Later Administration of Prenatal Magnesium Sulfate Does Not Reduce Cerebral Palsy

Magnesium sulfate is highly effective at preventing cerebral palsy and death in infants at risk of preterm birth when given during labor less than 30 weeks into pregnancy. It’s so effective, in fact, that many maternity departments routinely infuse it up to 34 weeks despite limited research.

A randomized controlled trial that enrolled 1,433 pregnant women through 24 hospitals in Australia and New Zealand between 2012 and 2018 looked for evidence of benefit when given later in the preterm period.

It didn’t find any.

The study results, published Tuesday, Aug. 15, 2023, in JAMA Network, showed no statistical difference between intervention and placebo groups in the primary outcome: cerebral palsy or death at two years’ corrected age (from birth minus the number of weeks a baby was born premature). There also were no differences in multiple secondary outcomes, such as major neurological disability and specific neurosensory impairments.

Researchers did find a significant reduction in neonatal respiratory distress syndrome.

Neither the study authors nor an accompanying editorial took the lack of evidence for the main and secondary outcomes to be final. Both noted, for example, that the sample size had turned out to be too small to detect statistically significant differences.

First author Caroline A. Crowther, M.D.. a professor of maternal and perinatal health at the University of Aukland Liggins Institute in Aukland, New Zealand and colleagues had estimated a 9.6% incidence of cerebral palsy or death in this specific population and powered the study accordingly. But the frequencies observed in the trial were much lower: 3.3% in the magnesium sulfate group and 2.7% in the placebo group.

“Nevertheless, given a lack of benefit in this current cohort of infants, care must be taken to avoid therapeutic creep and the potential for unintended harm, Judette Marie Louis, M.D., MPH, chair of the Department of Obstetrics and Gynecology at the University of South Florida Morsani College of Medicine in Tampa, Fla. and Tara Marie Randis, M.D., an associate professor in the department, wrote in the editorial.

They point out the potential risk of increased behavioral problems experienced by children exposed to magnesium. Additionally, Louis and Randis call attention to the risk to infants of a condition where meconium obstructs the small intestine; intestinal perforation; and necrotizing enterocolitis, which is a life-threatening inflammation of the intestine that can damage the colon and the intestine.

“The time has come to limit intrapartum magnesium for neurological protection to patients who are at risk to give birth before 30 weeks’ gestation," the editorial authors wrote.