Umbilical Cord Procalcitonin to Detect Early-Onset Sepsis in Newborns: A Promising Biomarker

Abstract

Background: Up to 7% of neonates born in high-income countries receive antibiotics for suspected early-onset sepsis (EOS). Culture-proven neonatal sepsis has a prevalence of 0.2%, suggesting considerable overtreatment. We studied the diagnostic accuracy of umbilical cord blood and infant blood procalcitonin (PCT) in diagnosing EOS to improve antibiotic stewardship. Methods: Umbilical cord blood PCT was tested in newborns ≥ 32 weeks of gestation. Groups were defined as following: A) culture-proven or probable EOS (n = 25); B) Possible EOS, based on risk factors for which antibiotics were administered for <72 h (n = 49); C) Risk factor(s) for EOS without need for antibiotic treatment (n = 181); D) Healthy controls (n = 74). Additionally, venous or capillary blood PCT and C-reactive protein (CRP) were tested if blood drawing was necessary for standard care. Results: Between June 2019 and March 2021, 329 newborns were included. Umbilical cord blood PCT was significantly higher in group A than in group C and D. No difference between venous or arterial samples was found. Sensitivity and specificity for cord blood procalcitonin were 83 and 62%, respectively (cut-off 0.1 ng/mL). Antepartum maternal antibiotic administration was associated with decreased PCT levels in both cord blood and infant blood directly postpartum in all groups combined. Conclusion: Umbilical cord blood PCT levels are increased in newborns ≥32 weeks with a proven or probable EOS and low in newborns with risk factors for infection, but PCT seems not a reliable marker after maternal antibiotic treatment. PCT could be useful to distinguish infected from healthy newborns with or without EOS risk factors.

Keywords: antibiotic stewardship; early-onset sepsis; neonatal infection; procalcitonin; umbilical cord blood.

Figure 1

Study design. Flow diagram demonstrating identification, screening and inclusion of participants. Group A: Newborns with proven or probable EOS and >72 h antibiotic treatment. Group B: Newborns with possible EOS, but antibiotics were discontinued <72 h. Group C: newborns with one risk factor for EOS that were not treated with antibiotics. Group D: Healthy controls. Asterisk (*) indicates the number of successfully executed PCT tests of the total available blood samples.

Figure 2

Procalcitonin in umbilical cord blood. Boxplot representing cord blood levels of procalcitonin (arterial and venous samples combined per group). Plots show dots per individual PCT level projected on top of boxplot with median and interquartile range. Counts per group: Group A: n = 9 (arterial n = 3, venous n = 6); Group B: n = 27 (arterial n = 11, venous n = 16); Group C: n = 166 (arterial n = 74, venous n = 92); Group D: n = 93 (arterial n = 44, venous n = 49). **p < 0.05, ***p < 0.01.

Figure 3

PCT and CRP postpartum. Boxplots with outliers (small dots) showing PCT and CRP values directly postpartum [(A): PCT, (C): CRP] and 24–48 h postpartum [(B): PCT, (D): CRP] for groups A, B and C. Samples per group are displayed as n = x at the corresponding boxplot. **p < 0.05.

Figure 4

Effect of maternal antibiotic treatment antepartum on PCT levels. Boxplots with outliers (dots) of PCT in umbilical cord blood, directly postpartum and 24–48 h postpartum. A separation was made for group A (A), group B (B), group C (C) and all groups combined (D). For umbilical cord blood samples, arterial and venous PCT levels were combined. Per sample moment results are stratified by whether the mother was given prophylactic antibiotic treatment (light blue) or not (darker blue). Numbers per group are presented under the corresponding boxplot. pp: postpartum. **p < 0.05; ***p < 0.01.

Figure 5

Sensitivity and specificity analysis. Receiver operating characteristic (ROC) curves of (A) umbilical cord PCT, (B) PCT in first venous blood sample postpartum, (C) CRP in first venous blood sample postpartum. AUC, Area under the curve.