Placental DNA Methylation, Maternal Hardship and Child Neurodevelopmental Outcomes

胎盘 DNA 甲基化、孕产妇困难和儿童神经发育结果

• 批准号: 9582867
• 负责人: Hudson Santos
• 金额: $ 13.22万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-26 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9582867
• 关键词: Affect; Affective; Affective Symptoms; Age; Archives; Award; Biological; Birth; Child; Child Health; Childhood; Chronic Disease; Cognitive; CpG dinucleotide; DNA Methylation; Data; Development; Discipline of Nursing; Early Intervention; Enrollment; Environment; Epigenetic Process; Etiology; Event; Extremely low gestational age newborn; Family; Female; Funding; Gene Expression; Genes; Goals; Home environment; Immersion Investigative Technique; Impaired cognition; Impairment; International; Intervention; Investigation; Life; Link; Longitudinal Studies; Mediating; Mediator of activation protein; Mentors; Methylation; Minority; Mothers; Neurocognitive; Neurodevelopmental Impairment; Neurologic; Nurses; Outcome; Participant; Pathway interactions; Perinatal; Phase; Placenta; Pregnancy; Premature Birth; Publications; Quality of life; Research; Research Personnel; Resources; Risk; Risk Factors; Sampling; Secure; Socioeconomic Factors; Specimen; Stress; Training Activity; United States National Institutes of Health; Work; base; biological adaptation to stress; career; cognitive function; cohort; experience; fetal; follow-up; hands on instruction; high risk infant; hypothalamic-pituitary-adrenal axis; improved; in utero; innovation; life time cost; low socioeconomic status; male; maternal stress; methyl group; nervous system disorder; neurodevelopment; novel; premature; premature neonates; prenatal; prevent; programs; psychological distress; social; socioeconomics; stressor; symposium

PROJECT SUMMARY/ABSTRACT The overall goal of this application is to establish relationships among DNA methylation, maternal hardship and neurodevelopmental impairment in extremely preterm children. The central hypothesis is that maternal hardship clusters are associated with neurodevelopmental outcomes, especially cognitive and affective impairment, in extremely preterm children and that this relationship is mediated by DNA methylation in the placenta. The study will examine a diverse sample of extremely preterm children (N = 889) drawn from the Extremely Low Gestational Age Newborns Study (ELGAN, #1UG3OD023348-01). ELGAN is a multi-center longitudinal study of the risk of neurologic disorders in extremely preterm children. I will combine existing data on (1) prenatal maternal hardship; (2) DNA methylation from placental specimens; and (3) neurodevelopmental impairment, specifically cognitive and affective outcomes at ages 2 and 10. Furthermore, I will be involved in the third phase of ELGAN follow-up to collect neurodevelopmental impairment data on participants at age 15. The Specific Aims are to (1) Establish maternal hardship clusters using prenatal socioeconomic and stressful life events factors; (2) Identify associations between maternal hardship clusters and child cognitive and affective outcomes at ages 2, 10 and 15 years; and (3) Determine the extent to which DNA methylation mediates the relationship between maternal hardship and cognitive and affective outcomes. This research aligns closely with NINR’s Innovative Question 2.6 on etiological pathways to prevent chronic illnesses with known risk factors in childhood. My research background is in nursing, with specific foci of maternal hardship, perinatal affective symptoms in minority and/or other vulnerable mothers, and related child outcomes. My short-term career goal is to expand my research to link maternal hardship to epigenetic mechanisms and neurodevelopmental outcomes among at-risk children. The proposed training activities will include formal didactic, hands-on instruction and research immersion in epigenetics, the biological bases of child neurodevelopment; experience in large interdisciplinary teams; responsible conduct in research; and publications and attendance at conferences. I have assembled an interdisciplinary mentoring team of internationally recognized experts. This award will move me to independence as a researcher, support my next steps in securing funding, and help me achieve my long-term goal of becoming a nurse leader in longitudinal research to prevent or minimize neurodevelopmental impairment related to maternal hardship among at-risk children. My subsequent R01 will explore additional epigenetic pathways related to hardship. I plan to use the 35 cohorts of the NIH Environment influences on Child Health Outcomes (ECHO Program; ~ 40,000 children by 2019), which includes ELGAN, to identify modifiable factors that could be potential targets for interventions.

项目摘要/摘要 该应用的总体目标是建立DNA甲基化，孕产妇困难和 极早儿童的神经发育障碍。中心假设是苦难 集群与神经发育结局相关，尤其是认知和情感障碍， 非常早产的孩子，这种关系是由plapeta中DNA甲基化介导的。研究 将检查从极低的妊娠中汲取的极早产儿（N = 889）的潜水员样本 年龄新生儿研究（Elgan，＃1UG3OD023348-01）。埃尔根（Elgan）是一项多中心的纵向研究 极端儿童的神经系统疾病。我将结合（1）产前遇到的现有数据； （2）来自斑点标本的DNA甲基化； （3）神经发育障碍，特别是认知障碍 以及2岁和10岁的情感结果。此外，我将参与Elgan随访的第三阶段 收集15岁参与者的神经发育障碍数据。具体目的是（1）建立 使用产前社会经济和压力大的生活事件因素的产妇困难集群； （2）识别 在2、10和 15年； （3）确定DNA甲基化介导母体之间关系的程度 艰辛，认知和情感结果。这项研究与Ninr的创新问题紧密相符 2.6关于预防儿童时期已知危险因素的慢性病的病因途径。我的研究 背景是护士，具有孕产妇困难的特定焦点，少数族裔和/或的围产期情感症状 其他脆弱的母亲和相关的儿童成果。我的短期职业目标是将我的研究扩展到 将物质困难与高危儿童的表观遗传机制和神经发育结局联系起来。 拟议的培训活动将包括正式的教义，动手教学和研究中的研究 表观遗传学，儿童神经发育的生物基础；在大型跨学科团队中经验； 负责任的研究行为；以及出版物和出席会议。我已经组装了 跨学科指导团队由国际认可的专家组成。这个奖项将使我进入独立 作为研究人员，支持我获得资金的下一步，并帮助我实现我的长期目标 纵向研究的护士领导者预防或最大程度地减少与 高危儿童的孕产妇艰辛。我随后的R01将探索其他表观遗传途径 与苦难有关。我计划使用NIH环境的35个队列对儿童健康成果的影响 （Echo计划；到2019年，包括Elgan在内的约40,000名儿童），以确定可修改的因素可能是 干预措施的潜在目标。