Noninvasive salivary biomarkers (PTX3, calprotectin, and IL-8) for early-onset neonatal pneumonia: case-control differences and exploratory discrimination

Objective Early-onset neonatal pneumonia (EONP) demands rapid recognition, but blood tests are invasive and may be delayed. This study evaluated whether noninvasive salivary pentraxin-3 (PTX3), calprotectin, and interleukin-8 (IL-8) differ between EONP and healthy controls and whether they reflect systemic inflammation. Methods EONP required respiratory distress within 72 h of birth, new infiltrates on chest radiograph and/or lung ultrasound, and ≥1 laboratory or microbiologic criterion: abnormal leukocyte indices (I/T ratio 0.16 or WBC/differential abnormality), hs-CRP ≥ 10 mg/L, PCT ≥ 0.5 ng/mL, or a positive blood/upper-airway culture with a compatible pathogen. Saliva was collected after definitive EONP diagnosis and immediately before systemic antibiotics in 100 EONP infants and 126 healthy controls. Biomarkers (PTX3, calprotectin, IL-8) were quantified by ELISA. Results EONP infants had higher salivary PTX3 (median 2.11 vs. 0.79 ng/mL), calprotectin (11.65 vs. 3.07 ng/mL), and IL-8 (15.02 vs. 4.67 pg/mL) than healthy controls. After adjustment, calprotectin and IL-8 remained independently associated with EONP, whereas PTX3 did not retain statistical significance. In case—control discrimination, using ROC-derived cut-offs, AUCs were 0.865 (PTX3), 0.967 (calprotectin), and 0.930 (IL-8); a combined three-marker model achieved AUC 0.978. Within EONP, salivary PTX3, calprotectin, and IL-8 correlated with systemic indices and modestly enriched for blood-culture—positive bacteremia (combined model AUC 0.707). Conclusions Noninvasive salivary PTX3, calprotectin, and IL-8 are substantially elevated in early-onset neonatal pneumonia and mirror systemic inflammation. The three-marker panel showed near-excellent discrimination vs. healthy controls and modest enrichment for culture-positive bacteremia, suggesting value as an adjunct to bedside assessment in this case–healthy-control setting. Performance in neonates with non-infectious respiratory distress should be validated in prospective cohorts.