What is the role of magnesium sulfate (MgSO4) in neuroprotection of the fetus?

From the Guidelines

Magnesium sulfate is recommended for fetal neuroprotection when delivery is anticipated before 32 weeks gestation. The standard regimen consists of a 4-6 gram IV loading dose administered over 20-30 minutes, followed by a maintenance infusion of 1-2 grams per hour until delivery or for a maximum of 24 hours. This therapy should be initiated when preterm birth is imminent or planned within 24 hours. The protective effect appears greatest when administered at least 4 hours before delivery, though even shorter durations offer some benefit. Magnesium sulfate works by reducing fetal cerebral injury through several mechanisms, including reduction of inflammatory cytokines, prevention of excitatory amino acid release, and stabilization of neuronal membranes. This treatment significantly reduces the risk of cerebral palsy and severe motor dysfunction in preterm infants, as supported by studies such as 1 and 1.

Key Considerations

• The medication should be discontinued after 24 hours if delivery has not occurred, as prolonged therapy offers no additional benefit and may increase maternal risks.
• Patients receiving magnesium sulfate should be monitored for potential side effects including flushing, nausea, headache, muscle weakness, and rarely respiratory depression or cardiac arrhythmias.
• Magnesium levels should be monitored, particularly in patients with renal dysfunction, with therapeutic levels typically between 4-7 mEq/L.
• The use of magnesium sulfate for neuroprotection is recommended by multiple guidelines, including those from the Society for Maternal-Fetal Medicine 1, highlighting its importance in improving outcomes for preterm infants.

Administration and Monitoring

• The standard regimen for magnesium sulfate administration should be followed, with adjustments made as necessary based on patient response and renal function.
• Close monitoring of fetal and maternal well-being is essential during magnesium sulfate therapy, with regular assessments of fetal heart rate, maternal blood pressure, and respiratory status.
• The decision to administer magnesium sulfate should be made on a case-by-case basis, taking into account the individual patient's risk factors and the potential benefits and risks of therapy, as discussed in studies such as 1 and 1.

From the FDA Drug Label

Magnesium is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability. Magnesium prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end-plate by the motor nerve impulse. Magnesium is said to have a depressant effect on the central nervous system (CNS), but it does not adversely affect the woman, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Continuous maternal administration of magnesium sulfate injection in pregnancy beyond 5 to 7 days can cause fetal abnormalities. Magnesium sulfate can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women.

Magnesium sulfate for neuroprotection of fetus:

• The FDA-approved use of magnesium sulfate does not include neuroprotection of the fetus.
• While magnesium sulfate has a depressant effect on the CNS, its use in pregnancy is cautioned against due to potential fetal abnormalities when administered beyond 5 to 7 days.
• Key points to consider:
  • Magnesium sulfate can cause fetal abnormalities with prolonged use.
  • Use of magnesium sulfate in pregnancy should be limited to 5 to 7 days.
  • The drug should be used with caution in pregnant women and only if clearly needed 2, 2, 2.

From the Research

Magnesium Sulfate for Fetal Neuroprotection

• Magnesium sulfate (MgSO4) has been proposed as a major step forward in preventing neurologic disability associated with preterm birth 3.
• The results of various randomized controlled trials (RCTs) on the use of MgSO4 for neuroprotection have shown that it reduces the risk of severe neurologic deficit, in particular, cerebral palsy in appropriately selected patients 3, 4.
• The standard regimen proposed in most guidelines is a dose of 4 g given intravenously 15 min continued by 1 g/h until maximum 24 h and minimum for 4 h 3.
• A recent study found that a total dose of 64 g was associated with the maximum protective effect, but other studies report on an increased risk of neonatal death with these high doses 3.
• The World Health Organization and many pediatric and obstetrical societies recommend the use of antenatal MgSO4 for fetal neuroprotection, with a minimal dose (e.g., 4 g loading dose ± 1 g/h maintenance dose over 12 h) to avoid potential deleterious effects 4, 5.

Clinical Guidelines and Recommendations

• Clinical guidelines for the use of MgSO4 for fetal neuroprotection vary in their recommendations, including upper gestational age, dose, duration, repeating treatment, and use of additional tocolytics 6.
• The Canadian guidelines recommend antenatal magnesium sulphate administration for fetal neuroprotection when women present at ≤33 + 6 weeks with imminent preterm birth, with a dose of 4 g loading dose followed by 1 g/h maintenance dose 5.
• The American College of Obstetricians and Gynecologists and the World Health Organization also recommend the use of MgSO4 for fetal neuroprotection, but with varying guidelines on dosage and gestational age cut-off 5, 7.

Benefits and Risks

• Antenatal MgSO4 reduces the risk of "death or cerebral palsy" (RR 0.85; 95% CI 0.74-0.98), "death or moderate-severe cerebral palsy" (RR 0.85; 95% CI 0.73-0.99), and "any cerebral palsy" (RR 0.71; 95% CI 0.55-0.91) at 2 years of age 5.
• However, high doses of MgSO4 may increase the risk of neonatal death and other serious side effects for both mother and neonate 3, 4.
• The benefits of MgSO4 for fetal neuroprotection must be weighed against the potential risks, and guidelines should be developed to maximize its administration among women at risk of preterm delivery before 32 weeks of gestation 4, 5.