OBJECTIVE: Free-radical-induced reperfusion injury has been recognised as an 
important cause of brain tissue damage after birth asphyxia. Allopurinol reduces 
the formation of free radicals, thereby potentially limiting the amount of 
hypoxia-reperfusion damage. In this study the long-term outcome of neonatal 
allopurinol treatment after birth asphyxia was examined.
DESIGN: Follow-up of 4 to 8 years of two earlier performed randomised controlled 
trials.
SETTING: Leiden University Medical Center, University Medical Center Groningen 
and University Medical Center Utrecht, The Netherlands.
PATIENTS: Fifty-four term infants were included when suffering from 
moderate-to-severe birth asphyxia in two previously performed trials.
INTERVENTION: Infants either received 40 mg/kg allopurinol (with an interval of 
12 h) starting within 4 h after birth or served as controls.
MAIN OUTCOME MEASURES: Children, who survived, were assessed with the Wechsler 
Preschool and Primary Scales of Intelligence test or Wechsler Intelligence Scale 
for Children and underwent a neurological examination. The effect of allopurinol 
on severe adverse outcome (defined as mortality or severe disability at the age 
of 4-8 years) was examined in the total group of asphyxiated infants and in a 
predefined subgroup of moderately asphyxiated infants (based on the amplitude 
integrated electroencephalogram).
RESULTS: The mean age during follow-up (n=23) was 5 years and 5 months (SD 1 
year and 2 months). There were no differences in long-term outcome between the 
allopurinol-treated infants and controls. However, subgroup analysis of the 
moderately asphyxiated group showed significantly less severe adverse outcome in 
the allopurinol-treated infants compared with controls (25% vs 65%; RR 0.40, 
95%CI 0.17 to 0.94).
CONCLUSIONS: The reported data may suggest a (neuro)protective effect of 
neonatal allopurinol treatment in moderately asphyxiated infants.