Clinical Value of Laboratory Biomarkers for the Diagnosis and Early Identification of Culture-Positive Sepsis in Neonates

BACKGROUND: Neonatal sepsis (NS) is an important cause of mortality and morbidity in newborn infants. However, early diagnosis of proven sepsis (culture-positive sepsis) is difficult. We aimed to define the best combination of biomarkers to diagnose the onset of neonatal sepsis, distinguish culture-positive neonatal sepsis and predict the time of confirmation of neonatal sepsis. METHODS: This retrospective cohort study was conducted from January 2016 to December 2020. Clinical characteristics and laboratory results were collected from the electronic medical records. Hematology profiles and biochemical indices were obtained upon hospital admission. Multivariate logistic regression analysis was used to evaluate the risk factors and construct a nomogram. The performance of the nomogram was evaluated by receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Multivariable linear regression was used to identify the association between admission-to-diagnosis interval (ADI) and correlated variables. RESULTS: Overall, 148 infants with neonatal sepsis (67 culture positive sepsis and 81 culture negative sepsis) and 150 controls were included. C-reactive protein (CRP) (p<0.001), platelets (PLT) (p=0.011), urea nitrogen (BUN) (p=0.001) and conjugated bilirubin (BC) (p=0.007) were independent risk factors for neonatal sepsis. The diagnostic nomogram based on CRP, PLT, BUN and BC showed excellent diagnostic accuracy for neonatal sepsis (AUC=0.928). The nomogram based on red blood cell distribution width (RDW) and mean platelet volume (MPV) was efficient in distinguishing proven neonatal sepsis from clinical sepsis, with an AUC of 0.700 in the training group and 0.689 in the validation group. Decision curve analysis (DCA) showed that the nomogram had good clinical utility. Multivariable analysis revealed gestational age, CRP, and MPV were significantly associated with admission-to-diagnosis interval in culture-positive sepsis (p < 0.001). CONCLUSION: Different combinations biomarkers were performant to diagnose the onset of neonatal sepsis, distinguish culture-positive neonatal sepsis, predict the time of confirmation, and aid in individual therapy.