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. 2022 Jul 22:10:908362.
doi: 10.3389/fped.2022.908362. eCollection 2022.

The Utility of Peripheral Blood Leucocyte Ratios as Biomarkers in Neonatal Sepsis: A Systematic Review and Meta-Analysis

Juanjuan Zhang  1 , Jun'an Zeng  1 , Liangjuan Zhang  1 , Xiping Yu  1 , Jinzhen Guo  1 , Zhankui Li  1
Affiliations

The Utility of Peripheral Blood Leucocyte Ratios as Biomarkers in Neonatal Sepsis: A Systematic Review and Meta-Analysis

Juanjuan Zhang et al. Front Pediatr. .

Abstract

Background: Early stage diagnosis of neonatal sepsis (NS) remains a major roadblock due to non-specific symptoms and the absence of precise laboratory index tests. The full blood count is a relatively cheap, universal, and rapid diagnostic test.

Method: This study assessed the diagnostic accuracies of immature-to-total neutrophil ratio (ITR), immature-to-mature neutrophil ratio (IMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) used in the diagnosis of NS. Included studies were retrieved by searching four major databases and relevant references, and reviewed based on the inclusion/exclusion criteria. Pooled sensitivities and specificities were calculated, I 2 was utilized to test for heterogeneity, and the source was investigated via meta-regression analysis.

Results: Finally, 38 studies passed the eligibility criteria. A total of thirty-one studies (6,221 neonates) included data on the ITR, eight studies (1,230 neonates) included data on the IMR, seven studies (751 neonates) included data on the NLR, and two studies (283 neonates) included data on the PLR. The summary sensitivity estimates with 95% confidence interval (CI) for the ITR, IMR, NLR, and PLR tests were, respectively, 0.74 (95% CI: 0.66-0.80), 0.74 (95% CI: 0.54-0.88), 0.73 (95% CI: 0.68-0.78), and 0.81 (95% CI: 0.55-1.00). The summary specificity values for the ITR, IMR, NLR, and PLR tests were 0.83 (95% CI: 0.77-0.87), 0.89 (95% CI: 0.80-0.94), 0.69 (95% CI: 0.57-0.79), and 0.93 (95% CI: 0.81-1.00), respectively. The area under the summary receiver operating characteristic curves for the ITR, IMR, and NLR tests were 0.85 (95% CI: 0.82-0.88), 0.91 (95% CI: 0.88-0.93), and 0.75 (95% CI: 0.71-0.79). The PLR could not be evaluated because only two studies included pertinent data.

Conclusion: The NLR test might not be sufficiently accurate in precisely diagnosing NS. The ITR and IMR tests alone can improve the accuracy of NS diagnosis, but the marked heterogeneity and the limited number of studies prevented us from reaching any definitive conclusions. Thus, further studies are warranted to validate these findings.

Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021247850].

Keywords: immature-to-mature neutrophil ratio; immature-to-total neutrophil ratio; meta-analysis; neonatal sepsis; neutrophil-to-lymphocyte ratio; platelet-to-lymphocyte ratio.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart depicting the study selection procedure.
FIGURE 2
FIGURE 2
Summary of the methodological quality of the studies according to the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) criteria.
FIGURE 3
FIGURE 3
Deeks funnel plots. Funnel plots evaluating publication bias of ITR (A), IMR (B), and NLR (C).
FIGURE 4
FIGURE 4
Summary of receiver operating characteristic curve for ITR (A), IMR (B), and NLR (C) with 95% confidence contour and 95% prediction contour. AUC, area under curve; SEN, sensitivity; and SPE, specificity.
FIGURE 5
FIGURE 5
Coupled forest plots showing sensitivity and specificity of ITR, IMR, NLR, and PLR for diagnosing neonatal sepsis.
See this image and copyright information in PMC

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References

    1. Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, Schlapbach LJ, Reinhart K, Kissoon N. The global burden of paediatric and neonatal sepsis: a systematic review. Lancet Respir Med. (2018) 6:223–30. 10.1016/s2213-2600(18)30063-8 - DOI - PubMed
    1. AbdAllah NB, Toraih EA, Al Ageeli E, Elhagrasy H, Gouda NS, Fawzy MS, et al. MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis. Sci Rep. (2021) 11:13374. 10.1038/s41598-021-92912-7 - DOI - PMC - PubMed
    1. Ognean ML, Boicean A, Sular F, Cucerea M. Complete blood count and differential in diagnosis of early onset neonatal sepsis. Rev Rom Med Lab. (2017) 25:101–8. 10.1515/rrlm-2016-0042 - DOI
    1. Can E, Hamilcikan S, Can C. The value of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio for detecting early-onset neonatal sepsis. J Pediatr Hematol Oncol. (2018) 40:e229–32. 10.1097/MPH.0000000000001059 - DOI - PubMed
    1. Russell CD, Parajuli A, Gale HJ, Bulteel NS, Schuetz P, de Jager CPC, et al. The utility of peripheral blood leucocyte ratios as biomarkers in infectious diseases: a systematic review and meta-analysis. J Infect. (2019) 78:339–48. 10.1016/j.jinf.2019.02.006 - DOI - PMC - PubMed

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