Key messages
Magnesium sulphate has previously been shown to be effective in treating and preventing eclampsia (fits or seizures that occur during or after the baby is born when the woman has raised blood pressure and protein in the urine).
Magnesium sulphate might cause undesirable effects in the woman or the baby (e.g. breathing problems).
It remains unclear what the best dose is and how best to give it.
What is pre-eclampsia and eclampsia?
Pre-eclampsia (or toxaemia) is a condition that is usually associated with raised blood pressure (hypertension) and protein in the urine. It can occur at any time during the second half of pregnancy or in the first few weeks after delivery. Consequences of severe pre-eclampsia include maternal fits (eclampsia), problems with the mother's liver and kidneys, death of the baby, and placental abruption (separation of the placenta from the uterine wall before birth of the baby).
Why is this is important for women with pre-eclampsia and eclampsia?
Magnesium sulphate is effective in preventing eclampsia in women who have pre-eclampsia and in treating women who experience an eclamptic convulsion to avoid severe maternal/infant illnesses and death. However, magnesium sulphate may cause undesirable effects (difficulties in breathing; a reduction in the amount of urine, which could damage the kidneys) in high doses and may need to be administered by experienced personnel.
What did we want to find out?
We wanted to find out if one way of administering magnesium sulphate (amount of drug; how and where to apply the drug, e.g. in the buttock, thigh, in the veins; and duration of administration) is better than another.
What did we do?
We searched for studies that looked at different ways of administering magnesium sulphate (amount of drug, method used to deliver the drug, and duration of administration). We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We searched for studies up to April 2022. We included 16 trials (3020 women): four trials (409 women) recruited women with eclampsia, and 12 trials (2611 women) recruited women with pre-eclampsia. Studies were carried out mostly in low- and middle-income countries.
In women with eclampsia: we are not confident in the evidence comparing the administration of lower doses or shorter regimens of magnesium sulphate versus a standard regimen because the studies were too small to show any difference, and it is possible that the people involved were aware of which treatment they were getting, which could have led to bias. The administration of magnesium sulphate in a shorter time than the usual 24 hours may lower the risk of flushing (red face); however, we have low confidence in this result because the study was too small.
In women with pre-eclampsia: we are uncertain if administering magnesium sulphate in a shorter time than usual or in lower doses makes any difference to the risk of the women having fits, severe illnesses, or unwanted effects because the studies were too small. Also we are not confident that the way of administering the drug results in any benefit or harm because the studies were too small to show any difference, and it is possible that the people involved were aware of which treatment they were getting.
What are the limitations of the evidence?
Three main factors reduced our confidence in the evidence. Firstly, people in many studies were aware of which treatment they were getting, which could have led to bias; however, this would be very difficult to prevent in future studies due to the characteristics of the intervention. Secondly, some of the studies provided little information on how they were done. Finally, some studies were very small. The results of further research could differ from the results of this review.
How up-to-date is this evidence?
The evidence is current to 29 April 2022.
Despite the number of trials evaluating various magnesium sulphate regimens for eclampsia prophylaxis and treatment, there is still no compelling evidence that one particular regimen is more effective than another. Well-designed randomised controlled trials are needed to answer this question.
Magnesium sulphate is the drug of choice for the prevention and treatment of women with eclampsia. Regimens for administration of this drug have evolved over the years, but there is no clarity on the comparative benefits or harm of alternative regimens. This is an update of a review first published in 2010.
To assess if one magnesium sulphate regimen is better than another when used for the care of women with pre-eclampsia or eclampsia, or both, to reduce the risk of severe morbidity and mortality for the woman and her baby.
We searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (29 April 2022), and reference lists of retrieved studies.
We included randomised trials and cluster-randomised trials comparing different regimens for administration of magnesium sulphate used in women with pre-eclampsia or eclampsia, or both. Comparisons included different dose regimens, intramuscular versus intravenous route for maintenance therapy, and different durations of therapy. We excluded studies with quasi-random or cross-over designs. We included abstracts of conference proceedings if compliant with the trustworthiness assessment.
For this update, two review authors assessed trials for inclusion, performed risk of bias assessment, and extracted data. We checked data for accuracy. We assessed the certainty of the evidence using the GRADE approach.
For this update, a total of 16 trials (3020 women) met our inclusion criteria: four trials (409 women) compared regimens for women with eclampsia, and 12 trials (2611 women) compared regimens for women with pre-eclampsia. Most of the included trials had small sample sizes and were conducted in low- and middle-income countries. Eleven trials reported adequate randomisation and allocation concealment. Blinding of participants and clinicians was not possible in most trials. The included studies were for the most part at low risk of attrition and reporting bias.
Treatment of women with eclampsia (four comparisons)
One trial compared a loading dose-alone regimen with a loading dose plus maintenance dose regimen (80 women). It is uncertain whether either regimen has an effect on the risk of recurrence of convulsions or maternal death (very low-certainty evidence).
One trial compared a lower-dose regimen with standard-dose regimen over 24 hours (72 women). It is uncertain whether either regimen has an effect on the risk of recurrence of convulsion, severe morbidity, perinatal death, or maternal death (very low-certainty evidence).
One trial (137 women) compared intravenous (IV) versus standard intramuscular (IM) maintenance regimen. It is uncertain whether either route has an effect on recurrence of convulsions, death of the baby before discharge (stillbirth and neonatal death), or maternal death (very low-certainty evidence).
One trial (120 women) compared a short maintenance regimen with a standard (24 hours after birth) maintenance regimen. It is uncertain whether the duration of the maintenance regimen has an effect on recurrence of convulsions, severe morbidity, or side effects such as nausea and respiratory failure. A short maintenance regimen may reduce the risk of flushing when compared to a standard 24 hours maintenance regimen (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.08 to 0.93; 1 trial, 120 women; low-certainty evidence).
Many of our prespecified critical outcomes were not reported in the included trials.
Prevention of eclampsia for women with pre-eclampsia (five comparisons)
Two trials (462 women) compared loading dose alone with loading dose plus maintenance therapy. Low-certainty evidence suggests an uncertain effect with either regimen on the risk of eclampsia (RR 2.00, 95% CI 0.61 to 6.54; 2 trials, 462 women) or perinatal death (RR 0.50, 95% CI 0.19 to 1.36; 2 trials, 462 women).
One small trial (17 women) compared an IV versus IM maintenance regimen for 24 hours. It is uncertain whether IV or IM maintenance regimen has an effect on eclampsia or stillbirth (very low-certainty evidence).
Four trials (1713 women) compared short postpartum maintenance regimens with continuing for 24 hours after birth. Low-certainty evidence suggests there may be a wide range of benefit or harm between groups regarding eclampsia (RR 1.99, 95% CI 0.18 to 21.87; 4 trials, 1713 women). Low-certainty evidence suggests there may be little or no effect on severe morbidity (RR 0.96, 95% CI 0.71 to 1.29; 2 trials, 1233 women) or side effects such as respiratory depression (RR 0.80, 95% CI 0.25 to 2.61; 2 trials, 1424 women).
Three trials (185 women) compared a higher-dose maintenance regimen versus a lower-dose maintenance regimen. It is uncertain whether either regimen has an effect on eclampsia (very low-certainty evidence). Low-certainty evidence suggests that a higher-dose maintenance regimen has little or no effect on side effects when compared to a lower-dose regimen (RR 0.79, 95% CI 0.61 to 1.01; 1 trial 62 women).
One trial (200 women) compared a maintenance regimen by continuous infusion versus a serial IV bolus regimen. It is uncertain whether the duration of the maintenance regimen has an effect on eclampsia, side effects, perinatal death, maternal death, or other neonatal morbidity (very low-certainty evidence).
Many of our prespecified critical outcomes were not reported in the included trials.