Melatonin as a Supportive Biomarker in Early-Onset Neonatal Sepsis: A Prospective Study.

Abstract

Background: Early-onset neonatal sepsis (EOS) remains a diagnostic challenge because clinical signs are nonspecific and blood cultures, although the diagnostic gold standard may yield false-negative results due to low blood volumes or maternal antibiotic exposure.

Purpose: To determine whether serum melatonin levels differ between term neonates with clinically suspected EOS and healthy controls, and to evaluate the diagnostic performance of melatonin relative to standard inflammatory markers.

Methods: This prospective case-control study included 84 term infants: 42 with clinically suspected EOS, defined according to the Centers for Disease Control and Prevention and National Institute for Health and Care Excellence criteria, and 42 controls. Blood cultures, complete blood count, C-reactive protein, and serum melatonin levels measured by enzyme-linked immunosorbent assay were obtained within 24 hours of life before antibiotic initiation. Receiver operating characteristic (ROC) analyses were performed for all suspected EOS cases and separately for culture-confirmed EOS.

Results: Eleven infants (26.2%) in the suspected EOS group had positive blood cultures. Mean melatonin levels were significantly lower in suspected EOS than in controls (193.5 ± 61.8 vs 231.6 ± 71.1 pg/mL; P = .010). However, melatonin levels did not differ significantly between culture-positive and culture-negative suspected EOS cases. ROC analysis for suspected EOS yielded an area under the curve of 0.628; a melatonin cutoff of 242 pg/mL provided 81% sensitivity but limited specificity (45.2%). ROC performance for culture-confirmed EOS was modest.

Implications for practice and research: Melatonin demonstrates limited diagnostic specificity and should be interpreted only as a supportive marker within a multimodal evaluation strategy.