Diagnosis of neonatal sepsis: the past, present and future

Pediatr Res. 2022 Jan;91(2):337-350. doi: 10.1038/s41390-021-01696-z. Epub 2021 Nov 2.


Sepsis remains a significant cause of neonatal mortality and morbidity, especially in low- and middle-income countries. Neonatal sepsis presents with nonspecific signs and symptoms that necessitate tests to confirm the diagnosis. Early and accurate diagnosis of infection will improve clinical outcomes and decrease the overuse of antibiotics. Current diagnostic methods rely on conventional culture methods, which is time-consuming, and may delay critical therapeutic decisions. Nonculture-based techniques including molecular methods and mass spectrometry may overcome some of the limitations seen with culture-based techniques. Biomarkers including hematological indices, cell adhesion molecules, interleukins, and acute-phase reactants have been used for the diagnosis of neonatal sepsis. In this review, we examine past and current microbiological techniques, hematological indices, and inflammatory biomarkers that may aid sepsis diagnosis. The search for an ideal biomarker that has adequate diagnostic accuracy early in sepsis is still ongoing. We discuss promising strategies for the future that are being developed and tested that may help us diagnose sepsis early and improve clinical outcomes. IMPACT: Reviews the clinical relevance of currently available diagnostic tests for sepsis. Summarizes the diagnostic accuracy of novel biomarkers for neonatal sepsis. Outlines future strategies including the use of omics technology, personalized medicine, and point of care tests.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • Humans
  • Infant, Newborn
  • Neonatal Sepsis / diagnosis*
  • Neonatal Sepsis / metabolism
  • Neonatal Sepsis / physiopathology
  • Point-of-Care Testing


  • Biomarkers