All premature infants < 1500 gm birth wt admitted within 8 hrs. of birth to one of the two study center NICU?s will be considered for possible inclusion in the study. Exclusion criteria include infants with known cerebral dysgenesis or in utero cerebral destructive events, or infants designated to receive limited life support interventions. After obtaining informed consent, cerebral oximetry optodes will be placed and NIRS data recorded continuously in time-locked manner with MAP via umbilical artery catheter. Daily 12-hr recordings for the first 5 days of life will be made. The NIRS-measured difference between oxyhemoglobin and deoxyhemoglobin, HbD, is assumed in this study to be an indicator of cerebral blood flow in these infants. The temporal and scalar relationship between the two signals (MAP and HbD) will be analyzed by means of coherence and transfer functions after visual screening by an investigator has eliminated artifact ridden segments. Results of this signal analysis will form the basis for categorizing each infant as either autoregulating or pressure-passive, and if the latter, will define degrees of severity of autoregulatory dysfunction. Extensive additional clinical data related to risk factors for PVL and hypoxia-ischemia will be recorded as obtained in the course of standard clinical care. These will include specific critical thresholds for hypercarbia, hypoxemia, and hypotensions; as well as serial measures of circulating cytokines. PVL will be detected by standard ultrasound imaging techniques, and by novel MRI and MR spectroscopic modalities. Scans will be obtained at the earliest feasible time and repeated at one year of age, at which time a standardized battery of neurologic and developmental examinations will be administered. With this design and methods, the investigators will test the following hypotheses: (1) concordant measures of cerebral and systemic hemodynamics using NIRS will distinguish autoregulating infants from pressure-passive infants; (2) critical abnormalities in MAP, PaO2 and PaCO2 will be associated with pressure-passive circulation; (3) higher circulating cytokine levels will be associated with pressure-passive circulation; (4) pressure-passive circulation is a precursor of PVL, and is associated with elevated lactate in cerebral white matter; (5) PVL visible in the neonatal period predicts abnormal myelin development, motor and cognitive handicap at one year of age.
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