Magnesium Sulfate and Protecting Against Cerebral Palsy?

Bret Stetka, MD; Rohan D'Souza, MD, MRCOG, FCPS, DNB, DGO, DFP; Amarnath Bhide, MD, FRCOG


February 22, 2011

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Hello, I'm Dr. Bret Stetka, Editorial Director at Medscape. Welcome to the F1000 Practice-Changing Minute, where we report commentaries from the Faculty of 1000 on highly rated studies that may change clinical practice. Our commentary today covers the study "A Randomized, Controlled Trial of Magnesium Sulfate for the Prevention of Cerebral Palsy," from Rouse and colleagues, published in The New England Journal of Medicine.[1] The Faculty of 1000 Medicine has given this a ranking of Changing Clinical Practice and Must Read with a factor of 8.

The following F1000 commentaries on this study were written by Drs. Rohan D'Souza and Amar Bhide of the Fetal Medicine Unit at St. George's Hospital NHS Trust, London, United Kingdom.

In their commentary on this study, Drs. Rohan D'Souza and Amarnath Bhide wrote:

Antenatal magnesium sulfate administered intravenously as a 6-g bolus followed by a continuous infusion of 2 g/hr should be given to women at risk of preterm labor for the prevention of cerebral palsy in the fetus.

Preterm infants that survive, and especially those less than 34 weeks, are at a significantly greater risk of neurologic impairment, such as sensory and cognitive dysfunction and cerebral palsy.[2] The development of cerebral palsy in these infants has been linked to the increased incidence of intraventricular hemorrhage (IVH).[3]

For almost 2 decades, magnesium sulfate has consistently been shown in case-control, observational, and animal studies to reduce the risk of IVH. However, its usage for this purpose hasn't gained widespread acceptance. A recent Cochrane review[4] that included 5 well-designed, randomized controlled trials (6145 babies) has concluded that when given antenatally to women at risk for preterm birth, magnesium sulfate has an established neuroprotective role for the preterm fetus, with minimal side effects to the mother. We have reviewed 1 of these 5 trials by Rouse and colleagues that was published in 2008 in the light of the recent Cochrane review.

This multicenter, placebo-controlled, double-blind trial recruited 2241 women at imminent risk for delivery between 24 and 31 weeks of gestation. Women were randomly assigned to either receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a continuous infusion of 2 g/hr or a matching placebo, and follow-up was achieved for 95.6% of the children. The primary outcome was the composite of stillbirth or infant death by 1 year of corrected age or moderate or severe cerebral palsy at or beyond 2 years of corrected age.

Although there was no difference in the risk for death in the 2 groups, moderate or severe cerebral palsy occurred significantly less frequently in the magnesium sulfate group (1.9% vs 3.5%; relative risk, 0.55; 95% confidence interval [CI], 0.32 to 0.95). No woman had a life-threatening event, highlighting the safety of magnesium sulfate therapy. The study authors concluded that fetal exposure to magnesium sulfate before anticipated early preterm delivery reduced the rate of cerebral palsy among survivors with no increased risk to the mother.

The Cochrane meta-analysis[4] has recently confirmed these findings by showing an absolute risk reduction of 1.60% in cerebral palsy following antenatal magnesium sulfate administration with 63 women needing to be treated to benefit 1 baby. There was no difference in fetal, neonatal, or pediatric mortality, and major maternal complications were rare.

This well-designed trial does not have many of the limitations of the subsequent meta-analysis that included the diverse inclusion and exclusion criteria, gestational ages when women were considered eligible, time of treatment prior to expected preterm birth, and drug treatment protocol. One of the limitations of this study is that reassessment of neurologic outcomes was only continued until 2 years of age, when a neurological diagnosis is not always certain. Follow-up at least into school-age would be ideal. Also, more research would need to be carried out to determine the dose and timing of administration and questions with regard to maintenance therapy and repeated doses.

The investigators of this trial and the subsequent Cochrane review have unequivocally recommended the antenatal use of magnesium sulfate for fetal neuroprotection in women deemed at a high risk for preterm labor, and this has been endorsed by various other authorities.[5,6] The American College of Obstetricians and Gynecologists in their committee opinion paper[6] have encouraged physicians electing to use magnesium sulfate for the purpose of fetal neuroprotection to develop specific guidelines in regard to inclusion criteria, treatment regimens, concurrent tocolysis, and maternal-fetal monitoring. This should encourage more widespread use of this easily available drug with the primary intention of reducing the risk for neurologic adverse outcomes in this vulnerable group of infants.

This concludes today's F1000 Practice-Changing Minute. I'm Bret Stetka. Thank you for listening.


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