Neonatal magnesium sulphate for neuroprotection: A systematic review and meta-analysis

Aim: To review the evidence of the effects of neonatal magnesium sulphate for neuroprotection in perinatal asphyxia and hypoxic-ischaemic encephalopathy (HIE). 

Method: This was a systematic review of randomized controlled trials (RCTs) (with meta-analysis) and non-RCTs assessing magnesium sulphate for treating perinatal asphyxia and HIE at 35 weeks or more gestation (primary outcomes: neonatal death and death or long-term major neurodevelopmental disability). 

Results: Twenty-five RCTs (2099 infants) and four non-RCTs (871 infants) were included, 23 in low- and middle-income countries (LMICs). In RCTs, reductions in neonatal death with magnesium sulphate versus placebo or no treatment (risk ratio [RR] = 0.68; 95% confidence interval [CI] = 0.53–0.86; 13 RCTs), and magnesium sulphate with melatonin versus melatonin alone (RR = 0.74; 95% CI = 0.58–0.95; one RCT) were observed. No difference in neonatal death was seen for magnesium sulphate with therapeutic hypothermia versus therapeutic hypothermia alone (RR = 0.66, 95% CI = 0.34–1.26; three RCTs), or magnesium sulphate versus phenobarbital (RR = 3.00; 95% CI = 0.86–10.46; one RCT). No reduction in death or long-term neurodevelopmental disability (RR = 0.52; 95% CI = 0.14–1.89; one RCT) but reductions in several short-term adverse outcomes were observed with magnesium sulphate. Evidence was low- to very-low certainty because of risk of bias and imprecision. 

Interpretation: Given the uncertainty of the current evidence, further robust neonatal magnesium sulphate research is justified. This may include high-quality studies to determine stand-alone effects in LMICs and effects with and after therapeutic hypothermia in high-income countries.