Investigating the Effect of Melatonin on Short-Term Prognosis of Neonatal Hypoxic-Ischemic Encephalopathy: A Randomized Controlled Trial

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal mortality with limited therapeutic options. This study evaluated the effect of melatonin on short-term outcomes in neonates with HIE. To determine whether adjunctive oral melatonin improves short-term clinical outcomes, including in-hospital survival, in neonates with HIE. A randomized controlled trial enrolled 80 neonates with HIE at Fatemieh Hospital, Hamadan, Iran (2021-2023). The intervention group (n=32) received standard treatment plus 10 mg/kg oral melatonin daily for 5 days, while the control group (n=48) received standard treatment alone. Outcomes included seizure frequency, hospital stay duration, time to initiate oral feeding, time to regain consciousness, adverse effects, and in-hospital survival. Baseline characteristics, HIE severity, medications for seizure control, and paraclinical/imaging findings were comparable between groups (all P>0.05). No significant adverse effects were observed. The intervention group had a higher survival rate (81.2%, 26/32) than the control group (52.1%, 25/48) (P=0.04). There were no significant differences in hospital length of stay, time to start feeding, or time to regain consciousness among surviving neonates (all P>0.05). Adjunctive melatonin may improve in-hospital survival in neonates with HIE and merits further evaluation as an additive therapy.