Regulation of Cerebral Blood Flow in Very Low Birth Weight Infants
Condition: Infant, Very Low Birth Weight; Infant, Premature, Diseases; Cerebral Hemorrhage
MeSH terms: Cerebral Hemorrhage; Infant, Premature, Diseases; Body Weight; Hemorrhage; Birth Weight
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Neonatal Intensive Care Unit
      
Keywords: very low birth weight infant; cerebral autoregulation; intraventricular hemorrhage; carbon dioxide; cerebral blood flow velocity; ultrasonography, Doppler, transcranial; cerebrovascular circulation