Giving intravenous magnesium sulfate to pregnant women at risk of preterm birth at 30 to 34 weeks’ gestation did not improve the primary endpoint of death or cerebral palsy in their offspring at 2 years of age, new research shows, although the study had limited power to detect small between-group differences.
Previous evidence has shown that administering magnesium sulfate to pregnant women at less than 30 weeks’ gestation improves the chance their infant will survive without cerebral palsy, and guidelines recommend this intervention, but there’s a lack of consensus regarding the optimal gestational age for its use.
The multisite MAGENTA trial included 1433 pregnant women at risk of preterm birth for whom delivery was anticipated or was planned to occur within 24 hours. The mean age of the cohort was 30.6 years. The women were randomly assigned to receive magnesium sulfate (4 g) or placebo intravenously at 30–34 weeks’ gestation.
Surviving children were assessed by a pediatrician as soon as possible to the children’s turning 2 years of age. The assessment included a neurologic examination to diagnose cerebral palsy, defined as loss of motor function and abnormalities of muscle tone and power.
Of the 1679 infants included in the analysis, about 81% were included for the primary outcome of death or cerebral palsy.
Death or cerebral palsy at 2 years occurred in 3.3% of children in the magnesium group and in 2.7% of the children in the placebo group (risk difference, 0.61%; 95% CI, -1.27% to 2.50%; adjusted relative risk [aRR] 1.19; 95% CI, 0.65 – 2.18; P = .57).
As for other outcomes, significantly fewer infants who were exposed to magnesium had neonatal respiratory distress syndrome (aRR, 0.85; 95% CI, 0.76 – 0.95) or chronic lung disease (aRR, 0.69; 95% CI, 0.48 – 0.99), but they had more behavioral problems: 10% had scores on the Child Behavior Checklist within the problem range, compared with 6% in the placebo group (aRR, 1.66; 95% CI, 1.03 to 2.68; P = .04.)
All adverse events (AEs) were more common in the magnesium group, including infusion-related outcomes such as nausea, vomiting, flushing, and infusion arm discomfort, but there were no serious cardiovascular or respiratory AEs from the study infusion.
The results can be used to aid decisions on the use of prenatal magnesium for women at risk of preterm birth, the authors write. They note that further follow-up is needed “to assess the balance of the possible benefits and harms” of magnesium later in childhood.
Although well designed, the study had “some considerations for interpretation,” including sample size, said Judette Marie Louis, MD, Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, and a colleague in an accompanying editorial. Decreasing the burden of cerebral palsy in infants born at later gestational ages “may best be achieved by developing strategies to mitigate specific morbidities occurring during the perinatal and postnatal periods,” such as hypoxic ischemic encephalopathy and intraventricular hemorrhage, they write.
The study was conducted by Caroline A. Crowther, MD, Liggins Institute and School of Medicine, University of Adelaide, Australia, and colleagues. It was published online August 15, 2023, in JAMA.
Because event rates for death and cerebral palsy were lower than predicted, the study lacked power to detect small but potentially important differences in risk of death or cerebral palsy. The primary outcome was only available for 81% of the infants. Patients were treated at hospitals in Australia and New Zealand, countries that have publicly funded, well-coordinated healthcare systems, so results may not be generalizable to other healthcare settings.
The study received support from the National Health and Medical Research Council in Australia and the Cerebral Palsy Alliance Research Foundation Australia. The study authors have disclosed no relevant conflicts of interest; Louis has received personal fees from Wolters Kluwer, Elsevier, and Cytyc Corporation.
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