Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus

RHL summary

22 January 2016

Key Findings

Child with cerebral palsy with his parents
Sadasiv Swain

It is widely known that preterm delivery is associated with an increase in adverse infant neurological conditions and deficits. These include: cerebral palsy, blindness, deafness and cognitive impairment.

  • When compared to placebo magnesium sulphate was associated with a decreased rate of cerebral palsy and gross motor impairment.
  • Magnesium sulphate was not shown to impact pediatric mortality or early-life neurological functioning.
  • Magnesium sulphate was not associated with any change in serious maternal side effects: respiratory depression, cardiac arrest, and death.

Evidence included in this review

Five RCTs were included in this review,for a total of 6145 infants. Four trials targeted the use of magnesium sulphate as a neuroprotective agent. One trial evaluated the primary outcome of magnesium sulphate for pre-eclampsia, neuroprotection being a secondary outcome.

Quality assessment

Overall it was deemed that there was a low risk of bias for the methodological quality of included trials.

Clinical implications

This review supports the use of magnesium sulphate for neuroprotection of the fetus in women at risk of preterm birth. One must weigh up the risk of minor side effects against the number needed to treat (63 women). This intervention is supported by a WHO recommendation for its use.

Further research

Further research should target long-term outcomes in early childhood. Alternatively, studies could seek the ideal dose and timing for administration of maintenance magnesium sulphate therapy.

Cochrane review

Citation: Doyle Lex W, Crowther Caroline A, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD004661. DOI:10.1002/14651858.CD004661.pub3.



Epidemiological and basic science evidence suggests that magnesium sulphate before birth may be neuroprotective for the fetus.


To assess the effects of magnesium sulphate as a neuroprotective agent when given to women considered at risk of preterm birth.

Search methods

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2008).

Selection criteria

Randomised controlled trials of antenatal magnesium sulphate therapy in women threatening or likely to give birth at less than 37 weeks' gestational age. For one subgroup analysis, studies were broadly categorised by the primary intent of the study into "neuroprotective intent", or "other intent (maternal neuroprotective - pre-eclampsia)", or "other intent (tocolytic)".

Data collection and analysis

At least two authors assessed trial eligibility and quality, and extracted data.

Main results

Five trials (6145 babies) were eligible for this review. Antenatal magnesium sulphate therapy given to women at risk of preterm birth substantially reduced the risk of cerebral palsy in their child (relative risk (RR) 0.68; 95% Confidence interval (CI) 0.54 to 0.87; five trials; 6145 infants). There was also a significant reduction in the rate of substantial gross motor dysfunction (RR 0.61; 95% CI 0.44 to 0.85; four trials; 5980 infants). No statistically significant effect of antenatal magnesium sulphate therapy was detected on paediatric mortality (RR 1.04; 95% CI 0.92 to 1.17; five trials; 6145 infants), or on other neurological impairments or disabilities in the first few years of life. Overall there were no significant effects of antenatal magnesium therapy on combined rates of mortality with cerebral palsy, although there were significant reductions for the neuroprotective groups RR 0.85; 95% CI 0.74 to 0.98; four trials; 4446 infants, but not for the other intent subgroups. There were higher rates of minor maternal side effects in the magnesium groups, but no significant effects on major maternal complications.

Authors' conclusions

The neuroprotective role for antenatal magnesium sulphate therapy given to women at risk of preterm birth for the preterm fetus is now established. The number of women needed to be treated to benefit one baby by avoiding cerebral palsy is 63 (95% confidence interval 43 to 155). Given the beneficial effects of magnesium sulphate on substantial gross motor function in early childhood, outcomes later in childhood should be evaluated to determine the presence or absence of later potentially important neurological effects, particularly on motor or cognitive function.