oxypurinol and Fetal-Hypoxia

To determine whether maternal allopurinol treatment during suspected fetal hypoxia would reduce the release of biomarkers associated with neonatal brain damage.. A randomised double-blind placebo controlled multicentre trial.. We studied women in labour at term with clinical indices of fetal hypoxia, prompting immediate delivery.. Delivery rooms of 11 Dutch hospitals.. When immediate delivery was foreseen based on suspected fetal hypoxia, women were allocated to receive allopurinol 500 mg intravenous (ALLO) or placebo intravenous (CONT).. Primary endpoint was the difference in cord S100ß, a tissue-specific biomarker for brain damage.. 222 women were randomised to receive allopurinol (ALLO, n=111) or placebo (CONT, n=111). Cord S100ß was not significantly different between the two groups: 44.5 pg/mL (IQR 20.2-71.4) in the ALLO group versus 54.9 pg/mL (IQR 26.8-94.7) in the CONT group (difference in median -7.69 (95% CI -24.9 to 9.52)). Post hoc subgroup analysis showed a potential treatment effect of allopurinol on the proportion of infants with a cord S100ß value above the 75th percentile in girls (ALLO n=5 (12%) vs CONT n=10 (31%); risk ratio (RR) 0.37 (95% CI 0.14 to 0.99)) but not in boys (ALLO n=18 (32%) vs CONT n=15 (25%); RR 1.4 (95% CI 0.84 to 2.3)). Also, cord neuroketal levels were significantly lower in girls treated with allopurinol as compared with placebo treated girls: 18.0 pg/mL (95% CI 12.1 to 26.9) in the ALLO group versus 32.2 pg/mL (95% CI 22.7 to 45.7) in the CONT group (geometric mean difference -16.4 (95% CI -24.6 to -1.64)).. Maternal treatment with allopurinol during fetal hypoxia did not significantly lower neuronal damage markers in cord blood. Post hoc analysis revealed a potential beneficial treatment effect in girls.. NCT00189007, Dutch Trial Register NTR1383.

Topics: Adult; Aldehydes; Allopurinol; Dinoprost; Double-Blind Method; Enzyme Inhibitors; Female; Fetal Blood; Fetal Hypoxia; Humans; Ketones; Male; Maternal-Fetal Exchange; Oxypurinol; Pregnancy; S100 Calcium Binding Protein beta Subunit; Xanthine Oxidase

To evaluate the transplacental effect of allopurinol, which acts as a xanthine oxidase inhibitor and free radical scavenger, on inhibiting the production of superoxides during intermittent partial umbilical cord occlusion.. Using four chronically instrumented fetal lambs, ewes received 400 mg allopurinol over a period of two hours. Concentrations of allopurinol and oxypurinol in blood samples from mothers and fetuses and fetal brain microdialysis perfusate were measured by HPLC. In another three cases the production of superoxide during intermittent umbilical cord occlusion was studied by measurement of chemiluminescence in perfusate before and after administration of Allopurinol.. (i) Allopurinol concentration in mothers had reached equilibrium by 30 min after starting administration and maintained a concentration about 6 mug/ml. Allopurinol concentration in fetuses increased gradually and reached 2.25 +/- 0.54 microg/ml at 120 min; (ii) Oxypurinol concentration in both mothers and fetuses increased during administration of allopurinol; (iii) Concentrations of allopurinol and oxypurinol in the perfusates reached 0.32 +/- 0.12 microg/ml, 0.53 +/- 0.22 microg/ml at 120 min respectively; and (iv) Administration of allopurinol significantly suppressed superoxide production during intermittent partial umbilical cord occlusion.. These results demonstrated a good transfer of allopurinol from mother to fetus and suggested the possibility of intrauterine treatment to inhibit fetal brain damage resulting from increased oxygen free radicals.

Topics: Allopurinol; Animals; Brain; Enzyme Inhibitors; Female; Fetal Hypoxia; Fetus; Free Radical Scavengers; Oxidative Stress; Oxypurinol; Placenta; Pregnancy; Reactive Oxygen Species; Sheep; Superoxides; Umbilical Cord; Xanthine Oxidase