Abstract
Understanding immunoregulation in newborns can help to determine the pathophysiology of neonatal sepsis and will contribute to improve the diagnosis, prognosis, and treatment and remains an urgent and unmet medical need to understand hyperinflammation or hypoinflammation associated with sepsis in newborns. This study included infants (up to 4 days old). The “sepsis” criteria was a positive blood culture. C-reactive protein demonstrates a strong dependence on the pathogen etiology. Therefore, its diagnostic odds ratio in Gram-positive bacteremia was 2.7 and the sensitivity was 45%, while Gram-negative was 15.0 and 81.8%, respectively. A neutrophil-lymphocyte ratio above 1 and thrombocytopenia below 50∗109 cells/L generally do not depend on the type of pathogen and have a specificity of 95%; however, the sensitivity of these markers is low. nCD64 demonstrated good analytical performance and was equally discriminated in both Gram (+) and Gram (−) cultures. The sensitivity was 87.5–89%, and the specificity was 65%. The HLA-DR and programmed cell death protein study found that activation-deactivation processes in systemic infection is different at points of application depending on the type of pathogen: Gram-positive infections showed various ways of activation of monocytes (by reducing suppressive signals) and lymphocytes (an increase in activation signals), and Gram-negative pathogens were most commonly involved in suppressing monocytic activation. Thus, the difference in the bacteremia model can partially explain the problems with the high variability of immunologic markers in neonatal sepsis.
Highlights
Sepsis of newborns is one of the most important issues in pediatrics, the third leading cause of death in the neonatal period
These data demonstrate that the sepsis caused by Gram-positive bacteria is a less stimulus for the production of C-reactive protein (CRP), the data for this group are more variable, and the median values do not differ. e significance of differences from the control is achieved only in the case of Gram-negative bacteremia (control vs. Gram (−), p 0.04)
We found that PD-1 expression on monocytes and lymphocytes differs fundamentally depending on the type of pathogen. us, for PD-1 on monocytes, mean fluorescence intensity (MFI) decreases with the Gram (+) pathogen group, and the difference between the two groups is significant (p 0.007)
Summary
Sepsis of newborns is one of the most important issues in pediatrics, the third leading cause of death in the neonatal period. Mortality rates range from 13% to 70% [1]. In Kazakhstan, the mortality rate from sepsis among children under one year of age increased to 4.3 in 2019, and in the Karaganda region, it was 8.68 per 1000 live births [2]. Little progress has been done in the treatment of neonatal sepsis in the last three decades. Diagnosis is crucial in the prevention of negative outcomes. An urgent and unsatisfied medical need for the diagnosis of sepsis-related hyperinflammation in newborns remains
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