Kim Annink

158 Chapter 7 hours after birth might be too late to reduce the peak of these toxic metabolites. Importantly, in none of the studies adverse side effects were seen. As expected, the conclusion of the Cochrane review including the studies of van Bel et al., Benders et al. and Gunes et al. stated, that there is not enough evidence to draw conclusions and that larger trials are needed (51). In combination with the idea that allopurinol should be given as early as possible, the hypothesis arose that antenatal administration of allopurinol in case of suspected fetal hypoxia might be more effective. Table 1: Overview or clinical studies with allopurinol in HIE Study Population Moment of administration and dosages Results Van Bel et al , 1998 Allopurinol (n=11) vs. controls (n=11) 20mg/kg i.v. within 4 hours after birth, 2nd dose of 20mg/kg i.v. 12 hours later (median allopurinol administration 170 min; range 68-210) Positive effect on free radical formation, electrical brain activity and a relative preservation of cerebral blood volume. No adverse events. Benders et al , 2006 Allopurinol (n=17) vs. placebo (n=15) 20mg/kg i.v. within 4 hours after birth, 2nd dose of 20mg/kg i.v. 12 hours later (median and range not shown) No effect on short term outcome in severely affected infants. No adverse events. Gunes et al , 2007 Allopurinol (n=30) vs. placebo (n=30) 20mg/kg i.v. within 2 hours after birth, second dose 12 hours later, then every 12 hours a dose for 3 days (median and range not shown) Better neurological outcome at 1 year of age. Serum NO decreased after allopurinol. No adverse events. Kaandorp et al , 2012 Allopurinol (n=28) vs. placebo (n=26) Follow-up study of Benders et al. and van Bel et al. at four to eight years of age Improved neurological outcome in moderately affected infants. No adverse events. Torrance et al , 2009 Allopurinol (n=27) vs. placebo (n=27) 500mg allopurinol i.v. antenatally (median allopurinol administration 56min before delivery; range 18-190) Reduction of S100ß levels in therapeutic allopurinol group. No adverse events.