thromboxane-b2 and Fetal-Growth-Retardation

All pregnancy-associated tissues are capable of producing prostaglandins including PGI2 and TXA2. In normal pregnancy there is a dominance of PGI2 over TXA2 which may contribute to the maternal circulatory adaptation to pregnancy. Furthermore, both fetoplacental PGI2 and TXA2 production are important regulators of the fetal blood supply. It has been clearly established that in pre-eclampsia PGI2 production decreases in the fetoplacental tissues and quite probably also in the maternal tissues. The effect of this change may be further exaggerated by the simultaneous stimulation in pre-eclampsia of TXA2 production. The reason for PGI2 deficiency is not known. Other vasoactive agents, such as endothelin, may act in concert with prostaglandins. Relative PGI2 deficiency is likely to exist also in IUGR and lupus anticoagulant syndrome of pregnancy. In the latter, lupus anticoagulant may directly inhibit the synthesis of PGI2. One study suggests PGI2 deficiency also in early pregnancies of women with a history of repeated abortions. Prostaglandin production increases during full-term labour, and similar but smaller changes also occur in preterm labour. A silent bacterial infection may trigger the onset of preterm labour through cytokine-stimulated increase of prostaglandin production. No data were found on prostaglandin production in post-term pregnancies. That oligo-polyhydramnios is possibly prostaglandin mediated is suggested by the control of polyhydramnios by indomethacin treatment. Smoking decreases the production of PGI2 and possibly increases that of TXA2, which may lead to decreased blood flow and IUGR. Which constituent of cigarette smoke exerts this effect is not known. Ethanol consumption causes aberrations in prostaglandin metabolism which cannot be directly connected with fetal alcohol effects.

Topics: Abortion, Habitual; Alcohol Drinking; Epoprostenol; Female; Fetal Growth Retardation; Humans; Lupus Erythematosus, Systemic; Obstetric Labor, Premature; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Prostaglandins; Smoking; Thromboxane A2; Thromboxane B2

To determine whether antenatal treatment (for > or = 14 days) with 100 mg aspirin daily, given to mothers with small for gestational age fetuses and abnormal umbilical Doppler, will increase birthweight.. Randomised, double-blind placebo controlled trial.. A tertiary referral centre.. Ninety-nine women, of whom 65 were treated for > or = 14 days (32 with aspirin and 33 with placebo) and comprised the study group. The entry criteria were: singleton pregnancy with ultrasound evidence of a small for gestational age fetus (abdominal circumference < 10%); previous anatomy scan < 20 weeks and no evidence of fetal abnormality; gestation between 24 and 36 weeks; umbilical artery Doppler resistance index > 95% for gestation; no previous aspirin treatment in pregnancy; and no contra-indication to aspirin treatment.. The mean duration of treatment was 30 days for aspirin treated, and 29 for placebo. No difference was found in birthweight or other measures of fetal growth or newborn morbidity between those treated with aspirin or placebo. Compliance, assessed by thromboxane B2 analysis, showed almost complete suppression of thromboxane B2 in aspirin treated women.. Low-dose aspirin did not increase birthweight in pregnancies where the fetus has abnormal umbilical Doppler and is thought to be small for gestational age.

Topics: Adult; Aspirin; Birth Weight; Double-Blind Method; Female; Fetal Growth Retardation; Humans; Platelet Aggregation Inhibitors; Pregnancy; Thromboxane B2; Ultrasonography, Doppler; Umbilical Cord

To examine the effect of maternal smoking in pregnancy on the production of two eicosanoids, thromboxane A(2) and prostacyclin I2, and their role in the pathogenesis of intrauterine growth restriction.. Prospective case control study enrolled smoking and non-smoking women at ≤14 weeks gestation. Maternal urine samples were obtained at ≤14, 28 and 36 weeks. High performance liquid chromatography tandem mass spectrometry (LC-MS-MS) was used to quantify 11-dehydrothromboxane B(2) (TX-M) and 2,3 dinor-6-ketoprostaglandin F1α (PG-M), stable urinary metabolites of thromboxane A(2) and prostacyclin I2. Confirmation of the smoking status was performed by quantitation of urinary nicotine metabolites. Data was analysed using SPSS and Stata(®).. Thirty five were enrolled in the smoking group and 32 in the non-smoking group. Smoking resulted higher levels of TX-M at ≤14, 28 and 36 weeks gestation. There was no difference in PG-M at any gestational time point between the two groups. The median customised birthweight centile in the smoking group was 17.0 (0-78) compared to 55.5 (4-100) in the non-smoking group (P<0.001). A causal relationship between elevated TX-M and IUGR could not be established.. Maternal smoking in pregnancy is associated with altered eicosanoid production in favour of the vasoconstrictor thromboxane A(2) which occurs early in the first trimester.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Case-Control Studies; Female; Fetal Growth Retardation; Humans; Pregnancy; Smoking; Thromboxane A2; Thromboxane B2; Young Adult

To study the pathophysiological changes and effective treatment of intrauterine growth retardation (IUGR).. Eighty-five cases with normal pregnancy and 58 IUGR women maternal red blood cell superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), serum lipid peroxide (LPO) and thromboxane B2 (TXB2), 6-keto-PGF1 alpha(6KP) were examined. IUGR group was divided into Ligustrazine group (LIG, 47 cases) and amino acid group (AAG, 11 cases) and treated accordingly.. In IUGR group, LPO increased and SOD, GSH-Px activity, 6KP value decreased abnormally, TXB2/6KP ratio significantly increased, which was negative correlated with SOD, GSH-Px activity and positive correlated with LPO level markedly. After treatment, all the changes were improved and almost reached normal range. The fetal outcome showed that the total effective rate was 95.7% in LIG, markedly higher than that in AAG (81.8%, P < 0.05), there was significant difference between LIG and AAG.. The balance of body oxidate/antioxidate system was disturbed and the uteroplacental-fetal circulation was obstracted in IUGR. Ligustrazine could inhibit oxygen free radical, rise SOD, GSH-Px activity, regulate TXA2/PGI2 balance, promote fetal growth.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Female; Fetal Growth Retardation; Free Radical Scavengers; Humans; Pregnancy; Pyrazines; Superoxide Dismutase; Thromboxane B2

We investigated the effects of thromboxane (TX) A2 in rats with ischemia-reperfusion-induced intrauterine growth retardation. A saline solution or OKY-046, a selective TXA2 synthetase inhibitor, was injected into the caudal vein of pregnant rats on gestation day 17 before the induction of 60-min uteroplacental ischemia. The fetuses and placentas were delivered and examined on gestation day 21. Blood from the uterine vein of the occluded horn shortly after uteroplacental ischemia was collected, and plasma concentrations of TXB2 and 6-keto-prostaglandin (PG) F1 alpha were determined in the other rats on gestation day 17. Treatment with OKY-046 prevented the ischemia-induced reduction in the fetal body and placental weights. The ratio of 6-keto-PGF1 alpha to TXB2 was significantly increased in the OKY-046-treated group. We conclude that the action of TXA2 might play a salient role in our model.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Embryonic and Fetal Development; Enzyme Inhibitors; Female; Fetal Growth Retardation; Injections, Intravenous; Methacrylates; Pregnancy; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Thromboxane B2; Thromboxane-A Synthase

The aim of this study was to investigate the possible association between Doppler velocimetry and synthesis of prostacyclin (PGI2) and thromboxane A2 (TxA2) in umbilical cord vessels. The hypothesis was that an altered balance between PGI2 and TxA2 production is associated with a change of artery flow resistance.. 17 cases with a suspicion of intrauterine growth retardation and 21 normal pregnancies were studied. The umbilical artery pulsatility index (PI) and venous mean velocity were recorded in vivo by Doppler velocimetry. Cord vessel prostanoid synthesis was determined in vitro. The Mann-Whitney U test and simple linear regression were used for statistical analyses.. The umbilical vessel synthesis of both PGI2 and TxA2 was in general lower in small-for-gestational age (SGA) cases (n = 10) compared to appropriate-for-gestational age (AGA) (n = 28). In the vein, the PGI2/TxA2 ratio was significantly lower in SGA cases. No certain correlations were found between umbilical artery PI and venous velocity, respectively, and PGI2 or TxA2, or their ratio.. The prostanoid synthesis was in general lower in SGA cases, resulting in a significantly lower PGI2/TxA2 ratio in the umbilical vein. This indicates that fetal growth retardation might be associated with a disturbed endothelial function in this vessel. The synthesis of PGI2 and TxA2 in the juxtaplacental umbilical cord vessels was not correlated to the umbilical artery PI or venous flow velocity. It is possible that an altered release of prostanoids in the placental vasculature and tissue accounts for the rise of umbilical artery flow resistance instead.

Topics: 6-Ketoprostaglandin F1 alpha; Blood Flow Velocity; Case-Control Studies; Endothelium, Vascular; Epoprostenol; Female; Fetal Blood; Fetal Growth Retardation; Gestational Age; Humans; Infant, Newborn; Pregnancy; Pulsatile Flow; Reproducibility of Results; Rheology; Thromboxane A2; Thromboxane B2; Ultrasonography, Doppler, Pulsed; Ultrasonography, Prenatal; Umbilical Arteries; Umbilical Veins

Our objective was to evaluate prostanoid release from the placentae of pregnancies complicated by severe intrauterine growth retardation (IUGR) and without hypertension, compared with placentae from normal, uncomplicated term pregnancies. A perifusion system was utilized to study the release of prostanoids 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2(TxB2), prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) from human placentae from pregnancies complicated by normotensive severe IUGR (n = 9, five at term and four preterm) and normal control pregnancies (n = 6). For each placenta, triplicate chambers of tissue were perifused at a rate of 6 ml/h, and samples were collected from hours 5-10. Prostanoids were measured using specific and sensitive radioimmunoassays. In the IUGR group, the basal placental production of the vasoconstrictor thromboxane was not increased, nor was the ratio of cumulative TxB2 to 6-keto-PGF1 alpha elevated compared with normal term controls. In three term IUGR placentae, the ratio was significantly decreased compared with controls. The basal placental production of the vasoconstrictor PGF2 alpha was likewise not increased compared with controls, nor was the ratio of PGF2 alpha to PGE2 elevated. Two of the placentae in the term IUGR group demonstrated significant elevations of PGE2 and 6-keto-PGF1 alpha. Overall, the IUGR placentae released normal or low normal levels of the prostanoids studied. The pattern of placental prostanoid release over time was similar to that of the normal term placentae. The term and preterm placentae of pregnancies complicated by severe IUGR did not exhibit an excess production of vasoconstrictor prostanoids. Therefore, strategies designed to reduce thromboxane production in severe IUGR without hypertension may be unjustified.

Topics: Case-Control Studies; Female; Fetal Growth Retardation; Humans; Hypertension; Placenta; Pregnancy; Pregnancy Complications, Cardiovascular; Prostaglandins; Thromboxane B2

Topics: Blood Platelets; Female; Fetal Growth Retardation; Humans; Hypertension; Platelet Activation; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboxane B2

Low dose Aspirin in pregnancy reduces the incidence of intra uterine growth retardation (IUGR) and pregnancy induced hypertension (PIH) in women at risk for these complications. To investigate if this drug, even in a low dose, could expose the newborn to hemorrhagic complications, we studied ten neonates whose mothers had been taking 50 mg/day of Aspirin from the 12th week of pregnancy until delivery and compared them with eight newborns whose mothers didn't take the drug. No hemorrhagic complications (emathemesis, ecchymoses or petechiae, subconjunctival hemorrhage, cephaloematomas etc.) were observed in the fetuses exposed to Aspirin or in the control group. No hemorrhagic lesions were found by ultrasound brain scan on the fourth day of life. Newborns exposed to Aspirin showed a significantly lower thromboxane concentration on the first day of life (median 73 ng/ml versus 217 ng/ml); however on the fourth day the level of serum thromboxane in the cases exposed reached the values of the unexposed ones (median 146 ng/ml versus 143 ng/ml). In conclusion low dose Aspirin in pregnancy can be considered a safe drug without and adverse effect on the newborn.

Topics: Aspirin; Birth Weight; Cerebral Hemorrhage; Female; Fetal Blood; Fetal Growth Retardation; Gestational Age; Humans; Hypertension; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Cardiovascular; Reference Values; Thromboxane B2

In this paper, the results of a pilot study of 3,4-dihydroxyacetophenone (DHAP) treatment for intrauterine growth retardation (IUGR) were reported. 20 out of 38 cases of IUGR were treated with DHAP and 18 with amino acid. Additionally, 170 normal pregnant women were served as control group. The following parameters have been observed and measured including uterine fundal height (UFH), body weight (BW), S/D ratio of umbilical artery (UmA), hemorheological indices, platelets aggregation, TXB2/6-keto-PGF1 alpha ratio and also fetal and neonatal various growth indices etc. After administration of DHAP, all the parameters almost restored to the normal range. The results expressed that the therapeutic effect of DHAP was much better than that of amino acid. It has also been verified by neonatal birth weight and fetal biparietal diameter. The clinical effective rate of DHAP treatment group was 90.00% which was significantly higher than that 74.00%, 79.00% of amino-acid treatment group. Meanwhile, the mechanism of DHAP has preliminarily been discussed.

Topics: 6-Ketoprostaglandin F1 alpha; Acetophenones; Female; Fetal Growth Retardation; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Pregnancy; Thromboxane B2

Topics: Female; Fetal Growth Retardation; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Thromboxane B2

High-dose supplements of fish oil reduce thromboxane synthesis in nonpregnant human subjects and were therefore proposed as a means of preventing various small-vessel disorders, including preeclampsia. The effect of fish oil on thromboxane metabolism in pregnancy was investigated in our study.. Sixteen normal pregnant women in the third trimester of pregnancy were treated with a daily ingestion of 6 gm fish oil capsules containing 1.6 gm of n-3 fatty acid. In five patients the treatment was stopped because of severe-flavored reflux and hiccups. Eleven patients completed 3 weeks of treatment. Twenty-four-hour urinary 11-dehydro-thromboxane B2 was measured by means of radioimmunoassay before and after completion of the study protocol in these 11 patients and in seven control pregnant women who did not receive the oil treatment.. A decrease ranging from 32% to 71%, in 24-hour urinary 11-dehydro-thromboxane B2 excretion (mean reduction from 1606 pg/mg creatinine to 779 pg/mg creatinine, p < 0.001) was found among the 11 fish oil-treated women. No change in excretion was found among the control women. No maternal, fetal, or neonatal bleeding disturbances occurred, and no laboratory changes in coagulation markers were observed.. High-dose n-3 fatty acid intake in pregnancy significantly reduces maternal thromboxane A2 synthesis. These results may provide a basis for a possible role of fish oil in managing patients at risk for preeclampsia.

Topics: Adult; Creatinine; Fatty Acids, Omega-3; Female; Fetal Growth Retardation; Fish Oils; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Third; Thromboxane A2; Thromboxane B2; Urea

Intra-uterine growth retardation, intra-uterine fetal death and pre-eclampsia have common abnormalities: A reduction of uteroplacental perfusion, lack of vasodilation of spiral arteries and subsequent thrombosis. These physiological processes have been explained by an imbalance between prostacyclin and thromboxane A2 production. Many studies have suggested that treatment with low-dose aspirin and steroids is effective in preventing pregnancy loss or pre-eclampsia, but the mechanism has not been established. We evaluated the effectiveness of these therapies in patients at risk for pregnancy loss with the aspect of intracellular ionized calcium mobilization. Low-dose aspirin directs the prostacyclin/thromboxane A2 balance to the dominance of prostacyclin and steroids suppress the activities of lupus anticoagulant or antiphospholipid antibodies. The intracellular ionized calcium concentration in platelets is decreased significantly after these therapies. Concerning the pathological examination of placenta, there were deposits of fibrin in only 2 out of 8 cases and there were no abnormal findings in the other 6 cases. These data show that the aggregation of platelets is suppressed in microvascular circulations. These therapies do not cause any adverse effect on the mother or fetus. It is concluded that low-dose aspirin therapy with steroids is useful for patients with a poor obstetrical history.

Topics: 6-Ketoprostaglandin F1 alpha; Aspirin; Calcium; Female; Fetal Death; Fetal Growth Retardation; Humans; Lupus Coagulation Inhibitor; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Thromboxane B2; Treatment Outcome