Procalcitonin and Interleukin-18 in Umbilical Cord Blood as Early Diagnostic Biomarkers for Early-Onset Neonatal Sepsis: A Case-Control Study

Background and Objective: Early-onset neonatal sepsis (EONS) is a major cause of neonatal morbidity and mortality globally, yet its early diagnosis remains challenging due to the limited availability of rapid, reliable biomarkers at the time of birth. This study aimed to analyze procalcitonin (PCT) and Interleukin-18 (IL-18) levels measured from umbilical cord blood as early diagnostic biomarkers for EONS. Materials and Methods: An observational case-control study was conducted on 66 neonates born with at least one EONS risk factor at four hospitals in Riau Province, Indonesia. Subjects were classified into an EONS group (n = 33) and a non-EONS group (n = 33). Umbilical cord blood PCT and IL-18 were measured using an enzyme-linked immunosorbent assay. Normality was assessed using the Shapiro-Wilk test. Between-group differences were analyzed using the Mann-Whitney U test (α = 0.05). Results: The PCT levels in umbilical cord blood were significantly higher in the EONS group compared to the non-EONS group [median 322.77 (range: 66.70-2599.57) pg/mL vs. 45.9 (4.90-321.97) pg/mL; p<0.001]. The IL-18 levels were similarly elevated [median 564.00 (216.40-1979.00) pg/mL vs. 107.60 (-19.60-773.38) pg/mL; p<0.001]. Maternal fever history was significantly more frequent in the EONS group (36.4% vs. 6.1%; p = 0.005), as was colored amniotic fluid (93.9% vs. 45.5%; p<0.001). Conclusion: Umbilical cord blood PCT and IL-18 levels are significantly elevated in neonates with EONS and may serve as early diagnostic biomarkers for EONS when measured at the time of birth. Their combined use may improve early risk stratification and clinical decision-making in at-risk neonates.