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.

项目总结/摘要 早产影响在美国出生的十分之一的婴儿，导致显著的发病率和经济损失。 成本极早产儿（VPT;胎龄<32周）的风险增加， 神经发育VPT婴儿经历增加的生理压力，而他们的照顾者经历 增加的心理痛苦-两者都与受损的神经发育有关。后生 修饰被认为是连接生理应激和VPT神经发育的可能机制 婴儿。拟议研究的主要目的是确定新生儿生理性 压力诱导表观遗传修饰，导致神经发育受损，以及照顾者如何 新生儿心理应激与神经发育的关系 结果。具体而言，拟议的研究旨在（1）创建和验证新生儿的新指标 新生儿生理应激对VPT新生儿表观遗传学的影响 修改和以后的神经发育在VPT婴儿;和（3）确定照顾者痛苦的影响， VPT婴儿的神经发育。这符合NICHD 2020年战略计划的科学优先事项-减少 神经发育障碍的发病率，通过提高其起源的认识， 发展过程，并确定潜在的目标和最佳时机进行干预。培训计划 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危险因素和病因机制。具体而言是 拟议的培训旨在通过增加表观遗传学分析方面的培训来提高PI的分子遗传学专业知识 通过密集的研讨会和实验室经验与专家导师，并扩大PI的定量 包括复杂的纵向分析。新生儿生理学的新教育与新训练 压力将为PI提供独特的专业知识，这将导致新的调查途径。最后，PI将 发展专业发展技能，这将是成功的终身助理教授的关键， 独立临床科学家爱荷华州大学的学术环境非常适合拟议的 研究和培训。教师具有先进的定量方法，表观遗传学， 新生儿生理学愿意为PI提供专家指导。新生儿医学部 每年都有许多关于早产的研究，并拥有基础设施，包括一支优秀的团队 临床研究护士和高危婴儿随访诊所，以支持拟议的研究。爱荷华州 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 并支持人类遗传学的研究。许多机构组织提供各种 有机会发展作为独立临床科学家成功所需的技能。