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Optimization of Maternal Magnesium Sulfate Administration for Fetal Neuroprotection and Cerebral Palsy Prevention
Abstract Number: BP-01
Abstract Type: Original Research
Magnesium sulfate (MgSO4) is indicated for neuroprotection of the fetus delivering at < 32 weeks’ gestation (1), however the optimal dosing schedule to prevent cerebral palsy is not known. The aim of the study was to identify the optimal therapeutic maternal magnesium drug exposure and concentrations to prevent cerebral palsy (CP) in the extremely preterm fetus.
We first developed a detailed population pharmacokinetic model describing magnesium disposition in pregnant women using multiple maternal and umbilical cord blood magnesium levels from 111 patients receiving antenatal MgSO4. We then applied our enriched population pharmacokinetic model to a prospective cohort of 1,905 deliveries to women at risk of preterm delivery who participated in the BEAM trial (2). We simulated the population-based individual maternal serum magnesium concentration at the time of delivery, and the total magnesium exposure for each woman in the cohort who received MgSO4. A logistic regression model was developed to determine the relationship between total magnesium exposure and magnesium concentration at time of delivery and the development of CP.
The incidence of CP in the cohort was 3.6% for women who received MgSO4 and 6.4% for controls. The population-estimated mean maternal magnesium concentration at the time of delivery in women who received MgSO4 (n=636) and did not deliver an infant (n=611) with CP was 4.87 mg/dL (95% CI = 4.79-4.94). The total magnesium exposure associated with the lowest probability of delivering an infant with CP was 64 g (95% CI = 30–98; Figure 1). Magnesium exposure was a better predictor of delivery of an infant without CP than magnesium concentration at the time of delivery. There was no observed dose-response effect among total magnesium exposure and magnesium concentration at the time of delivery and the severity of CP.
Our population-based estimates of magnesium disposition suggest that a total dose exposure of 64 grams is required to optimize fetal neuroprotection. Using a 6 g bolus and 2 g/hour maintenance infusion protocol, nearly 30 hours of MgSO4 administration would be required to optimize CP protection. Current MgSO4 dosing regimens may need to be modified to achieve adequate magnesium exposure prior to delivery to optimize fetal neuroprotection.
1. Am J Obstet Gynecol 2009;200: 595-609
2. N Engl J Med 2008;359(9):895-905