The role of magnesium sulfate (MgSO₄) in fetal neuroprotection

Prevention of neurologic disability associated with preterm birth is one of the major challenges in current perinatal medicine. Magnesium sulfate (MgSO₄), the focus of this review has been proposed as major step forward for that matter. MgSO₄ is easily accessible, cheap, and has been proposed as a mandatory part of the management of inevitable preterm birth. The results of the various RCT's on the use of MgSO₄ for neuroprotection has been the subject of many systematic reviews, other studies focused on dosing schedules, side effects and only a few focused on exploring magnesium's mechanism of action. Meanwhile, many guidelines worldwide have plugged MgSO₄ as an essential ingredient of daily best practice when managing inevitable preterm birth because it has been shown to reduce the risk of severe neurologic deficit, in particular, cerebral palsy in appropriately selected patients. The more premature, the greater benefit associated with the use of antenatal MgSO₄. The dose of 4 g given intravenously 15 min continued by 1 g/h until maximum 24 h and minimum for 4 h is the standard regiment proposed in most guidelines. It should be noted, however, that a recent study found that a total dose of 64 g was associated with the maximum protective effect. Only the protocol used by the largest RCT, the BEAM trial, with a loading dose of 6 g initially followed by a 2-g/h maintenance dose, if continued for 24 h would give a total dose over 50 g. Other studies report on an increased risk of neonatal death with these high doses. Several studies expressed concerns about the risk of serious side effects for both mother and neonate. The results from the systematic review showed that the most commonly used dosage, 4 g bolus continued by 1 g/h maintenance, did not increase neonatal mortality and other suspected neonatal complication such as neonatal asphyxia, spontaneous intestinal perforation, necrotizing enterocolitis, and feeding intolerance. Giving a single bolus injection of 4 g MgSO4 for stimulating BDNF production in highly "suspicious" preterm labor, and 4 g again when preterm birth become inevitable may be best from a safety perspective and also appears to have a stronger rationale.