Development of Cerebral Autoregulation in VLBW Infants

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.