Prenatal magnesium at 30-34 weeks does not reduce risk of death or cerebral palsy: MAGENTA trial

1. Efficacy: There was no significant difference in death or cerebral palsy at 2 years between those who received magnesium sulfate at 30-34 weeks’ gestation compared to the placebo group; albeit the study had limited power to detect minimally important differences.

2. Safety: Adverse effects (nausea, vomiting, flushing, dry mouth, dizziness, blurred vision) were greater in the pregnant individuals who received magnesium, but there were no serious cardiovascular or respiratory effects from the magnesium infusion.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Premature infants are at increased risk of cerebral palsy, a common childhood motor disorder associated with severe disability. Prenatal magnesium sulfate has become standard to protect fetal brains and lower cerebral palsy risk. However, there is no clear global consensus on when to administer it. The MAGENTA (Magnesium Sulfate at 30 to 34 Weeks’ Gestational Age) trial examined the impact of intravenous magnesium sulfate on pregnant individuals at risk of preterm birth between 30 to 34 weeks of gestation. The results showed no significant difference in death or cerebral palsy rates at 2 years between the magnesium and placebo groups. Interestingly, magnesium reduced respiratory distress syndrome and chronic lung disease in newborns but increased behavioral problems with an unknown biological basis. The study had limitations due to lower-than-expected events, which meant the sample size lacked the power to detect small differences between groups. These findings differ from earlier trials that found beneficial magnesium for reducing risk of cerebral palsy at earlier gestational ages but offer valuable insights for clinical decision-making surrounding the timing and necessity of prenatal magnesium sulfate administration.

Click to read the study in JAMA

Click to read an accompanying editorial in JAMA

Relevant Reading: Antenatal magnesium sulphate for the prevention of cerebral palsy in infants born preterm: a double-blind, randomised, placebo-controlled, multi-centre trial

In-Depth [randomized clinical trial]: This placebo-controlled randomized clinical trial involved 24 hospitals in Australia and New Zealand from January 2012 to April 2018. A total of 1433 pregnant individuals at risk of preterm birth and 1365 infants were enrolled in the study. Exclusion criteria included those with contraindications to magnesium sulfate (respiratory depression, hypotension, absent patellar reflexes, kidney failure or myasthenia gravis) and those who needed magnesium sulfate for treatment of preeclampsia. Participants were randomized to two groups, either receiving 4 g of magnesium or isotonic normal saline as placebo. The primary outcome was death (stillbirth, death before or after hospital discharge) or cerebral palsy in children at 2 years’ corrected age. At the follow-up, neurological, psychological and caregiver-reported assessments were also completed. There were 36 secondary outcomes that further assessed the health of the pregnant individual and infant. At 2 years, death or cerebral palsy was not statistically significant between groups, with an adjusted risk ratio of 1.19, p=0.57. Adverse events were 3.76 times more likely to occur in individuals who received magnesium versus placebo, but they tended to be minor infusion-related side effects and not life-threatening ones. Overall, the study conducted a thorough assessment of multiple health outcomes postnatally and contributed to the efficacy and safety profile of magnesium sulfate prenatally.

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