title: Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials.
abstract: 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.
  
  
  METHODS
  Follow-up of 4 to 8 years of two earlier performed randomised controlled trials.
  
  
  METHODS
  Leiden University Medical Center, University Medical Center Groningen and University Medical Center Utrecht, The Netherlands.
  
  
  METHODS
  Fifty-four term infants were included when suffering from moderate-to-severe birth asphyxia in two previously performed trials.
  
  
  METHODS
  Infants either received 40 mg/kg allopurinol (with an interval of 12 h) starting within 4 h after birth or served as controls.
  
  
  METHODS
  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.
authors.affiliation: Perinatal Center, Wilhelmina Children’s Hospital, University Medical Center Utrecht, The Netherlands.
authors.forename: Joepe J
authors.initials: JJ
authors.lastname: Kaandorp
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.forename: Sylvia
authors.initials: S
authors.lastname: Veen
authors.forename: Jan B
authors.initials: JB
authors.lastname: Derks
authors.forename: Floris
authors.initials: F
authors.lastname: Groenendaal
authors.forename: Monique
authors.initials: M
authors.lastname: Rijken
authors.forename: Elise
authors.initials: E
authors.lastname: Roze
authors.forename: Monica M A Uniken
authors.initials: MM
authors.lastname: Venema
authors.forename: Carin M A
authors.initials: CM
authors.lastname: Rademaker
authors.forename: Arend F
authors.initials: AF
authors.lastname: Bos
authors.forename: Manon J N L
authors.initials: MJ
authors.lastname: Benders
mesh_terms: D000493:Allopurinol / Q000627:therapeutic use*; D001238:Asphyxia Neonatorum / Q000150:complications* / Q000523:psychology; D001724:Birth Weight; D002658:Developmental Disabilities / Q000209:etiology / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D016166:Free Radical Scavengers / Q000627:therapeutic use; D005865:Gestational Age; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D007231:Infant, Newborn; D007360:Intelligence / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D016896:Treatment Outcome
chemical_list: D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D000493:Allopurinol