Antenatal Magnesium Sulfate Decreases Risk of Cerebral Palsy

CONTEXT Infants born prematurely have high risk to develop cerebral palsy. Antenatal interventions that have the potential to prevent premature delivery shall also aim to reduce risks to both mother and their infants. At the current time, there are limited data to suggest that such intervention exists. This study by Rouse et al. aimed to prevent death or cerebral palsy by administering MgSO 4 antenatally to women at high risk for spontaneous or indicated premature delivery. METHODS Multicenter randomized controlled trial in the United States.[Table 1]Table 1: Main resultsPopulation Inclusion Pregnant women (singletons/twins) at 24 to 31 week's gestation at high risk of spontaneous premature delivery due to rupture of membrane (ROM) (22-31 wk) or advanced labor (cervix 2-8 cm dilated) or planned to deliver within 2-24 hours. Exclusion Anticipated delivery within 2 hours; Dilated cervix >8 cm; ROM before 22 week's gestation; Unwillingness of the obstetrician to intervene for the benefit of the fetus; Major fetal anomalies or death; Hypertension/preeclampsia; Contraindications to magnesium sulfate; IV magnesium sulfate given within the previous 12 hours. Intervention MgSO 4 group 6 g of IV MgSO 4 over 20-30 min followed by 2 g/h continuous infusion and stopped after 12 hours if delivery is not imminent (no uterine contractions) and restarted if it is imminent. If stopped longer than 6 hours, then same bolus dose will be repeated as well. Control group Identical placebo Intervention will be discontinued if patient developed preeclampsia/eclampsia or reached 34 week's gestation. Outcomes Primary Composites of stillbirth/infant death at 1 year or moderate or severe cerebral palsy at 2 years. Secondary Various maternal and neonatal outcomes and complications including adverse side effects of MgSO 4, death, various degrees of cerebral palsy, and developmental delay measured by Gross Motor Function Classification System and Bayley Scales of Infants development II, respectively. Allocation Computer generated and stratified according to gestation, twins. Blinding Blinded (mothers, healthcare givers, outcome assessors). Follow-up Primary outcome was done in 95.6% of fetuses. RESULTS Although there was no statistical significant difference between groups in the main composite outcome of death or moderate or severe cerebral palsy, the risk of moderate or severe cerebral palsy was significantly lower in the MgSO 4 group. Moreover, there were no significant differences in other outcomes such death or other neonatal outcomes except for the need for mechanical ventilation, which was less in MgSO 4 group (relative risk (RR): 0.92, confidence interval (CI): 0.85-0.99). Administering MgSO 4 to women at less than 28 week's gestation had much better effect on moderate or severe cerebral palsy (RR: 0.45, CI: 0.23-0.87) but no effect when given at 28 week's gestation or more (RR: 1.00, CI: 0.38-2.65). In regard to the side effect, this study did not find any serious maternal or neonatal adverse outcome. COMMENTARY This study has shown the neuroprotective benefit of antennal MgSO 4 given to women at risk of premature delivery. Previously, there was doubt regarding the efficacy and safety. However, Cochrane Systematic Review has confirmed this effect. [1] Clinical practice guidelines have been developed in Australia and Canada. [2,3] The guidelines are similar but vary in some aspects such as doses and indications, but neuroprotection was their main aim. It is worth mentioning that the American College of Obstetric and Gynaecology has not yet recommended it routinely. [4] Currently, MgSO 4 is not an effective tocolytic agent. However, if the aim of prolonging gestation is to minimize maternal and neonatal mortality and morbidity, then it is sound to recommend MgSO 4 as it is the only potential tocolytic agent that has neuroprotective effect. In summary, MgSO 4 is being used in obstetric care for different indications. It has been shown to be effective for neuroprophalxis to decrease the risk of moderate to severe cerebral palsy. Based on the current evidence, we recommend administering MgSO 4 antenatally to women at high risk of premature delivery under individualized clinical practice guidelines. Abstracted from Rouse DJ, Hirtz DG, Thorn E, Varner MW, Spong CY, Mercer BM, et al. for the Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine units Network. A randomised, controlled trial of magnesium sulphate for the prevention of cerebral palsy. N Engl J Med 2008;359:895-905. ClinicalTrials.gov number, NCT00014989

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