As
neonatal sepsis is a severe condition, there is a call for reliable
biomarkers to differentiate between infected and noninfected newborns. Although blood culture has been considered as the gold standard, this analysis is still too slow and limited by false negative results. Use of CRP is hampered by a physiological 3-day increase, resulting in a low sensitivity to detect
sepsis at an early stage. A moderate diagnostic accuracy of other
acute phase proteins has been demonstrated (
serum amyloid A,
procalcitonin,
lipopolysaccharide binding protein,
mannose binding lectin and
hepcidin). In
neonatal sepsis, changed
chemokine/
cytokine levels are observed before those of
acute phase reactants. High
IL-6,
IL-8,
IL-10 and TNF-α concentrations are detected in infected infants. Soluble
interleukin-2 receptor has been used to identify
bacteremia, whereas low plasma
RANTES concentrations are characteristic for
septicemia. Several
cell adhesion molecules contribute to the pathogenesis of
sepsis. As an upregulated CD64 expression on granulocytes is found within 1-6h after bacterial invasion, serial CD64 measurements could guide
antibiotic therapy. An increased CD11b/CD18 density can improve the diagnosis, and a positive correlation between CD11b and the severity of systemic
inflammation has been reported. An early increase in sCD14-ST presepsin is also observed during
sepsis, whereas high sTREM-1 values in early-onset
neonatal sepsis (EOS) have been associated with mortality.
Biomarkers resulting from proteomics are also promising. A 4-biomarker 'mass restricted' score has been validated as diagnostic for intra-amniotic
infection and/or
inflammation. S100A8 in amniotic fluid is a strong predictor of an increased incidence of EOS. Proteomic analysis of cord blood has revealed altered
protein expression patterns. The ApoSAA score is useful for identifying
sepsis and could guide prescription of
antibiotics. (1)H-NMR and GC-MS metabolomics allow to diagnose
septic shock, which is associated with increased concentrations of 2-hydroxybutyrate,
2-hydroxyisovalerate, 2-methylglutarate,
creatinine,
glucose and
lactate.