Abstract

Prematurity is the leading cause of neonatal morbidity and mortality worldwide. Premature infants often require extended hospital stays, with increased risk of developing infection compared with term infants. A picture is emerging of wide-ranging deleterious consequences resulting from innate immune system activation in the newborn infant. Those who survive infection have been exposed to a stimulus that can impose long-lasting alterations into later life. In this review, we discuss sepsis-driven alterations in integrated neuroendocrine and metabolic pathways and highlight current knowledge gaps in respect of neonatal sepsis. We review established biomarkers for sepsis and extend the discussion to examine emerging findings from human and animal models of neonatal sepsis that propose novel biomarkers for early identification of sepsis. Future research in this area is required to establish a greater understanding of the distinct neonatal signature of early and late-stage infection, to improve diagnosis, curtail inappropriate antibiotic use, and promote precision medicine through a biomarker-guided empirical and adjunctive treatment approach for neonatal sepsis. There is an unmet clinical need to decrease sepsis-induced morbidity in neonates, to limit and prevent adverse consequences in later life and decrease mortality.

Highlights

  • Prematurity is the leading cause of neonatal morbidity and mortality worldwide

  • LPS and lipoteichoic acid (LTA) in combination with hypoxic ischemic injury to rats at postnatal day (PND) 7 resulted in an initial increase in glucose at 2 h followed by hypoglycemia, which lasted for 24 h [228]

  • Several lines of inquiry converge to confirm that sepsis in preterm and term babies and animal models of similar development stages induces significant disturbances to intertwined neuroendocrine and metabolic pathways

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Summary

NEONATAL SEPSIS

Neonatal sepsis is caused by bacteria, viruses, or fungi that impinge on normal development of newborn infants [18]. LOI poses challenges for homeostatic control systems of major body functions [18], and a number of physiological signs and clinical symptoms are evident in neonates with LOI These are used in clinical settings to instigate treatment for suspected infection [31,32,33]. More reliable and specific biomarkers for identification of LOI in term and preterm infants would improve our knowledge of the infectious epidemiology and advance precision medicine for empirical and adjunctive treatment of neonatal sepsis within the NICU, which may in turn lead to a reduction in antibiotic administration, with an associated decrease in morbidity and mortality associated with LOI. These include, but are not limited to, mechanical ventilation, administration of vasoactive or inotropic agents, as well as methods of glucose control [47]

INNATE IMMUNE SYSTEM
Dysregulated glucose metabolism Pyruvate and lactate
Energy Reserves in Preterm Infants
Lactate and Vitamin B Complex
Amino Acids
MULTIOMIC APPROACHES FOR IDENTIFICATION OF NEONATAL SEPSIS
SUMMARY AND CONCLUSIONS
Findings
AUTHOR CONTRIBUTIONS
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