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.

项目总结