Magnesium Sulfate in Severe Perinatal Asphyxia: A Randomized, Placebo-Controlled Trial

Abstract

Hypoxic-ischemic encephalopathy (HIE) is associated with high morbidity and mortality in the neonatal period and permanent neurodevelopmental deficits among survivors. Animal studies have shown beneficial effects of magnesium sulfate in perinatal asphyxia but only 1 uncontrolled human trial has shown beneficial effects of postnatal magnesium sulfate in neonates with perinatal asphyxia. This longitudinal randomized, placebo-controlled trial tested whether postnatal magnesium sulfate treatment could improve neurologic outcomes at discharge among term neonates with severe perinatal asphyxia. The study subjects were 40 term (≥37 weeks) neonates born at a tertiary-care hospital in India between 2004 and 2006 who were <6 hours of age at the time of admission. Infants were randomly assigned to receive infusions of either magnesium sulfate (250 mg/kg per dose (1 mL/kg per dose) over 1 hour, with 2 additional doses repeated at intervals of 24 hours (treatment group, n = 20) or 3 doses of normal saline (1 mL/kg per dose) 24 hours apart (placebo group, n = 20). Supportive care available for both groups when needed included respiratory and presser support. At admission, the percentage of patients with moderate and severe HIE were similar in the treatment and placebo groups (treated: 35% 7/20 and 65% 13/20 vs. placebo: 40% 8/20 and 60% 12/20). The mean serum magnesium concentration remained within the therapeutic range (at or above 1.2 mmol/L) for 72 hours after the first infusion. At discharge, neurologic abnormalities were present in 22% (4/18) of infants in the treatment group and in 56% (10/18) of infants in the placebo group. On day 14 of life, neuroimaging (head computed tomography) results were abnormal among fewer infants in the treatment group (16% 3/18) than in the placebo group (44% 8/18). At discharge, 77% (14/18) infants in the treatment group were receiving oral feeding through sucking compared with 37% (7/18) infants in the placebo group. Good short-term outcomes (a composite measure of no neurologic abnormality, normal neuroimaging and electroencephalographic findings, and oral feeding through sucking) were 77% ( 14/18) for patients in the treatment group, compared with 37% (7/18) for patients in the placebo group. These findings demonstrate that postnatal treatment with magnesium sulfate improves neurologic outcomes at discharge for term neonates with HIE. This is the first placebo-controlled study to show the efficacy of postnatal magnesium sulfate treatment in perinatal asphyxia.