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The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: An exploratory, randomized placebo controlled study.
Hofmeyr, GJ, Seuc, AH, Betrán, AP, Purnat, TD, Ciganda, A, Munjanja, SP, Manyame, S, Singata, M, Fawcus, S, Frank, K, et al
Pregnancy hypertension. 2015;(4):273-9
Abstract
BACKGROUND Epidemiological findings suggest that the link between poverty and pre-eclampsia might be dietary calcium deficiency. Calcium supplementation has been associated with a modest reduction in pre-eclampsia, and also in blood pressure (BP). METHODS This exploratory sub-study of the WHO Calcium and Pre-eclampsia (CAP) trial aims to determine the effect of 500mg/day elemental calcium on the blood pressure of non-pregnant women with previous pre-eclampsia. Non-pregnant women with at least one subsequent follow-up trial visit at approximately 12 or 24weeks after randomization were included. RESULTS Of 836 women randomized by 9 September 2014, 1st visit data were available in 367 women of whom 217 had previously had severe pre-eclampsia, 2nd visit data were available in 201 women. There was an overall trend to reduced BP in the calcium supplementation group (1-2.5mmHg) although differences were small and not statistically significant. In the subgroup with previous severe pre-eclampsia, the mean diastolic BP change in the calcium group (-2.6mmHg) was statistically larger than in the placebo group (+0.8mmHg), (mean difference -3.4, 95% CI -0.4 to -6.4; p=0.025). The effect of calcium on diastolic BP at 12weeks was greater than in those with non-severe pre-eclampsia (p=0.020, ANOVA analysis). CONCLUSIONS There is an overall trend to reduced BP but only statistically significant in the diastolic BP of women with previous severe pre-eclampsia. This is consistent with our hypothesis that this group is more sensitive to calcium supplementation, however results need to be interpreted with caution.
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Placental calcitriol synthesis and IGF-I levels in normal and preeclamptic pregnancies.
Halhali, A, Díaz, L, Barrera, D, Avila, E, Larrea, F
The Journal of steroid biochemistry and molecular biology. 2014;:44-9
Abstract
Placenta is an extrarenal source of calcitriol and pregnancy is associated with increased maternal serum levels of this hormone. It has been reported that insulin-like growth factor I (IGF-I) stimulates placental calcitriol synthesis and that circulating levels of both hormones are low in preeclampsia. Since calcitriol production has not been determined in placental homogenates in preeclampsia, the aim of the present study was to establish if placental calcitriol synthesis and IGF-I concentration are altered in this tissue obtained from preeclamptic pregnancies. Placental samples were obtained from 8 preeclamptic (PE group) and 8 normotensive (NT group) pregnant women. Calcitriol synthesis was determined using [(3)H]-25(OH)D3 (2.94nM) as precursor and [(3)H]-1,25(OH)2D3 produced was calculated as the percentage of radioactivity co-eluting with unlabelled 1,25(OH)2D3 after two successive high pressure liquid chromatographies. Placental IGF-I levels were determined by RIA. In addition, maternal and umbilical calcitriol and IGF-I levels were also determined in these 2 groups using radioreceptor assay and RIA, respectively. The results of the present study showed that placentas from both groups were able to convert [(3)H]-25(OH)D3 into more polar metabolites. In the PE group, placental [(3)H]-1,25(OH)2D3 synthesis was significantly lower than in the NT group (19.6±6.2 vs 29.9±8.1fmoles/200mg wet weight, P=0.013). Regarding IGF-I, its levels were significantly lower in placentas of the PE group than in the NT group (15.2±3.9 vs 21.6±4.9ng/g wet weight, P=0.012). Maternal and umbilical calcitriol levels were significantly lower in the PE than in the NT group (P<0.001). In the PE group, serum IGF-I levels were significantly lower only in the maternal circulation (P<0.05). In conclusion, placental calcitriol synthesis and IGF-I levels are low in preeclampsia which may contribute to decreased local placental functions related to these two hormones and/or to decreased maternal and fetal pool of 1,25(OH)2D3 during preeclamptic pregnancies. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.
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Magnesium sulphate for prevention of eclampsia: are intramuscular and intravenous regimens equivalent? A population pharmacokinetic study.
Salinger, DH, Mundle, S, Regi, A, Bracken, H, Winikoff, B, Vicini, P, Easterling, T
BJOG : an international journal of obstetrics and gynaecology. 2013;(7):894-900
Abstract
OBJECTIVE To compare magnesium sulphate concentrations achieved by intramuscular and intravenous regimens used for the prevention of eclampsia. SETTING Low-resource obstetric hospitals in Nagpur and Vellore, India. POPULATION Pregnant women at risk for eclampsia due to hypertensive disease. METHODS A pharmacokinetic study was performed as part of a randomised trial that enrolled 300 women comparing intramuscular and intravenous maintenance regimens of magnesium dosing. Data from 258 enrolled women were analysed in the pharmacokinetic study. A single sample was drawn per woman with the expectation of using samples in a pooled data analysis. MAIN OUTCOME MEASURES Pharmacokinetic parameters of magnesium distribution and clearance. RESULTS Magnesium clearance was estimated to be 48.1 dl/hour, volume of distribution to be 156 dl and intramuscular bioavailability to be 86.2%. The intramuscular regimen produced higher initial serum concentrations, consistent with a substantially larger loading dose. At steady state, magnesium concentrations in the intramuscular and intravenous groups were comparable. With either regimen, a substantial number of women would be expected to have serum concentrations lower than those generally held to be therapeutic. CONCLUSIONS Clinical implications were that a larger loading dose for the intravenous regimen should be considered; where feasible, individualised dosing of magnesium sulphate would reduce the variability in serum concentrations and might result in more women with clinically effective magnesium concentrations; and lower dose magnesium sulphate regimens should be considered with caution.
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A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia.
Belfort, MA, Anthony, J, Saade, GR, Allen, JC, ,
The New England journal of medicine. 2003;(4):304-11
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Abstract
OBJECTIVE Magnesium sulfate may prevent eclampsia by reducing cerebral vasoconstriction and ischemia. Nimodipine is a calcium-channel blocker with specific cerebral vasodilator activity. Our objective was to determine whether nimodipine is more effective than magnesium sulfate for seizure prophylaxis in women with severe preeclampsia. METHODS We conducted an unblinded, multicenter trial in which 1650 women with severe preeclampsia were randomly assigned to receive either nimodipine (60 mg orally every 4 hours) or intravenous magnesium sulfate (given according to the institutional protocol) from enrollment until 24 hours post partum. High blood pressure was controlled with intravenous hydralazine as needed. The primary outcome measure was the development of eclampsia, as defined by a witnessed tonic-clonic seizure. RESULTS Demographic and clinical characteristics were similar in the two groups. The women who received nimodipine were more likely to have a seizure than those who received magnesium sulfate (21 of 819 [2.6 percent] vs. 7 of 831 [0.8 percent], P=0.01). The adjusted risk ratio for eclampsia associated with nimodipine, as compared with magnesium sulfate, was 3.2 (95 percent confidence interval, 1.1 to 9.1). The antepartum seizure rates did not differ significantly between groups, but the nimodipine group had a higher rate of postpartum seizures (9 of 819 [1.1 percent] vs. 0 of 831, P=0.01). There were no significant differences in neonatal outcome between the two groups. More women in the magnesium sulfate group than in the nimodipine group needed hydralazine to control blood pressure (54.3 percent vs. 45.7 percent, P<0.001). CONCLUSIONS Magnesium sulfate is more effective than nimodipine for prophylaxis against seizures in women with severe preeclampsia.
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Oxidant stress in pre-eclampsia and essential hypertension.
Kumar, CA, Das, UN
The Journal of the Association of Physicians of India. 2002;:1372-5
Abstract
BACKGROUND Endothelial cell dysfunction may play a role in the pathobiology of pre-eclampsia and human essential hypertension. Vasodilators and platelet anti-aggregators such as prostacyclin and nitric oxide are produced by endothelial cells. The half-life of prostacyclin and nitric oxide are reduced by superoxide anion, whereas superoxide dismutase antagonizes its action. OBJECTIVES To estimate the plasma concentrations of nitric oxide and lipid peroxides and those of catalase and superoxide dismutase in patients with pre-eclampsia and essential hypertension. METHODS Patients of essential hypertension and pre-eclampsia were selected for the study. Nitric oxide and lipid peroxides were estimated in the plasma and anti-oxidants catalase and superoxide dismutase were estimated in the RBC membranes. RESULTS The ratio between lipid peroxides and nitric oxide was elevated and the activity of superoxide dismutase reduced in patients with pre-eclampsia and uncontrolled essential hypertension. CONCLUSION These results suggest that oxidants and anti-oxidants are altered in human essential hypertension and pre-eclampsia.