dinoprost and Hypertension--Pregnancy-Induced

Gestational hypertension (GH) and Preeclampsia, (PE) are the most complicated amongst hypertensive disorders of pregnancy. The mechanism that links hypertension in pregnancy to adverse maternal outcomes is not fully understood though some relate this to endothelial dysfunction originating from an imbalanced angiogenic regulators and oxidative stress biomarkers. This study assessed the correlation between angiogenic regulators and oxidative stress biomarker levels with adverse pregnancy outcomes among GH and PE participants.. A cohort of pregnant women who received antenatal care at the Obstetrics and Gynaecology department of the Komfo Anokye Teaching Hospital (KATH) were followed. During their antenatal visits, 100 developed PE and 70 developed GE, of these, 50 PE and 50 GH gave informed consent. Their blood samples were taken at time of diagnosis and 48 h post-partum. 50 other aged-matched women who did not develop neither GH nor PE were selected as controls. Placental growth factor (PLGF), soluble fms-like tyrosine kinase 1 (sFlt-1) and 8-epi-prostaglandin F2alpha (8-epi-PGF2α) levels were estimated by ELISA and total antioxidant capacity (T-AOC) was measured spectrophotometrically. Graphpad Prism was used for data analysis.. Median levels of sFlt-1, 8-epi-PGF2α and sFlt-1/PLGF were elevated among participants with PE co-existing with intrauterine fetal death (IUFD), placental abruptio, placental previa, HELLP syndrome and intrauterine growth restriction (IUGR) compared to PE without adverse outcomes (p = 0.041, p = 0.005, p = 0.0002). Levels of PLGF, T-AOC and PLGF/sFlt-1 were significantly reduced among participants with PE co-existing with IUFD, placental abruptio, placental previa, HELLP syndrome and IUGR compared to PE without adverse outcomes (p = 0.0013, p = 0.006, p < 0.0001). A significant negative correlation of IUGR (p = 0.0030; p < 0.0001), placental abruptio (p < 0.0001; p < 0.0001), IUFD (p < 0.0001; p < 0.0001), stillbirth (p = 0.0183 and p < 0.000), and postpartum haemorrhage (PPH) (p = 0.0420; p = 0.0044) were associated with both PLGF and T-AOC whilst a significant positive correlation of IUGR, placental abruptio (p < 0.0001; p < 0.0001), IUFD (p < 0.0001; p < 0.0001), stillbirth (p < 0.0001; p < 0.0001), and PPH (p = 0.0043; p = 0.0039) were observed with both sFlt-1 and 8-epi-PGF2α in PE.. Imbalance in the levels of angiogenic regulators and oxidative stress biomarkers correlates with adverse pregnancy outcomes among PE participants. Early identification of these imbalance would alert health care givers in anticipation of adverse pregnancy outcome and thus increased surveillance during pregnancy and parturition and measures to ameliorate the adverse outcome.

Topics: Adult; Angiogenic Proteins; Antioxidants; Biomarkers; Dinoprost; Female; Fetal Growth Retardation; Gestational Age; Humans; Hypertension, Pregnancy-Induced; Oxidative Stress; Placenta; Placenta Growth Factor; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnancy Proteins; Prospective Studies; Vascular Endothelial Growth Factor Receptor-1

Sodium supplementation given for 1 wk to nonpregnant rats induces changes that are adequate to maintain renal and circulatory homeostasis as well as arterial blood pressure. However, in pregnant rats, proteinuria, fetal growth restriction, and placental oxidative stress are observed. Moreover, the decrease in blood pressure and expansion of circulatory volume, normally associated with pregnancy, are prevented by high-sodium intake. We hypothesized that, in these pregnant rats, a loss of the balance between prooxidation and antioxidation, particularly in kidneys and heart, disturbs the normal course of pregnancy and leads to manifestations such as gestational hypertension. We thus investigated the presence of oxidative/nitrosative stress in heart and kidneys following high-sodium intake in pregnant rats. Markers of this stress [8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)) and nitrotyrosine], producer of nitric oxide [nitric oxide synthases (NOSs)], and antioxidants [superoxide dismutase (SOD) and catalase] were measured. Then, molecules (Na(+)-K(+)-ATPase and aconitase) or process [apoptosis (Bax and Bcl-2), inflammation (monocyte chemoattractant protein-1, connective tissue growth factor, and TNF-alpha)] susceptible to free radicals was determined. In kidneys from pregnant rats on 1.8% NaCl-water, NOSs, apoptotic index, and nitrotyrosine expression were increased, whereas Na(+)-K(+)-ATPase mRNA and activity were decreased. In the left cardiac ventricle of these rats, heightened nitrotyrosine, 8-iso-PGF(2alpha), and catalase activity together with reduced endothelial NOS protein expression and SOD and aconitase activities were observed. These findings suggest that oxidative/nitrosative stress in kidney and left cardiac ventricle destabilizes the normal course of pregnancy and could lead to gestational hypertension.

Topics: Aconitate Hydratase; Animals; Apoptosis; Dinoprost; Female; Gene Expression Regulation, Enzymologic; Heart; Hypertension, Pregnancy-Induced; Inflammation; Kidney; Nitric Oxide Synthase; Oxidative Stress; Pregnancy; Rats; Rats, Sprague-Dawley; Sodium; Sodium-Potassium-Exchanging ATPase

To explore the relationship between the levels of maternal oxidative stress and glycaemia during pregnancy and to compare the predictive values of 8-epimer of prostaglandin F(2alpha) (8-isoPGF(2alpha)) and mean arterial pressure (MAP) in midpregnancy for the development of hypertensive complications in later pregnancy.. Prospective observational study as an ancillary study to the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study.. Obstetric clinics and wards of a university teaching hospital in Hong Kong.. Selected women with singleton pregnancies attending the antenatal clinic.. Pregnant women who met HAPO inclusion criteria were recruited for the study. Glucose tolerance was assessed by a 75-g 2-hour oral glucose tolerance test (OGTT) at 24-32 weeks of gestation. Fasting plasma samples for 8-isoPGF(2alpha) estimation and urine samples for 8-isoPGF(2alpha) and 2,3-dinor 8-isoPGF(2alpha) assays were collected and blood pressures measured during the OGTT visit. Random plasma and urine samples were also obtained at 34-37 weeks. Glucose results were unblinded to the attending obstetrician if limits preset under the HAPO protocol were met.. Maternal plasma 8-isoPGF(2alpha) and urinary 8-isoPGF(2alpha) and 2,3-dinor 8-isoPGF(2alpha) both at the time of OGTT (24-32 weeks) and at 34-37 weeks of gestation. Incidence of pre-eclampsia and gestational hypertension.. Of the 408 women who attended for OGTT at 24-32 weeks, two met the glucose criteria for unblinding and 25 had missing 8-isoPGF(2alpha) values and thus were excluded from analysis. Of the 381 women, 338 (88.7%) attended for random plasma samples at 34-37 weeks. Significant correlations were observed between maternal fasting plasma isoprostane and both fasting (r= 0.20; P < 0.001) and 2-hour (r= 0.39; P < 0.001) plasma glucose levels at the time of OGTT. Gestational hypertension/pre-eclampsia occurred in 17 (4.2%) women, and at the time of OGTT, they had significantly higher fasting plasma 8-isoPGF(2alpha) (P < 0.001), urine 8-isoPGF(2alpha) (P < 0.005) and urine 2,3-dinor 8-isoPGF(2alpha) to creatinine ratios (P < 0.001), as well as higher MAP (P < 0.001) than women who remained normotensive. At 34-37 weeks, only random plasma 8-isoPGF(2alpha) was significantly higher (P < 0.001) among the women with gestational hypertension/pre-eclampsia.. Plasma markers of oxidative stress were positively correlated with plasma glucose at the time of OGTT (24-32 weeks). Women who subsequently developed gestational hypertension/pre-eclampsia had significantly higher plasma and urine markers of oxidative stress at the time of OGTT but only higher plasma markers at 34-37 weeks. Plasma 8-isoPGF(2alpha) appears to be a very good predictor of subsequent gestational hypertension/pre-eclampsia when measured at the time of OGTT, but its ability to discriminate deteriorates as pregnancy advances.

Topics: Adult; Blood Glucose; Dinoprost; Female; Glucose Tolerance Test; Humans; Hypertension, Pregnancy-Induced; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Prospective Studies

Hypertension in pregnancy is connected with increased rate of prematurity and perinatal morbility. 8-isoprostane and lipid peroxides are the oxidative stress indices, similar to the prostaglandins both connected with vessels restriction.. The aim of the study was to find the correlation between concentration of lipid peroxides and 8-isoprostane and the blood pressure in pregnancy.. The study was done in Dep. of Obstetrics and Gynaecology Medical University in Lodz in 2002-2005. The study group consisted of 78 women with diagnosed hypertension in pregnancy, the control group of 50 healthy pregnant women at the same gestational age. Lipid peroxides and 8-isoprostane were measured in maternal blood. The Oxis Immunoassay for 8-epi prostaglandin and LPO 586 were used. The results were expressed in ng/ml and microM.. The concentration of 8-isoprostane in women with hypertension was 0,0691 ng/ml, in women with hypertension and IUGR the value of 8-isoprostane was similar--0,0728 ng/ml. In women in normal pregnancy was lower--0,0541 ng/ml. Lipid peroxides and 8-isoprostane concentration in both hypertensive groups was higher than in group of normotensive pregnant women.. In pregnancies complicated by hypertension the concentration of vasorestrictive lipid peroxidation products is higher than in normotensive women and the antioxidative treatment may be used to decrease lipid peroxidation process.

Topics: Adult; Biomarkers; Case-Control Studies; Dinoprost; Female; Fetal Growth Retardation; Humans; Hypertension, Pregnancy-Induced; Lipid Peroxidation; Nitric Oxide; Nitric Oxide Synthase; Pregnancy; Reference Values; Retrospective Studies; Statistics, Nonparametric

Our aim was to evaluate the mode of delivery in pregnant women with hypertensive disorders and unfavorable cervix following induction of labor with vaginal application of prostaglandin E(2) (PGE(2)) near or at term, and to define the predictors of successful vaginal delivery in such women.. In a retrospective case-controlled study, pregnant women with hypertension, who underwent labor induction with PGE(2) tablets (study group, n = 284), were compared with women, who underwent elective induction of labor (group 2, n = 115), and women with normal spontaneous onset of labor (group 3, n = 510).. The rate of cesarean section (CS) was significantly higher in the study group (25.3%) than in group 2 (14.8%) and in group 3 (9%). Exclusion of the nulliparous women from the study and control groups yielded similar CS rates in the study group (16.9%) and in group 2 (11.1%). Women with pre-eclampsia and the women with chronic hypertension or pregnancy-induced hypertension had similar rates of CS. In logistic regression model, nulliparity, induction of labor with PGE(2), and maternal age, but not hypertensive disorders, were independently and significantly associated with increased risk of CS.. PGE(2) induction of labor is successful in approximately 75% of patients with hypertensive disorders and unfavorable cervix, with apparently no serious maternal or fetal complications. The induction of labor by itself, and not the hypertensive disorders in pregnancy, is independent risk factor for CS.

Topics: Administration, Intravaginal; Adult; Analysis of Variance; Cervical Ripening; Delivery, Obstetric; Dinoprost; Female; Gestational Age; Humans; Hypertension, Pregnancy-Induced; Labor, Induced; Logistic Models; Oxytocics; Pregnancy; Pregnancy Outcome