dinoprost 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

Blood oxygen level dependent (BOLD) contrast was used to monitor hypoxia induced by cloprostenol, a prostaglandin F(2alpha) (PGF(2alpha)) analog, in the rat embryo-placental unit (EPU). It is shown that administration of cloprostenol (0.025 mg/rat) at mid-gestation (day 16) reduced EPU oxygenation, as detected by BOLD contrast MRI, in correlation with induction of vascular endothelial growth factor (VEGF) gene (Vegfa) expression in the corresponding placenta (r = 0.56, p = 0.03). Elevated VEGF mRNA expression in response to cloprostenol treatment was also observed at early gestation (day 9) in the forming placenta (p = 0.04) and uterus (p = 0.03). Cloprostenol increased the expression levels of endothelin-1 (ET-1) gene (Edn1) (p = 0.03) and its corresponding peptide (p = 0.02) in the forming placenta, as well as the expression of the endothelin receptor type A (ETA) gene (Ednra) in both the forming placenta (p = 0.009) and the uterus (p = 0.01). The levels of the endothelin receptor type B (ETB) gene (Ednrb) were not affected in response to cloprostenol, but a significant elevation in the expression level of this receptor was observed in the uterus at mid- and late gestation (day 22) (p = 0.04 and 0.01 respectively), suggesting a role for ETB in the vasodilatory status of the pregnant uterus. It is suggested that PGF(2alpha) induces uteroplacental vasoconstriction in the rat, and that ET-1 may take part in mediating this effect, probably via activation of ETA receptor. The uteroplacental vasoconstriction induces hypoxia, as manifested by significant changes in BOLD MRI and by upregulation of VEGF.

Topics: Animals; Blotting, Western; Cell Hypoxia; Cloprostenol; Dinoprost; Endothelin-1; Endothelium, Vascular; Estrous Cycle; Female; Fetal Hypoxia; Gene Expression Regulation; Gestational Age; Hemoglobins; Magnetic Resonance Imaging; Oxygen; Placenta; Placentation; Pregnancy; Rats; Receptor, Endothelin A; Receptor, Endothelin B; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Uterus; Vascular Endothelial Growth Factor A; Vasodilation

Amniotic fluid infection promotes cytokine release, prostaglandin production, and premature labor. In several tissues local hypoxia also activates the secretion of cytokines. Many patients initially seen in premature labor carry small-for-gestational-age fetuses, a condition associated with intrauterine hypoxia. The purpose of our study was to determine whether a reduction in placental blood flow and subsequent acute hypoxia affects prostaglandin secretion by the placenta.. We chronically catheterized six pregnant sheep at 120 days of gestation. We placed catheters in the maternal and fetal femoral arteries and in the amniotic fluid cavity. A flow probe and snare were placed around the common uterine artery.. A 30-minute uterine circulation occlusion of 30% of its control value produced an increase in prostaglandin F metabolite from 790 +/- 157 to 944 +/- 184 pg/ml within 10 minutes (p < 0.01). Additional uterine blood flow reduction to 60% of control increased the amniotic fluid prostaglandin F metabolites concentration to 894 +/- 202 (p < 0.05, analysis of variance). No increase in mean intrauterine pressure was detected (p > 0.1).. We speculate that the prostaglandin increase in amniotic fluid in response to intrauterine hypoxia could eventually lead to premature labor. Whether the increase in prostaglandins is mediated by changes in cytokines is unknown at the present time.

Topics: Acute Disease; Amniotic Fluid; Analysis of Variance; Animals; Blood Gas Analysis; Dinoprost; Dinoprostone; Female; Fetal Blood; Fetal Hypoxia; Placenta; Pregnancy; Pressure