Document Type : Review Article
Authors
1
Department of Genetics, Faculty of Advanced Sciences and Technology, TeMS.C, Islamic Azad University, Tehran, Iran
2
Neonatal Health Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3
Department of Neonatology. NICU ward, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4
Department of Pediatrics, School of Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
5
Tehran University of Medical Sciences, Children’s Medical Center, Pediatric Center of Excellence, Tehran, Iran
10.22038/ijn.2025.92245.2796
Abstract
Background: Neonatal sepsis and encephalopathy are life-threatening conditions marked by excessive inflammation and oxidative stress, contributing to high morbidity and mortality in newborns. Melatonin, a multifunctional indoleamine with potent antioxidant, anti-inflammatory, and immunomodulatory properties, has emerged as a promising adjunctive therapy in neonatal care. This review summarizes current evidence on melatonin’s biological functions and its potential to reduce inflammation, oxidative damage, and improve neonatal outcomes.
Methods: A narrative review was conducted by searching PubMed, Scopus, Web of Science, and Google Scholar from 2000 to November 2025 using the keywords melatonin, neonatal sepsis, and methicillin-resistant Staphylococcus aureus (MRSA). Relevant experimental, preclinical, and clinical studies were identified, reviewed, and synthesized to provide an integrated overview of melatonin’s effects in neonatal sepsis and related inflammatory conditions.
Results: Preclinical studies indicate that melatonin downregulates pro-inflammatory cytokines (e.g., TNF-α, IL-6) while enhancing anti-inflammatory mediators such as IL-10. It also preserves mitochondrial function, mitigating oxidative injury and neuroinflammation. Early clinical trials report that melatonin administration in septic and asphyxiated neonates reduces inflammatory biomarkers, lowers oxidative stress, and is well tolerated without major adverse effects. Challenges remain, including the distinct pharmacokinetics of neonates, variable clearance rates, heterogeneous study populations, and limited sample sizes, which complicate dose optimization and definitive conclusions on efficacy and long-term safety.
Conclusion: Melatonin represents a safe and biologically potent adjunctive therapy for neonatal inflammatory disorders. Large-scale, multicenter randomized trials are warranted to establish standardized dosing, assess long-term neurodevelopmental outcomes, and confirm clinical efficacy in improving neonatal survival and recovery.
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