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 ofallopurinol 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.
RCT Entities:
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.
Authors: Joepe J Kaandorp; Jan B Derks; Martijn A Oudijk; Helen L Torrance; Marline G Harmsen; Peter G J Nikkels; Frank van Bel; Gerard H A Visser; Dino A Giussani Journal: Reprod Sci Date: 2013-06-21 Impact factor: 3.060
Authors: Nicola J Robertson; Sidhartha Tan; Floris Groenendaal; Frank van Bel; Sandra E Juul; Laura Bennet; Matthew Derrick; Stephen A Back; Raul Chavez Valdez; Frances Northington; Alistair Jan Gunn; Carina Mallard Journal: J Pediatr Date: 2012-02-09 Impact factor: 4.406
Authors: Joepe J Kaandorp; Manon J N L Benders; Carin M A Rademaker; Helen L Torrance; Martijn A Oudijk; Timo R de Haan; Kitty W M Bloemenkamp; Monique Rijken; Maria G van Pampus; Arie F Bos; Martina M Porath; Sidarto Bambang Oetomo; Christine Willekes; A W Danilo Gavilanes; Maurice G A J Wouters; Ruurd M van Elburg; Anjoke J M Huisjes; Saskia C M J E R Bakker; Claudia A van Meir; Jeannette von Lindern; Janine Boon; Inge P de Boer; Robbert Jp Rijnders; Corrie J W F M Jacobs; Cuno S P M Uiterwaal; Ben Willem J Mol; Gerard H A Visser; Frank van Bel; Jan B Derks Journal: BMC Pregnancy Childbirth Date: 2010-02-18 Impact factor: 3.007
Authors: Damián Pérez-Mazliah; María C Albareda; María G Alvarez; Bruno Lococo; Graciela L Bertocchi; Marcos Petti; Rodolfo J Viotti; Susana A Laucella Journal: Front Immunol Date: 2012-09-21 Impact factor: 7.561