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Preeclampsia-eclampsia is a major cause of morbidity and mortality in mothers, fetuses, and neonates worldwide, most devastating in developing nations. Its cause is still uncertain, and many controversies exist concerning its management. The World Health Organization is aware of this and is coordinating a series of systematic reviews that focus on the etiology and the best strategies for the screening, prevention, and treatment of preeclampsia. This article summarizes results from systematic reviews of randomized trials to prevent and manage preeclampsia. There is a prophylactic role of modest magnitude for low-dose aspirin but the number to treat (90 women) to avoid one case of preeclampsia still is considered high. Antioxidant and calcium supplement trials remain to be completed before firm conclusions can be rendered on their efficacy for prevention. Magnesium sulfate is effective in preventing and treating eclampsia, while severe hypertension (with or without proteinuria) requires drug therapy, but there appears to be no benefits to treating mild to moderate hypertension without proteinuria in pregnancy. Finally, our review focuses on the quality of data reviewed, suggesting the need for better evidence, and discusses the use of systematic reviews as a strategy to focus future research on this important area of reproductive medicine.
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PMID:Strategies to prevent and treat preeclampsia: evidence from randomized controlled trials. 1552 96

Vascular disease is one of the complicating features of diabetes mellitus. Magnesium deficiency has recently been proposed as a novel factor implicated in the pathogenesis of diabetes complications. Several studies have indicated that hypertension in diabetic patients is an independent altered reaction of blood vessels to neurotransmitters and circulating hormones. Since magnesium has been proposed to decrease vascular sensitivity to vasoconstrictor agents, the present study was designed to determine whether chronic magnesium sulfate administration could prevent vascular complications of STZ-induced diabetes in rats. The animals were divided into six groups: two groups served as controls and received tap water for 8 weeks, while in the other four groups, made diabetic with a single IV injection of 40 mg/kg STZ, two groups treated with magnesium sulfate (10 g/L) added to the drinking water, and the other two groups received tap water only. After 8 weeks, in 3 groups (control, diabetic and Mg-treated), left common carotid artery was cannulated for continuous recording of blood pressure. All animals in these groups were decapitated and blood samples were drawn for glucose, Ca and Mg measurements. In the 3 remaining groups (again divided into control, diabetic and Mg-treated), the mesenteric vascular bed was perfused according to the McGregor method, and descending thoracic aortas were used for measurement of elasticity. In diabetic rats, plasma glucose was significantly increased and plasma magnesium was significantly decreased compared to controls and Mg-treated animals. Although plasma magnesium of Mg-treated animals increased significantly, it failed to reach to the magnesium level of the control group. Ca/Mg ratio was also increased compared to the control and Mg-treated animals. Mean arterial blood pressure in diabetics was significantly higher than control and Mg-treated rats. Similarly, there was a significant difference in mean arterial blood pressure of Mg-treated rats compared to control animals. Baseline perfusion pressure of diabetic group was significantly higher than control and Mg-treated groups with intact and denuded endothelium. Magnesium sulfate treatment decreased mean perfusion pressure of mesenteric vascular bed in intact and denuded endothelium in comparison with non-treated diabetic rats. There was a significant increase in passive tension in the aorta of diabetic rats compared to control and Mg-treated rats. However, there was no significant difference between Mg-treated and control rats. From the results of this study it may be concluded that magnesium could control STZ-induced diabetes and prevent its vascular complications.
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PMID:Oral magnesium administration prevents vascular complications in STZ-diabetic rats. 1568 Mar 10

As the understanding for the mechanism of absorption and metabolism has not been clarified adequately, a lot of works about these issues are still carrying on. Changes in maternal blood and intracellular magnesium concentration during the early stage of pregnancy suggest magnesium may play important roles around the period of implantation. Alternation in absorption of the mineral from colon, in levels of maternal blood and those of intracellular magnesium, or in urinary excretion of magnesium during pregnancy suggest that contents of magnesium in the whole maternal body tend to be decreased with the course of pregnancy. On the other hand, in preeclamptic women lack of magnesium is existed showing a pathological level compared to normal pregnant women. The magnesium deficiency is speculated to have a relation with vascular hypertonus or eclamptic seizures. Magnesium sulfate is frequently used for first choice drug, as it is effective to improve the hypertension of preeclampsia, to prevent or to cure the seizures of eclampsia. The administration of magnesium sulfate to preeclamtic women is reasonable to improve magnesium deficiency, which may be one of pathophysiological aspects of preeclampsia.
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PMID:[Toxemie of pregnancy and magnesium]. 1569 59

Low-dose aspirin, but not vitamin C and vitamin E, has small to moderate benefits when used for the prevention of preeclampsia. There is however little to suggest that the course of manifest preeclampsia can be substantially affected by drug treatment. Antihypertensive therapy increases the risk of fetal growth restriction and is only indicated in severe hypertension to reduce the risk of maternal cerebral hemorrhage. Magnesium sulfate is the drug of choice for the prevention and treatment of eclampsia. Volume expansion as well as the use of steroids in preeclamptic patients without HELLP syndrome have failed to show any improvement. Delivery as the only definitive treatment is always beneficial for the mother whereas expectant management is in favor of a premature fetus. Decision-making largely depends on gestational age and severity of the disease.
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PMID:[Current recommendations for the treatment of preeclampsia]. 1791 66

Preeclampsia is defined as the association of pregnancy-induced hypertension and proteinuria of 300 mg/24h or more after 20 weeks gestation. It complicates 0.5 to 7% of pregnancies. It is a severe complication of pregnancy, which leads to persisting fetal morbidity and mortality. It is also responsible for maternal morbidity as placental abruption, HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) and eclampsia. Without treatment, maternal risks are high. Once the disease is confirmed, the treatment consists of ending the pregnancy. Corticosteroids for lung maturity have to be prioritized depending on the term. Antihypertensive drugs are used to limit maternal complications, in particular, in neurological form. Calcium pump inhibitors are increasingly used as a first line choice. Magnesium sulfate, which is probably not used enough in France, needs to be administered with care and strict monitoring. It can be used to prevent a recurrence of eclamptic fits or in the context of early severe preeclampsia with neurological irritability where an eclamptic fit seems imminent. Preventive treatment of preeclampsia consists essentially of low dose aspirin. The efficacy of this treatment is real but moderate. It decreases the risk of recurrence of preeclampsia by 10 to 15%, of prematurity by 8% and of perinatal mortality by 14%. These figures were recently corrected to 10% for the risk of recurrence of preeclampsia: RR=0.95; 90% CI; (0.84-0.97) and prematurity: RR=0.95; 90%CI; (0.83-0.98). It seems that it has no significant effect on intra-uterine growth restriction (IUGR) and perinatal death prevention. For the main outcome of preeclampsia, there was no evidence that women in any of subgroups as preexisting renal disease, preexisting diabetes or hypertension benefited more or less from the use of antiplatelet agents than those in any other subgroup.
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PMID:[Latest developments: management and treatment of preeclampsia]. 1805 75

Preeclampsia, a serious hypertensive complication of pregnancy characterized by new-onset hypertension and proteinuria after midpregnancy, is a multisystem disorder that often involves the central nervous system. Neurologic signs and symptoms include hyperreflexia, headaches, visual disturbance, seizures, and cerebral hemorrhage. Eclampsia-new-onset seizures in the setting of preeclampsia-usually occurs before or within 48 hours of delivery, but can present as late as 1 month postpartum (late postpartum eclampsia). Magnesium sulfate is the drug of choice to prevent and treat eclampsia, a recommendation validated through large, randomized, and placebo-controlled trials. This review describes the pathogenesis, clinical features, and treatment of eclampsia, focusing on recent observations regarding roles of circulating antiangiogenic factors in the pathogenesis of the neurologic complications of eclampsia.
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PMID:Advances in the understanding of eclampsia. 1862 61

The National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy has defined four categories of hypertension in pregnancy: chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia superimposed on chronic hypertension. A maternal blood pressure measurement of 140/90 mm Hg or greater on two occasions before 20 weeks of gestation indicates chronic hypertension. Pharmacologic treatment is needed to prevent maternal end-organ damage from severely elevated blood pressure (150 to 180/100 to 110 mm Hg); treatment of mild to moderate chronic hypertension does not improve neonatal outcomes or prevent superimposed preeclampsia. Gestational hypertension is a provisional diagnosis for women with new-onset, nonproteinuric hypertension after 20 weeks of gestation; many of these women are eventually diagnosed with preeclampsia or chronic hypertension. Preeclampsia is the development of new-onset hypertension with proteinuria after 20 weeks of gestation. Adverse pregnancy outcomes related to severe preeclampsia are caused primarily by the need for preterm delivery. HELLP (i.e., hemolysis, elevated liver enzymes, and low platelet count) syndrome is a form of severe preeclampsia with high rates of neonatal and maternal morbidity. Magnesium sulfate is the drug of choice to prevent and treat eclampsia. The use of magnesium sulfate for seizure prophylaxis in women with mild preeclampsia is controversial because of the low incidence of seizures in this population.
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PMID:Hypertensive disorders of pregnancy. 1864 16

Hypertensive disorders are the most common medical disorders of pregnancy and are associated with adverse maternal and perinatal outcomes. When considering pregnancy, women with pre-existing chronic hypertension should be screened for target organ damage, especially renal dysfunction. Since blood pressure usually decreases until midpregnancy and returns to, or exceeds, prepregnancy values in the third trimester, antihypertensive treatment can sometimes be withdrawn in low-risk women, and reintroduced if needed. Recommended antihypertensive drugs are labetalol, methyldopa and nifedipine. Angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and atenolol must be avoided. The occurrence of superimposed preeclampsia should be detected by appropriate clinical and laboratory evaluation. Preeclampsia is a multisystem maternal and fetal syndrome. The risk of preeclampsia is slightly reduced by low-dose aspirin and by calcium supplementation in women with low dietary calcium intake. For early-onset preeclampsia, expectant management improves perinatal outcomes, but requires close maternal and fetal surveillance. For acute management of severe hypertension, intravenous labetalol and oral nifedipine are recommended. Delivery is indicated in the presence of signs of maternal or fetal distress. Magnesium sulfate is indicated for the prophylaxis and the treatment of eclampsia. Most antihypertensive agents are compatible with breast feeding. Early-onset or severe preeclampsia increase the risk of remote chronic hypertension and cardiovascular disease.
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PMID:[Arterial hypertension in pregnancy]. 1894 85

Over half a million women die each year from pregnancy related causes, 99% in low and middle income countries. In many low income countries, complications of pregnancy and childbirth are the leading cause of death amongst women of reproductive years. The Millennium Development Goals have placed maternal health at the core of the struggle against poverty and inequality, as a matter of human rights. Ten percent of women have high blood pressure during pregnancy, and preeclampsia complicates 2% to 8% of pregnancies. Preeclampsia can lead to problems in the liver, kidneys, brain and the clotting system. Risks for the baby include poor growth and prematurity. Although outcome is often good, preeclampsia can be devastating and life threatening. Overall, 10% to 15% of direct maternal deaths are associated with preeclampsia and eclampsia. Where maternal mortality is high, most of deaths are attributable to eclampsia, rather than preeclampsia. Perinatal mortality is high following preeclampsia, and even higher following eclampsia. In low and middle income countries many public hospitals have limited access to neonatal intensive care, and so the mortality and morbidity is likely to be considerably higher than in settings where such facilities are available. The only interventions shown to prevent preeclampsia are antiplatelet agents, primarily low dose aspirin, and calcium supplementation. Treatment is largely symptomatic. Antihypertensive drugs are mandatory for very high blood pressure. Plasma volume expansion, corticosteroids and antioxidant agents have been suggested for severe preeclampsia, but trials to date have not shown benefit. Optimal timing for delivery of women with severe preeclampsia before 32 to 34 weeks' gestation remains a dilemma. Magnesium sulfate can prevent and control eclamptic seizures. For preeclampsia, it more than halves the risk of eclampsia (number needed to treat 100, 95% confidence interval 50 to 100) and probably reduces the risk of maternal death. A quarter of women have side effects, primarily flushing. With clinical monitoring serious adverse effects are rare. Magnesium sulfate is the anticonvulsant of choice for treating eclampsia; more effective than diazepam, phenytoin, or lytic cocktail. Although it is a low cost effective treatment, magnesium sulfate is not available in all low and middle income countries; scaling up its use for eclampsia and severe preeclampsia will contribute to achieving the Millennium Development Goals.
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PMID:The global impact of pre-eclampsia and eclampsia. 1946 2

The four major hypertensive disorders related to pregnancy are preeclampsia, chronic hypertension, preeclampsia superimposed upon chronic hypertension, and gestational hypertension. The development of hypertension and proteinuria in pregnancy is usually due to preeclampsia, particularly in a primigravida. These findings typically become apparent in the latter part of the third trimester and progress until delivery, but some women develop symptoms in the latter half of the second trimester, or intrapartum, or the early postpartum period. Preeclampsia is characterized as mild or severe. Severe hypertension, coagulopathy, thrombocytopenia, liver function abnormalities, and fetal growth restriction are features of severe disease. Laboratory evaluation should assess haemoglobin/hematocrit and platelet count, renal and hepatic function, as well as assessment of fetal well-being and growth. Timing of delivery is based upon gestational age, maternal and fetal condition, and the severity of preeclampsia. Maternal end organ dysfunction and nonreassuring tests of fetal well-being are indications for delivery at any gestational age. Antihypertensive treatment aims at protecting the mother from severe hypertensive encephalopathy, but may jeopardize the fetus. We recommend antenatal corticosteroids (betamethasone) be given to women with preeclampsia at 26 to 34 weeks of gestation. Magnesium sulfate is more effective than phenytoin for prevention of eclamptic seizures.
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PMID:[Treatment of severe preeclampsia: until when and for what risks/benefits?]. 2014 45


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