Magnesium sulfate prophylaxis in preeclampsia: Lessons learned from recent trials

In the US, the routine use of magnesium sulfate for seizure prophylaxis in women with preeclampsia is an ingrained obstetric practice. During the past decade, several observational studies and randomized trials have described the use of various regimens of magnesium sulfate to prevent or reduce the rate of seizures and complications in women with preeclampsia. There are only 2 double-blind, placebo-controlled trials evaluating the use of magnesium sulfate in mild preeclampsia. There were no instances of eclampsia among 181 women assigned to placebo, and there were no differences in the percentage of women who progressed to severe preeclampsia (12.5% in magnesium group vs 13.8% in the placebo group, relative risk [RR] 0.90; 95% CI 0.52-1.54). However, the number of women enrolled in these trials is too limited to draw any valid conclusions. There are 4 randomized controlled trials that compare the use of no magnesium sulfate, or a placebo vs magnesium sulfate, to prevent convulsions in patients with severe preeclampsia. The rate of eclampsia was 0.6% among 6343 patients assigned to magnesium sulfate vs 2.0 % among 6330 patients assigned to a placebo or control (RR 0.39; 95% CI 0.28-0.55). However, the reduction in the rate of eclampsia was not associated with a significant benefit in either maternal or perinatal outcome. In addition, there was a higher rate of maternal respiratory depression among those assigned magnesium sulfate (RR 2.06; 95% CI 1.33-3.18). The evidence to date confirms the efficacy of magnesium sulfate in reduction of seizures in women with eclampsia and severe preeclampsia; however, this benefit does not affect overall maternal and perinatal mortality and morbidities. The evidence regarding the benefit-to-risk ratio of magnesium sulfate prophylaxis in mild preeclampsia remains uncertain, and does not justify its routine use for that purpose.     

Pregnancy-related mortality from preeclampsia and eclampsia

OBJECTIVE: To examine the role of preeclampsia and eclampsia in pregnancy-related mortality. METHODS: We used data from the Centers for Disease Control and Prevention's Pregnancy Mortality Surveillance System to examine pregnancy-related deaths from preeclampsia and eclampsia from 1979 to 1992. The pregnancy-related mortality ratio for preeclampsia-eclampsia was defined as the number of deaths from preeclampsia and eclampsia per 100,000 live births. Case-fatality rates for 1988-1992 were calculated for preeclampsia and eclampsia deaths per 10,000 cases during the delivery hospitalization, using the National Hospital Discharge Survey. RESULTS: Of 4024 pregnancy-related deaths at 20 weeks' or more gestation in 1979-1992, 790 were due to preeclampsia or eclampsia (1.5 deaths/100,000 live births). Mortality from preeclampsia and eclampsia increased with increasing maternal age. The highest risk of death was at gestational age 20-28 weeks and after the first live birth. Black women were 3.1 times more likely to die from preeclampsia or eclampsia as white women. Women who had received no prenatal care had a higher risk of death from preeclampsia or eclampsia than women who had received any level of prenatal care. The overall preeclampsia-eclampsia case-fatality rate was 6.4 per 10,000 cases at delivery, and was twice as high for black women as for white women. CONCLUSION: The continuing racial disparity in mortality from preeclampsia and eclampsia emphasizes the need to identify those differences that contribute to excess mortality among black women, and to develop specific interventions to reduce mortality from preeclampsia and eclampsia among all women.     

Late postpartum eclampsia: a preventable disease?

OBJECTIVE: The purpose of this study was to determine whether there is a shift in the timing of eclampsia in relation to delivery and whether traditional symptoms precede impending postpartum eclampsia. STUDY DESIGN: A multicenter analysis of data from patients with eclampsia from March 1996 through February 2001 at the University of Cincinnati, the University of Tennessee, Memphis, and Central Baptist Hospital, Lexington. Data were collected regarding the relationship of the patient's first seizure to delivery, prodromal symptoms, neuroimaging studies, use of magnesium sulfate, antihypertensive therapy, and follow-up medical care. The analysis focused on women who had late postpartum eclampsia. RESULTS: During the study period, 89 patients were diagnosed with eclampsia. Twenty-nine women (33%) had postpartum eclampsia, of whom 23 women (79%) had late onset (>48 hours). Interestingly, only 5 of these 23 women (22%) had been previously diagnosed with preeclampsia. Twenty-one patients (91%) with late postpartum eclampsia had at least 1 prodromal symptom, and 12 patients (52%) had >1 symptom that heralded the seizure: 20 women (87%) had headache; 10 women (44%) had visual changes; 5 women (22%) had nausea or vomiting; and 2 women (9%) experienced epigastric pain. Only 7 of these 21 women (33%) sought care for their symptoms, of whom 6 women (86%) had clinical evidence of preeclampsia that was not considered by the treating physician. Among all patients with eclampsia, there were 7 cases of aspiration pneumonia, 3 cases of pulmonary edema, 3 cases of pleural effusion, 2 cases of disseminated intravascular coagulation, and no cases of maternal death. CONCLUSION: Current obstetric treatment in the United States has resulted in a shift of eclampsia toward the postpartum period, with most cases being seen as late post partum. To reduce the rate of late postpartum eclampsia, efforts should be directed to the education of the health care providers and patients regarding the importance of prompt reporting and evaluation of symptoms of preeclampsia during the postpartum period.     

The use of magnesium sulfate for women with severe preeclampsia or eclampsia diagnosed during the postpartum period

This was a systematic review of randomized controlled trials comparing anticonvulsants with placebo or no anticonvulsant for prevention (a) of eclampsia in women with severe preeclampsia diagnosed during the postpartum period or diagnosed before delivery but without previous treatment and (b) prevention of seizures recurrence in women with eclampsia postpartum. We did not find study with full inclusion criteria. However, a total of two randomised controlled trials meet inclusion criteria as subgroup analysis; one for severe preeclampsia diagnosed during the postpartum period and one for eclampsia postpartum. For severe preeclampsia diagnosed during postpartum, there was no clear difference between the groups reporting eclampsia (relative risk: 0.54, 95% confidence interval: 0.16–1.80). For seizure recurrence, magnesium sulfate was superior to diazepam, but there was no significant difference compared with phenytoin. No conclusion can be drawn on the role of magnesium sulfate post partum as established in antepartum pre-eclampsia/eclampsia management because of lack of powered randomised controlled trials.     

Eclampsia in Southern Alberta: Is There a Role for Seizure Prophylaxis in All Women with Gestational Hypertension?

Objective: To evaluate the predictability of eclampsia and explore the role for seizure prophylaxis in a population with a low frequency of seizure prophylaxis.Methods: A retrospective review was conducted of all women with eclampsia registered at the Foothills Hospital in Calgary, Alberta, between 1991 and 2000. The data collected included timing of seizure in relation to diagnosis of gestational hypertension (GHTN) and delivery, method of seizure prophylaxis (if any), and maternal characteristics.Results: During the study period, 3075 of 38 577 women (8.0%) were diagnosed with GHTN, with or without proteinuria or adverse conditions. Three percent had received magnesium sulfate for seizure prophylaxis. Of these 3075 women, 17 (0.6%) developed eclampsia, none of whom was receiving magnesium sulfate for seizure prophylaxis at the time. Of these, 10 women (59%) exhibited GHTN prior to their first seizure, including 6 women with GHTN with adverse conditions, 3 with GHTN with proteinuria but without adverse conditions, and 1 with GHTN without proteinuria or adverse conditions. Five of the 17 women had seizures that occurred prior to labour, 6 were intrapartum, and 6 were postpartum. Nine (53%) of the 17 women with eclampsia had their initial seizure after the diagnosis of GHTN and before 24 hours postpartum.Conclusion: Seizure prophylaxis for all the women with GHTN, from the time of diagnosis through 24 hours postpartum, may have been able to prevent as many as 53% of eclamptic episodes. Three hundred and seven women with GTHN would have to receive seizure prophylaxis to prevent one seizure.     

Examining the Use of Magnesium Sulfate to Treat Pregnant Women with Preeclampsia and Eclampsia: Results of a Program Assessment of Emergency Obstetric Care (EmOC) Training in India

Background

The aim of this study is to examine rates of magnesium sulfate utilization by emergency obstetric care trainees to treat preeclampsia–eclampsia in India. Secondarily, structural barriers are identified which limit the use of magnesium sulfate, highlighting limitations of emergency obstetric care training, which is a commonly implemented intervention in resource-poor settings.

Methods

Trainees’ curriculum specified magnesium sulfate treatment for eclampsia and severe preeclampsia. Case records were analyzed for preeclampsia–eclampsia diagnosis, magnesium sulfate utilization, delivery route, and maternal and neonatal outcomes from 13,238 reported deliveries between 2006 and 2012 across 75 district hospitals in 12 Indian states.

Results

Of 1320 cases of preeclampsia–eclampsia, 322 (24.4%) had eclampsia. Magnesium sulfate was given to 12.9% of preeclamptic and 54.3% of eclamptic women, with lower usage rates in rural communities. Among the 1308 women with preeclampsia–eclampsia, only 24 deaths occurred (1.8%). In contrast, among the 17,179 women without preeclampsia–eclampsia, there were 95 reported deaths (0.6%). Both maternal mortality ratios were found to be much higher than the Millennium Development Goal target of 0.15%. Magnesium sulfate administration was associated with a higher death rate in preeclamptic but not eclamptic women, representing possible confounding by severity.

Conclusion

To optimize resources spent on emergency obstetric care training, the consistent availability of magnesium sulfate should be improved in India. Increasing drug availability, implementing clinical guidelines around its administration, and training health-care providers on the identification and treatment of preeclampsia–eclampsia could lead to notable improvements in maternal and infant mortality.

     

Pregnancy and severe chronic hypertension: maternal outcome.

OBJECTIVE: To determine the maternal outcome associated with severe chronic hypertension during the second half of pregnancy. METHODS: An analysis of data obtained of women with severe chronic hypertension (> or = 160/110 mm Hg) and > or = 20 weeks' gestation who were hospitalized and delivered during a 5-year period. The pregnancy outcome data were collected retrospectively from medical records. Each patient was observed closely throughout hospitalization with intensive monitoring of the clinical status of both mother and fetus. Antihypertensive drugs were used for systolic or diastolic blood pressure > or = 160 and > or = 110 mm Hg, respectively. Women with superimposed preeclampsia received magnesium sulfate. The main outcome measures were peak of blood pressure, superimposed preeclampsia, and major maternal complications. RESULTS: Of 154 women studied, 111 (72%) had pregestational chronic hypertension, and 120 (78%) developed superimposed preeclampsia. The mean weeks' gestation was 34.5 +/- 4.6. Overall, 110 (71.4%) pregnancies were delivered by cesarean section. Maternal age and parity were significantly higher among women who had pregestational chronic hypertension than those who had chronic hypertension diagnosed during the first half of pregnancy. Abruptio placentae (8.4%), HELLP syndrome (8.4%), acute renal insufficiency (3.9%), pulmonary edema (1.3%), and postpartum hypertensive encephalopathy (1.3%) were the most frequent maternal complications. There were no maternal deaths, disseminated intravascular coagulation, or eclampsia. CONCLUSION: Three-quarters of women with severe chronic hypertension in the second half of pregnancy developed superimposed preeclampsia. Intensive monitoring of the clinical status of the mother was associated with low maternal morbidity and the absence of maternal deaths. Pregestational chronic hypertension does not change the maternal prognosis.     

Diagnosis, prevention, and management of eclampsia

The pathogenesis of eclamptic convulsions remains unknown. Cerebral imaging suggests that cerebral abnormalities in eclampsia (mostly vasogenic edema) are similar to those found in hypertensive encephalopathy. However, cerebral imaging is not necessary for the diagnosis or management of most women with eclampsia. The onset of eclamptic convulsions can be antepartum (38-53%), intrapartum (18-36%), or postpartum (11-44%). Recent data reveal an increase in the proportion of women who develop eclampsia beyond 48 hours after delivery. Other than early detection of preeclampsia, there are no reliable tests or symptoms for predicting the development of eclampsia. In developed countries, the majority of cases reported in recent series are considered unpreventable. Magnesium sulfate is the drug of choice for reducing the rate of eclampsia developing intrapartum and immediately postpartum. There are 4 large randomized trials comparing magnesium sulfate with no treatment or placebo in patients with severe preeclampsia. The rate of eclampsia was significantly lower in those assigned to magnesium sulfate (0.6% versus 2.0%, relative risk 0.39, 95% confidence interval 0.28-0.55). Thus, the number of women needed to treat to prevent one case of eclampsia is 71. Magnesium sulfate is the drug of choice to prevent recurrent convulsions in eclampsia. The development of eclampsia is associated with increased risk of adverse outcome for both mother and fetus, particularly in the developing nations. Pregnancies complicated by eclampsia require a well-formulated management plan. Women with a history of eclampsia are at increased risk of eclampsia (1-2%) and preeclampsia (22-35%) in subsequent pregnancies. Recommendations for diagnosis, prevention, management, and counseling of these women are provided based on results of recent studies and my own clinical experience.     

Blood loss at cesarean delivery in women on magnesium sulfate for preeclampsia

Objective: To evaluate the effect of magnesium sulfate for prevention of eclampsia on blood loss at time of cesarean delivery (CD).

Methods: We conducted an electronic based search using the following databases: MEDLINE, PUBMED and the Cochrane Library. The search terms were “magnesium sulfate”, “preeclampsia” and “randomized”. Inclusion criteria were randomized controlled trials of women with preeclampsia who delivered with or without magnesium sulfate therapy for seizure prophylaxis. Only trials with placebo or no treatment comparison groups were included. Primary outcome was postpartum hemorrhage. Secondary outcomes were estimated blood loss, change in hemoglobin, blood transfusion and eclampsia.

Results: Five trials met inclusion criteria. The incidence of postpartum hemorrhage was similar between the two groups [magnesium sulfate: 754/4482 (17%); no magnesium sulfate: 775/4427 (18%); RR 0.97, 95% CI 0.88–1.06]. There was no statistical difference between any of the other blood loss outcomes reported in the included studies. The rate of eclampsia with magnesium sulfate was significantly lower than with placebo (42/5604, 0.7%, versus 107/5600, 1.9%; RR 0.40, 95% CI 0.28–0.57).

Conclusions: Magnesium sulfate does not appear to affect blood loss intrapartum and postpartum in women with preeclampsia. Magnesium sulfate, therefore, should be continued during CD, given the benefit of seizure prophylaxis without any increased risk of hemorrhage.     

Expectant management of severe preeclampsia and preeclampsia superimposed on chronic hypertension between 24 and 34 weeks' gestation

BACKGROUND: Timing of delivery is difficult to judge in preeclampsia. OBJECTIVE: To compare the differences of maternal and perinatal outcome of patients with severe preeclampsia and essential hypertension with superimposed preeclampsia, with expectant management at 24-34 weeks' gestation. STUDY DESIGN: A retrospective review of a conservative regime using intravenous magnesium sulfate, glucocorticoids and antihypertensive drugs, monitored by serial liver function tests, full blood count, coagulation profile, and renal function tests. Fetal status was assessed by daily non-stress test and ultrasound twice by week. RESULTS: A total number of 100 women had severe preeclampsia and 29 superimposed preeclampsia. The average pregnancy prolongation was 8.4 and 8.5 days, respectively. Oliguria, abruption placentae and HELLP syndrome were frequent complications similar in each group. There were no cases of eclampsia or disseminated coagulopathy in either group. The total neonatal survival rate was 93% in both groups. CONCLUSION: Expectant management is equally safe in both superimposed preeclampsia and severe preeclampsia of early onset.     

Prophylaxis of eclamptic seizures: current controversies.

Treatment of this pathophysiologically poorly understood disease is controversial. Despite this uncertainty, the goals of management of the patient with preeclampsia and eclampsia are diagnosis, stabilization, and delivery of the baby. Stabilization refers to both mother and fetus and should include the prevention of eclampsia or the recurrence of eclamptic seizures. There are empiric data supporting the use of magnesium sulfate for the management of preeclampsia and eclampsia in North America, but there are few data to support its efficacy as a classic anticonvulsant. Until controlled trials are completed, we suggest that magnesium sulfate continue to be used in preeclampsia, with the addition of established anticonvulsant medications when eclampsia occurs. Data on established antiepileptic drugs such as diazepam and phenytoin support their use in treating patients with eclamptic seizures. As stated in an earlier review, "in treating preeclampsia, magnesium sulfate therapy may have a role and may moderate factors leading to eclampsia. Whether magnesium sulfate therapy may have some as yet unproved effect on epileptogenic foci or seizure propagation is not the important issue for the physician caring for the eclamptic patient. Until adequately designed therapeutic trials are available, it is our opinion that treatment should be based on the use of anticonvulsant drugs of established efficacy in seizure control and prophylaxis (p. 1363)."     

Cerebral hemodynamics in preeclampsia: cerebral perfusion and the rationale for an alternative to magnesium sulfate

Preeclampsia and eclampsia continue to be major causes of maternal death. Currently, approximately 18% of U.S. maternal deaths are attributed to hypertensive disorders and eclampsia, and several hundred women die from eclampsia and its complications every year. In the United States, preeclamptic women have received magnesium sulfate as a seizure prophylaxis agent for 3 decades, and this practice is becoming more widely accepted internationally. In addition to a recognized failure rate, there are financial, logistic, and safety concerns associated with the universal administration of magnesium sulfate. Many institutions in the developing world lack the necessary equipment and expertise to administer the medication, and many preeclamptic patients thus do not receive magnesium sulfate before their first seizure. As effective as it has been in reducing mortality from eclampsia, magnesium sulfate is also associated with appreciable morbidity and mortality from administration errors and magnesium toxicity. The availability of an easily administered, cheap, safe, and orally administered alternative to magnesium sulfate would be welcomed in the developing world and would provide an extremely useful alternative therapy to the current standard of care. Recent advances in the understanding of the pathophysiology of preeclampsia and eclampsia, primarily related to cerebral perfusion and blood flow, could allow us to reduce the seizure rate in treated preeclamptic women even further than what is currently reported. This article deals with the rationale behind the use of labetalol as an alternative to magnesium sulfate for the prevention of eclampsia. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that hypertensive diseases of pregnancy contribute a significant portion of today's maternal mortality, explain that methods of preventing eclampsia are not applicable worldwide, and state that understanding of the pathophysiology of preeclampsia/eclampsia may assist in developing safe and effective medications that can be used universally.     

Diagnosis and management of gestational hypertension and preeclampsia

Gestational hypertension and preeclampsia are common disorders during pregnancy, with the majority of cases developing at or near term. The development of mild hypertension or preeclampsia at or near term is associated with minimal maternal and neonatal morbidities. In contrast, the onset of severe gestational hypertension and/or severe preeclampsia before 35 weeks' gestation is associated with significant maternal and perinatal complications. Women with diagnosed gestational hypertension-preeclampsia require close evaluation of maternal and fetal conditions for the duration of pregnancy, and those with severe disease should be managed in-hospital. The decision between delivery and expectant management depends on fetal gestational age, fetal status, and severity of maternal condition at time of evaluation. Expectant management is possible in a select group of women with severe preeclampsia before 32 weeks' gestation. Steroids are effective in reducing neonatal mortality and morbidity when administered to those with severe disease between 24 and 34 weeks' gestation. Magnesium sulfate should be used during labor and for at least 24 hours postpartum to prevent seizures in all women with severe disease. There is an urgent need to conduct randomized trials to determine the efficacy and safety of antihypertensive drugs in women with mild hypertension-preeclampsia. There is also a need to conduct a randomized trial to determine the benefits and risks of magnesium sulfate during labor and postpartum in women with mild preeclampsia.     

Maternal and perinatal outcome of preeclampsia with an onset before 24 weeks' gestation. Audit in a tertiary referral center

OBJECTIVE: Preeclampsia, with an onset before 24 weeks' gestation is a rare but severe condition in pregnancy with little data of maternal and perinatal outcome, particularly after expectant management. We therefore, evaluated pregnancy outcome in these women at our department where temporising management was introduced as the standard policy in early onset preeclampsia. STUDY DESIGN: We analysed retrospectively all consecutive women with preeclampsia, with an onset before 24 weeks' gestation, between 1 January 1993 and 31 December 2002 at a tertiary university referral center. RESULTS: Twenty-six pregnancies, of which two were twin pregnancies, resulted in 65% of the women in at least one major maternal complication: maternal death (n=1), HELLP syndrome (n=16), eclampsia (n=5) and pulmonary edema (n=4). Thirty percent of these women presented already with serious morbidity at admission. The median prolongation of the pregnancy was 24 days (range 3-46 days). The overall perinatal mortality was 82%: 19 fetal deaths and 4 neonatal deaths. CONCLUSION: Early onset preeclampsia, with an onset before 24 weeks' gestation, results in considerable maternal and perinatal morbidity and mortality. Therefore, expectant management should not be considered as a routine treatment option in these patients.     

Postpartum seizure prophylaxis: using maternal clinical parameters to guide therapy

OBJECTIVE: To use individual patient clinical parameters to signal cessation of postpartum magnesium sulfate seizure prophylaxis for the spectrum of pregnancy-related hypertensive disorders. METHODS: This was a prospective study using clinical symptoms (absence of headache, visual changes, epigastric pain) and signs (sustained blood pressure less than 150/100 without need for acute antihypertensive therapy, spontaneous diuresis more than 100 mL per hour for no less than 2 hours) to signal cessation of intravenous magnesium sulfate postpartum in gravidas diagnosed with preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelets syndrome. Laboratory assessments (including proteinuria) were not used as criteria for drug discontinuation. RESULTS: Five hundred three patients were enrolled and classified according to American College of Obstetricians and Gynecologists criteria (mild preeclampsia, severe preeclampsia, chronic hypertension with superimposed preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelets syndrome). Maternal age, gestational age, and hours of magnesium therapy before delivery were not statistically different among groups. There was no significant difference in the duration of postpartum magnesium sulfate therapy among groups with the median duration of therapy 4 hours (range 2-77 hours). No eclamptic seizures occurred after magnesium discontinuation. Thirty-eight patients (7.6%) required reinstitution of magnesium therapy for 24 hours because of exacerbation of blood pressure (sustained blood pressure more than 160/110) associated with headache or visual changes. CONCLUSION: Clinical criteria, when compared with arbitrary protocols, can be used successfully to shorten the duration of postpartum magnesium sulfate administration for seizure prophylaxis in patients with pregnancy-related hypertensive disorders.     

The Management of Severe Preeclampsia with Intravenous Magnesium Sulphate, Hydralazine and Central Venous Catheterization

A prospective study of patients with severe preeclampsia managed by magnesium sulphate infusion for eclampsia prophylaxis, hydralazine infusion for vasodilatation and central venous catheterization for fluid monitoring is reported. In this preliminary report of 46 patients, there was no episode of eclampsia following treatment, no maternal death, and hypertension was well controlled in all patients. Of the 51 babies born, there were 7 stillbirths, and 4 neonatal deaths; 6 of the 7 stillbirths were less than 30 weeks' gestation, and 23 of the 46 patients were delivered by Caesarean section.     

Selective magnesium sulfate prophylaxis for the prevention of eclampsia in women with gestational hypertension

OBJECTIVE: To describe the incidence of eclampsia in women with mild gestational hypertension when only women with severe gestational hypertension are given magnesium sulfate prophylaxis. METHODS: This is a prospective 4(1/2)-year observational study. Those women who met our criteria for severe gestational hypertension received intravenous magnesium sulfate prophylaxis, and women with nonsevere hypertension did not. Data were collected at delivery to ascertain the incidence of eclampsia and maternal and neonatal morbidity. RESULTS: A total of 72,004 women were delivered during the study period, 6,431 had gestational hypertension, 3,935 met the criteria for severe disease and were given magnesium sulfate prophylaxis, 2,496 women with nonsevere hypertension were not treated. Eighty-seven women developed eclampsia, for an overall incidence of 1 in 828 deliveries, a 50% increase when compared with 5 preceding years where all women with gestational hypertension were given magnesium sulfate prophylaxis. Of the 2,496 women with nonsevere hypertension who were not treated, 27 had eclampsia (1 in 92). Women with eclampsia were more likely to require general anesthesia for cesarean delivery compared with hypertensive women without eclampsia (23% versus 4%, P < .001), but they had no additional morbidity. Infants of eclamptic mothers had more adverse outcomes than those without convulsions (12% versus 1%, P < .04). CONCLUSION: Selective magnesium sulfate prophylaxis results in an increased overall incidence of eclampsia because of more seizures in women with nonsevere gestational hypertension who are not given magnesium sulfate prophylaxis. LEVEL OF EVIDENCE: II-3.     

Magnesium sulfate in women with mild preeclampsia: a randomized controlled trial

OBJECTIVE: To determine whether magnesium sulfate prevents disease progression in women with mild preeclampsia. METHODS: A total of 222 women with mild preeclampsia were randomized to receive intravenous magnesium sulfate (n = 109) or matched placebo (n = 113). Mild preeclampsia was defined as blood pressure of at least 140/90 mm Hg taken on two occasions in the presence of new-onset proteinuria. Patients with chronic hypertension or severe preeclampsia were excluded. Patients were considered to have disease progression if they developed signs or symptoms of severe preeclampsia, eclampsia, or laboratory abnormalities of full or partial HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. RESULTS: The groups were similar with respect to maternal age, ethnicity, gestational age, parity, and maternal weight at enrollment. Fourteen women (12.8%) in the magnesium group and 19 (16.8%) in the placebo group developed severe preeclampsia after randomization (relative risk = 0.8, 95% confidence interval 0.4, 1.5, P =.41). None in either group developed eclampsia or thrombocytopenia. Women assigned magnesium had similar rates of cesarean delivery (30% versus 25%), chorioamnionitis (3% versus 2.7%), endometritis (5.3% versus 4.3%), and postpartum hemorrhage (1% versus 0.9%), compared to those assigned placebo. Neonates born to women assigned magnesium had similar mean Apgar scores at 1 and 5 minutes as those born to women assigned placebo (7.7 +/- 1.5 versus 7.8 +/- 1.6 and 8.7 +/- 0.7 versus 8.8 +/- 0.6, respectively). CONCLUSION: Magnesium sulfate does not have a major impact on disease progression in women with mild preeclampsia. Magnesium use does not seem to increase rates of cesarean delivery, infectious morbidity, obstetric hemorrhage, or neonatal depression.     

A systematic review of maternal and infant outcomes following magnesium sulfate for pre-eclampsia/eclampsia in real-world use

BackgroundEvidence from RCTs shows that magnesium sulfate reduces the risk of seizures and mortality for women with pre-eclampsia/eclampsia. However, it has been argued that outcomes within trials may not reflect real-world outcomes with the same intervention.ObjectiveTo assess whether outcomes for women with pre-eclampsia/eclampsia who received magnesium sulfate in the real world were comparable to those in RCTs.Search strategyEMBASE and MEDLINE were searched (January 1990–July 2010).Selection criteriaCohort, before-and-after, and serial cross-sectional studies were included. Participants were women with eclampsia who received magnesium sulfate or another anticonvulsant, and women with pre-eclampsia who received magnesium sulfate or no anticonvulsant. Primary outcomes were death (maternal, fetal, neonatal) or recurrent seizures.Data collection and analysisData were extracted independently by 2 reviewers.Main resultsSix studies (1831 women with eclampsia) were included, from academic centers in Bangladesh, India, Pakistan, and Nigeria, together with 2 population-based UK studies. Magnesium sulfate for eclampsia was associated with lower risks of maternal death, recurrent seizure, and major morbidity; for pre-eclampsia, it was associated with lower risks of eclampsia.ConclusionImprovements in maternal outcome with magnesium sulfate for pre-eclampsia/eclampsia in real-world use are comparable to those reported in RCTs.