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Meta-Analysis
. 2010 Nov 10;2010(11):CD000025.
doi: 10.1002/14651858.CD000025.pub2.

Magnesium sulphate and other anticonvulsants for women with pre-eclampsia

Lelia Duley  1 , A Metin Gülmezoglu, David J Henderson-Smart, Doris Chou
Affiliations
Meta-Analysis

Magnesium sulphate and other anticonvulsants for women with pre-eclampsia

Lelia Duley et al. Cochrane Database Syst Rev. .

Abstract

Background: Eclampsia, 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.

Objectives: To assess the effects of magnesium sulphate, and other anticonvulsants, for prevention of eclampsia.

Search strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (4 June 2010), and the Cochrane Central Register of Controlled Trials Register (The Cochrane Library 2010, Issue 3).

Selection criteria: Randomised trials comparing anticonvulsants with placebo or no anticonvulsant, or comparisons of different drugs, for pre-eclampsia.

Data collection and analysis: Two authors assessed trial quality and extracted data independently.

Main results: We 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).

Authors' conclusions: Magnesium 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.

PubMed Disclaimer

Conflict of interest statement

Lelia Duley is a principal investigator for the Magpie Trial, which compared magnesium sulphate with placebo and was, therefore, not involved in the assessment or data extraction of this trial.

Figures

1.1
1.1. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 1 Maternal death.
1.2
1.2. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 2 Eclampsia.
1.3
1.3. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 3 Serious maternal morbidity.
1.4
1.4. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 4 Stroke.
1.5
1.5. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 5 Pulmonary oedema.
1.6
1.6. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 6 Pneumonia.
1.7
1.7. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 7 Renal failure.
1.8
1.8. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 8 Renal dialysis.
1.9
1.9. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 9 Liver failure.
1.10
1.10. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 10 Coagulopathy.
1.11
1.11. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 11 Cardiac arrest.
1.12
1.12. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 12 Respiratory arrest.
1.13
1.13. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 13 Any antihypertensive therapy.
1.14
1.14. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 14 Rapid acting antihypertensives.
1.15
1.15. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 15 Progression from mild to severe pre‐eclampsia.
1.16
1.16. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 16 Toxicity.
1.17
1.17. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 17 Given calcium gluconate.
1.18
1.18. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 18 Side effects.
1.19
1.19. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 19 Problems at injection site.
1.20
1.20. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 20 Placental abruption.
1.21
1.21. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 21 Caesarean section.
1.22
1.22. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 22 Induction of labour.
1.23
1.23. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 23 Postpartum haemorrhage.
1.24
1.24. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 24 Manual removal of retained placenta.
1.25
1.25. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 25 In special care baby unit > 7 days.
1.26
1.26. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 26 Outcome for the women 2 years after the birth.
1.27
1.27. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 27 Stillbirths and neonatal deaths.
1.28
1.28. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 28 Mortality for the fetus or infant (by time of death).
1.29
1.29. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 29 Death or in special care baby unit > 7 days.
1.30
1.30. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 30 Apgar score < 7 at 5 minutes.
1.31
1.31. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 31 Intubated at place of birth.
1.32
1.32. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 32 Admission to special care baby unit.
1.33
1.33. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 33 Blood transfusion.
1.34
1.34. Analysis
Comparison 1 Magnesium sulphate versus none/placebo (subgroups by severity of pre‐eclampsia), Outcome 34 Outcome for the children at 18 months (corrected for gestation at birth).
2.1
2.1. Analysis
Comparison 2 Magnesium sulphate versus none/placebo (subgroups by whether delivered at trial entry), Outcome 1 Maternal death.
2.2
2.2. Analysis
Comparison 2 Magnesium sulphate versus none/placebo (subgroups by whether delivered at trial entry), Outcome 2 Eclampsia.
2.3
2.3. Analysis
Comparison 2 Magnesium sulphate versus none/placebo (subgroups by whether delivered at trial entry), Outcome 3 Serious maternal morbidity.
3.1
3.1. Analysis
Comparison 3 Magnesium sulphate versus none/placebo (subgroups by gestation at trial entry), Outcome 1 Maternal death.
3.2
3.2. Analysis
Comparison 3 Magnesium sulphate versus none/placebo (subgroups by gestation at trial entry), Outcome 2 Eclampsia.
3.3
3.3. Analysis
Comparison 3 Magnesium sulphate versus none/placebo (subgroups by gestation at trial entry), Outcome 3 Serious maternal morbidity.
3.4
3.4. Analysis
Comparison 3 Magnesium sulphate versus none/placebo (subgroups by gestation at trial entry), Outcome 4 Stillbirths and neonatal deaths.
3.5
3.5. Analysis
Comparison 3 Magnesium sulphate versus none/placebo (subgroups by gestation at trial entry), Outcome 5 Death or in special care baby unit > 7 days.
4.1
4.1. Analysis
Comparison 4 Magnesium sulphate versus none/placebo (subgroups by whether anticonvulsant before trial entry), Outcome 1 Maternal death.
4.2
4.2. Analysis
Comparison 4 Magnesium sulphate versus none/placebo (subgroups by whether anticonvulsant before trial entry), Outcome 2 Eclampsia.
4.3
4.3. Analysis
Comparison 4 Magnesium sulphate versus none/placebo (subgroups by whether anticonvulsant before trial entry), Outcome 3 Serious maternal morbidity.
4.4
4.4. Analysis
Comparison 4 Magnesium sulphate versus none/placebo (subgroups by whether anticonvulsant before trial entry), Outcome 4 Stillbirths and neonatal deaths.
4.5
4.5. Analysis
Comparison 4 Magnesium sulphate versus none/placebo (subgroups by whether anticonvulsant before trial entry), Outcome 5 Death or in special care baby unit > 7 days.
5.1
5.1. Analysis
Comparison 5 Magnesium sulphate versus none/placebo (subgroups by dose and route of administration for maintenance therapy), Outcome 1 Maternal death.
5.2
5.2. Analysis
Comparison 5 Magnesium sulphate versus none/placebo (subgroups by dose and route of administration for maintenance therapy), Outcome 2 Eclampsia.
5.3
5.3. Analysis
Comparison 5 Magnesium sulphate versus none/placebo (subgroups by dose and route of administration for maintenance therapy), Outcome 3 Stillbirths and neonatal deaths.
5.4
5.4. Analysis
Comparison 5 Magnesium sulphate versus none/placebo (subgroups by dose and route of administration for maintenance therapy), Outcome 4 Any reported side effects.
6.1
6.1. Analysis
Comparison 6 Magnesium sulphate versus phenytoin, Outcome 1 Eclampsia.
6.2
6.2. Analysis
Comparison 6 Magnesium sulphate versus phenytoin, Outcome 2 Complications of labour.
6.3
6.3. Analysis
Comparison 6 Magnesium sulphate versus phenytoin, Outcome 3 Caesarean section.
6.4
6.4. Analysis
Comparison 6 Magnesium sulphate versus phenytoin, Outcome 4 Mortality for the fetus or infant (by time of death).
6.5
6.5. Analysis
Comparison 6 Magnesium sulphate versus phenytoin, Outcome 5 Infant morbidity.
7.1
7.1. Analysis
Comparison 7 Magnesium sulphate versus diazepam, Outcome 1 Eclampsia.
7.2
7.2. Analysis
Comparison 7 Magnesium sulphate versus diazepam, Outcome 2 Caesarean section.
7.3
7.3. Analysis
Comparison 7 Magnesium sulphate versus diazepam, Outcome 3 Stillbirths and neonatal deaths.
8.1
8.1. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 1 Eclampsia.
8.2
8.2. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 2 Stroke.
8.3
8.3. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 3 Coagulopathy.
8.4
8.4. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 4 Respiratory problems.
8.5
8.5. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 5 Cardiac failure.
8.6
8.6. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 6 Respiratory depression.
8.7
8.7. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 7 Antihypertensive drug.
8.8
8.8. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 8 Oliguria.
8.9
8.9. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 9 Side effects.
8.10
8.10. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 10 Placental abruption.
8.11
8.11. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 11 Caesarean section.
8.12
8.12. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 12 Postpartum haemorrhage.
8.13
8.13. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 13 Respiratory distress syndrome.
8.14
8.14. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 14 Neonatal hypotonia.
8.15
8.15. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 15 Baby intubated.
8.16
8.16. Analysis
Comparison 8 Magnesium sulphate versus nimodipine, Outcome 16 Neonatal hypotension.
9.1
9.1. Analysis
Comparison 9 Magnesium chloride versus methyl dopa, Outcome 1 Other antihypertensive therapy.
9.2
9.2. Analysis
Comparison 9 Magnesium chloride versus methyl dopa, Outcome 2 Admission to special care baby unit.
10.1
10.1. Analysis
Comparison 10 Magnesium sulphate versus nitrate, Outcome 1 Eclampsia.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Mexico 1992 {published data only}
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South Africa 1998 {published data only}
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Taiwan 1995 {published data only}
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USA ‐ Alabama 1995 {published data only}
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USA ‐ Maryland 1993 {published data only}
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USA ‐ Memphis 1997 {published data only}
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USA ‐ Tennessee 2001 {published data only}
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References to studies excluded from this review

Abbade 2006 {published data only}
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Antartani 2006 {published data only}
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Begum 2002 {published data only}
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China 2000 {published data only}
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Chissell 1994 {published data only}
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Chowdhury 2009 {published data only}
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Ehrenberg 2006 {published data only}
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Fontenot 2005 {published data only}
    1. Fontenot MT, Lewis DF, Frederick JB, Wang Y, DeFranco EA, Groome LJ, et al. A prospective randomized trial of magnesium sulfate in severe preeclampsia: use of diuresis as a clinical parameter to determine the duration of postpartum therapy. American Journal of Obstetrics and Gynecology 2005;192:1788‐94. - PubMed
Ghahiri 2005 {published data only}
    1. Ghahiri A, Berjis K. A comparison between intravenous magnesium sulfate and oral magnesium chloride in mild preeclampsia. Journal of Research in Medical Sciences 2005;10(1):6‐9.
Hangarga 2001 {published data only}
    1. Hangarga US, Pragya S. A comparative study of phenytoin sodium with magnesium sulphate and Menon's regime in the treatment of eclampsia. Journal of Obstetrics and Gynecology of India 2001;51(3):68‐70.
Laiteerapong 1999 {published data only}
    1. Laiteerapong U, Leelahakorn S. Comparative study of serum magnesium levels attained from magnesium sulfate therapy for severe pre‐eclamptic patients between 1 gm/hr and 2 gm/hr regimen. Thai Journal of Obstetrics and Gynaecology 1999;11(4):281.
Li 1998 {published data only}
    1. Li M, Yang M, Qiu X. The effect of nimodipine on retinal blood flow in pregnancy induced hypertension. Zhonghua Fu Chan Ke Za Zh 1998; Vol. 33, issue 7:397‐9. - PubMed
Maheshwari 1989 {published data only}
    1. Maheshwari JR, Desai SV, Hansotia MD, Walvekar VR. Anti‐convulsant therapy in eclampsia. Journal of Postgraduate Medicine 1989;35(2):66‐9. - PubMed
Muhammad 2009 {published data only}
    1. Muhammad A, Ibrahim U, Nighat K, Muhammad Y, Abdullahi A. Low dose magnesium sulfate in the control of eclamptic fits: a randomized control trial. International Journal of Gynecology & Obstetrics 2009;107(Suppl 2):S277‐8.
Mundle 2009 {published data only}
    1. Mundle S, Regi A, Biswas B, Bracken H, Easterling T, Winikoff B. Preeclampsia in low‐resource settings: a randomized trial of IV MgSO4 via flow controlled pump. International Journal of Gynecology & Obstetrics 2009;107(Suppl 2):S278.
Nagar 1988 {published data only}
    1. Nagar S, Jain S, Kumari S, Ahuja L. Reassessment of therapy of eclampsia: comparison of mortality and morbidity of mother and fetus with parenteral magnesium sulphate and lytic cocktail therapy. Journal of Obstetrics and Gynaecology of India 1988;38(3):250‐5.
Neto 2000 {published data only}
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Ola 2004 {published data only}
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References to ongoing studies

USA ‐ Utah {published data only}
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References to other published versions of this review

Duley 2003
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