Is magnesium sulfate a safe and effective treatment for preterm labor?
Magnesium sulfate does not delay delivery when used in patients with preterm labor. Although magnesium sulfate is not associated with any serious adverse maternal outcomes, it may be associated with an increase in total fetal, neonatal, and infant mortality. (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)
Preterm birth, defined as occurring before 37 weeks of gestation, is the leading cause of neonatal death and is associated with several short- and long-term infant morbidities. Tocolytics, agents that inhibit uterine contractions, are commonly used to prevent or delay preterm birth. Magnesium sulfate is one of the most commonly used tocolytics in the United States.1 An earlier pooled analysis of five trials involving 6,145 infants with similar inclusion criteria found a statistically significant benefit of magnesium sulfate as a neuroprotective agent (relative risk [RR] = 0.68; 95% confidence interval [CI], 0.54 to 0.87; number needed to treat = 63).2
This review included 37 studies, with a total of 3,571 women, in which magnesium sulfate was compared with no treatment, placebo, or one of several alternative tocolytic agents. Studies varied with respect to the gestational ages included (less than 30 weeks to up to 37 weeks), loading dosage of magnesium sulfate (4 to 8 g per hour), and maintenance dosage (1 to 6 g per hour). Primary outcomes included birth within 48 hours of trial entry, serious maternal outcomes, and serious infant outcomes, including death. Secondary outcomes included maternal adverse drug reactions and infant admission to the neonatal intensive care unit.
Delivery within 48 hours of magnesium sulfate administration was reported in 19 trials that included 1,913 women. There were no significant differences in the risk of birth within 48 hours between women who received magnesium sulfate and those who received no medication, placebo, or any other tocolytic agent. The exact RR varied depending on the comparison agent, but none were statistically significant.
Serious infant outcomes, defined as death, chronic lung disease, grade III–IV intraventricular hemorrhage or periventricular leukomalacia, or major neurosensory disability, were reported in 18 trials. None of these reached statistical significance. Magnesium sulfate administration also did not have significant effects on any less serious neonatal morbidities studied, including five-minute Apgar score of less than 7, respiratory distress syndrome, need for assisted ventilation, or necrotizing enterocolitis.
When analyzed individually, the risks of death for fetuses, neonates, and infants were not significantly increased in those whose mothers were given magnesium sulfate vs. placebo. In the same regard, magnesium sulfate did not increase the risk of death for fetuses, neonates, and infants when compared with other tocolytic agents.3 However, when analyzed as an aggregate, the risk was increased (RR = 4.56; 95% CI, 1.00 to 20.86). It should be noted that these data are driven by the outcomes of one study of 167 patients, in which all the deaths occurred. Seven trials that included 930 women evaluated serious maternal outcomes, defined as death, cardiac arrest, respiratory arrest, or admission to an intensive care unit. None of these outcomes were reported in any of the seven trials.
Recent concern about safety has led the U.S. Food and Drug Administration to advise against the use of magnesium sulfate for more than five to seven days. This recommendation was specifically related to concerns about neonatal hypocalcemia and osteopenia.4 The American College of Obstetricians and Gynecologists has recommended that use of magnesium sulfate as a tocolytic be limited to 48 hours in women from 24 to 34 weeks' estimated gestational age.5
The current literature on magnesium sulfate in preterm labor presents a mixed picture of risks and benefits. However, it is clear that magnesium sulfate should not be used as a tocolytic agent. Family physicians should be aware that magnesium sulfate may be considered as a neuroprotective agent for neonates whose mothers have preterm labor after careful consideration of risks and benefits. However, more research is needed to identify which patients are likely to benefit from the addition of magnesium sulfate in the setting of preterm labor.