Presepsin (Soluble CD14 Subtype) as an Early Marker of Neonatal Sepsis and Septic Shock: A Prospective Diagnostic Trial

Abstract

In the context of suspected neonatal sepsis, early diagnosis and stratification of patients according to clinical severity is not yet effectively achieved. In this diagnostic trial, we aimed to assess the accuracy of presepsin (PSEP) for the diagnosis and early stratification of supposedly septic neonates. PSEP, C-reactive protein (CRP), and procalcitonin (PCT) were assessed at the onset of sepsis suspicion (T0), every 12-24 h for the first 48 h (T1-T4), and at the end of antibiotic therapy (T5). Enrolled neonates were stratified into three groups (infection, sepsis, septic shock) according to Wynn and Wong's definitions. Sensitivity, specificity, and area under the ROC curve (AUC) according to the severity of clinical conditions were assessed. We enrolled 58 neonates with infection, 77 with sepsis, and 24 with septic shock. PSEP levels were higher in neonates with septic shock (median 1557.5 pg/mL) and sepsis (median 1361 pg/mL) compared to those with infection (median 977.5 pg/mL) at T0 (p < 0.01). Neither CRP nor PCT could distinguish the three groups at T0. PSEP's AUC was 0.90 (95% CI: 0.854-0.943) for sepsis and 0.94 (95% CI: 0.885-0.988) for septic shock. Maximum Youden index was 1013 pg/mL (84.4% sensitivity, 88% specificity) for sepsis, and 971.5 pg/mL for septic shock (92% sensitivity, 86% specificity). However, differences in PSEP between neonates with positive and negative blood culture were limited. Thus, PSEP was an early biomarker of neonatal sepsis severity, but did not support the early identification of neonates with positive blood culture.

Keywords: biomarkers; inflammation; neonatal sepsis; newborn; presepsin; septic shock.

Figure 1

(A) Median PSEP levels at T0 (onset of symptoms) in the 3 groups of enrolled neonates. **, p < 0.01 after ANOVA with Dunn’s multiple comparisons test. Boxes indicate IQR, whiskers indicate 10° and 90° percentile, crosses indicate means. (B–D) Serial values (median) of PSEP, CRP and PCT in the 3 groups of neonates. T0: onset of symptoms, T1: 12 h, T2: 24 h, T3: 36 h, T4: 48 h, T5: end of antibiotic therapy. Repeated measures ANOVA with Tukey’s correction for multiple comparisons, p-values < 0.01 are marked as follows: *, infection vs. sepsis; #, infection vs. septic shock; +, sepsis vs. septic shock.

Figure 2

PSEP had a better performance in the early diagnosis of sepsis and septic shock compared to CRP and PCT. (A) ROC curves for PSEP at T0 in the overall population and (B) in the 3 different groups of neonates (control group = healthy neonates, [16]). ROC curves of PSEP (C), CRP (D) and PCT (E) at T0 in neonates with sepsis (group 2, orange line) or septic shock (group 3, red line) compared to neonates with infection (group 1).

Figure 3

Serial values (median, (IQR)) of PSEP in neonates with positive and negative blood culture. Repeated measures ANOVA with Tukey’s correction for multiple comparisons. *, p < 0.05. b.c.: blood culture.