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Pediatrics ; 124(1): 350-7, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19564319

RESUMO

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.


Assuntos
Alopurinol/administração & dosagem , Sangue Fetal/metabolismo , Hipóxia Fetal/metabolismo , Sequestradores de Radicais Livres/administração & dosagem , Troca Materno-Fetal/fisiologia , Fatores de Crescimento Neural/sangue , Proteínas S100/sangue , Adulto , Alopurinol/sangue , Cromatografia Líquida de Alta Pressão/métodos , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Hipóxia Fetal/prevenção & controle , Feto/efeitos dos fármacos , Feto/fisiologia , Sequestradores de Radicais Livres/sangue , Humanos , Projetos Piloto , Gravidez , Subunidade beta da Proteína Ligante de Cálcio S100 , Adulto Jovem
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