ABSTRACT
OBJECTIVE: To 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. METHODS: A 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. RESULTS: A 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. CONCLUSIONS: The 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.