Epigenetic Predictors of Impairment in Very Preterm Infants

极早产儿损伤的表观遗传预测因子

• 批准号: 9320798
• 负责人: Barry M. Lester
• 金额: $ 29.38万
• 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 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9320798
• 关键词: Address; Adult; Affect; Age; Behavior; Biology; Brain Injuries; Candidate Disease Gene; Cheek structure; Chronic Disease; Cost Analysis; DNA Methylation; DNA Sequence; Data; Data Analyses; Development; Environment; Epigenetic Process; Funding; Gene Expression; Genetic; Gestational Age; Goals; Heritability; Hypoxia; Impaired cognition; Impairment; Infant; Infant Mortality; Inflammatory; Intervention; Lead; Measures; Medical; Methods; Mitotic; Molecular; Neonatal; Neonatal Intensive Care Units; Outcome; Outcome Measure; Parents; Performance; Premature Birth; Premature Infant; Public Health; Risk; Role; Sampling; Specimen; Structure; Swab; Time; Uncertainty; Variant; Visit; Woman; behavioral impairment; brain cell; caregiving; cost; epigenetic marker; experience; genome-wide; high risk; infant morbidity; methylation pattern; neurobehavior; neurobehavioral; parent grant; postnatal; public health relevance; therapy development

 DESCRIPTION (provided by applicant): We are currently conducting a study ("Neonatal Neurobehavior and Outcomes in Very Preterm Infants," 1R01HD072267-01A1) of infants born <30 weeks postmenstrual age (PMA). These infants experience potentially devastating brain injuries associated with immaturity, hypoxic insults, and inflammatory exposures and are at high risk for developing neuromotor, cognitive, and behavioral impairments that persist through adulthood. However, for the majority of infants, there is no reliable method during their stay in the Neonatal Intensive Care Unit (NICU) to distinguish infants who will go on to develop later impairments from those who will not. The goal of the "parent" grant is to determine which infants born <30 weeks PMA are at greatest risk for impaired development using a neurobehavioral assessment (the NICU Network Neurobehavioral Scale or NNNS) and a medical risk score. In this proposed study, we have added an objective that enhances and is within the scope of the "parent grant"; the study of epigenetic markers that regulate gene expression and could suggest molecular mechanisms involved in our study findings. We are collecting cheek swabs shortly before discharge from the NICU and at the 24-month outcome visit to be used for the epigenetic analysis. The epigenetic measures were not included in the parent grant because the cost to cover the analysis of these data was prohibitive. This application is a request for funds for the analysis of the epigenetic data already being collected in the parent grant. The addition of epigenetics is potentially of great importance and highly likely to increase the impact of the study.

 描述（由申请人提供）：我们目前正在对经后小于30周（PMA）出生的婴儿进行一项研究（“极早产儿的新生儿神经行为和结局”，1 R 01 HD 072267 - 01 A1）。这些婴儿经历与不成熟、缺氧损伤和炎症暴露相关的潜在破坏性脑损伤，并且具有发展神经运动、认知和行为障碍的高风险，这些障碍持续到成年。然而，对于大多数婴儿来说，在他们留在新生儿重症监护室（NICU）期间，没有可靠的方法来区分哪些婴儿会继续发展后期损伤，哪些不会。“父母”补助金的目标是使用神经行为评估（NICU网络神经行为量表或NNNS）和医疗风险评分来确定哪些出生于PMA <30周的婴儿发育受损的风险最大。在这项拟议的研究中，我们增加了一个目标，增强了“父母补助金”的范围内;调节基因表达的表观遗传标记的研究，并可能表明我们的研究结果中涉及的分子机制。我们在从NICU出院前不久和24个月结局访视时收集脸颊拭子，用于表观遗传学分析。表观遗传测量不包括在父母补助金中，因为分析这些数据的费用太高。这项申请是对已经在父母补助金中收集的表观遗传数据进行分析的资金请求。表观遗传学的增加可能非常重要，并且极有可能增加研究的影响。