Kim Annink

157 Allopurinol: old drug, new indication in neonates? no significant improvement of adverse long-term neurodevelopmental outcome (allopurinol 8% vs. controls 11%, p=1.000) or mortality (allopurinol 54% vs. controls 62%, p=0.376) in the overall analysis. However, when only the moderately asphyxiated infants were analyzed, a significant improvement of long-term outcome was found in the allopurinol treated infants compared to the controls. In moderately affected infants, 65% of controls had a severe adverse outcome, defined as death or severe neurodevelopmental disabilities, compared to 25% of the allopurinol treated infants (p=0.047) (48). This follow-up study suggested a positive effect of allopurinol in moderately asphyxiated infants on neurological outcome, but not in severely asphyxiated infants. This is in line with a previous study on neonatal head cooling after acute perinatal asphyxia in term infants (49) and the previously discussed animal studies (41,42). However, the numbers of this follow-up study were very small, therefore the results should be interpreted with caution (48). The most recent RCT investigating the benefit of postnatal allopurinol in neonates with HIE was performed by Gunes et al. in Turkey. Thirty neonates were treated for three days with two dosages of 20 mg/kg allopurinol per day, with the first dose being administered within two hours after birth. The control group of thirty neonates received a placebo. This study was not blinded in order to enable the investigators to monitor side effects. Free radical production, measured by NO concentrations in the serum, was decreased after the administration of allopurinol compared to controls. NO concentrations in the cerebrospinal fluid were comparable between the groups. Adverse outcome at 1 year of age, was reduced in the allopurinol group compared to placebo (39.3% vs. 53.6%, p<0.05). Adverse outcome was defined as cerebral palsy, Bayley score < -2SD, blindness and/or deafness. Mortality did not differ between the groups. No adverse side effects of allopurinol were seen (50). Although this study is larger than the other two, the sample size is still not large enough to draw conclusions about the neuroprotective effect of allopurinol. Furthermore, a longer neurological follow-up is essential to determine the actual effect of allopurinol on the long-term in HIE. Additionally, pharmacokinetic analysis would have been valuable since this study used other dosing protocols than the previous studies. It can be concluded from these clinical studies that allopurinol might be neuroprotective in moderately affected infants, but is not effective when the brain damage is too severe. Considering that the onset of free radical production is immediately after the onset of reperfusion, administration of allopurinol within four 7