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).