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Umbilical cord blood culture in neonatal early-onset sepsis: a systematic review and meta-analysis

Abstract

Background

Peripheral blood culture (PBC) is considered the gold standard for diagnosis of neonatal early-onset sepsis (EOS), but its diagnostic value can be questioned. We aimed to systematically asses the diagnostic test accuracy (DTA) of umbilical cord blood culture (UCBC) for EOS.

Methods

A systematic literature search was performed in PubMed, Embase, Web of Science, and the Cochrane Library. Studies performing UCBC for the diagnosis of EOS were included.

Results

A total of 1908 articles were screened of which 17 were included. Incidences of positive PBC and UCBC were low in all studies. There was a large heterogeneity in the consistency between positive PBC and UCBC outcomes. PBC had a pooled sensitivity of 20.4% (95% CI 0.0–40.9) and specificity of 100.0% (95% CI 100.0–100.0) compared to 42.6% (95% CI 12.7–72.4%) and 97.8% (95% CI 93.1–100.0) of UCBC for clinical EOS, defined as clinical sepsis regardless of PBC outcomes.

Conclusions

This systematic review shows that, compared to PBC, UCBC has higher sensitivity and comparable specificity for clinical EOS and might be considered as diagnostic test for EOS. Due to the limited number of studies, low incidences of EOS cases, and the imperfect reference standards for EOS, results should be interpreted cautiously.

Impact

  • This is the first systematic review and meta-analysis investigating the diagnostic test accuracy of umbilical cord blood culture for neonatal early-onset sepsis.

  • Peripheral blood culture is considered the gold standard for diagnosis of neonatal early-onset sepsis, but its value for this specific diagnosis can be questioned. Umbilical cord blood culture has higher sensitivity and comparable specificity for diagnosis of neonatal early-onset sepsis compared to peripheral blood culture, circumventing the risk for iatrogenic anemia and consequently might be used as a diagnostic tool for early-onset sepsis.

  • Quality of evidence was regarded as low due to imperfect diagnostic methods of neonatal early-onset sepsis.

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Fig. 1: Flow diagram of the study selection.
Fig. 2: Summary of risk of bias and applicability concerns.
Fig. 3: Risk of bias and applicability concerns graph.
Fig. 4: Forest plot of umbilical cord blood culture consistency with paired peripheral blood culture results.
Fig. 5: Forest plot of peripheral blood culture and umbilical cord blood culture for diagnosis of clinically diagnosed sepsis.
Fig. 6: Summary of the receiver operating characteristic plot of the diagnostic test accuracy of peripheral blood culture and the diagnostic test accuracy of umbilical cord blood culture for diagnosis of clinically diagnosed early-onset sepsis.

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Acknowledgements

We thank Dr. Mariska Leeflang, associate professor at the department of epidemiology and expert in the field of diagnostic test accuracy reviews, for her help and advice in the statistical analysis outlined in this manuscript.

Funding

This work was supported by The Stichting Zeldzame Ziektefonds. The funding sources had no role in the design of the study, collection and analysis of data, interpretation of results, and decision to publish.

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Contributions

All listed authors meet the Pediatric Research authorship requirements. No others meeting the criteria have been omitted. T.H.D. and D.H.V. designed the study and had overall responsibility of the study. T.H.D. and R.d.V. performed the systematic search. T.H.D. and D.H.V. selected eligible studies and extracted relevant data. T.H.D. and D.H.V. assessed the risk of bias. T.H.D., W.O., and D.H.V. performed the meta-analyses. T.H.D., A.H.L.C.v.K., T.G.J.d.M., W.O., and D.H.V. interpreted the data and results. T.H.D. and D.H.V. drafted the manuscript. All other authors critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript.

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Correspondence to Thomas H. Dierikx.

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Dierikx, T.H., van Kaam, A.H.L.C., de Meij, T.G.J. et al. Umbilical cord blood culture in neonatal early-onset sepsis: a systematic review and meta-analysis. Pediatr Res 92, 362–372 (2022). https://doi.org/10.1038/s41390-021-01792-0

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