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

Abstract

Maternal allopurinol/oxypurinol crosses the placenta during fetal hypoxia. In fetuses/newborns with therapeutic allopurinol/oxypurinol concentrations in cord blood, lower plasma levels of the brain injury marker protein S-100B were detected. A larger allopurinol trial in compromised fetuses at term seems warranted. The allopurinol dosage must be adjusted to achieve therapeutic fetal allopurinol/oxypurinol concentrations.

Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials

“…A recent pilot study in this respect, performed by our research group, showed a significant inversed correlation between the levels of fetal allopurinol and S100B (a clinically used marker for brain damage) in cord blood 26. A large multicenter randomised clinical trial on maternal treatment with allopurinol in case of signs of fetal hypoxia is now running in the Netherlands (NCT00189007) to investigate whether or not maternal allopurinol treatment can further improve the long-term outcome of neonates exposed to (severe) fetal hypoxia 27…”

“…Because of the vast amount of toxic free-radicals, an important reason for post-HI damage to the immature brain is produced during the HI event itself and in particular upon reperfusion and reoxygenation in the first 30 to 60 min after birth, we suggest that earlier treatment might be more effective. By intravenous administration of allopurinol to the mother when fetal distress, an important determinant of perinatal asphyxia, is suspected, therapeutic levels of allopurinol and its active metabolite oxypurinol can be reached even before birth 25 26. In this way, therapeutic levels of allopurinol are already available upon reperfusion, thereby reducing the formation of toxic free-radicals in an earlier and crucial stage, namely during maximal free-radical formation.…”

Antioxidant Therapies: A Potential Role in Perinatal Medicine

“…However, preliminary results from a small number of patients suggest that it has been difficult to achieve therapeutic cord blood levels of allopurinol and oxypurinol in compromised pregnancies. Nevertheless, where therapeutic levels of allopurinol/oxypurinol were achieved, the babies did have lower levels of S100B [60], consistent with a possible neuroprotective effect.…”

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

“…The method was linear between 0.5 and 25 mg/L with a lower limit of quantification of 0.2 mg/L for both compounds 23. Based on earlier studies, allopurinol is known to actively inhibit xanthine oxidase at plasma concentrations exceeding 2.0 μg/mL 12 24…”

“…The dose of allopurinol was based on a study in healthy pregnancies15 and on our pilot study 12. This dose of 500 mg is the maximum dosage approved in adults as a single intravenous injection 16…”