Article Text

DOES MATERNAL ALLOPURINOL REDUCE FETAL OXIDATIVE STRESS DURING PERINATAL HYPOXIA–ISCHAEMIA?
  1. M J Benders1,
  2. H L Torrance1,
  3. J B Derks1,
  4. C M Rademaker2,
  5. F Groenendaal1,
  6. A F Bos3,
  7. G H Visser1,
  8. G Buonocore4,
  9. F vanBel1
  1. 1Department of Perinatology, University Medical Center Utrecht, Wilhelmina Children’s Hospital, Utrecht, The Netherlands
  2. 2Department of Pharmacy, University Medical Hospital Utrecht, Utrecht, The Netherlands
  3. 3Department of Perinatology, University Medical Center Groningen, Groningen, The Netherlands
  4. 4Department of Neonatology, University of Siena, Siena, Italy

Abstract

Background Allopurinol inhibits xanthine oxidase and prevents free radical formation during early reoxygenation and reperfusion after perinatal hypoxia–ischaemia (PHI). The efficacy of postnatal allopurinol is questionable because administration may be too late to prevent free radical production. Maternal allopurinol treatment during PHI may be more effective for fetal and neonatal neuroprotection.

Objective To evaluate oxidative stress reduction after maternal allopurinol treatment during PHI in newborns.

Methods Women in labour (gestational age >36 weeks) with PHI were treated with a single allopurinol dose or placebo (double-blind randomised). Allopurinol and oxypurinol concentrations, oxidative stress (isoprostane, free iron (N-bromophethalimide; NBPI), hydroperoxide, thiol groups) parameters were determined (umbilical cord blood).

Results 28 mothers were treated with allopurinol (500 mg intravenously), 26 with placebo. Allopurinol and oxypurinol levels were therapeutic in mothers (3.9 + 2.3 and 3.5 + 1.5 mg/l, respectively), but not always in fetuses (1.7 + 1.5 and 1.5 + 0.9 mg/l, respectively). Therefore, the allopurinol group was divided into allopurinol-positive (>2.5 μg/ml) and allopurinol-negative (<2.5 μg/ml) subgroups. Fetal hypoxia was comparable between groups as expressed by lactate (8.6 + 3.5 vs 8.5 + 2.3 mmol/l). Hydroperoxide and NPBI tended to be, and thiol groups were, significantly lower in allopurinol positive compared with placebo. S100-B in cord blood (as an indicator of neuronal damage) was lower in allopurinol positive versus placebo (p<0.05).

Conclusions Allopurinol passes the placenta, although fetal levels are marginal. The lower S100-B, as an indicator of neuronal damage, together with the lower free-radical load in allopurinol-positive fetuses suggest neuroprotection during antenatal treatment of PHI.

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