What is the role of magnesium sulfate (MgSO4) in neuroprotection for preterm infants?

Magnesium Sulfate for Neuroprotection in Preterm Infants

Magnesium sulfate should be administered 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

Mechanism and Evidence

• Magnesium sulfate serves as a neuroprotective agent for preterm infants by reducing the risk of cerebral palsy and improving motor development outcomes 1, 2
• Meta-analyses have demonstrated that antenatal magnesium sulfate reduces the risk of:
  • "Death or cerebral palsy" (RR 0.85; 95% CI 0.74 to 0.98) 2
  • "Any cerebral palsy" (RR 0.71; 95% CI 0.55 to 0.91) 2
  • "Moderate-to-severe cerebral palsy" (RR 0.60; 95% CI 0.43 to 0.84) 2
  • "Substantial gross motor dysfunction" (inability to walk without assistance) (RR 0.60; 95% CI 0.43 to 0.83) 2, 3

Dosing Protocol

• The recommended dosing regimen is:
  • Loading dose: 4g intravenous (IV) over 20 minutes 4
  • Maintenance dose: 1g/hour until delivery 4
  • Maximum duration: 12 hours without exceeding a cumulative dose of 50g 4
• The BEAM trial, which was the largest randomized controlled trial, used a higher dosing protocol of 6g loading dose followed by 2g/hour maintenance dose 5
• Recent evidence suggests that a total dose of 64g may be associated with maximum protective effect, though concerns about neonatal mortality with higher doses have been raised 5

Timing and Patient Selection

• Magnesium sulfate should be administered when preterm birth is imminent or planned before 32 weeks' gestation 1, 2
• The neuroprotective effect applies to both single and multiple pregnancies, regardless of the cause of prematurity 4
• Although data for the periviable period (22-25 weeks) are limited, magnesium sulfate prophylaxis is still recommended if delivery of a potentially viable infant is anticipated 1
• The more premature the infant, the greater the benefit associated with antenatal magnesium sulfate 5

Safety Considerations

• No serious maternal adverse effects or adverse effects in newborns have been documented at recommended doses 4
• For women with preeclampsia, magnesium sulfate serves dual purposes: prevention of eclamptic seizures and fetal neuroprotection 1
• Premature newborns exposed to maternal magnesium sulfate therapy may have high magnesium levels in the first days of life 6
• Monitoring is essential as these infants have limited ability to excrete excessive magnesium due to low postnatal glomerular filtration rates during the first week of life 6
• Magnesium intake must be carefully managed in newborns whose mothers received magnesium sulfate before delivery 6

Implementation Challenges

• Despite strong evidence and cost-effectiveness, practice surveys indicate insufficient and heterogeneous use of magnesium sulfate across different maternity wards 7
• Since 2010, an increasing number of obstetrical societies have recommended its use, including the International Federation of Gynecology and Obstetrics, World Health Organization, and American College of Obstetricians and Gynecologists 1, 7

Future Directions

• Considering the established neuroprotective benefits of antenatal administration, postnatal magnesium sulfate administration is being explored as a potential extension of this therapy 7
• Further randomized controlled trials are needed to assess the efficacy of postnatal administration 7