Outcomes of Neonates with Hypoxic-Ischemic Encephalopathy Treated with Magnesium Sulfate: A Systematic Review with Meta-analysis

Objective: To assess magnesium sulfate (MgSO₄) as a neuroprotective agent in hypoxic-ischemic encephalopathy. Study design: For this systematic review, PubMed, EMBASE, the Cochrane Library, EMCARE, and MedNar were searched in November 2022 for randomized controlled trials (RCTs). Meta-analysis was conducted using Stata 16.0 and RevMan 5.3. Results: Twenty RCTs with a total sample size of 1485 were included, of which 16 were from settings where therapeutic hypothermia (TH) was not offered. Regarding MgSO₄ in settings where TH was not offered, only 1 study evaluated composite outcome of death or disability at ≥18 months and reported such poor outcome in 8 of 14 control infants and 4 of 8 in the MgSO₄ group. MgSO₄ was not associated with mortality (RR, 0.86; 95% CI, 0.72-1.03; 13 RCTs) or hypotension (RR, 1.02; 95% CI, 0.88-1.18; 5 RCTs). Thirteen studies reported that MgSO₄ improved in-hospital outcomes, such as reduced seizure burden and improved neurological status at discharge. MgSO₄ reduced the risk of poor suck feeds (RR, 0.52; 95% CI, 0.40-0.68; 6RCTs) and abnormal electroencephalogram (RR, 0.64; 95% CI, 0.45-0.93; 5 RCTs). Certainty of evidence was moderate for mortality and low or very low for other outcomes. For studies with MgSO₄ as an adjunct to TH, none reported on death or neurodevelopmental disability at ≥18 months. MgSO₄ was not associated with mortality (RR, 0.65; 95% CI, 0.34-1.27; 3 RCTs) or hypotension (RR, 1.0; 95% CI, 0.71-1.40; 3 RCTs). Conclusions: Evidence around long-term outcomes of MgSO₄ when used with or without TH was scant. MgSO₄ therapy may improve in-hospital neurological outcomes without affecting mortality in settings where TH is not offered. Well-designed RCTs for neuroprotection are needed, especially in low-resource settings. Trial registration: “Open Science Forum” (https://doi.org/10.17605/OSF.IO/FRM4D).