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Evidence summaries

Magnesium Sulphate for Women at Risk of Preterm Birth for Neuroprotection of the Foetus

Antenatal magnesium sulphate therapy for women at risk of preterm birth is effective for reducing the risk of cerebral palsy in the child. Level of evidence: "A"

An individual participant data meta-analysis 2 assessing the neuroprotective benefits for babies of antenatal magnesium sulphate for women at risk of preterm birth included 5 trials with a total of 5 493 women and 6 131 babies. Overall, there was no clear effect of magnesium sulphate treatment compared with no treatment on death or CP (RR 0.94, 95% CI 0.85 to 1.05; 5 trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with magnesium sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99; 4 trials, n=4 448), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41. For the primary outcome of severe maternal outcome potentially related to magnesium sulphate treatment, no events were recorded from the 2 trials providing data. No effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17; 5 trials, 6 131 babies) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13; 4 trials, 4 448 babies). For cerebral palsy in survivors, magnesium sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87; 5 trials, 4 601 babies, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87; 4 trials, 3 988 babies, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which magnesium sulphate treatment was given, the total dose received, or whether maintenance therapy was used.

A Cochrane review [Abstract] 1 included 5 studies with a total of 6 145 infants. Four studies included women who were likely to give birth early and magnesium was used for neuroprotection, although one study also had a tocolytic arm to the study. The fifth study was designed to evaluate whether magnesium prevented eclampsia in women with pre-eclampsia. Antenatal magnesium sulphate therapy given to women at risk of preterm birth substantially reduced the risk of cerebral palsy in their child (RR 0.68, 95% CI 0.54 to 0.87; 5 studies, n= 6145). There was also a significant reduction in the rate of substantial gross motor dysfunction (RR 0.61, 95% CI 0.44 to 0.85; 4 studies, n= 5980). No statistically significant effect was detected on paediatric mortality (RR 1.04, 95% CI 0.92 to 1.17; 5 studies, n= 6145), 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; 4 studies, n= 4446), but not for the other intent subgroups.

A Practice guideline 3 assessed antenatal magnesium sulphate for fetal neuroprotection. Magnesium sulphate reduced the risk of death or CP (RR 0.85; 95% CI 0.74 to 0.98; 4 trials, n=4446), moderate-to-severe CP (RR 0.60; 95% CI 0.43 to 0.84; 3 trials, n=4250), and substantial gross motor dysfunction at 2 years of age (inability to walk without assistance) (RR 0.60; 95% CI 0.43 to 0.83; 3 trials, n=4287).

    References

    • Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2009;(1):CD004661. [PubMed].
    • Crowther CA, Middleton PF, Voysey M et al. Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis. PLoS Med 2017;14(10):e1002398. [PubMed]
    • Magee LA, De Silva DA, Sawchuck D et al. No. 376-Magnesium Sulphate for Fetal Neuroprotection. J Obstet Gynaecol Can 2019;41(4):505-522. [PubMed]

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