A Randomized Controlled Trial on the Efficacy of Intravenous Magnesium Therapy in Perinatal Asphyxia in a Resource-poor Setting

Objective: This study was conducted in the Neonatal Intensive Care Unit (NICU) of a teaching hospital situated in a rural area of Bihar to ascertain the impact of postnatal magnesium sulfate (MgSO4) infusion on moderately to severely asphyxiated neonates. Methods: This single-blind, parallel-group, prospective, longitudinal, randomized controlled trial (RCT) was carried out to study the effect of postnatal magnesium sulfate (MgSO4) infusion on the mortality and neurological morbidity of term (born at 37-42 weeks of gestation) and post-term (>42 weeks of gestation) neonates with severe perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) stage II (moderate) or III (severe) (Sarnat & Sarnat staging) at 24 hours,at 7 days andat discharge. Fifty (50) patients of severe perinatal asphyxia with HIE stage II or above admitted over a period of 6 months were included in the study. The patients were assigned randomly in two groupsone group of 25 neonates received 3 doses of intravenous MgSO4 infusion at 250 mg/kg/dose (0.5 mL/Kg/dose of inj. MgSO4 (50% w/v) 24 hours apart, and the other 25 neonates did not receive this treatment. Other supportive care as per protocol for perinatal asphyxia was given to the patients in both the groups equally. Outcomes: The incidence of moderate (stage II) and severe (stage III) encephalopathy at NICU admission was the same in both the groups, that is, 18 (72.0%) and 7 (28.0%), respectively. The MgSO4-treated group had an eventual mortality rate of 5.6% (1 out of 18) for neonates with stage II (moderate) encephalopathy and 42.8% (3 out of 7) for those with stage III (severe) encephalopathy. On the other hand, the group that was not given MgSO4 suffered a mortality of 22.2% (4 out of 18) among newborns with HIE stage II (moderate encephalopathy) and 85.7% (6 out of 7) for stage III (severe) encephalopathy.Seizures were present on day 1 in all the 18 patients (100%) with stage II (moderate) encephalopathy in both the control and the treatment groups, but while only 2 (11.1%) of them in the treatment arm still had seizures at 24 hours of admission, 6 (33.3%) of neonates with moderate encephalopathy (HIE stage II) in the control arm had electroencephalographic (EEG) evidence of active seizures at 24 hours, even though all the patients with seizures were treated according to the same standard protocol for neonatal seizures due to perinatal asphyxia. Similarly, the proportion of neonates able to feed orally by day 7 of admission was 71.4% (15 out of the surviving 21) in the MgSO4-treated group, whereas only 33.3% (5 out of the surviving 15) could suckle orally by that time in the control group. At discharge, abnormal neurological findings upon examination using the NeoNeuro& Up scoring by Ellison were present in 28.6% of the surviving newborns (6 out of 21 surviving) and 24.0% (6 out of 25) of the total in the treatment group. The control group had abnormal neurological findingsin 60.0% of surviving neonates (9 out of 15 surviving) and 36.0% (9 out of 25) of the total number of babies in the control group. No significant adverse effects of MgSO4 were observed at the used dosage on hemodynamic parameters and respiration. Conclusion: Intravenous MgSO4 therapy decreases mortality and neurological morbidity in neonates with moderate (stage II) to severe (stage III) perinatal asphyxia and improves short-term outcomes.