Comparative Diagnostic Performance of RDW-to-Albumin and CRP-to-Albumin Ratios in Neonatal Sepsis: A Retrospective Cohort Study

Background/Objectives: Neonatal sepsis remains a major cause of morbidity and mortality worldwide, underscoring the critical need for early and accurate diagnostic biomarkers. This study aimed to evaluate the predictive value of the red cell distribution width-to-albumin ratio (RAR) for the diagnosis of neonatal sepsis and to compare its diagnostic performance with the C-reactive protein-to-albumin ratio (CAR) and other hematological parameters. Methods: This retrospective cohort study was conducted in the Neonatology Department of Karadeniz Technical University Faculty of Medicine between January 2015 and June 2025. A total of 874 neonates with a gestational age > 36 weeks were included: 411 with blood culture-confirmed sepsis (108 Gram-negative, 303 Gram-positive) and 463 healthy controls. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis, with optimal cut-off values determined by the Youden index. Results: RAR demonstrated modest diagnostic accuracy for neonatal sepsis, with an area under the curve (AUC) of 0.647 (95% CI: 0.61–0.69), a cut-off value of 5.108, sensitivity of 50.7%, and specificity of 76.7%. RAR was significantly elevated in the Gram-negative group compared with Gram-positive cases and controls (p < 0.001). However, the clinical significance of this subgroup difference requires further investigation. In multivariable logistic regression analysis, RAR remained independently associated with culture-confirmed neonatal sepsis after adjustment for gestational age, birth weight, sex, and mode of delivery (aOR = 2.190, 95% CI: 1.838–2.608, p < 0.001). Among all evaluated markers, CAR achieved the highest diagnostic performance (AUC: 0.981, sensitivity: 88.5%, specificity: 98.7%, PPV: 98.4%, NPV: 90.7%, LR+: 68.47), followed by C-reactive protein (AUC: 0.978), while neutrophil-to-lymphocyte ratio showed the lowest discriminatory ability (AUC: 0.592). Conclusions: RAR showed limited standalone discriminatory performance for culture-confirmed neonatal sepsis, although its association with sepsis remained significant after adjustment for relevant demographic and perinatal factors. CAR demonstrated significantly greater discriminatory performance than RAR. Further studies are needed to determine whether RAR provides incremental value when incorporated into multivariable diagnostic models.