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Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials
  1. Joepe J Kaandorp1,
  2. Frank van Bel1,
  3. Sylvia Veen2,
  4. Jan B Derks1,
  5. Floris Groenendaal1,
  6. Monique Rijken2,
  7. Elise Roze3,
  8. Monica MA Uniken Venema4,
  9. Carin MA Rademaker5,
  10. Arend F Bos3,
  11. Manon JNL Benders1
  1. 1Perinatal Center, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2Department of Neonatology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3Department of Neonatology, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, The Netherlands
  4. 4Department of Medical Psychology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
  5. 5Department of Clinical Pharmacy, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
  1. Correspondence to Manon JNL Benders, Perinatal Center, University Medical Center Utrecht, Perinatal Center, Lundlaan 6, KE 04.123.1, PO box 85090, 3508 AB, Utrecht, The Netherlands; m.benders{at}


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.

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  • Ethics approval The local ethical committees of the Leiden University Medical Center, the University Medical Center Groningen and the University Medical Center Utrecht.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.