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      The combination of procalcitonin and C-reactive protein or presepsin alone improves the accuracy of diagnosis of neonatal sepsis: a meta-analysis and systematic review

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          Abstract

          Background

          Sepsis is an important cause of neonatal morbidity and mortality; therefore, the early diagnosis of neonatal sepsis is essential.

          Method

          Our aim was to compare the diagnostic accuracy of procalcitonin (PCT), C-reactive protein (CRP), procalcitonin combined with C-reactive protein (PCT + CRP) and presepsin in the diagnosis of neonatal sepsis. We searched seven databases to identify studies that met the inclusion criteria. Two independent reviewers performed data extraction. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under curve (AUC), and corresponding 95% credible interval (95% CI) were calculated by true positive (TP), false positive (FP), false negative (FN), and true negative (TN) classification using a bivariate regression model in STATA 14.0 software. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, and corresponding 95% CI were the primary outcomes. Secondary outcomes included the sensitivity and specificity in multiple subgroup analyses.

          Results

          A total of 28 studies enrolling 2661 patients were included in our meta-analysis. The pooled sensitivity of CRP (0.71 (0.63, 0.78)) was weaker than that of PCT (0.85 (0.79, 0.89)), PCT + CRP (0.91 (0.84, 0.95)) and presepsin (0.94 (0.80, 0.99)) and the pooled NLR of presepsin (0.06 (0.02, 0.23)) and PCT + CRP (0.10 (0.05, 0.19)) were less than CRP (0.33 (0.26, 0.42)), and the AUC for presepsin (0.99 (0.98, 1.00)) was greater than PCT + CRP (0.96 (0.93, 0.97)), CRP (0.85 (0.82, 0.88)) and PCT (0.91 (0.89, 0.94)). The results of the subgroup analysis showed that 0.5–2 ng/mL may be the appropriate cutoff interval for PCT. A cut-off value > 10 mg/L for CRP had high sensitivity and specificity.

          Conclusions

          The combination of PCT and CRP or presepsin alone improves the accuracy of diagnosis of neonatal sepsis. However, further studies are required to confirm these findings.

          Electronic supplementary material

          The online version of this article (10.1186/s13054-018-2236-1) contains supplementary material, which is available to authorized users.

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          Most cited references22

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          Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection.

          Barbara Stoll, Nellie I Hansen, Ira Adams-Chapman … (2004)
          Neonatal infections are frequent complications of extremely low-birth-weight (ELBW) infants receiving intensive care. To determine if neonatal infections in ELBW infants are associated with increased risks of adverse neurodevelopmental and growth sequelae in early childhood. Infants weighing 401 to 1000 g at birth (born in 1993-2001) were enrolled in a prospectively collected very low-birth-weight registry at academic medical centers participating in the National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth outcomes were assessed at a comprehensive follow-up visit at 18 to 22 months of corrected gestational age and compared by infection group. Eighty percent of survivors completed the follow-up visit and 6093 infants were studied. Registry data were used to classify infants by type of infection: uninfected (n = 2161), clinical infection alone (n = 1538), sepsis (n = 1922), sepsis and necrotizing enterocolitis (n = 279), or meningitis with or without sepsis (n = 193). Cognitive and neuromotor development, neurologic status, vision and hearing, and growth (weight, length, and head circumference) were assessed at follow-up. The majority of ELBW survivors (65%) had at least 1 infection during their hospitalization after birth. Compared with uninfected infants, those in each of the 4 infection groups were significantly more likely to have adverse neurodevelopmental outcomes at follow-up, including cerebral palsy (range of significant odds ratios [ORs], 1.4-1.7), low Bayley Scales of Infant Development II scores on the mental development index (ORs, 1.3-1.6) and psychomotor development index (ORs, 1.5-2.4), and vision impairment (ORs, 1.3-2.2). Infection in the neonatal period was also associated with impaired head growth, a known predictor of poor neurodevelopmental outcome. This large cohort study suggests that neonatal infections among ELBW infants are associated with poor neurodevelopmental and growth outcomes in early childhood. Additional studies are needed to elucidate the pathogenesis of brain injury in infants with infection so that novel interventions to improve these outcomes can be explored.
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            Procalcitonin increase after endotoxin injection in normal subjects.

            C Bohuon, J. Love, M Assicot … (1994)
            As procalcitonin concentrations have been shown to be elevated in patients with septicemia and gram-negative infections in particular, we proceeded to investigate the effect of endotoxin, a product of gram-negative bacteria, on procalcitonin concentrations in normal human volunteers. Endotoxin from Escherichia coli 0113:H10:k, was injected i.v. at a dose of 4 mg/kg BW into these healthy volunteers. Blood samples were obtained before and 1, 2, 4, 6, 8, and 24 h after injection of the endotoxin. Each patient's cardiovascular and overall clinical status was monitored over this period. The patients developed chills and rigors, myalgia, and fever between 1-3 h. Tumor necrosis factor-alpha levels increased sharply at 1 h and peaked at 90 min, reaching the baseline concentration thereafter by 6 h. Interleukin-6 levels increased more gradually, peaking at 3 h and reaching the baseline concentration at 8 h. The procalcitonin concentration, which was undetectable (< 10 pg/mL) at 0, 1, and 2 h, was detectable at 4 h and peaked at 6 h, maintaining a plateau through 8 and 24 h (4 ng/mL). There was no elevation of calcitonin concentrations, which remained below 10 pg/mL, the lowest sensitivity of the assay. Procalcitonin was measured by a two-antibody immunoradiometric assay specific for this peptide, with no cross-reactivity with calcitonin, katacalcin, or calcitonin gene-related peptide. We conclude that endotoxin induces the release of procalcitonin systemically, that this increase is not associated with an increase in calcitonin, and that the increase in procalcitonin associated with septicemia in patients may be mediated through the effect of endotoxin described here. Whether procalcitonin participates in the mechanisms underlying inflammation remains to be investigated.
            Article 0 comments Cited 142 times – based on 0 reviews     Review now
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              Procalcitonin used as a marker of infection in the intensive care unit.

              A Giuseppe, D Mercan, Peter J. Vincent … (1999)
              To determine the value of procalcitonin (ProCT) as a marker of infection in critically ill patients. Prospective, observational study. Medicosurgical department of intensive care (31 beds). One hundred eleven infected and 79 noninfected patients. None. ProCT and C-reactive protein (CRP) concentrations were monitored daily. The best cutoff values for ProCT and CRP were 0.6 ng/mL and 7.9 mg/dL, respectively. Compared with CRP, ProCT had a lower sensitivity (67.6 vs. 71.8), specificity (61.3 vs. 66.6), and area under the receiver operating characteristic curve (0.66 vs. 0.78, p < .05). The combination of ProCT and CRP increased the specificity for infection to 82.3%. In the infected patients, plasma ProCT, but not CRP, values were higher in nonsurvivors than in survivors. Infected patients with bacteremia had higher ProCT concentrations than those without bacteremia, but similar CRP concentrations. ProCT levels were particularly high in septic shock patients. ProCT is not a better marker of infection than CRP in critically ill patients, but it can represent a useful adjunctive parameter to identify infection and is a useful marker of the severity of infection.
              Article 0 comments Cited 77 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Lin Ruan: Ruanlin187@163.com
                Guan-Yu Chen: 741755319@qq.com
                Zhen Liu: lz361@sina.com
                Yun Zhao: 191840044@qq.com
                Guang-Yu Xu: xgy1945@qq.com
                Shu-Fang Li: 550702075@qq.com
                Chun-Ni Li: 1170095203@qq.com
                Lin-Shan Chen: 441777635@qq.com
                Zheng Tao: 369483974@qq.com
                Journal
                Journal ID (nlm-ta): Crit Care
                Title: Critical Care
                Publisher: BioMed Central (London )
                ISSN (Print): 1364-8535
                ISSN (Electronic): 1466-609X
                Publication date (Electronic): 21 November 2018
                Publication date PMC-release: 21 November 2018
                Publication date Collection: 2018
                Volume: 22
                Electronic Location Identifier: 316
                Affiliations
                [1 ]ISNI 0000 0004 1798 2653, GRID grid.256607.0, Departments of Anesthesiology, , Guangxi Medical University Affiliated Tumor Hospital, ; Naning, Guangxi China
                [2 ]ISNI 0000 0004 1798 2653, GRID grid.256607.0, Departments of Respiratory Oncology, , Guangxi Medical University Affiliated Tumor Hospital, ; Naning, Guangxi China
                [3 ]ISNI 0000 0004 1798 2653, GRID grid.256607.0, Departments of Urology, , Guangxi Medical University Affiliated Tumor Hospital, ; Naning, Guangxi China
                Article
                Publisher ID: 2236
                DOI: 10.1186/s13054-018-2236-1
                PMC ID: 6249912
                PubMed ID: 30463590
                SO-VID: f9077be6-5f52-48de-af9d-7f36d6a1d192
                Copyright © © The Author(s). 2018
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 19 July 2018
                Date accepted : 15 October 2018
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Emergency medicine & Trauma
                Keywords: meta-analysis,systematic review,procalcitonin,c-reactive protein,neonatal sepsis
                Data availability:
                ScienceOpen disciplines: Emergency medicine & Trauma
                Keywords: meta-analysis, systematic review, procalcitonin, c-reactive protein, neonatal sepsis

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