Development of Cerebral Autoregulation in VLBW Infants

这项建议概述了一个研究极低出生体重(VLBW)(501-1500克出生体重)婴儿大脑自动调节的发展及其在脑损伤中的作用的计划。尽管重症监护有所改善，但极低出生体重儿的脑损伤仍然是一个重大的健康问题。这是由于早产儿的发生率增加和极低出生体重儿最容易发生脑室出血的存活率增加所致。强有力的证据表明，自我调节功能紊乱在这些损伤的发病机制中起着重要作用。自动调节是一种维持持续血液流向大脑的机制，尽管出生后年龄差异很大，但对极低出生体重婴儿的自动调节是如何发展的知之甚少。一种新的集成监测系统将用于验证中央假设，即极低出生体重儿的大脑自我调节能力是发育获得的，其破坏与脑损伤有关。将确定极低出生体重儿自我调节能力的个体发育概况。对于那些缺乏自动调节的人，将评估出生后发育的时间进程。然后，将建立自我调节缺失与脑损伤之间的关系。出生第一天头部超声检查正常的200名极低出生体重儿将被登记。脑血流速度的连续1小时测量(经颅多普勒超声)将与使用多变量分析的同时血压测量进行比较，在调整了动脉血气的变化后(连续血气监测仪)，以确定自动调节能力(在生命的前3天每天两次，第4-7天一次)。将对每个人和胎龄(23-25，26-28，大于或等于29周；足月37-42周)组的数据进行分析。这项研究的结果将帮助我们认识到极低出生体重儿最容易发生脑损伤的时间，以便及时启动预防和干预策略。Jeffrey R.Kaiser博士将利用阿肯色医学大学强大的指导、受保护的研究时间和出色的学术资源来实现他成为一名独立研究员的目标。

This proposal outlines a program to study the development of cerebral autoregulation in very low birth weight (VLBW) (501-1500 grams birth weight) infants, and its role in brain injury. Despite improvements in intensive care, brain injury in VLBW infants remains a significant health problem. This is due to the increasing incidence of prematurity and increasing survival rates of VLBW infants most prone to developing intraventricular hemorrhage. Overwhelming evidence suggests that disturbances of autoregulation are important in the pathogenesis of these injuries. Autoregulation is a mechanism that maintains constant blood flow to the brain despite wide variations in postnatal ages, little is known about how autoregulation develops in VLBW infants. A novel integrated monitoring system will be used to test the central hypotheses that cerebral autoregulatory capacity in VLBW infants is developmentally acquired and its disruption is associated with brain injury. The ontogenetic profile of autoregulatory capacity in VLBW infants will be determined. In those who lack autoregulation, the postnatal time course for development will be assessed. Then the relationship between the absence of autoregulation and brain injury will be established. Two hundred VLBW infants who have normal finding on a cranial ultrasound on day of life 1 will be enrolled. Continuous 1-hour measurements of cerebral blood flow velocity (transcranial Doppler ultrasound) will be compared to simultaneous blood pressure measurements using multivariate analysis, after adjusting for variations in arterial blood gases (continuous blood gas monitor), to determine autoregulatory capacity (twice daily during the first 3 days of life and one on days 4-7). Data will be analyzed for each individual and for gestational age (23-25, 26-28, and greater than or equal to 29 weeks'; full term is 37-42 weeks') groups. Results from this study will help us recognized when VLBW infants are most vulnerable to developing brain injury, allowing prevention and intervention strategies to be initiated in a timely fashion. Dr. Jeffrey R. Kaiser will take advantage of the strong mentoring, protected research time and outstanding academic resources of the University of Arkansas for Medical Sciences to reach his goal of becoming an independent investigator.