Epigenetics Embedding of Oral Feeding Skill Development in Preterm Infants

早产儿口腔喂养技能发展的表观遗传学嵌入

• 批准号: 10552061
• 负责人: Thao T Griffith
• 金额: $ 13.99万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-18 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10552061
• 关键词: Achievement; Address; Admission activity; Affect; Age; Assessment tool; Behavioral; Biological; Biological Markers; Brain; Breathing; Cells; Clinical; DNA; DNA Methylation; Data; Deglutition; Desire for food; Development; Developmental Delay Disorders; Discharge Plannings; Eating; Eating Behavior; Enrollment; Epigenetic Process; Exposure to; Failure to Thrive; Feeding behaviors; Future; Genes; Gestational Age; Glucocorticoids; Goals; Growth; Health; Health Care Costs; Hospitalization; Hydrocortisone; Hypothalamic structure; Impairment; Infant; Infant Health; Knowledge; Modeling; Modification; Movement; NR3C1 gene; Neonatal; Neonatal Intensive Care Units; Neuronal Plasticity; Oral; Outcome; Physiological; Pituitary Gland; Premature Infant; Process; Regulation; Research; Risk; Role; Saliva; Sampling; Stress; System; Variant; biobehavior; biological adaptation to stress; early life stress; experience; feeding; high risk; hospital readmission; imprint; longitudinal, prospective study; neonatal care; neonatal period; neurobehavior; neurobehavioral; novel; nutrition; oral motor; personalized management; promoter; recruit; response; skill acquisition; skills; stressor; sucking

PROJECT SUMMARY/ABSTRACT Preterm infants admitted to the Neonatal Intensive Care Unit (NICU) endure a multitude of stressors. Early life stress may exceed their adaptive capacity and impede achievement of developmental milestones, such as oral feeding. Up to 70% of NICU preterm infants are challenged to feed orally, leading to failure to thrive, prolonged hospitalization, and high healthcare costs up to $200K per infant. There is considerable variation in the clinical progression of oral feeding skill development across preterm infants, with some infants having more difficulty than others. Robust evidence demonstrates that oral feeding skills require intact neurobehaviors. Early life stress disrupts neurobehavior development, which may compromise achievement of oral feeding skills. Yet, the extent to which early life stress impairs oral feeding skill development and the biomechanism whereby this occurs are unknown. Exposure to early life stress during sensitive periods of neuroplasticity results in epigenetic imprinting of stress response systems. Early life stress results in epigenetic modification of glucocorticoid-related genes, i.e., DNA methylation (DNAm) of NR3C1 and HSD11B2, which alters hypothalamic pituitary adrenocortical (HPA) regulation of cortisol levels and cortisol reactivity, disrupting neurobehaviors. Epigenetic modifications due to early life stress are durable and may affect infants’ health far beyond the neonatal period, increasing risk for life-long maladaptive feeding behaviors and poor health. The purpose of this study is to determine the extent to which early life stress, reflected by DNAm of NR3C1 and HSD11B2 gene promoters, compromises oral feeding skill development. In this prospective longitudinal study, we will enroll 60 clinically stable preterm infants (28-32 weeks gestational age). We will evaluate early life stress, DNAm of NR3C1 and HSD11B2 gene promoters, cortisol reactivity, neurobehaviors, and oral feeding skill development during NICU stay and at 2-weeks post-discharge. The following specific aims will be addressed. Aim 1. Determine the association among early life stress, cortisol reactivity, and oral feeding skill development. Aim 2. Determine the extent to which DNAm of NR3C1 and HSD11B2 is associated with cortisol reactivity and/or neurobehaviors. Aim 3. Determine the association among early life stress, DNAm of NR3C1 and HSD11B2, and oral feeding skill development. The proposed study will positively impact neonatal care by contributing novel knowledge that clarifies biobehavioral mechanisms whereby early life stress compromises progression of oral feeding skill development. The findings hold significant promise to identify modifiable processes that can be targeted to promote optimal oral feeding, better nutrition, and lower risk for life-long maladaptive eating behaviors.

项目摘要/摘要 接受新生儿重症监护病房（NICU）的早产婴儿忍受了多种压力源。早期生活 压力可能超出其适应能力，并阻碍了发展里程碑的成就，例如口头 进食。多达70％的NICU早产儿面临口服喂食，导致不繁殖，延长 住院和高度医疗保健费用高达每位婴儿$ 200万美元。临床上有变化 早产儿的口服喂养技能发展的发展，有些婴儿有更多困难 比其他人。强有力的证据表明，口服喂养技能需要完整的神经行为。早期生活 压力会破坏神经行为的发展，这可能会损害口服喂养技能的成就。然而， 早期生活压力在多大程度上会损害口服喂养技能的发展以及生物力学 发生是未知的。在敏感的神经塑性期间暴露于早期生活压力会导致 压力反应系统的表观遗传印记。早期生活压力导致表观遗传修饰 糖皮质激素相关的基因，即NR3C1和HSD11B2的DNA甲基化（DNAM），它改变了 皮质醇水平和皮质醇反应性的下丘脑垂体肾上腺皮质（HPA）调节 神经行为。由于早期生活压力而引起的表观遗传修饰持久，可能会影响婴儿的健康 除了新生儿时期，增加了终身适应不良的喂养行为和健康状况不佳的风险。 这项研究的目的是确定NR3C1和DNAM反映的早期生活压力的程度 HSD11B2基因启动子损害口服喂养技能的开发。在这项前瞻性纵向研究中 我们将招募60名临床稳定的早产儿（胎龄28-32周）。我们将评估早期生活 应力，NR3C1和HSD11B2基因启动子的DNAM，皮质醇反应性，Neurobehaviors和口服喂养 NICU逗留期间的技能开发和分期后2周。以下具体目标将是 解决。目标1。确定早期生活压力，皮质醇反应性和口服喂养技能之间的关联 发展。 AIM 2。确定NR3C1和HSD11B2的DNAM与皮质醇有关的程度 反应性和/或神经行为。目标3。确定早期生命压力之间的关联，NR3C1的DNAM 和HSD11B2，以及口服喂养技能开发。拟议的研究将通过 有助于阐明生物行为机制的新颖知识，从而使早期压力妥协 口服喂养技能发展的进展。这些发现具有巨大的希望，可以识别可修改 可以针对促进最佳口服喂养，更好的营养和降低终身风险的过程 适应不良的饮食行为。