Lelia Duley

The global impact of pre-eclampsia and eclampsia.

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.

Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: A randomised placebo-controlled trial

BACKGROUNDnAnticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate.nnnMETHODSnEligible women (n=10141) had not given birth or were 24 h or less postpartum; blood pressure of 140/90 mm Hg or more, and proteinuria of 1+ (30 mg/dL) or more; and there was clinical uncertainty about magnesium sulphate. Women were randomised in 33 countries to either magnesium sulphate (n=5071) or placebo (n=5070). Primary outcomes were eclampsia and, for women randomised before delivery, death of the baby. Follow up was until discharge from hospital after delivery. Analyses were by intention to treat.nnnFINDINGSnFollow-up data were available for 10,110 (99.7%) women, 9992 (99%) of whom received the allocated treatment. 1201 of 4999 (24%) women given magnesium sulphate reported side-effects versus 228 of 4993 (5%) given placebo. Women allocated magnesium sulphate had a 58% lower risk of eclampsia (95% CI 40-71) than those allocated placebo (40, 0.8%, vs 96, 1.9%; 11 fewer women with eclampsia per 1000 women). Maternal mortality was also lower among women allocated magnesium sulphate (relative risk 0.55, 0.26-1.14). For women randomised before delivery, there was no clear difference in the risk of the baby dying (576, 12.7%, vs 558, 12.4%; relative risk 1.02, 99% CI 0.92-1.14). The only notable difference in maternal or neonatal morbidity was for placental abruption (relative risk 0.67, 99% CI 0.45-0.89).nnnINTERPRETATIONnMagnesium sulphate halves the risk of eclampsia, and probably reduces the risk of maternal death. There do not appear to be substantive harmful effects to mother or baby in the short term.ARTICLES Summary Background Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate.

Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data

BACKGROUNDnPre-eclampsia is a major cause of mortality and morbidity during pregnancy and childbirth. Antiplatelet agents, especially low-dose aspirin, might prevent or delay pre-eclampsia, and thereby improve outcome. Our aim was to assess the use of antiplatelet agents for the primary prevention of pre-eclampsia, and to explore which women are likely to benefit most.nnnMETHODSnWe did a meta-analysis of individual patient data from 32,217 women, and their 32,819 babies, recruited to 31 randomised trials of pre-eclampsia primary prevention.nnnFINDINGSnFor women assigned to receive antiplatelet agents rather than control, the relative risk of developing pre-eclampsia was 0.90 (95% CI 0.84-0.97), of delivering before 34 weeks was 0.90 (0.83-0.98), and of having a pregnancy with a serious adverse outcome was 0.90 (0.85-0.96). Antiplatelet agents had no significant effect on the risk of death of the fetus or baby, having a small for gestational age infant, or bleeding events for either the women or their babies. No particular subgroup of women was substantially more or less likely to benefit from antiplatelet agents than any other.nnnINTERPRETATIONnAntiplatelet agents during pregnancy are associated with moderate but consistent reductions in the relative risk of pre-eclampsia, of birth before 34 weeks gestation, and of having a pregnancy with a serious adverse outcome.

Magnesium sulphate and other anticonvulsants for women with pre‐eclampsia

BACKGROUNDnEclampsia, the occurrence of a seizure (fit) in association with pre-eclampsia, is rare but potentially life-threatening. Magnesium sulphate is the drug of choice for treating eclampsia. This review assesses its use for preventing eclampsia.nnnOBJECTIVESnTo assess the effects of magnesium sulphate, and other anticonvulsants, for prevention of eclampsia.nnnSEARCH STRATEGYnWe searched the Cochrane Pregnancy and Childbirth Groups Trials Register (4 June 2010), and the Cochrane Central Register of Controlled Trials Register (The Cochrane Library 2010, Issue 3).nnnSELECTION CRITERIAnRandomised trials comparing anticonvulsants with placebo or no anticonvulsant, or comparisons of different drugs, for pre-eclampsia.nnnDATA COLLECTION AND ANALYSISnTwo authors assessed trial quality and extracted data independently.nnnMAIN RESULTSnWe included 15 trials. Six (11,444 women) compared magnesium sulphate with placebo or no anticonvulsant: magnesium sulphate more than a halved the risk of eclampsia (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.29 to 0.58; number needed to treat for an additional beneficial outcome (NNTB) 100, 95% CI 50 to 100), with a non-significant reduction in maternal death (RR 0.54, 95% CI 0.26 to 1.10) but no clear difference in serious maternal morbidity (RR 1.08, 95% CI 0.89 to 1.32). It reduced the risk of placental abruption (RR 0.64, 95% CI 0.50 to 0.83; NNTB 100, 95% CI 50 to 1000), and increased caesarean section (RR 1.05, 95% CI 1.01 to 1.10). There was no clear difference in stillbirth or neonatal death (RR 1.04, 95% CI 0.93 to 1.15). Side effects, primarily flushing, were more common with magnesium sulphate (24% versus 5%; RR 5.26, 95% CI 4.59 to 6.03; number need to treat for an additional harmful outcome (NNTH) 6, 95% CI 5 to 6).Follow-up was reported by one trial comparing magnesium sulphate with placebo: for 3375 women there was no clear difference in death (RR 1.79, 95% CI 0.71 to 4.53) or morbidity potentially related to pre-eclampsia (RR 0.84, 95% CI 0.55 to 1.26) (median follow-up 26 months); for 3283 children exposed in utero there was no clear difference in death (RR 1.02, 95% CI 0.57 to 1.84) or neurosensory disability (RR 0.77, 95% CI 0.38 to 1.58) at age 18 months.Magnesium sulphate reduced eclampsia compared to phenytoin (three trials, 2291 women; RR 0.08, 95% CI 0.01 to 0.60) and nimodipine (one trial, 1650 women; RR 0.33, 95% CI 0.14 to 0.77).nnnAUTHORS CONCLUSIONSnMagnesium sulphate more than halves the risk of eclampsia, and probably reduces maternal death. There is no clear effect on outcome after discharge from hospital. A quarter of women report side effects with magnesium sulphate.

Magnesium sulphate versus diazepam for eclampsia

BACKGROUNDnEclampsia, the occurrence of a seizure in association with pre-eclampsia, remains a rare but serious complication of pregnancy. A number of different anticonvulsants are used to control eclamptic fits and to prevent further fits.nnnOBJECTIVESnThe objective of this review was to assess the effects of magnesium sulphate compared with diazepam when used for the care of women with eclampsia. Magnesium sulphate is compared with phenytoin and with lytic cocktail in other Cochrane reviews.nnnSEARCH STRATEGYnWe searched the Cochrane Pregnancy and Childbirth Groups Trials Register (30 September 2010) and CENTRAL (2010, Issue 3).nnnSELECTION CRITERIAnRandomised trials comparing magnesium sulphate (intravenous or intramuscular administration) with diazepam for women with a clinical diagnosis of eclampsia.nnnDATA COLLECTION AND ANALYSISnTwo authors assessed and extracted data independently.nnnMAIN RESULTSnWe have included seven trials, involving 1396 women. Three trials (1030 women) were good quality. Magnesium sulphate was associated with a reduction in maternal death (seven trials;1396 women; risk ratio (RR) 0.59, 95% confidence interval (CI) 0.38 to 0.92) and recurrence of seizures (seven trials;1390 women; RR 0.43, 95% CI 0.33 to 0.55) compared to diazepam. There were no clear differences in other measures of maternal morbidity.There was no clear difference in perinatal mortality (four trials; 788 infants; RR 1.04, 95% CI 0.81 to 1.34) or neonatal mortality (four trials; 759 infants; RR 1.18, 95% CI 0.75 to 1.84). In the magnesium sulphate group, fewer liveborn babies had an Apgar score less than seven at one minute (two trials; 597 babies; RR 0.75, 95% CI 0.65 to 0.87) or at five minutes (RR 0.70, 95% CI 0.54 to 0.90), and fewer appeared to need intubation at the place of birth (two trials; 591 infants; RR 0.67, 95% CI 0.45 to 1.00). There was no difference in admission to a special care nursery (four trials; 834 infants; RR 0.91, 95% CI 0.79 to 1.05), but fewer babies in the magnesium sulphate group had a length of stay more than seven days (three trials 631 babies; RR 0.66, 95% CI 0.46 to 0.96).nnnAUTHORS CONCLUSIONSnMagnesium sulphate for women with eclampsia reduces the risk ratio of maternal death and of recurrence of seizures, compared with diazepam.

Magnesium sulphate versus phenytoin for eclampsia

BACKGROUNDnEclampsia, the occurrence of a seizure in association with pre-eclampsia, remains a rare but serious complication of pregnancy. A number of different anticonvulsants have been used to control eclamptic fits and to prevent further seizures.nnnOBJECTIVESnThe objective of this review was to assess the effects of magnesium sulphate compared with phenytoin when used for the care of women with eclampsia. Magnesium sulphate is compared with diazepam and with lytic cocktail in other Cochrane reviews.nnnSEARCH STRATEGYnWe searched the Cochrane Pregnancy and Childbirth Groups Trials Register (30 April 2010).nnnSELECTION CRITERIAnRandomised trials comparing magnesium sulphate (intravenous or intramuscular administration) with phenytoin for women with a clinical diagnosis of eclampsia.nnnDATA COLLECTION AND ANALYSISnTwo review authors assessed trial quality and extracted data.nnnMAIN RESULTSnWe have included data from seven trials, involving 972 women. One large trial (775 women) was of good quality. Magnesium sulphate was associated with a substantial reduction in the recurrence of seizures, when compared to phenytoin (six trials, 972 women; risk ratio (RR) 0.34, 95% confidence interval (CI) 0.24 to 0.49). The trend in maternal mortality favours magnesium sulphate, but the difference does not reach statistical significance (three trials, 847 women; RR 0.50, 95% CI 0.24 to 1.05). There were reductions in the risk of pneumonia (one trial, RR 0.44, 95% CI 0.24 to 0.79), ventilation (one trial, RR 0.68, 95% CI 0.50 to 0.91) and admission to an intensive care unit (one trial, RR 0.67, 95% CI 0.50 to 0.89) associated with the use of magnesium sulphate rather than phenytoin.For the baby, magnesium sulphate was associated with fewer admissions to a special care baby unit (SCBU) (one trial, 518 babies; RR 0.73, 95% CI 0.58 to 0.91) and fewer babies who died or were in SCBU for more than seven days (one trial, 643 babies; RR 0.77, 95% CI 0.63 to 0.95) than phenytoin. There was no clear difference in perinatal deaths (two trials, 665 babies; (RR 0.85, 95% CI 0.67 to 1.09).nnnAUTHORS CONCLUSIONSnMagnesium sulphate, rather than phenytoin, for women with eclampsia reduces the risk ratio of recurrence of seizures, probably reduces the risk of maternal death, and improves outcome for the baby. Magnesium sulphate is the drug of choice for women with eclampsia. The use of phenytoin should be abandoned.

Dietary calcium supplementation for prevention of pre-eclampsia and related problems: a systematic review and commentary

Backgroundu2002 Calcium supplementation during pregnancy may reduce the risk of hypertensive disorders of pregnancy.

Management of pre-eclampsia.

Pre-eclampsia is part of a spectrum of conditions known as the hypertensive disorders of pregnancy (box 1).1 A multisystem disorder usually associated with raised blood pressure and proteinuria, pre-eclampsia is relatively common, affecting 2-8% of pregnancies. Although outcome is often good, pre-eclampsia can be devastating and life threatening for both mother and baby (box 2), particularly in developing countries.2 It may also lead to an increased risk of cardiovascular disease in later life.nnAlthough the cause is not fully understood, factors thought to have a role include genes, the placenta, the immune response, and maternal vascular disease.3 Inadequate blood supply to the placenta leads to endothelial dysfunction, which accounts for the secondary changes in maternal target systems (such as platelet aggregation and vasoconstriction) responsible for the signs and symptoms of pre-eclampsia (box 3).nnEffective care includes identification and referral of women at high risk, prompt diagnosis with prevention and treatment of complications, and timely delivery (the only definitive cure). This review summarises current evidence on management of pre-eclampsia.nnWe searched The Cochrane Database of Systematic Reviews , the trials register of the Cochrane Pregnancy and Childbirth Group, CENTRAL and EMBASE for systematic reviews and randomised trials. Searches were updated in November 2005. Details of the search strategy are summarised on bmj.com. We also identified systematic reviews of studies assessing risk factors for pre-eclampsia. References for trials and reviews are on bmj.com.w1-w28nnAssessment usually begins when a woman presents to a general practitioner or midwife requesting antenatal care (box 4). Women at high risk are then offered further visits and testing, with referral for specialist care.4 Screening of low risk women is based primarily on blood pressure measurement and urine analysis. The search for additional tests continues.5 Despite initial optimism for uterine artery …

Methodological and technical issues related to the diagnosis, screening, prevention, and treatment of pre-eclampsia and eclampsia

In contrast with advances made in treating or eliminating many other serious disorders, severe morbidity and mortality associated with pre‐eclampsia/eclampsia remain among the leading problems that threaten safe motherhood, particularly in developing countries. This article reviews technical issues related to diagnosis, screening, prevention, and treatment of pre‐eclampsia and identifies corresponding needs. The authors stress the lack of standardized definitions of pre‐eclampsia and eclampsia and discuss problems in blood‐pressure measurements and assessment of urinary protein. They summarize the evidence for prevention strategies and screening tests for early detection. For treatment, magnesium sulfate has been proven effective, but not widely used. The authors outline priorities for narrowing the identified gaps and emphasize the need for coordinated efforts to reduce the morbidity and mortality due to pre‐eclampsia/eclampsia. They conclude that the mystery of this disease must be resolved to achieve primary prevention of it.

Exercise or other physical activity for preventing pre‐eclampsia and its complications

BACKGROUNDnThe association between an increase in regular physical activity and a reduction in the risk of hypertension is well documented for non-pregnant people. It has been suggested that exercise may help prevent pre-eclampsia and its complications. Possible adverse effects of increased physical activity during pregnancy, particularly on the risk of preterm birth and fetal growth restriction, are unclear. It is, therefore, important to assess whether exercise reduces the risk of pre-eclampsia and its complications and, if so, whether these benefits outweigh the risks.nnnOBJECTIVESnTo assess the effects of exercise, or increased physical activity, on prevention of pre-eclampsia and its complications.nnnSEARCH STRATEGYnWe searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 1), and EMBASE (2002 to February 2005).nnnSELECTION CRITERIAnStudies were included if these were randomised trials evaluating the effects of exercise or increased physical activity during pregnancy for women at risk of pre-eclampsia.nnnDATA COLLECTION AND ANALYSISnTwo review authors independently selected trials for inclusion and extracted data. Data were entered on Review Manager software for analysis, and double checked for accuracy.nnnMAIN RESULTSnTwo small, good quality trials (45 women) were included. Both compared moderate intensity regular aerobic exercise with maintenance of normal physical activity during pregnancy. The confidence intervals were wide and crossed the line of no effect for all reported outcomes including pre-eclampsia (relative risk 0.31, 95% confidence interval 0.01 to 7.09).nnnAUTHORS CONCLUSIONSnThere is insufficient evidence for reliable conclusions about the effects of exercise on prevention of pre-eclampsia and its complications.