Effect of Magnesium Sulfate Given for Neuroprotection Before Preterm Birth: A Randomized, Controlled Trial

Abstract

Some observational studies show that, in very preterm births, magnesium sulfate treatment is associated with a lower risk of intraventricular hemorrhage (IVH), which predisposes to cerebral palsy (CP), but no large randomized trials have been reported. The present randomized, controlled study examined the efficacy of magnesium sulfate in 1062 women having fetuses younger than 30 weeks for whom birth was expected (or planned) within 24 hours. They were assigned to receive a loading infusion of 8 mL of a 0.5-g/mL solution of magnesium sulfate (4 g) or isotonic saline solution in 20 minutes followed by a maintenance infusion of 2 mL/hour for up to 24 hours or until birth. Surviving children were followed up at a corrected age of 2 years by developmental pediatricians and psychologists who did not know the treatment assignment. Baseline maternal characteristics were similar for the treatment and control groups and typical of a high-risk population. The median gestational age at the outset was 27 weeks. The most common primary reason for preterm birth was preterm labor, followed by preeclampsia, antepartum hemorrhage, and chorioamnionitis. Pregnancy outcomes were comparable in the 2 groups, and there was no substantial difference in mean birth weights. Primary outcomes, including death, CP in a surviving infant, and CP in an infant who died were all less frequent in actively treated women but the differences were not statistically significant. Causes of infant death were similar in the 2 groups. No major adverse maternal side effects were noted in either group. In particular, respiratory depression was not more frequent in actively treated women. Significantly more of these women had a decrease of more than 15 mm Hg in diastolic blood pressure. Minor maternal adverse effects, including tachycardia, nausea, discomfort, dizziness, and blurred vision, were more frequent after magnesium infusion. There were no substantial group differences in rates of major IVH, cystic periventricular leukomalacia, chronic lung disease, necrotizing enterocolitis, the need for mechanical ventilation, or time in the hospital. There was, however, a higher rate of substantial motor dysfunction in the magnesium-treated group. No major differences were found in rates of blindness, deafness, or developmental delay. Adverse outcomes were less frequent in magnesium-treated patients than in control subjects in this study. Although not statistically significant, the differences are viewed as potentially being clinically important. The present findings do not, however, warrant routine prenatal magnesium sulfate as a neuroprotective measure in very preterm infants.