Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 64 1 2026 02 18 11694 11694 Nahid Kiani Department of Pediatrics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Maryam Shokouhi Solfi Department of Pediatrics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. AND Clinical Research Development Unit of Fatemieh Hospital, Hamadan University of Medical Sciences, Hamadan, Iran. Mohammad Kazem Sabzehei Department of Pediatrics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Fatemeh Eghbalian Department of Pediatrics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Nasrin Jiraiyaae Department of Community Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Behnaz Basiri Department of Pediatrics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. AND Clinical Research Development Unit of Fatemieh Hospital, Hamadan University of Medical Sciences, Hamadan, Iran. 2025 06 09 2025 11 09 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. https://acta.tums.ac.ir/index.php/acta/article/view/11694 https://acta.tums.ac.ir/index.php/acta/article/download/11694/6009