Using prophylactic, but not tocolytic, magnesium sulfate to reduce cerebral palsy related to prematurity: what dose, and what about infant mortality?

Strategies for the prevention of cerebral palsy (CP) remain incompletely characterized. Recognizing that half of all cases are associated with preterm delivery (Australian CP Register Report, 2009), research protocols aimed at reducing its prevalence have focused on interventions in pregnancies at risk for preterm birth. Compelling data from recent clinical trials have led to an emerging consensus favoring the use of antenatal magnesium sulfate for preterm neuroprophylaxis. Unresolved, however, is the critical question regarding the "best dose". Acknowledging that any substance in high enough doses becomes toxic, the "best dose" is really the least dose that achieves efficacy, while minimizing potential toxicity among susceptible fetuses. Importantly, credible evidence from these CP prevention trials indicates that antenatal magnesium sulfate, if dosed appropriately, may also decrease infant mortality--a worthy goal in its own right. Accordingly, whether we achieve (a) reduction in CP only, (b) simultaneous reduction in CP and infant mortality, or (c) CP reduction offset by possibly increased pediatric mortality, may depend on selection of dose. In this Opinion paper, we review the findings of all major randomized trials that tested the magnesium hypothesis for prevention of CP. In addition, we discuss future research, in progress, that is hoped to refine estimates of best dose.