Optimization of Maternal Magnesium Sulfate Administration for Fetal Neuroprotection: Application of a Prospectively Constructed Pharmacokinetic Model to the BEAM Cohort

The aim of the study was to identify the optimal therapeutic maternal magnesium drug exposure and maternal serum concentration to prevent cerebral palsy in the extremely preterm fetus. We applied a previously constructed pharmacokinetic model adjusted for indication to a large cohort of pregnant women receiving magnesium sulfate to prevent cerebral palsy in their preterm offspring at 20 different US academic centers between December 1997 and May 2004. We simulated the population-based individual maternal serum magnesium concentration at the time of delivery and the total magnesium dose for each woman who received magnesium sulfate to determine the relationship between maternal serum magnesium level at the time of delivery and the development of cerebral palsy. Among 1905 women who met inclusion criteria, the incidence of cerebral palsy in the cohort was 3.6% for women who had received magnesium sulfate and 6.4% for controls. The simulated maternal serum concentration at delivery associated with the lowest probability of delivering an infant with cerebral palsy was 4.1 mg/dL (95%CI 3.7 to 4.4). Our population-based estimates of magnesium disposition suggest that to optimize fetal neuroprotection and prevent cerebral palsy, magnesium sulfate administration should target a maternal serum magnesium level between 3.7 and 4.4 mg/dL at delivery.