Neonatal Stress in Very Preterm Infants: Longitudinal Effects on Epigenetics and Neurodevelopment

极早产儿的新生儿应激：对表观遗传学和神经发育的纵向影响

• 批准号: 10570368
• 负责人: Allison Marie Momany
• 金额: $ 9.88万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-09 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570368
• 关键词: 2 year old; 37 weeks gestation; Affect; Age; Biological; Birth; Blood Pressure; Buffers; Caregivers; Child; Clinic; Clinical; Clinical Nursing Research; Complex; DNA Methylation; Data; Development; Developmental Process; Distress; Educational workshop; Environment; Epigenetic Process; Etiology; Faculty; Future; Genes; Gestational Age; Goals; Heart Rate; Hospitalization; Human; Human Genetics; Hydrocortisone; Hydroxyprogesterone; Impairment; Incidence; Infant; Infrastructure; Institution; Intervention; Investigation; Iowa; Knowledge; Lead; Level of Evidence; Life; Link; Literature; Measures; Mediating; Mentors; Mentorship; Methods; Modification; Molecular Genetics; Morbidity - disease rate; National Institute of Child Health and Human Development; Neonatal; Neonatology; Neurodevelopmental Deficit; Neurodevelopmental Disability; Neurodevelopmental Disorder; Outcome; Oxygen; Physiological; Physiology; Premature Birth; Premature Infant; Prevention; Procedures; Research; Research Personnel; Research Support; Risk; Risk Factors; Sampling; Scientist; Severities; Statistical Models; Strategic Planning; Stress; Training; Training and Education; Translating; United States; Universities; Variant; biological adaptation to stress; career; caregiver stress; early childhood; economic cost; effective intervention; experience; extreme prematurity; follow-up; genetic analysis; high risk; high risk infant; improved; indexing; infancy; laboratory experience; longitudinal analysis; member; neglect; neonatal morbidity; neurodevelopment; novel; premature; professor; programs; psychological distress; research study; skill acquisition; skills; success; tenure track

PROJECT SUMMARY/ABSTRACT Preterm birth affects 1 in 10 infants born in the United States, resulting in significant morbidity and economic cost. Children who are born very preterm (VPT; gestational age<32 weeks) have increased risk for impaired neurodevelopment. VPT infants experience increased physiologic stress while their caregivers experience increased psychological distress—both are associated with impaired neurodevelopment. Epigenetic modifications are proposed as a possible mechanism linking physiologic stress and neurodevelopment in VPT infants. The main objective of the proposed research is to identify the mechanisms by which neonatal physiologic stress induces epigenetic modifications that contribute to impaired neurodevelopment, as well as how caregiver distress moderates the relationship between longitudinal neonatal physiologic stress and neurodevelopmental outcomes. Specifically, the proposed research aims to (1) create and validate novel indices of neonatal physiologic stress in VPT infants; (2) identify the effects of neonatal physiologic stress on epigenetic modifications and later neurodevelopment in VPT infants; and (3) determine the effects of caregiver distress on neurodevelopment in VPT infants. This aligns with the NICHD Strategic Plan 2020 scientific priority—to reduce the incidence of neurodevelopmental disorders by improving the understanding of their origins in the developmental process and identifying potential targets and optimal timing for intervention. The training plan includes several components necessary to reach the PI’s goal of becoming an independent clinical scientist, studying early life risk factors and etiological mechanisms in neurodevelopmental disorders. Specifically, the proposed training aims to enhance the PI’s molecular genetic expertise by adding training in epigenetic analyses via intensive workshops and laboratory experiences with an expert mentor and to expand the PI’s quantitative expertise to include complex longitudinal analyses. The new education and training on neonatal physiological stress will provide the PI with unique expertise that will lead to new avenues of investigation. Finally, the PI will develop professional development skills that will be critical for success as a tenure track assistant professor and independent clinical scientist. The academic environment at the University of Iowa is well-suited for the proposed research and training. Faculty members with expertise in advanced quantitative methods, epigenetics, and neonatal physiology are willing to provide expert mentorship to the PI. The Division of Neonatology conducts numerous research studies on preterm birth each year and has the infrastructure, including an outstanding team of clinical research nurses and a high-risk infant follow-up clinic, to support the proposed research. The Iowa Institute of Human Genetics provides researchers with a state-of-the-art, high-throughput genetic analysis facility and supports research focused on human genetics. Numerous institutional organizations provide a variety of opportunities to develop the skills necessary for success as an independent clinical scientist.

项目概要/摘要 早产影响了美国出生的十分之一的婴儿，导致严重的发病率和经济损失 早产儿（VPT；胎龄<32周）的受损风险增加。 VPT 婴儿在照顾者时会经历更大的生理压力。 心理困扰增加——两者都与表观遗传受损有关。 修改被认为是连接 VPT 中生理应激和神经发育的可能机制 拟议研究的主要目的是确定新生儿生理的机制。 压力会引起表观遗传修饰，从而导致神经发育受损，以及照顾者如何 痛苦调节纵向新生儿生理应激与神经发育之间的关系 具体来说，拟议的研究旨在 (1) 创建并验证新的新生儿指数。 (2) 确定新生儿生理应激对表观遗传的影响 VPT 婴儿的改变和后来的神经发育；(3) 确定照顾者的痛苦对 这与 NICHD 2020 年战略计划的科学重点一致——减少 通过提高对神经发育障碍起源的了解来降低神经发育障碍的发生率 发展过程并确定潜在目标和最佳干预时机。 包括实现 PI 成为独立临床科学家的目标所需的几个组成部分， 研究神经发育障碍的早期生命危险因素和病因机制。 拟议的培训旨在通过增加表观遗传学分析培训来增强 PI 的分子遗传学专业知识 通过与专家导师的密集研讨会和实验室经验，并扩大 PI 的定量 专业知识包括复杂的纵向分析新生儿生理学的新教育和培训。 压力将为 PI 提供独特的专业知识，从而带来新的调查途径。 培养专业发展技能，这对于成为终身教授助理教授至关重要 爱荷华大学的学术环境非常适合所提议的项目。 研究和培训具有先进定量方法、表观遗传学和 新生儿生理学愿意为 PI 提供专家指导。 每年有大量关于早产的研究，并拥有基础设施，包括优秀的团队 临床研究护士和高危婴儿随访诊所，以支持爱荷华州的拟议研究。 人类遗传学研究所为研究人员提供最先进的高通量遗传分析设施 并支持以人类遗传学为重点的研究。许多机构组织提供各种服务。 培养作为独立临床科学家取得成功所需技能的机会。