A novel method to detect bacterial infection in premature infants: Using a combination of inflammatory markers in blood and saliva

Background: Opportunistic infection leads to high morbidity and mortality in premature babies due to their immature immune system. Biomarkers in blood have been reported to detect bacterial infection in neonates. However, serial blood exams pose iatrogenic anemia in premature babies. Thus, this study aimed to identify cytokines in saliva, which can help to diagnose bacterial infection in premature babies via a non-invasive method. Methods: Premature neonates were enrolled from Aug. 2012 to Feb. 2015 after completing informed consent. Babies with congenital anomalies, bronchopulmonary dysplasia, necrotizing enterocolitis and any surgical indicated diseases were excluded. Salivary samples collection and septic work-up were performed when bacterial infection was clinically suspected, as well as one week after antimicrobial treatment. The level of salivary cytokines was detected by MILLPLEX® MAP and analyzed by Mann-Whitney U test. Results: There were 16 episodes of bacterial infection in 10 cases. Culture-positive group had significantly higher levels of salivary Interleukin (IL) 6, IL-8, macrophage inflammatory protein (MIP)1α, MIP-1β and tumor necrosis factor (TNF)-α than that in the culture-negative group (p = 0.002, 0.006, 0.001, <0.001, 0.009), and blood C-reactive protein and sugar as well (p < 0.001, 0.026). After adjusting postmenstrual age by logistic regression, blood sugar level was the most significant biomarker (p = 0.019). In combination of blood and salivary biomarkers, blood sugar higher than 67 mg/dL and salivary IL-6 higher than 367.25 pg/mL concurrently, would accurately detect bacterial infection in premature babies. Conclusion: This non-invasive method might help us to accurately diagnose bacterial infection in premature babies.