2）研究参与者在15年和18岁时的神经发育结果 年龄和3）胎盘表观遗传变异，这种机制可以在生命早期将炎症联系起来 神经发育障碍。 在该项目的前两年（UG3阶段）调查人员，来自Elgan团队将参加 可以在整个Echo联盟实施的研究设计，并努力协调数据 整个人群组成了财团。在提案的第二年，我们将开始评估 Elgan队列的成员使用标准化的神经发育，当时他们达到15岁 评估和大脑磁共振成像（MRI）。我们还将完成对 产前环境暴露，早期炎症和神经发育之间的关系 损害，使用来自Elgan队列的现有数据。此外，我们将完成表观遗传学的分析 胎盘标本中的标记在伊尔根研究参与者出生时收集了。这些 数据将在拟议项目的最后5年（UH3阶段）中使用。 如果满足预先指定的里程碑，则该项目将过渡到UH3阶段。标准化 神经发育评估和脑磁共振成像（MRI）将作为研究完成 参与者达到15年。随着参与者达到18岁，神经发育评估将再次 完成。在18年的评估中，我们将获得血液以研究激活的表观遗传标记 先天免疫，然后我们可以将其与生命早期全身性炎症的现有数据联系起来。 该项目的UH3阶段的具体目标是检查早期生物标志物之间的关系 炎症（有关新生儿全身炎症的现有数据和胎盘表观遗传学的新数据）和 神经发育障碍至18岁。要解决的总体假设是 产前暴露会引发早期炎症，从而增加神经发育的风险 障碍。该项目的创新方面包括其纵向观点，考虑胎盘 表观遗传学作为将产前暴露与儿童结局联系起来的机制，并评估广泛的范围 神经发育结果。这项研究有可能告知疗法的发展 针对预防或改善认知障碍的表观遗传过程，从而提高生活质量 对于每年在美国，每年生存早产的16,000个人。