Plasma volume expansion in the treatment of pre-eclampsia. Nutritional factors and rest reduce pregnancy-induced hypertension and pre-eclampsia in positive roll-over test primigravidas. Effects of diuretics on plasma volume in pregnancies with long-term hypertension. Low-molecular-weight heparin lowers the recurrence rate of preeclampsia and restores the physiological vascular changes in angiotensin-converting enzyme DD women. Treatment of severe preeclampsia with antithrombin concentrate: results of a prospective feasibility study. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial. Supplementary calcium in prevention of pre-eclampsia. Trial of prophylactic administration of TXA2 synthetase inhibitor, ozagrel hydrochloride, for preeclampsia. A small randomised trial of low-dose aspirin in women at high risk of pre-eclampsia.
The effects of plasma volume expansion with hyperosmolar solutions with the use of dextran 40 and plasmanate were studied in a controlled manner in 32 primiparous pre-eclamptic patients. The patients who were being studied received either dextran 40 (Rheomacrodex) or plasmanate in addition to the routine treatment with sedatives, bed rest, and magnesium sulfate when indicated. The patients were randomly assigned by blind draw to control (13), dextran (10), and plasmanate (nine) groups. The renal status of all patients was evaluated prior to volume expansion therapy. Patients were monitored for blood pressure, proteinuria, output of urine, hematocrit, and creatinine clearance. There was significant improvement in hemoconcentration and output of urine, and a trend toward a lowering of the mean arterial blood pressure in patients who were receiving plasmanate or dextran for volume expansion. 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. 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. Data from literature report that angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism affects the recurrence of preeclampsia and that low-molecular-weight heparin (LMWH) prevents adverse outcomes in thrombophilic women. We investigated the effect of LMWH on the pregnancy outcome, on maternal blood pressure values, and on uteroplacental flow in ACE DD nonthrombophilic women with history of preeclampsia. Eighty nonthrombophilic ACE DD women were randomized in 2 groups: 41 treated with dalteparin 5000 IU/day and 39 untreated (control group). Women underwent 24-hour automated blood pressure monitoring in the preconceptional period and every 2 weeks from weeks 8 to 36 and transabdominal color flow/pulsed Doppler examination at weeks 16, 20, and 24. LMWH reduced the risk of clinical negative outcomes (74.1% reduction of preeclampsia and 77.5% reduction of fetal growth restriction) and the severity (88.3% reduction of early onset of preeclampsia and 86.4% reduction of early onset of fetal growth restriction). In treated women, the relative risk for preeclampsia was 0.26 (P=0.02), and the relative risk for fetal growth restriction was 0.14 (P<0.001). Systolic (P=0.002) and diastolic (P=0.002) blood pressures, as well as awake (P=0.04) and asleep (P=0.01) period values, and the resistance indexes of both uterine arteries (P=0.002) were lower in the treated group. LMWH reduces the recurrence of preeclampsia, of negative outcomes, and the resistance of uteroplacental flow, and also prevents maternal blood pressure increase in ACE DD homozygote women with a previous history of preeclampsia. The prospective feasibility study was designed to determine whether treatment with antithrombin (AT) concentrates could be used for patients with severe preeclampsia to provide clinical efficacy without the full systemic antihypertensive drug. Twenty-nine severe preeclamptic patients (24 to 36 weeks of gestation, gestosis index [GI] >/= 6 points) were randomized to receive AT (1500 U/day) or not. AT was given intravenously once daily for 7 consecutive days. Twenty-four hours of continuous infusion of 5000 U/day of unfractionated heparin was given simultaneously in both groups. There were no statistical differences in the clinical profiles of the two groups. Maternal symptoms were evaluated from the difference of GI before and after treatment, and fetal findings were evaluated from the changes of the biophysical profile score. Improvement was significantly greater in the AT group for both the GI ( P = 0.046) and the biophysical profile score ( P = 0.022). The improvement of coagulation parameters was also evaluated. The improvement of plasmin-plasmin inhibitor complex (PPIC), D-dimer levels, and platelet counts was observed in the AT group compared with the non-AT group. The coagulation index as a composite coagulation test parameter showed a significantly improvement in the AT group. No adverse events related to AT were observed. Given that AT plus heparin was significantly better than treatment with heparin alone for improvement of both GI and biophysical profile of infant, it is suggested that therapy with AT alone might be effective enough for severe preeclampsia. Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia.
                283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study.
                Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002).
                Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations. 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. In an attempt to investigate the prophylactic effect of a thromboxane A2 (TXA2) synthetase inhibitor on pregnant women with a high risk of preeclampsia, the following clinical study was undertaken.
                Forty pregnant women were randomly allocated to control or treatment groups. Ozagrel Hydrochloride (400 mg/day, orally) and placebo were started at 20 weeks of gestation and continued until delivery.
                Seventeen of 20 (85%) women in the control group developed preeclampsia, whereas 9 of 20 (45%) in the treatment group developed preeclampsia. Ozagrel Hydrochloride significantly (p < 0.01) reduced the occurrence of preeclampsia, and the incidence of both hypertension (p < 0.05) and proteinuria (p < 0.01) was significantly less in the treatment group compared with the control group. One month after administration, the mean plasma concentration of TXB2, a metabolite of TXA2, was significantly decreased (p < 0.01) to 62.4 +/- 13.6%, whereas that of 6-keto prostaglandin F1 alpha, a metabolite of PGI2, was significantly increased (p < 0.01) to 206.7 +/- 52.8%. There were no maternal or fetal side effects observed.
                It seems likely that Ozagrel Hydrochloride could be used for the prevention of preeclampsia in high-risk pregnant women. To determine if aspirin (ASA) therapy reduces the incidence of pre-eclampsia in women at high risk of this condition.
                Randomised clinical trial. We recruited pregnant women with gestational age at randomisation <14 weeks, who satisfied the following criteria: chronic hypertension, history of severe pre-eclampsia or eclampsia or intrauterine growth retardation (IUGR) or intrauterine foetal death. Nineteen women in the no-treatment group and 16 in the ASA group were successfully followed up.
                The mean birthweight was higher in the ASA group than in the no-treatment group (2790 g (S.D. 340 g) versus 2616 g (S.D. 779 g)), but the difference was not statistically significant. We found no statistically significant differences between the groups in the proportion of infants with birthweight below 2500 g (13.3% versus 29.4%) and the number of cases with pregnancy-induced hypertension (PIH)/pre-eclampsia (31.3% versus 36.8%).
                These limited data give some support to the potential favourable effect of early treatment with ASA in pregnant women at risk of PIH and IUGR.
There is insufficient evidence for any reliable estimates of the effects of plasma volume expansion for women with pre-eclampsia.
[Note: The 14 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]