Magnesium sulfate and other anticonvulsants for women with pre-eclampsia
Magnesium sulfate more than halves the risk of eclampsia, and probably reduces the risk of maternal death. A quarter of women have side-effects, notably flushing. The lack of clarity on what constitutes severe pre-eclampsia may render this intervention difficult to implement. Women at low risk of pre-eclampsia may not be suitable candidates for treatment with magnesium sulfate.
RHL Commentary by Khan KS
1. EVIDENCE SUMMARY
This review compares the effectiveness of magnesium sulfate with other anticonvulsants among women with pre-eclampsia. There is clear evidence in favour of magnesium sulfate as it reduces the risk of eclampsia and that of maternal mortality, though the latter effect did not reach the conventional 5% level of statistical significance. The severity of pre-eclampsia where anticonvulsant treatment in this heterogeneous condition is warranted is not clear.
This review seems to be methodologically sound. However, the use of summary Number-Needed-to Treat statistic (NNT) is too simplistic. Pre-eclampsia is a heterogeneous condition with substantially different baseline risks of eclampsia in various subgroups of pregnant women (1). Hence, calculating average NNTs from pooled meta-analysis results can be seriously misleading (2). This is because NNTs are sensitive to changing baseline risk (3). The lower the risk, the higher the NNT, and the lower the expectation of benefit from anticonvulsant therapy. Conversely, the higher the baseline risk, the lower the NNT, and the higher the expectation of benefit and the more inclined the health care workers would be to recommend, and women to accept, anticonvulsant therapy. Therefore, in order to apply the results of the systematic review we require information about the benefit tailored according to variations in baseline risks, (4, 5, 6) and not average NNTs across all risk groups as reported in this review (see applicability of the results below).
2. RELEVANCE TO UNDER-RESOURCED SETTINGS
2.1. Magnitude of the problem
Women with pre-eclampsia in under-resourced settings are at a higher risk of developing convulsions (eclampsia) and dying from it. The incidence of eclampsia in pregnant women is not well established in developing countries, but it is estimated to be one case in 100–1700 women (7, 8, 9, 10). Among women with severe pre-eclampsia, one or two cases of eclampsia are expected in every 100 cases.
2.2. Applicability of the results
This systematic review’s average relative effect size can be used to compute NNTs, comparing magnesium sulfate with no anticonvulsant or placebo, among various subgroups of pre-eclampsia. If it is assumed that the baseline incidence of eclampsia in women with mild pre-eclampsia is one in 1000, then the NNT to prevent one case of eclampsia would be 1695 (95% confidence interval [CI]: 1409–2382). On the other hand, if it is assumed that the baseline incidence of eclampsia in women with severe pre-eclampsia is one in 50 women then the NNT to prevent one case of eclampsia would be 85 (95% CI: 71–120). Appreciation of this difference is critical in making decisions about use magnesium sulfate in pre-eclampsia to prevent eclampsia.
2.3. Implementation of the intervention
It would be feasible to implement the intervention to treat women with pre-eclampsia with magnesium sulfate. The difficulty lies in finding a way to define the severity of pre-eclampsia. Low-risk cases, considering the high NNT, may not be suitable candidates for treatment with magnesium sulfate but currently there are no clear definitions.
In settings, where magnesium sulfate is not readily available, additional efforts at the policy level may be required to obtain supplies of this essential drug.
3. RESEARCH
Research is needed to identify which women with pre-eclampsia are likely to benefit from the use of magnesium sulfate for the prevention of eclampsia.
References
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- Smeeth L, Haines A, Ebrahim S. Numbers needed to treat derived from meta-analyses—sometimes informative, usually misleading. BMJ 1999;318:1548–1551.
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- Rothwell PM. Can overall results of clinical trials be applied to all patients. The lancet 1995;345:1616–1619.
- Smith GD, Egger M. Who benefits from medical interventions. BMJ 1994;308:72-74.
- Bianchi LR, Navarrete AI, Ortega I, Eckolt E, Caroca A, Sandoval L, Vargas E, Palavecino L, Toro C. Estudio Clinico de la eclampsia. Revista Chilena de obstetricia y ginecologia 1998;53:128-133.
- Castro MA. La eclampsia en el Hospital de Maternidade Rafael Calvo. Revista Colombiana obstetricia y ginecologia 1989;40:235-244.
- World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy. Geographic variation in the incidence of hypertension in pregnancy. American journal of obstetrics and gynecology 1988;158:80-83.
- Bergstroem S, Povey G, Songane F, Ching C. Seasonal incidence of eclampsia and its relationship to meteorological data in Mozambique. Journal of perinatal medicine 1992;20:153-158.
This document should be cited as: Khan KS. Magnesium sulfate and other anticonvulsants for women with pre-eclampsia: RHL commentary (last revised: 8 September 2003). The WHO Reproductive Health Library; Geneva: World Health Organization.