Dysregulated microRNA expression in neonatal sepsis: validation study of potential novel biomarkers

Background Neonatal sepsis remains, to this day, a significant problem in perinatal care for term and preterm infants. Incidence and mortality are staggeringly high, as 4 in 10 infants with sepsis die or experience a significant disability resulting from sepsis. Previous studies have identified microRNAs (miRNAs) as potential biomarkers of neonatal sepsis in the context of inflammatory diseases. Methods We assembled a cohort of 64 newborns with sepsis and 21 control patients without signs of systemic infection. Specimens of peripheral blood were collected and processed. Total RNA enriched for small RNA was extracted from blood plasma. Based on a literature search, we decided to measure levels of circulating miRNAs (hsa-miR-29a-3p, hsa-miR-96-5p, hsa-miR-185-5p, hsa-miR-16-5p, hsa-miR-15a-5p, hsa-miR-132-3p, hsa-miR-223-3p, hsa-miR-26a-5p) using quantitative polymerase chain reaction. The results have been normalized to the average expression of all measured miRNAs and analyzed using GraphPad Prism 8 statistical software. C-reactive protein (CRP) was systematically assessed in all patients, and correlations between CRP and selected miRNAs (miR-15a, miR-132, miR-223) were analyzed. Results Among the cohort, 19 patients were diagnosed with early-onset sepsis (EOS) and 45 with late-onset sepsis (LOS). Blood cultures were positive in 45% of cases, with Staphylococcus epidermidis , Escherichia coli , and Staphylococcus aureus being the most common pathogens. Differential expression of seven miRNAs was analyzed, revealing that miR-15a, miR-132, and miR-223 were significantly dysregulated in septic patients, with miR-15a being the most prominent ( p  = 0.0009). miR-15a showed significant dysregulation during the acute phase of the disease, returning to baseline levels by day 7. However, miR-15a and miR-223 were significantly dysregulated in patients with higher nSOFA scores, suggesting a potential link with sepsis severity. Conclusion This study proves that miRNAs could be biomarkers for neonatal sepsis. Notably, miR-15a and miR-223 were significantly dysregulated in patients with higher nSOFA scores, indicating their potential as predictive biomarkers for severe disease progression. These findings highlight the potential of miRNAs as diagnostic and prognostic tools that could be used to improve patient stratification, personalized treatment, and outcomes in cases of neonatal sepsis. This study provides the first independent evaluation of these findings.