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Review
. 2017 Apr 24;17(1):302.
doi: 10.1186/s12879-017-2396-7.

Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a meta-analysis

Giuseppe Pontrelli  1 , Franco De Crescenzo  2   3 , Roberto Buzzetti  2 , Alessandro Jenkner  2   4 , Sara Balduzzi  5 , Francesca Calò Carducci  4 , Donato Amodio  4 , Maia De Luca  4 , Sara Chiurchiù  4 , Elin Haf Davies  6 , Giorgia Copponi  2 , Alessandra Simonetti  2   4 , Elena Ferretti  2 , Valeria Di Franco  2   7 , Virginia Rasi  2 , Martina Della Corte  2 , Luca Gramatica  2 , Marco Ciabattini  8 , Susanna Livadiotti  2 , Paolo Rossi  2   4
Affiliations
Review

Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a meta-analysis

Giuseppe Pontrelli et al. BMC Infect Dis. .

Abstract

Background: A number of biomarkers have been studied for the diagnosis of sepsis in paediatrics, but no gold standard has been identified. Procalcitonin (PCT) was demonstrated to be an accurate biomarker for the diagnosis of sepsis in adults and showed to be promising in paediatrics. Our study reviewed the diagnostic accuracy of PCT as an early biomarker of sepsis in neonates and children with suspected sepsis.

Methods: A comprehensive literature search was carried out in Medline/Pubmed, Embase, ISI Web of Science, CINAHL and Cochrane Library, for studies assessing PCT accuracy in the diagnosis of sepsis in children and neonates with suspected sepsis. Studies in which the presence of infection had been confirmed microbiologically or classified as "probable" by chart review were included. Studies comparing patients to healthy subjects were excluded. We analysed data on neonates and children separately. Our primary outcome was the diagnostic accuracy of PCT at the cut-off of 2-2.5 ng/ml, while as secondary outcomes we analysed PCT cut-offs <2 ng/ml and >2.5 ng/ml. Pooled sensitivities and specificities were calculated by a bivariate meta-analysis and heterogeneity was graphically evaluated.

Results: We included 17 studies, with a total of 1408 patients (1086 neonates and 322 children). Studies on neonates with early onset sepsis (EOS) and late onset sepsis (LOS) were grouped together. In the neonatal group, we calculated a sensitivity of 0.85, confidence interval (CI) (0.76; 0.90) and specificity of 0.54, CI (0.38; 0.70) at the PCT cut-off of 2.0-2.5 ng/ml. In the paediatric group it was not possible to undertake a pooled analysis at the PCT cut-off of 2.0-2.5 ng/ml, due to the paucity of the studies.

Conclusions: PCT shows a moderate accuracy for the diagnosis of sepsis in neonates with suspected sepsis at the cut-off of 2.0-2.5 ng/ml. More studies with high methodological quality are warranted, particularly in neonates, studies considering EOS and LOS separately are needed to improve specificity.

Trial registration: PROSPERO Identifier: CRD42016033809 . Registered 30 Jan 2016.

Keywords: Biological markers; Child; Infant; Meta-analysis; Procalcitonin; Sepsis; Systemic inflammatory response syndrome.

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Figures

Fig. 1
Fig. 1
Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow chart. Literature search and selection. *One study assessed both neonates and children over 44 weeks of gestational age
Fig. 2
Fig. 2
Representation in the ROC space of neonatal studies. Representation in the ROC space of studies on PCT for diagnosis of sepsis in neonatal age, divided by cut-off subgroup, and summary sensitivity and specificity points along with their 95% confidence and prediction regions. (ROC, receiver operating characteristic). Legend: formula image PCT neon – cut-off <2 formula image PCT neon – cut-off > 2.5 formula image PCT neon – cut-off =2/2.5
Fig. 3
Fig. 3
Galbraith plot. Heterogeneity of selected neonatal studies. Galbraith plot for neonatal studies. The standardised lnDOR = lnDOR/se was plotted (y-axis) against the inverse of the se (1/se) (x-axis). A regression line going through the origin was calculated, together with 95% boundaries (starting at +2 and −2 on the y-axis). (DOR, diagnostic odds ratio)
Fig. 4
Fig. 4
Representation in the ROC space of paediatric studies. Representation in the ROC space of the studies of PCT for diagnosis of sepsis in paediatric age, divided by cut-off subgroup, and summary sensitivity and specificity points along with their 95% confidence and prediction regions. (ROC, receiver operating characteristic). Legend: formula image PCT paed – cut-off <2 formula image PCT paed – cut-off > 2.5 formula image PCT paed – cut-off =2/2.5
Fig. 5
Fig. 5
Galbraith plot. Heterogeneity of selected paediatric studies. Galbraith plot for paediatric studies. The standardised lnDOR = lnDOR/se was plotted (y-axis) against the inverse of the se (1/se) (x-axis). A regression line going through the origin was calculated, together with 95% boundaries (starting at +2 and −2 on the y-axis). (DOR, diagnostic odds ratio)
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