Maternal Allopurinol During Fetal Hypoxia Lowers Cord Blood Levels of the Brain Injury Marker S-100B

Abstract

It has been suggested that early postnatal administration of allopurinol, a xanthine oxidase inhibitor, might reduce perinatal brain damage because of intrapartum asphyxia. This double-blind randomized pilot study investigated whether maternal treatment with allopurinol in a population of pregnant women in late labor with signs of fetal hypoxia would reduce fetal cord serum concentrations of non-protein-bound iron, or other free radicals and S-100, a protein marker of central nervous system damage. The subjects of the study were 53 women in labor (54 fetuses) at >36 weeks' gestation, and who had signs of fetal distress (indicated by abnormal or nonreassuring fetal heart rate tracing or fetal scalp pH of 2 mg/L for allopurinol and/or >4 mg/L for oxypurinol), and significantly higher compared with fetal arterial cord concentrations. Therapeutic concentrations were also found in the cord blood of 15 allopurinol-treated newborns. However, 12 had sub-therapeutic levels. For this reason, 3 treatment groups were created: therapeutic allopurinol (n = 15), sub-therapeutic allopurinol (n = 12), and placebo (n = 27). The therapeutic allopurinol group had significantly lower plasma S-100B concentrations compared with the subtherapeutic allopurinol and placebo groups (P < 0.01 for both). Moreover, the concentration of non-protein-bound iron was significantly less in therapeutic allopurinol cord blood cord samples than that in the subtherapeutic allopurinol and placebo groups (P < 0.05 for both). The investigators believe that this is the first study to demonstrate that maternal allopurinol/oxypurinol can cross the placenta during fetal hypoxia, and that therapeutic concentrations can reduce serum levels of markers associated with brain asphyxia. These findings should be confirmed in a larger study using higher doses.