Abstract
BackgroundAntenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment.MethodsBibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively.ResultsA total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised trials. Case reports supported an association between iatrogenic overdose of magnesium sulphate and life-threatening consequences.ConclusionsAppropriate administration of antenatal magnesium sulphate was not shown to be associated with serious maternal adverse effects, though an increase in 'minor’ adverse effects and treatment cessation was shown. Larger trials are needed to determine optimal regimens, achieving maximal effectiveness with minimal adverse effects, for each antenatal indication for use. Vigilance in the use of magnesium sulphate is essential for women’s safety.
Highlights
Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation
Life-threatening maternal adverse effects of magnesium sulphate are considered extremely rare in obstetrics [8], severe consequences of magnesium toxicity including respiratory arrest, cardiac arrest and death have been detailed in case reports
In view of the extremely widespread use of antenatal magnesium sulphate in obstetric practice, in this systematic review we aimed to quantify the extent of maternal adverse effects attributed to treatment, explore any variation in risk estimates between study designs, and to assess how such maternal adverse effects vary according to different regimens for administration and different indications for use
Summary
Widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. The ‘well recognised’ and more commonly reported maternal adverse effects of magnesium sulphate include flushing, increased warmth and sweating due to the peripheral vasodilatory effects of magnesium, and nausea, vomiting, headaches, muscle weakness, blurred vision, and intravenous (IV) or intramuscular (IM) site pain or discomfort [8]. Though such maternal adverse effects may be considered comparatively ‘minor,’ they have been associated with the need for early cessation of this therapy, which has benefits when used for maternal and fetal neuroprotection [4,7]
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