A randomised placebo controlled trial of loop diuretics in moderate/severe pre-eclampsia, following delivery. Supplementary calcium in prevention of pre-eclampsia. Treatment of hypertension in patients with pre-eclampsia: a prospective parallel-group study comparing dihydralazine with urapidil. Postpartum preeclampsia management with furosemide: a randomized clinical trial. Effects of diuretics on plasma volume in pregnancies with long-term hypertension. Trial of calcium to prevent preeclampsia. Nifedipine or hydralazine as a first-line agent to control hypertension in severe preeclampsia. A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia. Nutritional factors and rest reduce pregnancy-induced hypertension and pre-eclampsia in positive roll-over test primigravidas.
Nineteen patients with pre-eclampsia were randomised to receive 40 mg of frusemide or placebo by mouth daily for 7 days in the first post-partum week. Outcome measures included mean and maximum blood pressure, the need for additional antihypertensive treatment during that period and mean length of hospital stay. There were no statistically significant differences in outcome between the treatment and placebo groups although there was a trend to more rapid lowering of blood pressure following delivery in those receiving frusemide. To study the effect of calcium supplementation on reduction of pre-eclampsia in Iranian women at high risk of pre-eclampsia.
                Thirty pregnant women at high risk of developing pre-eclampsia were randomized to 2 g of daily calcium and placebo. Subjects and investigators were blinded to treatment allocation. The inclusion criteria were positive rollover test, having at least one risk factor for pre-eclampsia, between 28 and 32 weeks of pregnancy, and blood pressure less than 140/90 (mm Hg). Exclusion criteria were having any chronic condition. Pre-eclampsia was defined as systolic/diastolic blood pressure over 140/90 plus proteinuria. All the subjects were followed up to delivery.
                A sevenfold reduction in the occurrence of pre-eclamsia were seen among the calcium group compared with the placebo group (7 out of 15 developed pre-eclampsia in control group vs. 1 out of 15 in calcium group, P=0.014). No major effect on pregnancy induced hypertension was seen (66% in placebo and 76% in calcium group developed hypertension) but the onset of hypertension was delayed 3 weeks in the calcium group. A longer duration of pregnancy was seen in calcium than placebo (mean+/-S.D.=37+/-2 for calcium and 34+/-2 for placebo, P<0.05). Infants born to the calcium group, on average, were 552 g heavier than infants born to the placebo group, P<0.05.
                Calcium supplementation is beneficial for preventing pre-eclampsia among Iranian women at high risk of developing pre-eclampsia. The primary objective of treatment in women with severe hypertension and pre-eclampsia is to prevent complications such as encephalopathy and haemorrhage. In many countries dihydralazine is considered the drug of choice for treating hypertension in pregnancy, because it now has been used safely for about 30 years, and the introduction of a new drug in pregnancy is a difficult task with partially unknown hazards. In some other countries combined alpha- and beta-blockers are also used. Taking into account that some patients with pre-eclampsia do not respond to dihydralazine and the drug has serious side-effects like headache and reflex tachycardia, there is some need for developing alternative treatment strategies using drugs that are more adequate for pregnancy than dihydralazine.
                Urapidil is a post-synaptic alpha 1 adrenoceptor antagonist, which is widely used to control hypertensive crises unrelated to pregnancy. Since it is known that pre-eclampsia is associated with increased sympathetic activity, administration of an alpha 1 adrenoceptor antagonist provides a reasonable therapeutic basis. So far there is only one report describing the i.v. use of urapidil in the treatment of hypertension in pregnancy unresponsive to dihydralazine and one report which describes the oral use of urapidil. In an earlier pilot study we examined the dose range for i.v. application of urapidil necessary for adequate blood pressure control in patients with pre-eclampsia. In the present randomized controlled study 26 white women with pre-eclampsia and hypertension in pregnancy were included. Treatment was not blinded. During the initial period of intensive intravenous treatment all subjects were under constant surveillance by a physician and a nurse.
                Effective prolonged control of blood pressure (values below 150/100 mmHg) was achieved in all patients of the two groups. In one patient of the dihydralazine group signs of lightheadedness and near syncope were noted. After this side-effect of dihydralazine the patient was treated with urapidil. At the end of the observation period the maternal heart rate in the dihydralazine group was higher than in the urapidil group.
                Since urapidil decreased the high blood pressure in patients with pre-eclampsia without serious side-effects urapidil appears preferable superior to dihydralazine. The haemodynamic effects of urapidil were more predictable than those of dihydralazine. The reduction of intracerebral pressure could be an additional advantage of urapidil in the treatment of patients with pre-eclampsia. This investigation was undertaken to estimate whether a brief postpartum course of furosemide for patients with preeclampsia benefits recovery and shortens hospitalization by enhancing diuresis, lessening severe hypertension, and reducing the need for antihypertensive therapy.
                Two hundred sixty-four patients with preeclampsia were enrolled. After spontaneous onset of postpartum diuresis and discontinuation of intravenous magnesium sulfate, patients were randomly assigned to receive either no therapy or 20 mg oral furosemide daily for 5 days with oral potassium supplementation. Patient outcomes were compared between treatment groups with regard to classification of hypertensive disease.
                Only postpartum patients with severe preeclampsia (n = 70) who received furosemide compared with controls had significantly lower systolic blood pressure by postpartum day 2 (142 +/- 13 mm Hg compared with 153 +/- 19 mm Hg, P < .004) and required less antihypertensive therapy during hospitalization (14% compared with 26%, P = .371) and at discharge (6% compared with 26%, P = .045). No benefit was shown for patients with mild preeclampsia (n = 169) or superimposed preeclampsia (n = 25). Neither length of hospitalization nor frequency of delayed postpartum complications was positively affected by the intervention.
                Brief postpartum furosemide therapy for patients with severe preeclampsia seems to enhance recovery by normalizing blood pressure more rapidly and reducing the need for antihypertensive therapy. Shortening of hospitalization and reduction of delayed postpartum complications were not benefitted. The purpose of this randomized, prospective study was to investigate the effects of diuretics on plasma volume findings and perinatal outcome in pregnancies complicated by mild long-term hypertension. Twenty patients were in their first trimester and were receiving diuretics at time of entry to the study: Ten patients were allowed to continue their diuretic medication throughout pregnancy (diuretic group), whereas for the other 10 patients, diuretics were discontinued immediately. Plasma volume was serially measured throughout pregnancy with the use of the Evans blue dye-dilution technique. Initial plasma volume was similar in the two groups. However, in the diuretic group, subsequent plasma volume findings at various stages of gestation were markedly reduced when compared to respective plasma volume findings in the other group. In addition, plasma volume expansion was minimal in the diuretic group (mean increase of 18%), whereas it was normal in the other group (mean increase of 52%). Two patients in the diuretic group and one patient in the other group required other antihypertensive medication. There was no difference in perinatal outcome between the two groups. These results suggest that in hypertensive pregnancies, diuretics prevent normal plasma volume expansion without influencing perinatal outcome. Previous trials have suggested that calcium supplementation during pregnancy may reduce the risk of preeclampsia. However, differences in study design and a low dietary calcium intake in the populations studied limit acceptance of the data.
                We randomly assigned 4589 healthy nulliparous women who were 13 to 21 weeks pregnant to receive daily treatment with either 2 g of elemental calcium or placebo for the remainder of their pregnancies. Surveillance for preeclampsia was conducted by personnel unaware of treatment-group assignments, using standardized measurements of blood pressure and urinary protein excretion at uniformly scheduled prenatal visits, protocols for monitoring these measurements during the hospitalization for delivery, and reviews of medical records of unscheduled outpatient visits and all hospitalizations.
                Calcium supplementation did not significantly reduce the incidence or severity of preeclampsia or delay its onset. Preeclampsia occurred in 158 of the 2295 women in the calcium group (6.9 percent) and 168 of the 2294 women in the placebo group (7.3 percent) (relative risk, 0.94; 95 percent confidence interval, 0.76 to 1.16). There were no significant differences between the two groups in the prevalence of pregnancy-associated hypertension without preeclampsia (15.3 percent vs. 17.3 percent) or of all hypertensive disorders (22.2 percent vs. 24.6 percent). The mean systolic and diastolic blood pressures during pregnancy were similar in both groups. Calcium did not reduce the numbers of preterm deliveries, small-for-gestational-age births, or fetal and neonatal deaths; nor did it increase urolithiasis during pregnancy.
                Calcium supplementation during pregnancy did not prevent preeclampsia, pregnancy-associated hypertension, or adverse perinatal outcomes in healthy nulliparous women. Pre-eclampsia is one of the most serious and common complications of pregnancy. Nifedipine, a calcium channel blocker, and the vasodilator hydralazine have both been used as antihypertensive agents in this condition. The aim of this study was to determine which of these two agents is the most appropriate antihypertensive in the management of severe pre-eclampsia.
                One hundred and twenty-six pre-eclamptic patients with a gestational age of more than 20 weeks were randomized to receive either 8 mg nifedipine sublingually or 5-10 mg intravenous hydralazine. Women with a history of heart failure and women receiving antihypertensive treatment during the course of the current pregnancy were excluded. For each patient the following data were recorded; the number of drug administrations, the time needed to control blood pressure, mean urinary output, the time interval between effective control and a new hypertensive crisis after each drug administration and relevant adverse effects in mother or fetus.
                Effective control of blood pressure was achieved in both treatment arms. Data analysis indicated significantly fewer drug administrations in the nifedipine arm of the study. The time interval before a new hypertensive crisis following initial effective control of blood pressure was significantly longer in the nifedipine group when compared with hydralazine. Effective control of blood pressure was achieved more rapidly in multiparous patients receiving nifedipine (p=0.026). Mean urinary output before and after delivery was greater in the nifedipine arm of the study. There were no significant differences between the two groups in other variables. In addition, in neither group were there any serious adverse effects in mother or fetus.
                Nifedipine is safe and more effective than hydralazine in controlling blood pressure in severe pre-eclampsia. It has the added advantage of being cheaper and more widely available than the latter and is easily administered. To determine whether the administration of prophylactic intravenous magnesium sulphate reduces the occurrence of eclampsia in women with severe pre-eclampsia.
                Randomised controlled trial.
                A tertiary referral obstetric unit.
                Eight hundred and twenty-two women with severe pre-eclampsia requiring termination of pregnancy by induction of labour or caesarean section.
                The women were randomised to receive either placebo (saline) or magnesium sulphate intravenously. The investigators were blinded to the contents of the pre-mixed solutions.
                The occurrence of eclampsia in the two groups.
                The data of 699 women were evaluated. Fourteen were withdrawn after randomisation. The overall incidence of eclampsia was 1.8%. Of 345 women who received magnesium sulphate, one developed eclampsia (0.3%); in the placebo group, 11/340 women (3.2%) developed eclampsia (relative risk 0.09; 95% confidence interval 0.01-0.69; P = 0.003).
                The use of intravenous magnesium sulphate in the management of women with severe pre-eclampsia significantly reduced the development of eclampsia. The possibility of reducing pregnancy-induced hypertension and preeclampsia in primigravidas with low doses of nutritional factors and relative rest in the left lateral position was investigated in a randomized controlled, double-blind trial.
                Seventy-four normotensive women at 28-29 weeks' gestation, judged to be at risk of PIH or pre-eclampsia because they presented with a mean blood pressure of 80 mmHg or higher and a positive roll-over test, were studied. The treatment protocol was received by 37 women and the other 37 women received standard antenatal control until delivery.
                Twenty-nine (78.3%) women in the control group developed PIH and/or pre-eclampsia, as opposed to only 4 (10.8%) cases in the treatment group (P < 0.001). There were no adverse effects of treatment in mothers or in infants.
                This protocol reduces PIH and pre-eclampsia in primigravidas judged to be at risk of hypertension. Further studies are required to evaluate prostacyclin and prostaglandin E2 changes.
There is insufficient evidence to draw reliable conclusions about the effects of diuretics on prevention of pre-eclampsia and its complications. However, from this review, no clear benefits have been found from the use of diuretics to prevent pre-eclampsia. Taken together with the level of adverse effects found, the use of diuretics for the prevention of pre-eclampsia and its complications cannot be recommended.