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、轨迹和预测因素

• 批准号: 10662382
• 负责人: Todd M Everson
• 金额: $ 63.15万
• 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 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662382
• 关键词: 37 weeks gestation; Acceleration; Adult; Adverse event; Affect; Age; Aging; Algorithms; Attention; Award; Behavioral; 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; Predisposition; 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; biological development; biomarker identification; cohort; early childhood; epigenetic marker; epigenetic regulation; epigenetic variation; epigenomics; examination questions; experience; extreme prematurity; follow-up; genome-wide analysis; high risk; histone methyltransferase; improved; medical complication; neural; neurobehavior; neurobehavioral; neurodevelopment; neurotransmission; novel; postnatal; predictive tools; programs; psychosocial; response; 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 早产儿在童年时期经历不良发育结果的风险增加， 这给这些婴儿及其家庭造成了沉重的负担。行为领域的最新研究 表观基因组学已经表明早产可能对表观遗传调节具有长期影响， 差异DNA甲基化与认知和行为功能的变异性有关。然而，缺乏 发表的文献中的纵向表观基因组数据，因此尚不清楚是否与早产相关 表观基因组变异在儿童时期持续存在，或者如果早期生活中的表观基因组差异预示着以后的生活， 发展成果。DNA甲基化也可用于估计表观遗传年龄加速， 作为成人退行性疾病的潜在危险因素，已受到越来越多的关注。但 一些证据表明，表观遗传衰老可能与儿童时期的积极发展特征有关。 利用我们之前的研究项目（R 01 HD 084515 - 01 A1）的资金，我们研究了早期生活与 医学并发症和神经行为与DNA甲基化和表观遗传年龄，确定了许多 在我们的极早产儿（诺维）队列中存在显著关系。然而，这些研究是横断面的， 并应通过重复测量表观基因组数据来跟进。诺维队列也是 入选NIH环境对儿童健康结果的影响（ECHO）联盟 (UG3 OD 23347），并被选中进入下一阶段的授予（UH 3 OD 23347）， 资助支持我们的孩子到7岁的广泛的表型特征，包括许多 神经发育评估因此，我们建议在我们先前工作的基础上进行竞争性更新 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 一项在严格表型化的婴儿队列中进行的DNA甲基化和表观遗传衰老的纵向研究， 早产（小于30周妊娠）。我们的目标是研究新生儿医疗并发症和 神经行为反应影响儿童期DNA甲基化和表观遗传衰老的轨迹， 这些轨迹是否与神经发育轨迹相一致，或者是否为以后的损伤提供了信息。 我们还旨在开发一种算法，将儿童期表观基因组因素与其他已知风险相结合。 提高预测哪些婴儿发育风险最高的准确性的因素 损伤我们研究的成功完成将为早期的 非常早产儿的生活经历影响了DNA甲基化模式和表观遗传衰老， 儿童期，描述这些表观遗传因素如何与后来的发展结果相关联，并提供 这是一种预测工具，用于识别最有可能出现发育障碍的儿童。

项目成果

Epigenetic age acceleration, neonatal morbidities, and neurobehavioral profiles in infants born very preterm.

• DOI: 10.1080/15592294.2023.2280738
• 发表时间: 2023-12
• 期刊: EPIGENETICS
• 影响因子: 3.7
• 作者: Paniagua, Uriel;Lester, Barry M.;Marsit, Carmen J.;Camerota, Marie;Carter, Brian S.;Check, Jennifer F.;Helderman, Jennifer;Hofheimer, Julie A.;Mcgowan, Elisabeth C.;Neal, Charles R.;Pastyrnak, Steven L.;Smith, Lynne M.;DellaGrotta, Sheri A.;Dansereau, Lynne M.;O'Shea, T. Michael;Everson, Todd M.
• 通讯作者: Everson, Todd M.