Melatonin, an adjuvant for neonatal sepsis: a systematic review and meta-analysis

Introduction: Neonatal sepsis remains a serious health problem in some countries, especially in developing countries, like Indonesia. The standard treatment for sepsis is the administration of antibiotics. Melatonin, a hormone produced by the pineal gland, has beneficial effects in fighting free radicals, antioxidants, anti-inflammatory, and anti-apoptotic effects. However, in newborns, melatonin is minimally detectable. Adjuvant therapy is required for the deterrence and neonatal sepsis therapy. This study aims to systematically review and perform a meta-analysis of melatonin as an adjunctive therapy in treating neonatal sepsis with the addition of the most recent articles. Methods: Databases of electronics used such as PubMed, Embase, and the Cochrane Central Controlled Trials Register were searched systematically in October 2022 for clinical trials reporting the efficacy of melatonin as adjunctive therapy for neonatal sepsis. We compared treatment responses between groups using serum C-reactive protein (CRP) levels as an endpoint biomarker. Data analysis was performed to appraise the quality of enrolled studies using a comprehensive metaanalysis Revman 5.4 and bias tool risk of the Cochrane Collaboration. Results: Four trials with a total of 175 subjects were listed in the systematic review and meta-analysis. Pooled analysis showed a statistically significant mean difference in serum CRP level (mg/L) between groups 24 hours after adjuvant melatonin therapy (-1.63 mg/L; 95% CI: -3.20 to -0.054; P=0.043). Conclusion: Melatonin as an adjunctive therapy significantly lowers CRP levels. Larger, sample size studies are necessary to establish clear clinical benefits of this treatment.