What is the role of Magnesium Sulfate in pregnant women?

From the Guidelines

Magnesium sulfate is strongly recommended for pregnant women with severe preeclampsia or eclampsia to prevent and treat seizures, as well as for fetal neuroprotection in women at risk of preterm birth before 32 weeks, as it has been shown to approximately halve the rate of eclampsia, with approximately 100 women needing MgSO4 to prevent 1 seizure 1.

Key Considerations

• The standard dosing regimen includes a loading dose of 4-6 grams IV over 20-30 minutes, followed by a maintenance infusion of 1-2 grams per hour, typically continuing for 24 hours after delivery or the last seizure.
• In low-resource settings, all women with preeclampsia should receive MgSO4 for convulsion prophylaxis, typically a loading dose of 4 g IV or 10 g IM, followed by 5 g IM every 4 hours or an infusion of 1 g/h until delivery and for at least 24 hours postpartum 1.
• The use of MgSO4 should be guided by a consistent policy that incorporates appropriate monitoring, recognition of the risks of MgSO4 infusions, and assessment of maternal and fetal outcomes, with calcium gluconate available as an antidote in case of magnesium toxicity.

Administration and Monitoring

• Common side effects of MgSO4 include flushing, sweating, nausea, feeling of warmth, and injection site pain.
• Serious toxicity can cause respiratory depression, loss of deep tendon reflexes, and cardiac arrest, so monitoring of reflexes, respiratory rate, urine output, and serum magnesium levels is essential during administration.
• The experts suggest application of the 2020 SFAR/CNGOF formalised expert recommendations on management of patients with severe pre-eclampsia, which stipulated that magnesium sulfate should be administered antenatally to women with severe pre-eclampsia and at least one clinical sign of seriousness to reduce the risk of eclampsia, with a strong agreement (GRADE 1+) 1.

Clinical Decision-Making

• The decision to use MgSO4 should be based on the individual patient's risk factors and clinical presentation, with consideration of the potential benefits and risks of treatment.
• In highly specialized centers and high-income settings, selective use of MgSO4 in women with preeclampsia is reasonable, while in low-resource settings, all women with preeclampsia should receive MgSO4 for convulsion prophylaxis.

From the FDA Drug Label

Magnesium sulfate can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralization, osteopenia and other skeletal abnormalities with continuous maternal administration of magnesium sulfate for more than 5 to 7 days FETAL HARM: Continuous administration of magnesium sulfate beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia.

Magnesium Sulfate Use in Pregnant Women:

• Magnesium sulfate should be used during pregnancy only if clearly needed.
• Continuous administration of magnesium sulfate beyond 5 to 7 days can cause fetal harm, including hypocalcemia, skeletal demineralization, and osteopenia.
• The use of magnesium sulfate for more than 5 to 7 days may cause fetal abnormalities, and the shortest duration of treatment that can lead to fetal harm is not known 2 2.
• If magnesium sulfate is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established.

From the Research

Administration and Pharmacokinetics of Magnesium Sulfate

• Magnesium sulfate (MgSO4) is commonly used for the treatment of eclampsia and prophylaxis of eclampsia in patients with severe pre-eclampsia, typically administered via intramuscular or intravenous routes 3.
• The intramuscular regimen involves a 4 g intravenous loading dose, followed by 10 g intramuscularly and then 5 g intramuscularly every 4 hours in alternating buttocks, while the intravenous regimen involves a 4 g dose followed by a maintenance infusion of 1 to 2 g/h 3.
• After administration, about 40% of plasma magnesium is protein-bound, with the unbound magnesium ion diffusing into various bodily spaces, including across the placenta and into the fetus and amniotic fluid 3.

Clinical Usage and Toxicity

• The pharmacokinetic profile of MgSO4 can be described by a 2-compartment model, with a rapid distribution phase followed by a slower elimination phase 3.
• The clinical effect and toxicity of MgSO4 are linked to its concentration in plasma, with a suggested concentration of 1.8 to 3.0 mmol/L for treating eclamptic convulsions 3.
• Maternal toxicity is rare when MgSO4 is carefully administered and monitored, with warning signs including loss of patellar reflex at plasma concentrations between 3.5 and 5 mmol/L, respiratory paralysis at 5 to 6.5 mmol/L, and cardiac arrest at concentrations exceeding 12.5 mmol/L 3.

Efficacy and Safety in Pre-eclampsia and Eclampsia

• Magnesium sulfate is an evidence-based anticonvulsant drug used to prevent and control eclampsia, with controversy surrounding its routine administration in cases of pre-eclampsia without severe features 4.
• A systematic review of published reports on eclampsia found that a significant number of eclamptic women had normal blood pressure or mild-to-moderate hypertension immediately before seizure, supporting the initiation of magnesium sulfate prophylaxis in all women with mild pre-eclampsia 4.
• An integrative review of the literature found a low incidence of severe adverse reactions to magnesium sulfate, including absent patellar reflex, respiratory depression, and maternal death, suggesting that concerns about safety and toxicity should be mitigated 5.

Recommendations and Guidelines

• Magnesium sulfate has been indicated for women with preeclampsia with different severe features, and its use is recommended for patients with all severe features of preeclampsia, not only those with neurological symptoms 6.
• A qualitative evidence synthesis explored perceptions and experiences of healthcare providers, administrators, and policy-makers regarding factors affecting the use of magnesium sulfate, identifying key themes including provider competence and confidence, capability of health systems, and knowledge translation 7.