Table 1.

Potential biomarkers of the endothelial glycocalyx in neonatal sepsis.

Biomarkers	Biological Role	Changes in Neonatal Sepsis	AUC	Ref
Matrix metalloproteinase-9 (MMP-9)	Zinc-dependent proteinase, is released by various inflammatory cells, predominantly neutrophils and macrophages. Implicated in oxidative stress, inflammation and lung injury.	Augmented in septic neonates (LOS) and downregulated in non-survivor patients. In vitro, increased in E. coli-infected neonatal monocytes, and inhibit cell-contact-dependent phagocytosis-induced cell death and may help to reduce long-term inflammation in newborns through this mechanism.	Not described in the literature	[73,74,102,103]
Matrix metalloproteinase-8 MMP-8	A neutrophil-derived collagenase Degrade collagen type I. present in macrophages, fibroblasts, epithelial cells, and other immune cells. MMP-8 has non-collagen proteolytic targets, including pro-inflammatory chemokines. In sepsis, its levels were increased. MMP-8 promotes leukocyte adhesion to HUVECs.	In EOS increased with other molecules such as IL-6, TNF-α, HSP 70, PCT, and CRP. In VLBW with LOS the elevation of MMP-8 mRNA expression and activity in septic shock correlated with decreased survival and increased organ failure in pediatric patients and associated with TNF-α. MMP-8 is associated with poor prognosis in sepsis.	0.607 (95% CI = 0.524–0.685)	[75,76,104,105]
Inter-alpha inhibitor proteins IαIp	Serine protease, it is prominent among the histone-precipitated proteins. IαIP is composed to light and heavy chains (HC). In inflammation, IαIP interacts with TNF-stimulated gene six protein (TSG-6), which supports trans-esterification of HC to HA. In sepsis, IαIp inhibit granzymes and other proteases reducing their toxic proteolytic activity.	In NS the level of IαIp was decreased. Its levels were inversely correlated to 28-day mortality rates and illness severity.	0.94 (95% CI = 0.92–0.96, p < 0.0001)	[96,106,107]
Endocan	Endothelial mediator, it mainly inhibits leukocyte diapedesis rather than leukocyte rolling or adhesion to the endothelial cells both in vitro and in vivo.	Increased in NS and remained high until the third day, returning to their normal values on day 7. It is increased in the case of LOS. It is proven in the diagnosis of sepsis, and sepsis severity but its prognostic value was better compared with procalcitonin.	0.73 (95% CI = 0.597–0.871, p = 0.004) 0.80 (95% CI = 0.674–0.923, p < 0.001)	[99,100,108]

AUC: Area under the curve; CI: confidence interval.