Development of Cerebral Autoregulation in VLBW Infants

本研究旨在研究极低出生体重儿（VLBW）（501-1500克出生体重）脑自动调节的发展及其在脑损伤中的作用。尽管重症监护有所改善，但VLBW婴儿的脑损伤仍然是一个重大的健康问题。这是由于最容易发生脑室内出血的VLBW婴儿的早产发生率增加和存活率增加。大量证据表明，自我调节的紊乱在这些损伤的发病机制中很重要。尽管出生后年龄差异很大，但自我调节是一种维持大脑持续血流量的机制，对于VLBW婴儿的自我调节如何发展知之甚少。一种新型的综合监测系统将被用于检验VLBW婴儿的大脑自我调节能力是发育获得性的，其破坏与脑损伤有关的中心假设。将确定VLBW婴儿的自我调节能力的个体发生特征。对于那些缺乏自我调节能力的人，将评估出生后的发育过程。从而建立脑损伤与自我调节缺失之间的关系。将招募200名在出生第一天的颅骨超声检查中发现正常的VLBW婴儿。在调整动脉血气变化（连续血气监测）后，将连续1小时测量脑血流速度（经颅多普勒超声）与使用多变量分析同时测量血压进行比较，以确定自身调节能力（在生命的前3天每天两次，第4-7天每天一次）。将对每个个体和胎龄（23-25周、26-28周、大于或等于29周；足月为37-42周）组的数据进行分析。本研究的结果将帮助我们认识到VLBW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. Kaiser博士将利用阿肯色大学强大的指导、受保护的研究时间和优秀的学术资源来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.