New technologies are needed to identify critically-ill infants at risk for abnormal neurological development. This project will determine if the measurement of the glucose production rate (GPR) by stable isotope technology can enhance the assessment of brain damage in newborn infants. The basis of this approach to the development of simplified techniques for the study of CNS metabolic function is the linear correlation between estimated brain weight and whole- body glucose turnover found in premature infants to adults (r=0.94). Preliminary studies have also shown that infants with extensive loss of cortical brain mass have low GPR. Our pilot study of GPRs in critically-ill newborns demonstrated that 10/11 infants, with a GPR of less than 50% of the expected value predicted by weight, died or did not progress past fetal stages of neurological development. In a contract, GPRs of six critically ill, but neurologically normal infants, studied on two or more occasions, varied an average of only 18% over the course of the infant in neonatal intensive care unit. These data suggest that the finding of a low GPR may complement existing technology in the early identification of infants with neurologic damage. We propose to test the hypothesis that a low GPR is an early predictor of neonatal death or severe brain injury. To assess the sensitivity and specificity of the GPR as a clinical test, it is also necessary to establish the normal range of the GPR. We will establish a range by determination of the GPR in a minimum of 100 critically ill infants whose neurological outcomes are normal. To accomplish these aims, we will perform gas chromatography- mass spectrometry analysis of six 0.3cc serum samples obtained from the infants during a bedside, four-hour infusion of dideuteroglucose. These studies will test the correlations between low GPR and neurological outcome. Establishment of a low GPR as an early predictor of abnormal brain cell metabolic activity will facilitate the identification of neurologically damaged infants and assist in the evaluation of new therapeutic modalities for the treatment of brain injury.
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