Development of Cerebral Autoregulation in VLBW Infants

该提案概述了一项研究极低出生体重（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，但极低出生体重婴儿的脑损伤仍然是一个重要的健康问题。这是由于早产的发生率增加和极低出生体重婴儿的存活率增加，极低出生体重婴儿最容易发生脑室内出血。压倒性的证据表明，紊乱的自动调节是重要的，在这些损伤的发病机制。尽管出生后年龄差异很大，但自动调节是一种维持恒定脑血流的机制，对VLBW婴儿自动调节的发展知之甚少。一种新的综合监测系统将被用来测试的中心假设，大脑自动调节能力在VLBW婴儿发育获得和其中断与脑损伤。将确定VLBW婴儿自身调节能力的个体发育特征。在缺乏自动调节的患者中，将评估出生后发育的时间进程。然后建立自动调节的缺乏和脑损伤之间的关系。将入组200名出生第1天头颅超声检查结果正常的VLBW婴儿。在调整动脉血气变化（连续血气监测仪）后，将脑血流速度（经颅多普勒超声）的连续1小时测量值与使用多变量分析的同步血压测量值进行比较，以确定自动调节能力（出生后前3天每天两次，第4-7天一次）。将分析每个个体和胎龄（23-25、26-28和大于或等于29周;足月为37-42周）组的数据。这项研究的结果将帮助我们认识到甚低出生体重婴儿何时最容易发生脑损伤，从而及时启动预防和干预策略。Jeffrey R.博士凯泽将利用阿肯色州大学医学科学学院强大的指导、受保护的研究时间和优秀的学术资源，实现他成为一名独立研究者的目标。

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.