Available evidence now suggests that magnesium sulfate administered to mothers prior to early preterm delivery reduces the risk of cerebral palsy in surviving neonates. The American College of Obstetricians and Gynecologists along with the Society for Maternal-Fetal Medicine state that physicians who choose to administer magnesium sulfate for neuroprotection should do so in accordance with one of the larger randomized trials. Due to the heterogeneity of the methods, many clinicians may find it difficult to proceed with a therapeutic protocol that adheres to the available literature. Here, we present one reasonable approach that identifies the specific patients who qualify for magnesium sulfate therapy, and it outlines a treatment algorithm while addressing retreatment and concomitant tocolysis.
Observational data in the 1990s pointed to an association between decreased neurological morbidities in preterm infants and exposure to magnesium sulfate. Since this observation, the use of magnesium for neuroprotection to decrease the rate of cerebral palsy has been examined in 5 randomized controlled trials. Individually, the primary outcomes in each of these studies showed no difference when a composite measure of infant death or cerebral palsy was investigated. Only on secondary analysis was benefit seen in decreasing the rate of gross motor dysfunction. A metaanalysis by Doyle et al published in 2009 showed a significant reduction in cerebral palsy in infants exposed to magnesium sulfate (relative risk, 0.71; 95% confidence interval [CI], 0.55–0.91). Additionally, the composite measure of infant death or cerebral palsy was likewise reduced in fetuses exposed to magnesium (relative risk, 0.85; 95% CI, 0.74–0.98). Because the analysis showed these benefits, and because there was no statistical increase in the rate of fetal or infant death with magnesium sulfate therapy, the authors concluded that the evidence now supports antenatal magnesium as a neuroprotective agent against cerebral palsy in fetuses <32 weeks. Subsequent metaanalyses have shown similar findings.
With the recent surge of publications regarding magnesium benefits to neonates, the American College of Obstetricians and Gynecologists (ACOG) and Society for Maternal-Fetal Medicine released a joint clinical opinion in March 2010. The opinion states that “available evidence suggests that magnesium sulfate given before anticipated early preterm birth reduces the risk of cerebral palsy in surviving infants.” It then points out that physicians who choose to use magnesium sulfate for neuroprotection should do so in accordance with the protocols of one of the larger trials.
One of the difficulties faced by the clinician is that the 2 largest trials utilized different protocols for magnesium administration and dosing. Many clinicians may find it challenging to create a protocol that properly adheres to the available studies. In addition, no specific guidelines exist to help with patient selection other than to recommend its use in women “at increased risk” of preterm delivery. Given the poor positive predictive value of most recognized risk factors for preterm birth, clinicians may find it difficult to identify patients who are optimal candidates for magnesium sulfate use for neuroprotection. Thus, at present, the clinician who simply wants to know “who to treat” and “how to treat” in order to be in compliance with the protocols of the published studies finds few helpful answers in the available literature or recommendations from professional organizations.
Our purpose is to provide recommendations for one regimen of magnesium sulfate administration for neuroprotection of the neonate that is specific and reflects current literature. Given the current status of the literature, it is clear that other approaches are equally appropriate.
Proposed protocol
We propose the administration of magnesium sulfate for neuroprotection to women who meet one of the criteria in the Figure . This Figure also presents an algorithm for the administration of this medication to eligible mothers. Patients are considered eligible for magnesium sulfate for neuroprotection if they have a pregnancy with a gestational age between 23 weeks and 31 weeks and 6 days. This extends below the Rouse et al protocol because many institutions will begin neonatal resuscitation at a gestational age <24 weeks. Modifications to our protocol can be made depending upon individualized institutional practices regarding the lower limit of gestational age where neonatal resuscitation will be attempted.
