Advances in neonatal intensive care have increased survival for infants born <1000 g or extremely low birthweight (ELBW). However, the high rate of neurology and developmental disability remains a significant concern. Prevention of brain injury is now a major focus of neonatal research. Few techniques exist to permit early and accurate prognosis of neurologic sequelae. Cranial ultrasound (US) and magnetic resonance imaging (MRI) have been used to detect structural abnormalities which may be useful in predicting neuromotor and neurocognitive deficits. However, up to 30% of ELBW infants with normal US have adverse outcomes, and MRI cannot be performed when an infant is critically ill. The amplitude-integrated electroencephalogram (aEEG) is a non-invasive, bedside instrument which allows real-time monitoring of brain function and has recently been shown to be a useful predictor of outcome in term infants with hypoxic-ischemic encephalopathy. Preliminary studies in premature infants indicate that aEEG correlates with neuroimaging abnormalities and neurodevelopmental delay. We propose a prospective, multi-center study to evaluate the use of the aEEG in the ELBW population. We seek to determine if the background pattern, the development of sleep-wake cycles, and the presence of seizures correlate with neurodevelopmental impairment at 18-22 months corrected age. We also seek to examine whether findings on aEEG correlate with findings on neuroimaging, including intraventricular hemorrhage, ventriculomegaly, and white matter injury. ELBW infants enrolled in the NICHD Neonatal Research Network Generic Data Base and its follow-up component provide an established cohort of subjects to enroll in this study. Proper study design, execution and development of predictive models is essential to the success of this project. To this end, we propose this research as an integrated part of a 3-year Mentored Specialized Clinical Investigator Award, during which Dr. Alexis Davis (the candidate) will complete a Master's in Epidemiology in the Department of Health Research and Policy at Stanford University under the mentorship of Dr. Krisa Van Meurs and Dr. David Stevenson. Training in outcomes research, clinical study design, and biostatistics is essential to the development of an independent clinical investigator. A mentoring committee of highly experienced clinical investigators, biostatisticians, and developmental experts will guide the candidate during the award period. ? ? ?
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