Magnesium Sulfate for Neuroprotection

Last Update: May 2020

Background:

Cerebral palsy describes a group of disorders affecting the development of movement and posture, causing activity limitation, and which are attributable to non-progressive disturbances. The prevalence of cerebral palsy (CP) in the U.S. population is estimated to be 3.6 per 1000 live births. Preterm birth is a major risk factor for CP, with infants born prior to 34 weeks accounting for 25% of all new cases.

A possible role for antenatal magnesium sulfate (MgSO4) exposure in reducing the risk of CP was proposed based on Level 3 evidence published in 1995.1  More recently, three large, randomized placebo-controlled trials of antenatal MgSO4 for fetal neuroprotection have been reported. 2-4  The results of these trials provide strong support for the utilization of MgSO4 to lower the risk of CP among the survivors of early preterm birth.

Two meta-analyses of these studies suggest that antenatal MgSO4 reduced the risk of any type of CP by 30% and the risk of handicapping CP by 40 – 45%.5-6

Eligible Candidates:

Antenatal magnesium sulfate should be considered for use in women at high risk of delivery before 32 weeks of gestation, mainly in those with premature rupture of membranes, labor in active phase, and planned delivery within 24 hours. The benefit of using MgSO4 beyond 32 weeks for fetal neuroprotection is unproven. The following are suggested criteria:

• 24 0/7 – 31 6/7 week gestations
• High risk for spontaneous or indicated preterm delivery

Delivery should not be delayed solely for the purpose of treatment with MgSO4, should such a delay be potentially detrimental to the mother or fetus.

Suggested Regimen:

There is currently inadequate evidence to suggest the best dosing regimen or duration of therapy. The following regimen is that used in the BEAM study, the largest U.S. study6:

• 6 gram loading dose over 20 – 30 minutes
• 2 gram / hour maintenance dose
• At least 3 hours of MgSO4 infusion is recommended prior to delivery.
• If delivery does not occur after 12 hours or is no longer considered imminent, the MgSO4 infusion can be discontinued and resumed when delivery is again considered imminent.
• If 6 hours have passed between the discontinuation of therapy and its re-initiation, another bolus should be given.

Like all medications, MgSO4 has the potential for adverse reactions. Therefore, caution should be exercised in its use and patients should be closely monitored for common associated side effects.

References:

1. Nelson KB, Grether JK. Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants? Pediatrics 1995;95:263-9.
2. Crowther CA, Hiller JE, Doyle LW, et al. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. JAMA 2003;290:2669-76.
3. Magpie Trial Follow-up Study Collaborative. The Magpie trial: a randomized trial comparing magnesium sulphate with placebo for pre-eclampsia: outcome for children at 18 months. BJOG 2007;114:289-99.
4. Rouse DJ, HIrtz DG, Thom E, Varner MW, Spong CY, Mercer BM, eta al. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008;359:895-905.
5. Conde-Agudelo A, Romero R. Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks’ gestation: a systematic review and metaanalysis. Am J Obstet Gynecol. 2009.
6. Constantine, MM, Weiner SJ. Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants. Obstet Gynecol. 2009 114:354-64.