Nonprotein-bound iron in postasphyxial reperfusion injury of the newborn

Objective. To investigate if the availability of nonprotein-bound iron after birth asphyxia is related to the severity of the postasphyxial injury and neurodevelopmental outcome. Methods. Nonprotein-bound iron (bleomycin assay) and thiobarbituric-acid-reactive species, an index of oxidative lipid damage, were measured in plasma of 50 newborn infants (gestational age >34 weeks) between 0 to 8 hours, 8 to 16 hours, and 16 to 24 hours after birth. Three groups were compared : healthy infants (n = 20), moderately asphyxiated infants (n = 15), who were neurologically normal during the first 24 hours after birth and severely asphyxiated infants (n = 15), who developed abnormal neurological signs in the first 24 hours after birth. Results. In the severely asphyxiated infants, liver enzymes, creatinine, urea, and uric acid concentrations were significantly elevated. Eleven severely asphyxiated infants were brain-damaged, 9 of them died during the neonatal period. Nonprotein-bound iron was detectable in 30% of the control, 60% of the moderately asphyxiated, and 80% of the severely asphyxiated infants. During the whole study period nonprotein-bound iron concentration was significantly elevated in severely asphyxiated infants as compared with controls. Three of the four severely asphyxiated infants who had a normal outcome at 1 year of age, had no detectable nonprotein-bound iron during the study period. Stepwise logistic regression analysis with neurodevelopmental outcome at 1 year of age (normal versus adverse/death) as dependent variable and all the measured parameters for organ damage as independent variables revealed that the nonprotein-bound iron concentration at 0 to 8 hours after birth was the most significant variable and at the same time the only variable that entered the model, in relation to neurodevelopmental outcome. Thiobarbituric-acid-reactive species tended to be higher in severely asphyxiated infants, suggesting oxidative lipid damage. Conclusion. Nonprotein-bound iron may play an important role in oxidative damage-mediated postasphyxial brain injury and subsequent neurodevelopmental outcome.