Early-Onset Neonatal Sepsis: Inflammatory Biomarkers and MicroRNA as Potential Diagnostic Tools in Preterm Newborns

Janec, Petr; Mojžíšek, Marek; Pánek, Martin; Haluzík, Martin; Živný, Jan; Janota, Jan

doi:10.14712/fb2023069050173

Folia Biologica > Archive > 2023, Vol. 69 > Issue 5-6 > Early-Onset Neonatal Sepsis:…

Fol. Biol. 2023, 69, 173-180

https://doi.org/10.14712/fb2023069050173

Early-Onset Neonatal Sepsis: Inflammatory Biomarkers and MicroRNA as Potential Diagnostic Tools in Preterm Newborns

Petr Janec¹, Marek Mojžíšek², Martin Pánek¹, Martin Haluzík³, Jan Živný⁴, Jan Janota^2,4,5

¹Department of Neonatology, Masaryk Hospital Ústí nad Labem, Krajská zdravotní, Ústí nad Labem, Czech Republic
²Neonatal Unit, Department of Obstetrics and Gynaecology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
³Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
⁴Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
⁵Department of Neonatology, Thomayer University Hospital, Prague, Czech Republic

Received December 2023
Accepted January 2024

Mortality and morbidity of newborns with sepsis can be improved by early and accurate diagnosis and targeted therapy. To evaluate the early molecular events associated with inflammation and infection, we evaluated markers of endothelial activation and injury and circulating plasma miRNAs in preterm newborns with sepsis. The study group consisted of newborns with gestational age ≤ 32 weeks, with culture-positive early-onset neonatal sepsis (sepsis group, N = 8), and as a control group, we enrolled newborns without sepsis (control group, N = 12). Soluble markers of inflammation were measured using Luminex-based multiplex assay. Platelet-free plasma RNA was used to construct the library for miRNA sequencing analysis. Normalized counts were calculated and used to measure differential expression of individual detected miRNAs. We found a significant increase of interleukin 18 (IL-18) in the cord blood of the sepsis group (mean ± SEM, 104.7 ± 30.4 pg/ml vs 52.7 ± 5.6 pg/ml, P = 0.02). In peripheral blood of sepsis group patients, we found a significant increase of VEGF-A compared to controls (196.0 ± 70.5 pg/ml vs 59.6 ± 8.5 pg/ml, P = 0.02). In the cord blood plasma, eight miRNAs had significantly differential expression (P < 0.05), four miRNAs were up-regulated and four miRNAs down-regulated. In peripheral blood plasma, all nine miRNAs with significant differential expression were up-regulated. In conclusion, in early-onset neonatal sepsis, IL-18 and VEGF-A might be considered in diagnostic workup. Early-onset sepsis in preterm newborns is associated with significant changes in the circulating miRNA pattern.

Supplementary materials: Supplementary Table S1 and Supplementary Table S2