Maternal allopurinol during fetal hypoxia lowers cord blood levels of the brain injury marker S-100B
Helen L Torrance, Manon J Benders, Jan B Derks, Carin M A Rademaker, Arie F Bos, Paul Van Den Berg, Mariangela Longini, Giuseppe Buonocore, MariaElena Venegas, Hernando Baquero, Gerard H A Visser, Frank Van Bel, Helen L Torrance, Manon J Benders, Jan B Derks, Carin M A Rademaker, Arie F Bos, Paul Van Den Berg, Mariangela Longini, Giuseppe Buonocore, MariaElena Venegas, Hernando Baquero, Gerard H A Visser, Frank Van Bel
Abstract
Background: Fetal hypoxia is an important determinant of neonatal encephalopathy caused by birth asphyxia, in which hypoxia-induced free radical formation plays an important role.
Hypothesis: Maternal treatment with allopurinol, will cross the placenta during fetal hypoxia (primary outcome) and reduce S-100B and free radical formation (secondary outcome).
Methods: In a randomized, double-blind feasibility study, 53 pregnant women in labor (54 fetuses) with a gestational age of >36 weeks and fetal hypoxia, as indicated by abnormal/nonreassuring fetal heart rate tracing or fetal scalp pH of <7.20, received 500 mg of allopurinol or placebo intravenously. Severity of fetal hypoxia, brain damage and free radical formation were assessed by arterial cord blood lactate, S-100B and non-protein-bound-iron concentrations, respectively. At birth, maternal and cord blood concentrations of allopurinol and its active metabolite oxypurinol were determined.
Results: Allopurinol and oxypurinol concentrations were within the therapeutic range in the mother (allopurinol > 2 mg/L and/or oxypurinol > 4 mg/L) but not always in arterial cord blood. We therefore created 3 groups: a placebo (n = 27), therapeutic allopurinol (n = 15), and subtherapeutic allopurinol group (n = 12). Cord lactate concentration did not differ, but S-100B was significantly lower in the therapeutic allopurinol group compared with the placebo and subtherapeutic allopurinol groups (P < .01). Fewer therapeutic allopurinol cord samples had measurable non-protein-bound iron concentrations compared with placebo (P < .01).
Conclusions: 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.
Trial registration: ClinicalTrials.gov NCT00189007.
Source: PubMed