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

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

61 Citaten (Scopus)
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Samenvatting

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 (rimary 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

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. Pediatrics 2009; 124: 350-357

Originele taal-2English
Pagina's (van-tot)350-357
Aantal pagina's8
TijdschriftPediatrics
Volume124
Nummer van het tijdschrift1
DOI's
StatusPublished - jul-2009

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