What is the role of intravenous (IV) magnesium sulfate (MgSO4) in neuroprotection, based on randomized controlled trials (RCTs)?

Intravenous Magnesium Sulfate for Neuroprotection in Preterm Birth: Evidence from RCTs

Intravenous magnesium sulfate is strongly recommended for fetal neuroprotection when preterm delivery is anticipated before 32 weeks' gestation, as it significantly reduces the risk of cerebral palsy without increasing mortality. 1, 2

Efficacy of Magnesium Sulfate for Neuroprotection

• Randomized controlled trials have demonstrated that antenatal magnesium sulfate therapy given to women at risk of preterm birth substantially reduces the risk of cerebral palsy in their children (Relative Risk 0.68; 95% CI 0.54 to 0.87) 3
• The most recent meta-analysis (2024) confirms that magnesium sulfate reduces cerebral palsy (RR 0.71,95% CI 0.57-0.89) and the combined outcome of death or cerebral palsy (RR 0.87,95% CI 0.77-0.98) 4
• Significant reduction in substantial gross motor dysfunction (RR 0.61; 95% CI 0.44 to 0.85) has been observed in infants whose mothers received magnesium sulfate 3
• The number needed to treat to prevent one case of cerebral palsy is 63 (95% CI 43 to 87) 3

Timing and Indications

• Magnesium sulfate should be administered when preterm delivery is anticipated before 32 weeks' gestation 1, 2
• Although data specific to the periviable period (22-25 weeks) are limited, magnesium sulfate prophylaxis is still recommended if delivery of a potentially viable infant is anticipated 2, 1
• Magnesium sulfate is particularly indicated in cases of fetal growth restriction with absent end-diastolic flow (delivery recommended by 33-34 weeks) or reversed end-diastolic flow (delivery recommended by 30-32 weeks) 2

Dosing Regimens

• Standard regimen: 4g IV loading dose over 15-20 minutes, followed by 1g/hour maintenance infusion until delivery or for a maximum of 24 hours 5
• Alternative regimen (BEAM trial): 6g loading dose followed by 2g/hour maintenance dose 5
• A single bolus of 4g may be sufficient to stimulate brain-derived neurotrophic factor (BDNF) production in cases of suspected preterm labor, with another 4g when preterm birth becomes inevitable 5
• Magnesium sulfate injection (50%) must be diluted to a concentration of 20% or less prior to IV infusion 6

Safety Considerations

• Maternal side effects include flushing, sweating, and in some cases, respiratory depression 6
• Monitor maternal reflexes (particularly patellar reflex) and respiratory rate (should remain ≥16 breaths/minute) 6
• Serum magnesium levels should be monitored, with therapeutic levels for neuroprotection typically ranging from 2.5 to 5 mEq/L 6
• Have injectable calcium salt immediately available to counteract potential magnesium toxicity 6
• Use with caution in patients with renal impairment, as magnesium is eliminated solely by the kidneys 6
• No significant increase in neonatal mortality or complications such as neonatal asphyxia, spontaneous intestinal perforation, necrotizing enterocolitis, or feeding intolerance has been observed with standard dosing regimens 5

Contraindications and Precautions

• Caution when administering with CNS depressants, neuromuscular blocking agents, or cardiac glycosides 6
• Prolonged use (beyond 5-7 days) may cause fetal abnormalities including hypocalcemia and skeletal demineralization 6
• Newborns may show signs of magnesium toxicity, including neuromuscular or respiratory depression, especially with continuous IV infusion for more than 24 hours preceding delivery 6

Implementation Considerations

• Despite strong evidence and guideline recommendations, practice surveys indicate insufficient and heterogeneous use of magnesium sulfate for neuroprotection 7
• Magnesium sulfate for fetal neuroprotection is considered a cost-effective strategy 7
• Administration should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities 6

Future Research Directions

• Longer-term benefits and harms for children beyond 2 years of age require further investigation 4
• The generalizability of findings to low- and middle-income countries needs to be established 4
• Postnatal administration of magnesium sulfate for neuroprotection is being considered and should be assessed in randomized controlled trials 7