Fetal Neuroprotection by Magnesium Sulfate: From Translational Research to Clinical Application

Despite improvements in perinatal care, preterm birth still occurs regularly and the associated brain injury and adverse neurological outcomes remain a persistent challenge. Antenatal magnesium sulfate administration is an intervention with demonstrated neuroprotective effects for preterm births before 32 weeks of gestation (WG). Owing to its biological properties, including its action as an N-methyl-d-aspartate receptor blocker and its anti-inflammatory effects, magnesium is a good candidate for neuroprotection. In hypoxia models, including hypoxia-ischemia, inflammation, and excitotoxicity in various species (mice, rats, pigs), magnesium sulfate preconditioning decreased the induced lesions' sizes and inflammatory cytokine levels, prevented cell death, and improved long-term behavior. In humans, some observational studies have demonstrated reduced risks of cerebral palsy after antenatal magnesium sulfate therapy. Meta-analyses of five randomized controlled trials using magnesium sulfate as a neuroprotectant showed amelioration of cerebral palsy at 2 years. A meta-analysis of individual participant data from these trials showed an equally strong decrease in cerebral palsy and the combined risk of fetal/infant death and cerebral palsy at 2 years. The benefit remained similar regardless of gestational age, cause of prematurity, and total dose received. These data support the use of a minimal dose (e.g., 4 g loading dose ± 1 g/h maintenance dose over 12 h) to avoid potential deleterious effects. Antenatal magnesium sulfate is now recommended by the World Health Organization and many pediatric and obstetrical societies, and it is requisite to maximize its administration among women at risk of preterm delivery before 32 WG.