The role of IL-6 for predicting neonatal sepsis: a systematic review and meta-analysis

Lobat Shahkar, Abbasali Keshtkar, Arezou Mirfazeli, Ali Ahani, Gholamreza Roshandel, Lobat Shahkar, Abbasali Keshtkar, Arezou Mirfazeli, Ali Ahani, Gholamreza Roshandel

Abstract

Objective: Neonatal sepsis (NS) is a common and life-threatening disorder in infants. Previous studies showed that interleukin-6 (IL-6) may be a valid non-invasive and rapid method for diagnosis of NS. We conducted this review to assess the validity of IL-6 for predicting NS.

Methods: This was a systematic review with meta-analysis. Embase, Medline and Web of Science databases were searched between January 1990 and December 2009. The search terms used were "cytokine", "neonate", "sepsis" and "interleukin-6". We used standard methods recommended for meta analyses of diagnostic test evaluations. The analysis was based on a summary ROC (SROC) curve. Meta-regression analysis was used to assess the effects of some confounding factors on the results of meta-analysis. Potential presence of publication bias was tested using funnel plots and the Egger test.

Findings: Meta-analysis was performed on 13 publications including 353 infants with sepsis and 691 control infants. The pooled sensitivity and specificity of IL-6 was 0.79 and 0.84, respectively. The maximum joint sensitivity and specificity (i.e., the Q value) in SROC curve was 0.82 and the area under curve (AUC) was 0.89 (95% CI: 0.84-0.94). Meta-regression analysis showed that the diagnostic accuracy of IL-6 was not affected by confounding variables. The evaluation of publication bias showed that the Egger test was not significant (P=0.07).

Conclusion: IL-6 seems to be a valid marker for predicting NS. It may be considered for early diagnosis of sepsis in neonatal care units.

Keywords: Cytokines; Interlukin-6; Meta-analysis; Neonate; Sepsis.

Figures

Fig. 1
Fig. 1
Flow diagram of the process of identifying and including references for the systematic review
Fig. 2
Fig. 2
Forest plot of estimates of sensitivity and specificity of IL-6 for predicting neonatal sepsis. •=point estimates of sensitivity and specificity from each study; error bars=95% CIs; numbers= reference numbers of studies cited in the reference list. Pooled estimates were as follows: sensitivity, 0.79 (95% CI, 0.74 to 0.83); specificity, 0.84 (95% CI, 0.81 to 0.87)
Fig. 3
Fig. 3
Summary ROC curve for assessment of the diagnostic accuracy of IL-6 to predict neonatal sepsis.
Fig. 4
Fig. 4
Funnel plot for the assessment of potential publication bias in IL-6 assay. •=Each study in the metaanalysis; center line = SDOR. The result of the Egger test for publication bias was not significant (P= 0.07).

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