The effect of melatonin on the immune system and the treatment of neonatal sepsis

Introduction: Neonatal sepsis is a leading cause of morbidity and mortality, particularly in preterm infants, involving systemic inflammation and oxidative stress. Melatonin, with its antioxidant, anti-inflammatory, and immunomodulatory properties, has emerged as a potential adjuvant to standard antibiotic therapy. This systematic review and meta-analysis synthesizes evidence from randomized controlled trials (RCTs) and clinical studies from 2000 to 2025 evaluating melatonin's efficacy and safety in neonatal sepsis. Materials and Methods: Databases including PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov were searched for RCTs and trials on melatonin as adjuvant in neonatal sepsis. Inclusion: studies 2000-2025, neonates (<28 days), confirmed sepsis, melatonin vs. control (antibiotics alone). Outcomes: biomarkers (C-reactive protein or CRP, Malondialdehyde or MDA, Interlukine or IL-6/8), sepsis scores, mortality, hospital stay, adverse events. Results: Nine RCTs (n=354 neonates) included. Melatonin (typically 20 mg oral, single or divided) reduced CRP at 24h (P<0.001) and MDA (P<0.001). Improved sepsis recovery at 72h (P<0.001). Mortality lower (P<0.001), no adverse events. Preterm subgroup showed enhanced benefits. Conclusions: Melatonin improves biomarkers and outcomes in neonatal sepsis safely, but Larger RCTs needed for confirmation and dosing.