Kim Annink

161 Allopurinol: old drug, new indication in neonates? childhood diseases (60, 61). Though this study was not designed to study gender differences, gender differences should be taken into account in future research (59). No adverse events occurred in the allopurinol group (59). A limitation of this study was that most infants had no or only mild asphyxia, which resulted in underpowered results (59). None of the infants were diagnosed with HIE after inclusion. The reason for the relatively high amount of mildly asphyxiated infants is that antenatal monitoring has a poor predictive value for actual perinatal asphyxia with a lot of false positive cases (59). Taking this into account, a very large RCT would be needed to estimate the actual effect of antenatal allopurinol administration. Although antenatal administration of allopurinol in girls with HIE might be promising, it is not optimal either because of the difficulties to predict which infants will be born with perinatal asphyxia in the daily practice: actual asphyxiated babies might be missed and there will be a lot of overtreatment of fetuses without relevant hypoxia. Therefore early, neonatal allopurinol administration might be a more suitable design for future studies. Other indications Allopurinol has also been tested in other neonatal populations in which free radical formation leads to cell damage. The study of Derks et al. that was discussed earlier, already suggested a beneficial cardioprotective effect of antenatal allopurinol in animals. Infants undergoing cardiac surgery experience periods of hypoxia, which is known to lead to brain damage and especially to white matter injury (62,63). Allopurinol might also have neuroprotective effects next to the possible cardioprotective effects in neonates with congenital heart diseases. Serum uric acid levels after allopurinol administration were decreased in infants with a hypoplastic left heart syndrome (HLHS) compared to baseline. This suggests that the xanthine-oxidase pathway is activated in HLHS and that allopurinol can inhibit this pathway (64). In a RCT including infants with a congenital heart disease, allopurinol or placebo was administered before, during and after heart surgery with deep hypothermic circulating arrest (65). Infants with HLHS (n=131) as well as infants with other congenital heart diseases (n=187) were treated in this trial. In the infants with HLHS death, seizures, coma and/or cardiac events occurred in 38% of the infants in the allopurinol group and in 60% of infants in the placebo group (p=0.01) (65). This suggested a neuroprotective and cardioprotective 7