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Evidence summaries

Magnesium Sulphate for Eclampsia and Pre-Eclampsia

Magnesium sulphate (Mg) is effective for eclampsia and pre-eclampsia. Level of evidence: "A"

A Cochrane review [Abstract] 1 included 7 trials involving 972 patients. Magnesium sulphate was associated with a substantial reduction in the recurrence of seizures when compared to phenytoin (OR 0.34, 95% CI 0.24 to 0.49; 6 studies, n=972). The trend in maternal mortality also favours magnesium sulphate, but this difference is not statistically significant (RR 0.50, 95% CI 0.24 to 1.05; 3 studies, n=847). There were reductions in the risk of pneumonia (RR 0.44, 95% CI 0.24 to 0.79; 1 study), ventilation (RR 0.68, 95% CI 0.50 to 0.91; 1 study) and admission to an intensive care unit (RR 0.67, 95% CI 0.50 to 0.89; 1 study) 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) (RR 0.73, 95% CI 0.58 to 0.91; 1 study, 518 babies) and fewer babies who died or were in SCBU for more than seven days (RR 0.77, 95% CI 0.63 to 0.95; 1 study, 643 babies) than phenytoin. There was no clear difference in perinatal deaths (RR 0.85, 95% CI 0.67 to 1.09; 2 studies, 665 babies).

Another Cochrane review on Mg versus lytic cocktail 2 (abstract , review [Abstract]) included 3 studies with a total of 397 subjects. Mg was better than lytic cocktail at preventing further seizures (RR 0.06, 95% CI 0.03 to 0.12; 3 studies, n=397; NNT 2, 95% CI 2 to 3) and was associated with fever maternal deaths (RR 0.14, 95% CI 0.03 to 0.59; 3 studies, n=397). Magnesium sulphate was also associated with less respiratory depression (RR 0.12, 95% CI 0.02 to 0.91; 2 studies, n=198), less coma (RR 0.04, 95% CI 0.00 to 0.74; 1 study,n=108), and less pneumonia (RR 0.20, 95% CI 0.06 to 0.67; 2 studies, n=307). There was no clear difference in the RR for any death of the baby (RR 0.35, 95% CI 0.05 to 2.38; 2 studies, 177 babies).

A third Cochrane review 3 (abstract , review [Abstract]) included 7 trials involving 1441 women. Most of the data were from trials of good quality; however, the allocated treatments could not be blinded after randomisation. Mg was associated with a reduction in maternal death when compared to diazepam (6 trials, n=1336; relative risk [RR] 0.59, 95% CI 0.37-0.94) and with a reduction in the risk recurrence of further fits (7 trials, n=1441; RR 0.44, 95% CI 0.34-0.57). There were few differences in any other measures of outcome, except for fewer Apgar scores less than seven at five minutes (2 trials, 597 babies; RR 0.72, 95% CI 0.55 to 0.94) and fewer babies with a length of stay in special care baby unit more than seven days (3 trials, 631 babies; RR 0.66, 95% CI 0.46 to 0.95) associated with Mg. There is no clear evidence of any other effects on maternal morbidity, or on perinatal morbidity or mortality.

Another Cochrane review [Abstract] 4 included 15 studies with a total of 15 892 subjects; 6 studies with a total of 11 444 women compared magnesium sulphate with placebo orno anticonvulsant. There was more than a halving in the risk of eclampsia associated with magnesiumsulphate (RR 0.41, 95% CI 0.29 to 0.58; NNT 100, 95% CI 50 to 100). The risk of dyingwas non-significantly reduced by 46% for women allocated magnesium sulphate (RR 0.54,95% CI 0.26 to 1.10). For serious maternal morbidity RR was 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; NNT 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 0.93to 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; NNTH 6, 95% CI 5 to 6). Follow-up was reported by one trial comparing magnesium sulphate with placebo: therewas no clear difference in death (RR 1.79, 95% CI 0.71 to 4.53; 3 375 women) or morbiditypotentially related to pre-eclampsia (RR 0.84, 95% CI 0.55 to 1.26) (median follow-up26 months). In children (n=3 283) exposed in utero there was no clear difference indeath (RR 1.02, 95% CI 0.57 to 1.84) or neurosensory disability (RR 0.77, 95% CI 0.38to 1.58) at age 18 months. Magnesium sulphate reduced eclampsia compared to phenytoin (RR 0.08, 95% CI 0.01 to0.60; 3 studies, n=2 291) and nimodipine (RR 0.33, 95% CI 0.14 to 0.77; 1 study, n=1 650).

A systematic review of non-randomized studies 5 assessed available data from non-randomized studies on the comparative efficacy and safety of alternative magnesium sulfate regimens to complement the evidence from the Cochrane review. 5 studies were included. Compared with standard regimens, lower-dose regimens appeared equally as good in terms of preventing seizures (OR 1.02, 95% CI 0.46 to 2.28; 4 studies, n=899), maternal morbidity (OR 0.47, 95%CI 0.32 to 0.71; 3 studies, n=796), and fetal and/or neonatal mortality (OR 0.87, 95%CI 0.38 to 2.00, 4 studies, n=800). Comparison of loading dose only with maintenance dose regimens showed no differences in seizure rates (OR 0.99, 95%CI 0.22 to 4.50; 2 studeis, n=146), maternal morbidity (OR 0.53, 95%CI 0.15 to 1.93; 2 studies, n=146), maternal mortality (OR 0.63, 95%CI 0.05 to 7.50; 2 studeis, n=146), and fetal and/or neonatal mortality (OR 0.49, 95%CI 0.23 to 1.03; 2 studeis, n=146).

    References

    • Duley L, Henderson-Smart DJ, Chou D. Magnesium sulphate versus phenytoin for eclampsia. Cochrane Database Syst Rev 2010;(10):CD000128. [PubMed].
    • Duley L, Gülmezoglu AM, Chou D. Magnesium sulphate versus lytic cocktail for eclampsia. Cochrane Database Syst Rev 2010;(9):CD002960. [PubMed].
    • Duley L, Henderson-Smart D. Magnesium sulphate versus diazepam for eclampsia. Cochrane Database Syst Rev 2003;(4):CD000127. [PubMed]
    • Duley L, Gülmezoglu AM, Henderson-Smart DJ et al. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev 2010;(11):CD000025. [PubMed]
    • Pratt JJ, Niedle PS, Vogel JP et al. Alternative regimens of magnesium sulfate for treatment of pr-eclampsia and eclampsia: a systematic review of non-randomized studies. Acta Obstet Gynecol Scand 2016;95(2):144-56. [PubMed]

Primary/Secondary Keywords