Advances in newborn intensive care have lead to dramatic improvements in survival for the most premature infants-often weighing 1 pound at birth. Unfortunately, cerebral palsy, mental retardation, and developmental delay affect more than 10,000 of these premature infants in the U.S. annually. In his studies, Dr. Jeffrey R. Kaiser is trying to understand why these premature infants are at such high risk of brain injury, and to learn ways to prevent injury. Experts believe that disturbances of brain blood flow regulation are important in causing these injuries. Using a novel continuous monitoring system, Dr. Kaiser is able to determine an infant's capacity for normal brain blood flow regulation. Contrary to previous thinking, he has shown that many of these babies in fact due have normal regulation of their brain blood flow. He has observed that brain blood flow may be disturbed during suctioning of the breathing tube. Further, he has also shown that infants with high carbon dioxide, those not breathing well, have impaired regulation of their brain blood flow. Thus, even stable infants are prone to disturbed brain regulation during routine intensive care, which may lead to bleeding in the brain and long-term neurologic problems. Dr. Kaiser will study up to 200 infants to determine 1) the developmental pattern of normal regulation of cerebral blood flow; 2) in those with impaired regulation, determine when it develops during the first week of life; and 3) determine the relationship between impaired brain blood flow regulation and brain injury. Results from this study will help us recognize when premature infants are most vulnerable to developing brain injury, allowing prevention and intervention strategies to be initiated in a timely fashion.

This proposal outlines a program to study the development of cerebral autoregulation in very low birth weight (VLBW) (less than 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 those 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 blood pressure. However, because previous studies have pooled data from infants with different gestational and postnatal ages, little is known about how autoregulation develops in VLBW infants. A novel monitoring system will be used to test the central hypotheses that cerebral autoregulatory capacity in VLBW infants is developmentally acquired and that 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 findings 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 measurements of blood pressure 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 once on days 4-7). Results will be analyzed for each individual and for gestational age groups (23-25, 26-28, and greater than 29 weeks'). Results from this study will help us recognize when VLBW infants are most vulnerable to developing brain injury, allowing prevention and intervention strategies to be initiated in a timely fashion. Dr. Jeffrey 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.

Inclusion Criteria:

• Very low birth weight infants, ventilated, umbilical arterial catheter in place

Exclusion Criteria:

• Infants with serious congenital anomalies and chromosomal abnormalities
• Infants not intubated
• Infants without umbilical arterial catheter
• Infants without parental consent

Neonatal Intensive Care Unit