A Review on the Role of Melatonin in Neonatal Sepsis Caused by Methicillin-Resistant Staphylococcus Aureus Publisher



Kordkatouli M ; Noripour S ; Alizadeh P ; Mehri M ; Asgarzadeh L ; Veysizadeh M
Source: Iranian Journal of Neonatology Published:2026

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. Copyright© 2026 Kordkatouli M et al.