Value of Serum miRNA 146a as Biomarker for Early Diagnosis of Neonatal Sepsis

Abstract

Neonatal sepsis (NS) is regarded as one of the most common causes of morbidity and mortality among neonates worldwide. However, the magnitude of the problem is higher in low income countries, in spite of recent improvement of neonatal health care units. Accurate and early diagnosis of NS is the corner stone toward better therapeutic approach and safe outcome. C-reactive protein is currently used however it has been reported to have a low specificity and to rise in blood of cases with a delay of 24 hours than other biomarkers like inerleukin-16 or procalcitonin. Therefore, identification of new biomarkers with high specificity and sensitivity is extremely needed. The current study aimed to detect changes in miR-146a serum expression levels among NS cases, neonates at high risk to develop sepsis and healthy control neonates and to assess the value of serum miR-146a as early indicator of NS. qPCR was used for detection of miR-146a serum expression among different study groups. Serum miR-146a showed differential expression of statistical significance within study groups, with the highest level in NS group and the lowest in healthy controls. Moreover, serum miR-146a showed a significant positive correlation with the CRP titer in NS group. Receiver operating characteristic (ROC) curve analysis revealed that best cut off value for miR-146a was at 0.539 relative units, with a sensitivity of 91.7%, specificity of 100% and 95.7% accuracy. As regard to CRP, the best ROC curve was at 18 mg/dL with 100% sensitivity, 86.4% specificity and 93.5% accuracy. Combination of miR-146a and CRP increased specificity, sensitivity and accuracy to 100%. Furthermore, in multivariate logistic regression analysis, only CRP and miR-146a were considered as independent risk factor for prediction of sepsis within high risk neonates. In conclusion, serum miR-146a may be a promising predictor for sepsis within the high risk neonates. However, large-scale prospective studies are required to confirm our findings.