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Antenatal Magnesium Sulfate and Neurologic Outcome in Preterm Infants: A Systematic Review

Doyle, Lex W. MD, FRACP1,2,3; Crowther, Caroline A. MD, FRANZCOG4; Middleton, Philippa MPH4; Marret, Stéphane MD, PhD5

doi: 10.1097/AOG.0b013e3181a60495

OBJECTIVE: To systematically review rates of neurologic outcomes reported in childhood for the preterm fetus exposed to antenatal magnesium sulfate.

DATA SOURCES: We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register, CENTRAL (The Cochrane Library 2008, Issue 3), relevant references from retrieved articles, and abstracts submitted to major congresses.

METHODS OF STUDY SELECTION: We sought all randomized controlled trials (RCTs) of antenatal magnesium sulfate with neurologic outcomes reported for the fetus.

TABULATION, INTEGRATION, AND RESULTS: Five eligible RCTs with 6,145 fetuses were identified; in four studies (4,446 fetuses) the primary intent was neuroprotection of the fetus. Methods of the Cochrane Collaboration were used to analyze the data. Antenatal magnesium sulfate therapy given to women at risk of preterm birth substantially reduced the risk of cerebral palsy in their children (relative risk [RR] 0.69; 95% confidence interval [CI] 0.54–0.87; five trials; 6,145 infants). The number needed to treat to prevent one case of cerebral palsy was 63 (95% CI 43–155). Moreover, there was a significant reduction in the rate of substantial gross motor dysfunction (RR 0.61; 95% CI 0.44–0.85; four trials; 5,980 infants). No statistically significant effect of antenatal magnesium sulfate therapy was detected on pediatric mortality (RR 1.01; 95% CI 0.82–1.23; five trials; 6,145 infants), or on other neurologic impairments or disabilities in the first few years of life. There were no significant effects of antenatal magnesium sulfate on combined rates of mortality with neurologic outcomes, except in the studies where the primary intent was neuroprotection, where there was a reduction in death or cerebral palsy (RR 0.85; 95% CI 0.74–0.98; four trials; 4,446 infants).

CONCLUSION: Antenatal magnesium sulfate therapy given to women at risk of preterm birth is neuroprotective against motor disorders in childhood for the preterm fetus.

Magnesium sulfate given to women threatening to deliver preterm reduces the chance that the surviving neonate will have cerebral palsy.

From the 1Royal Women’s Hospital, the 2University of Melbourne, and 3Murdoch Childrens Research Institute, Melbourne, Victoria, Australia; the 4Discipline of Obstetrics and Gynaecology, the University of Adelaide, Adelaide, South Australia, Australia, and the 5Department of Neonatal Medicine, University Hospital, Rouen, France.

See related editorial on page 1202.

Supported in part by grants from the National Health and Medical Research Council (Project Grants 34295 and 350326), Department of Health and Ageing, Australia.

The authors thank the Chief Investigators and Steering Committees of the MAGPIE Trial Collaborative Group and the MAGPIE Trial Follow-up Study Collaborative Group for providing unpublished data from the MAGPIE trial.

Corresponding author: Lex W. Doyle, Department of Obstetrics and Gynaecology, 7th floor Women’s Research Precinct, The Royal Women’s Hospital, 20 Flemington Road, Parkville Victoria 3052, Australia; e-mail:

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2009 by The American College of Obstetricians and Gynecologists.