The diagnostic accuracy of presepsin, procalcitonin and C-reactive protein in newborns with early-onset neonatal sepsis: single-center prospective study
AbstractEarly-onset neonatal sepsis (EONS) continued to rise over the past 30 years and remains the leading cause of morbidity, and mortality among newborns. Diagnostics need to determine the generalization of the infection process as accurately as possible and lead to the study of the significant biomarkers of the systemic inflammatory response. Their kinetics and reference values are specific to newborns. Routinely used biomarkers are C-reactive protein and procalcitonin. Presepsin (PSP) is a soluble form of the CD14 glycoprotein (sCD14-ST) and has been actively studied in the last decade. It reflects the participation of the first line of protection against pathogens and expresses on granulocytes and macrophages hPSP. Studies focused on the diagnostic accuracy of PSP show variable results. The main object of research in neonatology was term and late preterm babies. Studies devoted to the assessment of the clinical informativeness of various combinations of biomarkers in EONS deserve special attention.
Objective. Assessment of the diagnostic accuracy of levels of PSP at the age of 2 and 12±4 h of life, procalcitonin (PCT) and C-reactive protein (CRP) at the age of 48–72 h of life, and their combination in blood in newborns with EONS.
Material and methods. A single-center prospective study was conducted, which included newborns of gestational age 23/4–41 weeks who were admitted to the NICU after the birth in a serious condition due to the development of respiratory and/or cardiovascular disorders, and who had at least two clinical signs of EONS in the first hours of life. On the 1st day of life, the examination included blood culture, complete blood count (CBC), PSP level, at 48–72 h of life, a repeat of the CBC, levels of CRP and PCT were performed. PSP concentration determined at 2 time points: during the first 2 h after birth (T2), and at the age of 12±4 h of life (T12). Newborns were divided into 2 groups depending on the presence of EONS: the main group – newborns with EONS (n=145), and the control group – newborns without an infectious disease (n=127). Statistical analysis of the data conducted using SPSS V.26 software.
Results. The analysis showed the highest diagnostic accuracy of PSP level at the age of 12±4 h of life with an AUC of 0.759±0.031 (95% CI 0.697–0.782) (p<0.0001) with a cut-off value for predicting EONS of 383.0 pg/ml with Se 70.1% and Sp 68.7%, NPV 68%, PPV 70,4% compared with the measurement at the age of 2 h of life; the median of PSP at the age of 12±4 h in newborns with EONS was 468.5 (361.5–684.5) pg/ml. Analysis of the dynamics of PSP at points T2 and T12 showed a significant increase in PSP level over time in the main group by 12 h of life (p=0.0003), in contrast to the control group, where PSP level did not increase (p=0.32). The diagnostic accuracy of PCT at 48–72 h of life demonstrated Se 72.6% and Sp 97.3% with an AUC of 0.857±0.027 (95% CI 0.803–0.911; p<0.00001) with a cut-off value of 2.64 ng /ml, NPV 96%, PPV 72%, in contrast to CRP, in which AUC was 0.685±0.039 with low sensitivity and specificity, and a cut-off value was chosen corresponding to 99% specificity – 4.88 mg/l. The total diagnostic accuracy of PSP at 12±4 h of life, PCT, and CRP at the age of 48–72 h was 87.5%, with Se 86.3% and Sp 89.7%, with a total AUC of 0.928±0.019 (p<0.00001).
Conclusion. The highest diagnostic accuracy of presepsin as a marker of early neonatal sepsis was determined at the age of 12±4 h of life. The cut-off value for PSP level at the age of 12±4 h of life for predicting EONS was 383.0 pg/ml (Se 70.1% and Sp 68.7%). The use of a combination of systemic inflammatory response markers: PSP level at 12±4 h of life, followed by a study of PCT and CRP levels in the interval of 48–72 h, increases the efficiency of diagnosing EONS (Se 86.3% and Sp 89.7%).
Keywords:early onset neonatal sepsis; presepsin; procalcitonin; C-reactive protein; newborns
Funding. Reagents for determination of presepsin were provided by representatives of the “Deacon” company.
Conflict of interest. The authors declare no conflict of interest.
Contribution. Concept and design of the study, statistical data processing, text writing – Balashova E.N., Sharafutdinova D.R.; laboratory analysis, formation of a laboratory database, writing the text – Sukhova Yu.V., Kessler Yu.V.; collection and processing of material, formation of a database – Titova K.Yu., Menshikova A.A.; general management, collection information, editing – Ionov O.V., Kirtbaya A.R., Ryndin A.Yu., Ivanets T.Yu.; concept and design of the study, editing – Degtyarev D.N.
For citation: Balashova E.N., Sharafutdinova D.R., Sukhova Yu.V., Kessler Yu.V., Titova K.Yu., Menshikova A.A., Kirtbaya A.R., Ryndin A.Yu., Ivanets T.Yu., Ionov O.V., Degtyarev D.N. The diagnostic accuracy of presepsin, procalcitonin and C-reactive protein in newborns with early-onset neonatal sepsis: single-center prospective study. Neonatologiya: novosti, mneniya, obuchenie [Neonatology: News, Opinions, Training]. 2023; 11 (3): 10–21. DOI: https://doi.org/10.33029/2308-2402-2023-11-3-10-21 (in Russian)
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