Integrated analysis of autonomic biomarkers in prematurity-related ventilatory control: Determination of neurorespiratory maturation and predictors of co-morbidity risk

早产相关通气控制中自主生物标志物的综合分析：神经呼吸成熟度的确定和共病风险的预测因子

• 批准号: 10006025
• 负责人: AARON HAMVAS
• 金额: $ 53.06万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10006025
• 关键词: Affect; Age; Algorithms; Autonomic nervous system; Biological Markers; Bronchopulmonary Dysplasia; Cardiac; Cardiovascular Physiology; Cardiovascular system; Cerebrovascular Physiology; Cerebrum; Chemoreceptors; Child; Chronic; Clinical; Development; Diagnostic; Disease; Disease Outcome; Documentation; Early identification; Family; Future; Health Care Costs; Hospitalization; Hour; Hypoxia; Impairment; Individual; Infant; Infant Development; Intervention; Late pregnancy; Life; Lung; Lung diseases; Measurement; Measures; Medical Records; Methods; Monitor; Morbidity - disease rate; Motor; Neonatal; Nervous System Physiology; Neurologic; Outcome; Outcome Measure; Oxygen; Pathogenesis; Pattern; Peripheral; Pharmaceutical Preparations; Physiologic Monitoring; Physiological; Pregnancy; Premature Birth; Premature Infant; Regulation; Reporting; Research; Resolution; Risk; Role; Sensory; Severities; Stratification; Testing; Time; base; cerebrovascular; clinical application; comorbidity; innovation; insight; member; nervous system development; neural circuit; novel strategies; physiologic model; premature; prospective; resilience; respiratory; respiratory morbidity; response

Project Summary The broad long-term objective of the proposed study is to use comprehensive state-of-the-art high-fidelity monitoring to investigate physiological biomarkers of autonomic neurorespiratory maturation with integrated analysis of autonomic nervous system (ANS) responses in preterm infants, and to evaluate their role in ventilatory instability, bronchopulmonary dysplasia (BPD), and co-morbidities including impaired neuromotor development in the 1st year of life. SPECIFIC AIM 1 will establish the spectrum and developmental trajectory of ANS maturation/function using 20-hour high-resolution recordings of ventilatory, cardiovascular, and cerebrovascular physiology during typical endogenous daily activity (32 and 36 weeks; 3 months) and brief evoked hypoxic, hyperoxic, and hypercarbic challenges of peripheral and central chemoreceptors to unmask latent autonomic and respiratory instability (36 weeks; 3 and 12 months). Aim 1 tests the hypothesis that individual and integrated metrics of ANS function will demonstrate maturational patterns that impart resilience or vulnerability to physiologic challenges. SPECIFIC AIM 2 will determine respiratory and neurodevelopmental morbidity throughout the 1st year of life using a composite Respiratory Morbidity Severity Score that includes need for respiratory support, medications, or hospitalization (3, 6, 9, 12 months), and the Neurological, Sensory, Motor, Developmental Assessment (3, 6, 12 months) as clinically applicable outcome measures, and will associate these measures with ANS development and function. Aim 2 tests the hypothesis that infants demonstrating delayed ANS maturation or vulnerability to physiologic perturbations will require more respiratory interventions and will demonstrate neuromotor delays in the 1st year of life. SPECIFIC AIM 3 will determine endotypes of autonomic neurorespiratory stability and maturation through trajectory analysis and integrated physiological modeling. Aim 3 tests the hypothesis that trajectory analysis will reveal 3 autonomic maturation patterns (1)anticipated maturation with ability to withstand physiologic perturbations; 2)anticipated maturation without ability to withstand physiologic perturbations; and 3)delayed or disordered maturation with an inability to maintain physiologic stability even in the absence of environmental perturbations) that will predict varying degrees of respiratory morbidity and neuromotor impairment at 1 year. This novel approach will establish the role of autonomic neurorespiratory maturation in stability of oxygenation throughout the 1st year of life, provide insight into BPD pathogenesis, allow prospective identification of at-risk infants, and permit development of mechanism-specific interventions that have potential to impact thousands of families and billions of dollars in healthcare costs each year in the U.S., alone.

项目概要 拟议研究的广泛长期目标是使用综合的、最先进的高保真度 监测以研究自主神经呼吸成熟的生理生物标志物 分析早产儿自主神经系统（ANS）反应，并评估其在 通气不稳定、支气管肺发育不良 (BPD) 以及神经运动受损等合并症 生命第一年的发育。具体目标 1 将建立以下领域的谱系和发展轨迹： 使用 20 小时高分辨率的呼吸、心血管和呼吸记录记录 ANS 的成熟/功能 典型内源性日常活动（32 和 36 周；3 个月）期间的脑血管生理学和简要 诱发外周和中枢化学感受器的缺氧、高氧和高碳挑战以揭示真相 潜在的自主神经和呼吸不稳定（36 周；3 和 12 个月）。目标 1 检验假设 ANS 功能的单独和综合指标将展示赋予弹性的成熟模式 或对生理挑战的脆弱性。具体目标 2 将确定呼吸和神经发育 使用综合呼吸系统发病严重程度评分来评估生命第一年的发病率，其中包括 需要呼吸支持、药物或住院（3、6、9、12 个月）以及神经系统、 感觉、运动、发育评估（3、6、12 个月）作为临床适用的结果测量，以及 将这些措施与 ANS 的发展和功能联系起来。目标 2 检验婴儿的假设 证明 ANS 成熟延迟或对生理扰动的脆弱性需要更多 呼吸干预，并将在生命的第一年表现出神经运动延迟。具体目标 3 将 通过轨迹分析确定自主神经呼吸稳定性和成熟的内型 综合生理建模。目标 3 测试轨迹分析将揭示 3 个自主神经的假设 成熟模式 (1) 具有承受生理扰动能力的预期成熟； 2）预期 成熟时无法承受生理扰动； 3) 成熟延迟或紊乱 即使在没有环境扰动的情况下也无法维持生理稳定性），这将预测 1 年时出现不同程度的呼吸系统疾病和神经运动障碍。这种新颖的方法将 确定自主神经呼吸成熟在整个第一年氧合稳定性中的作用 生活，深入了解 BPD 发病机制，允许前瞻性识别高危婴儿，并允许 制定有可能影响数千个家庭的针对具体机制的干预措施 仅在美国，每年的医疗费用就高达数十亿美元。