What is the role of magnesium sulfate in the treatment of preterm labor?

Updated: Dec 17, 2018
  • Author: Michael G Ross, MD, MPH; Chief Editor: Carl V Smith, MD  more...
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Answer

Magnesium sulfate is widely used as the primary tocolytic agent because it has similar efficacy to terbutaline with far better tolerance. Common maternal side effects include flushing, nausea, headache, drowsiness, and blurred vision. The mother should be monitored for toxic effects, such as respiratory depression or even cardiac arrest, that can occur at supratherapeutic levels. In addition, magnesium sulfate readily crosses the placenta and may lead to respiratory and motor depression of the neonate.

Although magnesium sulfate is approved to prevent seizures in preeclampsia and for control of seizures in eclampsia, its use for preterm labor is off-label. In 2013, the FDA issued a safety alert warning not to exceed 5-7 days of continuous IV magnesium sulfate when the agent is used for preterm labor. [25, 26, 27] Longer treatment duration may lead to hypocalcemia in the developing fetus and result in neonates with skeletal abnormalities related to osteopenia. Hypermagnesemia causes hypocalcemia as a result of a decrease in the secretion of parathyroid hormone. [27]

Several observational studies have reported an association of antenatal treatment with magnesium sulfate for preterm labor or preeclampsia with a decreased risk of cerebral palsy in low birth weight or preterm infants. [31, 32, 33] While the use of magnesium sulfate for the prevention of cerebral palsy in preterm infants has been recently suggested, it has yet to receive universal acceptance.

Antenatal magnesium sulfate should be considered for use in women at high risk of delivery before 34 weeks' gestation, mainly in those with premature rupture of membranes, active labor, and planned delivery within 24 hours. Loading and maintenance doses, and the duration of the treatment specifically for neuroprotection should not normally exceed 6 g, 1-2 g/h, and 24 hours, respectively.

The use of magnesium sulfate usually requires baseline maternal laboratory evaluation, including CBC count and serum creatinine level, urine output greater than 30 mL/h, normal vital signs, and appropriate maternal mentation. The initial recommended loading dose is 4-6 g IV over 20 minutes, followed by a maintenance dose of 1-4 g/h depending on urine output and persistence of uterine contractions.

Maintenance of magnesium sulfate therapy requires careful assessment of maternal mentation, visual symptoms, DTRs, and cardiac rate with discontinuation whenever evidence of toxicity exists. Urine output should be carefully monitored and ideally maintained at greater than 50 mL/h. Limiting intravenous intake to prevent pulmonary edema may be prudent. Oral intake can be maintained at the discretion of the provider. Serum magnesium levels may be obtained 1 hour after the loading dose and then every 6 hours and the maintenance dosage should be titrated to maintain a serum level of 4-8 mg/dL.

Since the primary therapeutic goal of tocolysis is to delay preterm delivery within 48 hours from the initiation of steroid prophylaxis, little evidence suggests that extended MgSO4 therapy is beneficial. The authors recommend discontinuing magnesium sulfate therapy after 48 hours in most patients unless the gestational age is less than 28 weeks when a gain of an additional 3-4 days may significantly reduce neonatal morbidity and mortality. Due to the risk of toxicity, consulting an MFM specialist may be beneficial if magnesium sulfate is to be continued for more than 72 hours. Since no clinical evidence suggests that oral beta-mimetics, subcutaneous terbutaline pump, or oral magnesium compounds are effective in delaying preterm birth, alternative tocolysis is not currently recommended after the discontinuation of IV MgSO4 therapy.

When acute mild toxicity exists in the presence of normal urine output, magnesium sulfate should be temporarily discontinued until the serum magnesium level and DTRs return to normal. If the toxicity symptoms are life threatening, administering 1 g of calcium gluconate by slow intravenous push and strongly considering not reinstituting magnesium sulfate despite the return to normal levels is recommended.


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