Magnesium Sulfate as an Adjunct to Therapeutic Hypothermia in the Management of Term Infants with Hypoxic-Ischemic Encephalopathy: A Randomized, Parallel-Group, Controlled Trial.

objectiveTo evaluate whether magnesium sulfate and therapeutic hypothermia in combination decreases mortality and/or major neurodevelopmental disability at 1 y of age among term neonates with hypoxic-ischemic encephalopathy.

methodsA total of 134 term neonates were randomized to receive intravenous magnesium sulfate at a dose of 250 mg/kg (at 8 mg/kg/min) once daily for 3 d starting within 6 h after birth along with therapeutic hypothermia in the intervention group and therapeutic hypothermia alone in the comparator group. The primary outcome was the composite outcome of mortality and/or major neurodevelopmental disability (Developmental Assessment Scale for Indian Infants score < 70) at 1 y of age.

resultsA total of 115 infants were included in the primary analysis. The composite primary outcome occurred in 14 (24%) infants in the intervention group and 19 (33%) infants in the comparator group, and the difference was not statistically significant (p = 0.30; relative risk 0.72; 95% confidence interval 0.40-1.30). The secondary outcomes including neonatal mortality, major neurodevelopmental disability at 1 y of age, neurological status at discharge, level of oxidative stress markers, and adverse effects including hypotension and respiratory depression requiring support were also comparable between the groups.

conclusionsThe combination of magnesium sulfate and therapeutic hypothermia did not improve the composite outcome of neonatal mortality and/or major neurodevelopmental disability at 1 y of age. TRAIL REGISTRATION: Clinical Trials Registry of India (CTRI/2018/06/014594), prospectively registered.