“This is the first clinical study to investigate whether maternal treatment of the hypoxic fetus may lead to a reduction of the devastating consequences of birth asphyxia,” lead author Dr. Helen L. Torrance, from University Medical Center, Utrecht, the Netherlands, and colleagues note in the July issue of Pediatrics.
Hypoxia-induced free radical formation plays a key role in the brain injury seen with fetal hypoxia, according to the report. As such, treatment with allopurinol, a free radical scavenger at higher doses, may offer some benefit. Prior research has shown that allopurinol can cross the placenta, but it was unclear if this also occurred during fetal hypoxia.
The current study featured 53 pregnant women (54 fetuses) in labor at >36 weeks’ gestation with fetal hypoxia who were randomized to receive allopurinol 500 mg or placebo intravenously.
In the allopurinol group, therapeutic levels of the drug were found in all maternal blood samples. Among the 27 fetuses in that group, 15 of the cord blood samples had therapeutic levels and 12 had subtherapeutic levels.
Cord blood levels of S-100B, a brain injury marker, were significantly reduced in the 15 fetuses with therapeutic allopurinol levels compared with the 12 fetuses who had subtherapeutic levels and the 27 who received placebo. Free radical formation, as assessed with non-protein-bound iron levels, was also reduced in the therapeutic allopurinol group.
In light of these findings, “a larger allopurinol trial in compromised fetuses at term seems warranted,” the authors state. “The allopurinol dosage must be adjusted to achieve therapeutic fetal allopurinol/oxypurinol concentrations,” they add.