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Magnesium sulphate prevented eclampsia in women with pre-eclampsia
  1. Robert Burrows, MD
  1. Monash Medical Centre
 Clayton, Victoria, Australia

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 QUESTION: In women with pre-eclampsia, does magnesium sulphate reduce the risk of eclampsia and improve pregnancy outcome?

    Design

    Randomised (allocation concealed*), blinded (clinicians, patients, data collectors, and data analysts),* placebo controlled trial with follow up to discharge from hospital after delivery (MAGnesium sulphate for Prevention of Eclampsia [MAGPIE] Trial).

    Setting

    175 hospitals in 33 countries.

    Patients

    10 141 women who had not yet given birth or had delivered within <24 hours, had pre-eclampsia (diastolic blood pressure [BP] ≥90 mm Hg, systolic BP ≥140 mm Hg on ≥2 occasions, and proteinuria ≥1+), and clinical uncertainty existed about the use of magnesium sulphate. Exclusion criteria were hypersensitivity to magnesium, hepatic coma with risk of renal failure, or myasthenia gravis. 99.7% of women were included in the analysis.

    Intervention

    Women were allocated to magnesium sulphate (n=5071) or placebo (n=5070). Magnesium sulphate could be given intravenously (IV) or intramuscularly (IM). Standard treatment was a loading dose of 8 ml (4 g of magnesium sulphate) followed by 24 hour maintenance therapy of 2 ml/hour (IV) (1 g/hour magnesium sulphate or placebo) or two 10 ml IM injections (5 g magnesium sulphate or placebo) (1 into each buttock) and 10 ml every 4 hours. An eclampsia rescue pack was included in each treatment pack in case of eclamptic seizure.

    Main outcome measures

    Eclampsia and death of the baby before hospital discharge (including stillbirths). Secondary outcomes were maternal death and a composite outcome of serious maternal morbidities.

    Main results

    Analysis was by intention to treat. Fewer women who received magnesium sulphate had eclampsia than did women who received placebo (table). For the 8775 women who were randomised before delivery, the groups did not differ significantly for death of the infant (table). The groups did not differ for maternal death or serious maternal morbidities (table).

    Magnesium sulphate v placebo to prevent eclampsia†

    Conclusion

    In women with pre-eclampsia, magnesium sulphate reduced the risk of eclampsia, but did not significantly improve other pregnancy outcomes.

    Commentary

    In 1995, the Eclampsia trial1 showed that magnesium sulphate was superior to diazepam or phenytoin in reducing the prevalence of recurrent eclamptic seizures. This group of investigations and collaborators has now logically moved from treatment to prevention of the primary eclamptic episode. The MAGPIE trial showed that magnesium sulphate was effective regardless of severity of pre-eclampsia, gestational age at trial entry, or whether delivery had occurred. In the Magpie trial and the earlier Eclampsia trial, maternal mortality was reduced but failed to reach statistical significance; however, future meta-analysis will improve power in this regard. Neither study showed any effect on perinatal mortality.

    Magnesium sulphate was not effective in reducing the eclamptic rate in countries with a low perinatal mortality rate. It must be noted, however, that less severe cases were involved in these countries and the sample size was small.

    The safety of magnesium sulphate at the trial doses is now beyond dispute having been given in several healthcare situations to thousands of participants. Given its safety, effectiveness, and low cost, it is imperative that a concerted effort be made to educate healthcare workers and to make this intervention available to every facility caring for pregnant women. In areas where magnesium sulphate is already used extensively, investigators might want to adjust dosing schedules or run trials to determine if a different dose brings more benefit. One major question concerns the inclusion of participants receiving anticonvulsive interventions before randomisation (approximately 9%). These interventions were, however, equally distributed between magnesium sulphate and placebo groups. Magnesium sulphate showed no effect in this group of patients when analysed separately, but this lack of difference may be a factor of sample size rather than noneffectiveness or dampening effect of the loading dose of magnesium sulphate.

    References

    View Abstract

    Footnotes

    • Sources of funding: UK Medical Research Council; UK Department for International Development; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction.

    • For correspondence: Dr L Duley, Resource Centre for Randomised Trials, Oxford, UK. lelia.duley{at}ndm.ox.ac.uk

    • * See glossary.

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