Prevalence and overlap of white blood cell counts, procalcitonin and C-reactive protein in neonates with invasive bacterial infections.

Background: Neonatal invasive bacterial infections (IBIs) are associated with substantial mortality. We aimed to elucidate the prevalence and overlapping effects of white blood cell (WBC), procalcitonin (PCT), and C-reactive protein (CRP) in neonates with IBIs. Methods: We conducted a retrospective cohort study in 17 Chinese hospitals from 2012 to 2021. Full-term neonates who had suspected IBIs and underwent blood cultures and lumbar punctures were enrolled. We investigated the prevalence of WBC counts, PCT, CRP, and their combinations for predicting IBIs risk. Results: Of 1,825 patients, 121 were identified with early-onset IBIs and 314 with late-onset IBIs. Restricted Cubic Spline plots indicated positive relationships between PCT, CRP levels and IBIs risk, but PCT curve was relatively flat in early-onset IBIs. A U-shaped association was found between leukocyte counts and late-onset IBIs risk, whereas no such correlation in early-onset cases was found. Neonates with normal WBC counts, elevated PCT and CRP accounted for the highest proportion in early-onset IBIs (28.1%), as did those with leukocytosis, increased PCT and CRP in late-onset IBIs (26.1%). Heat map showed that the highest overlapping risks of early- [adjusted odds ratio (aOR) =23.6; 95% confidence interval (CI): 5.7-98.4] and late-onset IBIs (aOR =30.3, 95% CI: 12.7-72.3) were both in leukopenia with increased PCT and CRP. Statistical interaction effects were affirmed between leukopenia and elevated PCT in both IBIs types. Conclusions: Leukocyte counts, PCT, CRP and their overlaps contribute unequally in neonatal IBIs risk assessment, with differences observed even for the same combinations between early- and late-onset IBIs. This multi-marker approach provides new perspectives on rapidly and conveniently identifying neonates at high risk of IBIs for further clinical management.