Objective: To evaluate the diagnostic and prognostic performance of salivary C-reactive protein (CRP), serum amyloid A (SAA), and hematologic indices in term neonates with early-onset (EOS) and late-onset sepsis (LOS), and to assess whether a composite score integrating these parameters improves risk stratification.

Patients and Methods: In this prospective case–control study in a tertiary neonatal intensive care unit (NICU) (June 2022–October 2024), 240 term neonates were enrolled (80 EOS, 80 LOS, 80 healthy controls). Salivary CRP, serum CRP, serum SAA, and complete blood counts were obtained at enrollment. Diagnostic accuracy was assessed by receiver operating characteristic (ROC) analysis, and prognostic associations with in-hospital mortality, mechanical ventilation, and NICU length of stay by multivariable regression. A composite score combining salivary CRP, SAA, and platelet count was developed and tested.

Results: Serum SAA and salivary CRP showed high diagnostic accuracy (AUC 0.94 and 0.91), outperforming serum CRP (AUC 0.88; all p<0.001). Platelet count was the strongest independent predictor of mortality (adjusted OR 0.78 per 10×10⁹/L; p=0.004). LOS carried higher mortality (28.8% vs 20.0%), longer NICU stay (median 14 vs 9 days; p<0.001), and greater multidrug-resistant exposure. The composite score stratified neonates into low-, intermediate-, and high-risk groups with progressively higher mortality, ventilation need, and hospitalization (p<0.001).

Conclusions: Combining SAA, salivary CRP, and platelet count offers an accurate, practical approach for diagnosing and risk-stratifying neonatal sepsis. Validation in larger multicenter cohorts is warranted.