Epigenetic Markers, Trajectories and Predictors of Neurodevelopment in Childhood among Infants Born Very Preterm

极早产婴儿童年时期神经发育的表观遗传标记、轨迹和预测因子

• 批准号: 9816756
• 负责人: Todd M Everson
• 金额: $ 71.63万
• 依托单位: WOMEN AND INFANTS HOSPITAL-RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9816756
• 关键词: 37 weeks gestation; Acceleration; Adult; Adverse event; Affect; Age; Aging; Algorithms; Attention; Award; Behavioral; Biologic Development; Birth; Cell Proliferation; Characteristics; Child; Child Health; Childhood; Chronology; Cognitive; Collection; Complex; DNA Methylation; Data; Degenerative Disorder; Development; Epigenetic Process; Exhibits; Family; Funding; Genes; Goals; Grant; Impaired cognition; Impairment; Infant; Life; Life Experience; Link; Literature; Live Birth; Longitudinal Studies; Longitudinal observational study; Lung; Maintenance; Measures; Medical; Methods; Methylation; Mood Disorders; Nature; Neonatal; Neonatal Intensive Care Units; Newborn Infant; Outcome; Pattern; Perinatal; Phase; Phenotype; Pregnancy; Premature Birth; Premature Infant; Psychosocial Factor; Public Health; Publishing; Research; Risk; Risk Factors; Role; Site; Structure; Time; United States National Institutes of Health; Variant; Work; autism spectrum disorder; behavioral impairment; cohort; early childhood; epigenetic marker; epigenetic regulation; epigenetic variation; epigenomics; experience; follow-up; genome-wide analysis; high risk; histone methyltransferase; improved; medical complication; neurobehavior; neurobehavioral; neurodevelopment; neurotransmission; novel; postnatal; predictive tools; programs; psychosocial; relating to nervous system; response; sample collection; synaptic function

Project Summary Infants born very preterm are at increased risk of experiencing adverse developmental outcomes in childhood, resulting in substantial burdens for those infants and their families. Recent research in the field of behavioral epigenomics has indicated that preterm birth may have long term impacts on epigenetic regulation and that differential DNA methylation is linked to variability in cognitive and behavioral function. However, there is a lack of longitudinal epigenomic data in the published literature and thus it is unclear if preterm-associated epigenomic variations are persistent in childhood, or if epigenomic differences in early life are predictive of later developmental outcomes. DNA methylation can also be used to estimate epigenetic age acceleration which has received increasing attention as a potential risk factor for degenerative diseases in adults. However, there is some evidence that epigenetic aging may be related to positive developmental characteristics in childhood. With funds from our prior award (R01 HD084515-01A1), we studied the relationships between early life medical complications and neurobehavior with DNA methylation and epigenetic age, identifying numerous notable relationships in our cohort of very preterm infants (NOVI). However, these studies were cross-sectional in nature and should be followed up with repeated measure of epigenomic data. The NOVI cohort was also selected for inclusion in the NIH Environmental Influences on Child Health Outcomes (ECHO) consortium (UG3 OD23347) and selected to proceed to the next phase of the award (UH3 OD23347) which provides funding to support extensive phenotypic characterization of our children through age 7, including numerous neurodevelopmental assessments. Thus, we are proposing a competitive renewal to build on our prior work and leverage the extensive and high-quality outcome data being obtained through ECHO. We propose a longitudinal study of DNA methylation and epigenetic aging in a rigorously phenotyped cohort of infants that were born very preterm (< 30 weeks gestation). We aim to study how neonatal medical complications and neurobehavioral responses influence trajectories of DNA methylation and epigenetic aging in childhood, and whether these trajectories track with neurodevelopmental trajectories or are informative for later impairments. We also aim to develop an algorithm that incorporates childhood epigenomic factors with other known risk factors to improve the precision of predictions about which infants are at highest risk of developmental impairments. The successful completion of our study will provide novel and rich data demonstrating the early life experiences among very preterm infants that influence patterns of DNA methylation and epigenetic aging in childhood, characterize how those epigenetic factors are linked to later developmental outcomes, and provide a predictive tool to identify children that are at greatest risk later developmental impairment.

项目摘要 出生的婴儿非常早产是在童年时期出现不良发育结果的风险， 为这些婴儿及其家人造成了巨大的负担。行为领域的最新研究 表观基因组学表明，早产可能对表观遗传调节产生长期影响，并且 差异DNA甲基化与认知和行为功能的变异性有关。但是，缺乏 已发表的文献中的纵向表观基因组数据，因此尚不清楚早产相关是否相关 童年时期的表观基因组变异是持续的，或者如果早期生命中的表观基因组差异可以预测以后 发展结果。 DNA甲基化也可用于估计表观遗传年龄的加速度 作为成年人退行性疾病的潜在危险因素，人们受到了越来越多的关注。但是，那里 有一些证据表明表观遗传衰老可能与儿童期的积极发育特征有关。 有了我们先前奖项的资金（R01 HD084515-01A1），我们研究了早期生活之间的关系 与DNA甲基化和表观遗传时代的医学并发症和神经行为，确定了许多 在我们的早产儿（NOVI）中，有着显着的关系。但是，这些研究是横断面的 在本质上，应重复测量表观基因组数据。诺维队列也是 被选为NIH环境对儿童健康结果的影响（ECHO）财团 （UG3 OD23347），并被选为下一阶段的奖励（UH3 OD23347） 资金以支持我们7岁的孩子的广泛表型表征，包括许多 神经发育评估。因此，我们正在提议竞争性更新以建立我们的先前工作 并利用通过Echo获得的广泛和高质量的结果数据。我们提出了一个 在严格表现出的婴儿队列中，对DNA甲基化和表观遗传衰老的纵向研究 出生于非常早产（妊娠30周）。我们旨在研究新生儿医学并发症和 神经行为反应影响儿童时期DNA甲基化和表观遗传衰老的轨迹，以及 这些轨迹是神经发育轨迹的轨迹还是为以后的损害提供信息。 我们还旨在开发一种算法，该算法将童年的表观基因组因素与其他已知风险结合在一起 提高预测精度的因素 障碍。我们研究的成功完成将提供新颖而丰富的数据，证明早期 非常早产的婴儿的生活经历，这些婴儿影响了DNA甲基化和表观遗传衰老的模式 童年时期，表征这些表观遗传因素如何与以后的发展结果联系在一起，并提供 一种预测工具，可确定以后发育障碍的风险最大的儿童。