In:
Pediatrics, American Academy of Pediatrics (AAP), Vol. 124, No. 1 ( 2009-07-01), p. 350-357
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 & gt;36 weeks and fetal hypoxia, as indicated by abnormal/nonreassuring fetal heart rate tracing or fetal scalp pH of & lt;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 & gt; 2 mg/L and/or oxypurinol & gt; 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 & lt; .01). Fewer therapeutic allopurinol cord samples had measurable non–protein-bound iron concentrations compared with placebo (P & lt; .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.
Type of Medium:
Online Resource
ISSN:
0031-4005
,
1098-4275
DOI:
10.1542/peds.2008-2228
Language:
English
Publisher:
American Academy of Pediatrics (AAP)
Publication Date:
2009
detail.hit.zdb_id:
1477004-0
