Use of melatonin as adjunctive therapy in neonatal sepsis: A systematic review and meta-analysis

Background: Sepsis remains one of the major causes of neonatal mortality and morbidity. Increased production of free radicals and pro-inflammatory cytokines, combined with the innately low levels of plasma antioxidants in neonates, have been implicated in the pathogenesis and complications of neonatal sepsis. To date, few clinical trials on the beneficial effects of exogenous melatonin on improvement of clinical outcomes in septic neonates have been conducted. Methods: The electronic databases including PubMed, Embase, and Cochrane Central Register of Controlled Trials were systematically searched on July 2017 for clinical studies that reported the effects of melatonin as an adjuvant therapy in neonatal sepsis. Serum levels of C-reactive protein (CRP) as biomarker endpoint and recovery of sepsis as clinical endpoint were used to compare treatment responses between groups. The Risk of Bias Assessment tool for Non-Randomized Studies (RoBANS) and the Cochrane Collaboration Risk of Bias tool were used to assess the quality of included studies. Results: Three studies with a total of 120 participants were included in the systematic review and meta-analysis. Pooled analysis revealed statistically significant mean differences in CRP serum levels (mg/L) between groups at 24 h post-adjunctive therapy with melatonin (-1.739 mg/L; 95% CI: -3.205 to -0.273; P = 0.020). Additionally, adjunctive therapy with melatonin significantly improved clinical condition of sepsis in neonates from the intervention group, compared to the control group, within 3 days of therapy (RR: 2.212; 95% CI: 1.452 to 3.371; P < 0.0005). Conclusions: Findings showed that administration of melatonin as adjunctive therapy significantly reduced an inflammatory biomarker and improved sepsis status in neonate. Larger scale studies with higher validity are needed to demonstrate clear clinical benefits of the therapy.