Maternal allopurinol administration during suspected fetal hypoxia: a novel neuroprotective intervention? A multicentre randomised placebo controlled trial

Arch Dis Child Fetal Neonatal Ed. 2015 May;100(3):F216-23. doi: 10.1136/archdischild-2014-306769. Epub 2014 Dec 15.


Objective: To determine whether maternal allopurinol treatment during suspected fetal hypoxia would reduce the release of biomarkers associated with neonatal brain damage.

Design: A randomised double-blind placebo controlled multicentre trial.

Patients: We studied women in labour at term with clinical indices of fetal hypoxia, prompting immediate delivery.

Setting: Delivery rooms of 11 Dutch hospitals.

Intervention: When immediate delivery was foreseen based on suspected fetal hypoxia, women were allocated to receive allopurinol 500 mg intravenous (ALLO) or placebo intravenous (CONT).

Main outcome measures: Primary endpoint was the difference in cord S100ß, a tissue-specific biomarker for brain damage.

Results: 222 women were randomised to receive allopurinol (ALLO, n=111) or placebo (CONT, n=111). Cord S100ß was not significantly different between the two groups: 44.5 pg/mL (IQR 20.2-71.4) in the ALLO group versus 54.9 pg/mL (IQR 26.8-94.7) in the CONT group (difference in median -7.69 (95% CI -24.9 to 9.52)). Post hoc subgroup analysis showed a potential treatment effect of allopurinol on the proportion of infants with a cord S100ß value above the 75th percentile in girls (ALLO n=5 (12%) vs CONT n=10 (31%); risk ratio (RR) 0.37 (95% CI 0.14 to 0.99)) but not in boys (ALLO n=18 (32%) vs CONT n=15 (25%); RR 1.4 (95% CI 0.84 to 2.3)). Also, cord neuroketal levels were significantly lower in girls treated with allopurinol as compared with placebo treated girls: 18.0 pg/mL (95% CI 12.1 to 26.9) in the ALLO group versus 32.2 pg/mL (95% CI 22.7 to 45.7) in the CONT group (geometric mean difference -16.4 (95% CI -24.6 to -1.64)).

Conclusions: Maternal treatment with allopurinol during fetal hypoxia did not significantly lower neuronal damage markers in cord blood. Post hoc analysis revealed a potential beneficial treatment effect in girls.

Trial registration number: NCT00189007, Dutch Trial Register NTR1383.

Keywords: Allopurinol; Fetal asphyxia; Gender difference; Neuroprotection; S100B.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aldehydes / blood
  • Allopurinol / blood
  • Allopurinol / therapeutic use*
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Double-Blind Method
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Fetal Blood / chemistry
  • Fetal Hypoxia / drug therapy*
  • Humans
  • Ketones / blood
  • Male
  • Maternal-Fetal Exchange
  • Oxypurinol / blood
  • Pregnancy
  • S100 Calcium Binding Protein beta Subunit / blood
  • Xanthine Oxidase / antagonists & inhibitors*


  • Aldehydes
  • Enzyme Inhibitors
  • Ketones
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • 8-epi-prostaglandin F2alpha
  • Allopurinol
  • Dinoprost
  • Xanthine Oxidase
  • Oxypurinol

Associated data

  • NTR/NTR1383