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ORIGINAL RESEARCH article

Front. Pediatr.

Sec. Pediatric Pulmonology

Noninvasive Salivary Biomarkers (PTX3, calprotectin, and IL-8) for Early-Onset Neonatal Pneumonia: Case-Control Differences and Exploratory Discrimination

Provisionally accepted
  • 1Pediatric Department, The First People' s Hospital of Jiashan, Jiaxing, China
  • 2Neonatology Department, Children' s Hospital of Fudan University, Shanghai, China

The final, formatted version of the article will be published soon.

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 versus 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.

Keywords: calprotectin, Early-onset neonatal pneumonia, Interleukin-8, Pentraxin 3 (PTX3), salivary biomarkers

Received: 17 Nov 2025; Accepted: 28 Jan 2026.

Copyright: © 2026 Wang and Laishuanwang@yahoo.com. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yan-Nan Wang

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