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The use of intravenous magnesium sulfate prior to preterm birth at 30 to 34 weeks' gestation failed to improve survival and incidence of cerebral palsy among infants up to 2 years post-delivery, the randomized MAGENTA trial showed.

In the primary outcome analysis that included 1,365 children, death or cerebral palsy assessed by a pediatrician at 2 years' corrected age occurred in 3.3% of those in the magnesium group and 2.7% of those in the placebo group (adjusted relative risk [RR] 1.19, 95% CI 0.65-2.18, P=0.57), reported Caroline Crowther, MD, of the University of Auckland in New Zealand, and colleagues.

Looking at each outcome separately, there were 12 deaths in the magnesium group versus seven deaths in the placebo group by 2 years of age (aRR 1.50, 95% CI 0.58-3.86, P=0.40), while 1.6% versus 1.7%, respectively, had cerebral palsy (aRR 0.98, 95% CI 0.43-2.23, P=0.96), they noted in .

In an email to MedPage Today, Crowther noted that "cerebral palsy remains the most frequent cause of severe motor disability in childhood and preterm birth is a principal risk factor. As there is no cure for cerebral palsy, primary prevention is of importance."

"Although clinical practice guidelines worldwide now recommend the use of prenatal magnesium sulfate prior to preterm birth for fetal neuroprotection, there is a lack of consensus, due to limited data, as to the optimal gestational ages for its use," she added.

The study authors pointed out that their "trial's findings contrast with trials that identified a benefit of intravenous magnesium for children born at earlier gestational ages. The reason for the lack of effect in the age range of 30 to 34 weeks' gestation is unclear."

"The risk differences for the combined outcome of death or cerebral palsy, and its components of death and cerebral palsy in the current trial, are consistent with the treatment effect and CIs reported in [a prior] among the age subgroups of 30 to 31 weeks' gestation and 32 weeks' gestation or longer," they wrote. "It is possible that the mechanism of brain injury by which extremely preterm birth leads to cerebral palsy may be different from mechanisms relevant at later gestational ages."

In an , Judette Marie Louis, MD, MPH, and Tara Marie Randis, MD, MS, both of the University of South Florida in Tampa, noted that concerns about other adverse outcomes with the administration of prenatal magnesium have been reported over the past decade.

"Most of these concerns have focused on gastrointestinal complications in infants born before 25 weeks' gestation, including an increased risk of meconium-related ileus, spontaneous intestinal perforation, and necrotizing enterocolitis," they wrote. "A 2019 designed to examine the association between prenatal magnesium sulfate administration, perinatal death, and other unintended adverse neonatal outcomes revealed no clear link, providing reassurance regarding the safety of this practice."

"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," they concluded. "The time has come to limit intrapartum magnesium for neurological protection to patients who are at risk to give birth before 30 weeks' gestation."

Of note in the current study, newborns in the magnesium group were less likely to have respiratory distress syndrome compared with the placebo group (34% vs 41%, respectively; aRR 0.85, 95% CI 0.76-0.95), as well as chronic lung disease (5.6% vs 8.2%; aRR 0.69, 95% CI 0.48-0.99) during hospitalization at birth.

However, children exposed to magnesium were more likely to have overall behavioral scores within the clinical problem range: 10% in the magnesium group compared with 6% in the placebo group (aRR 1.66, 95% CI 1.03-2.68, P=0.04).

"Significant findings for some of the secondary outcomes were unexpected, particularly the neonatal benefits of less respiratory distress syndrome and chronic lung disease in babies exposed to magnesium sulfate," Crowther said. "The suggestion of more behavioral problems in children whose mothers were given magnesium sulfate was also unexpected, although later follow-up to early school age in previous trials has not shown such differences between children exposed or not."

In the , 56% of the mothers in the magnesium group had a cesarean delivery versus 61% in the placebo group (aRR 0.91, 95% CI 0.84-0.99), but more women in the magnesium group had a major postpartum hemorrhage (3.4% vs 1.7%, respectively; aRR 1.98, 95% CI 1.01-3.91).

This study was conducted at 24 Australian and New Zealand hospitals from January 2012 to April 2018. The researchers enrolled 1,433 pregnant individuals. Mean age was 30.6; 3.2% self-identified as Aboriginal or Torres Strait Islander, 16.5% as Asian, 5.7% as Māori, 4.3% as Pacific, and 67.4% as white. Of the 1,679 infants, 81% were included in the primary outcome analysis: 691 were randomized to 4-g intravenous magnesium sulfate and 674 were given placebo.

The primary outcome was death (stillbirth, death of a live-born infant before hospital discharge, or death after hospital discharge) before 2 years' corrected age or cerebral palsy (loss of motor function and abnormalities of muscle tone and power assessed by a pediatrician) at 2 years' corrected age.

Overall, there were no serious cardiovascular or respiratory adverse outcomes from the study infusion among mothers. Adverse events such as nausea, vomiting, flushing, arm discomfort, dry mouth, dizziness, and blurred vision occurred in 77% of those in the magnesium group compared with 20% of the placebo group.

Crowther and colleagues noted that because event rates for death and cerebral palsy were lower than predicted, the sample size "lacked power to detect small but potentially important differences in the risk of death or cerebral palsy."

In addition, the study's findings are most likely only generalizable to similar healthcare settings, which in this case were publicly funded and well-coordinated facilities in two high-income countries.

"Further assessment on the efficacy and safety of magnesium for neuroprotection in lower-resource settings is warranted," they wrote.

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