Biomarkers In Neonatal Sepsis Research Articles

Pitfalls in the Interpretation of Biomarkers in Neonatal Sepsis

Background: In India, 25%–65% of neonatal deaths are due to sepsis. Since it produces nonspecific symptoms, it is difficult to diagnose and manage. The present study assessed the value of brain natriuretic peptide (BNP) and C-reactive protein (CRP) to predict sepsis along with blood culture. Materials and Methods: Samples were collected from 90 neonates with suspected sepsis, submitted for blood culture, CRP by latex agglutination kit, and BNP by ELISA. Results: Of the 90 cases, blood culture was positive in 25 (28%) cases, BNP in 45 (50%) cases, and CRP in 36 (40%) cases. BNP was positive among 25 (100%) blood culture-positive cases. CRP, BNP, and blood culture were positive in 16 (18%) cases. Conclusion: Although BNP is an equally good marker in predicting sepsis, it is not widely available. Hence, screening by serial CRP along with blood culture alone reinforces the diagnosis.

Assessment of Platelet Indices as Biomarker for Neonatal Sepsis

Introduction: There is a need to increase the diagnostic capability of the traditional septic screen by adding additional markers. Platelet indices are one such marker that is readily available in routine hemogram reports. Materials and Methods: In this cross-sectional study, all newborn babies were recruited who had signs or symptoms of sepsis or had high-risk factors. Those who had clinical sepsis with positive cultures and/or a positive sepsis screen were classified under group “cases” ( n = 174), whereas all neonates suspected to have sepsis but who had a negative blood culture and a negative sepsis screen were classified under group “control” ( n = 126). Blood culture, sepsis screen, and platelet indices [platelet count, mean platelet volume (MPV), and platelet distribution width (PDW)] were performed on all babies. Babies with congenital or acquired causes of platelet abnormalities (including medication use by mothers with antiplatelet activity) were excluded from this study. Results: In this study, a total of 300 newborn babies were recruited for final analyses. Overall culture positivity was 38%. The mean platelet count was lower in the cases group ( P < 0.001). MPV and PDW were higher in septic babies with statistically significant differences ( P < 0.0001 and P = 0.012, respectively). Thrombocytopenia was the most sensitive marker (85.60%). However, it had low specificity (28.2%). On combining all three platelet markers, specificity increased to 48.4% (with a sensitivity of 64.5%) in detecting babies with neonatal sepsis. The sensitivity of the septic screen alone was 58% (with a specificity of 32.62%). When combining the sepsis screen and platelet indices, the specificity for the diagnosis of neonatal sepsis increased to 62.6%. On receiver operator curve analyses, thrombocytopenia had the highest area under the curve (0.692), followed by MPV (0.644). Conclusion: Platelet indices may be used as sensitive markers in combination with traditional sepsis screening to make an early diagnosis of neonatal sepsis.

The relationship between platelet to lymphocyte ratio with neonatal sepsis at Wangaya General Hospital

Background: Neonatal sepsis is still a major health problem throughout the world and one of the leading causes of morbidity and mortality in neonates. This disease often goes undetected and causes death. The diagnosis and treatment of neonatal sepsis is still a problem today. According to current research, the platelet-to-lymphocyte ratio (PLR) plays a significant role in the inflammatory process. This study aims to contribute to the research on whether PLR is connected with the incidence of neonatal sepsis and can be used as a biomarker of neonatal sepsis. Methods: This cross-sectional observational analytic study examines the link between platelet-to-lymphocyte ratio and neonatal sepsis. Based on medical records, this investigation's total number of samples was 36 newborns. Results: From June 2022 to June 2023, there were 539 newborns in the hospital. The prevalence of neonatal sepsis was 23 neonates (4,2%) and there were 14 neonates (2,6%) that fulfilled the criteria in this study. Based on the characteristics of PLR, the mean value in neonatal sepsis was found to be 125.71. Bivariate analysis using statistical Chi-square revealed that PLR had a p-value of 0.009, odds ratio of 6.7, and 95% CI of 1.5 - 29.6. Conclusion: There was a correlation between PLR and neonatal sepsis in Wangaya Hospital. Patients with increased PLR were six times the odds of having neonatal sepsis compared to patients with non-increased PLR.

Blood Biomarkers of Neonatal Sepsis with Special Emphasis on the Monocyte Distribution Width Value as an Early Sepsis Index.

Background and Objectives: Early detection of neonatal sepsis is critical because it is potentially fatal. Therefore, sepsis biomarkers of sufficient sensitivity and specificity are needed. This study aimed to evaluate the utility of peripheral blood parameters as neonatal sepsis biomarkers and the diagnostic performance of the monocyte distribution width (MDW) in sepsis in a neonatal intensive care unit. Materials and Methods: A cross-sectional study was conducted from September 2019 to August 2020 at the King Saud University Medical City in Riyadh, Saudi Arabia. Samples were collected and organised as follows: 77 study cases were subdivided into two subgroups (other health complication (49) and sepsis (28)), and there were 70 controls. The causative microorganisms of neonatal sepsis were isolated. Peripheral blood samples were collected from each neonate in an ethylenediaminetetraacetic acid tube for a complete blood count and a leukocyte differential count. Moreover, the receiver operating characteristic (ROC) curve analysis was used to measure the diagnostic performance of the MDW. Results: The haematological parameters and neonatal sepsis cases had a considerable correlation. The MDW was the most significant haematological parameter. The ROC analysis of the MDW demonstrated that the area under the curve was 0.89 (95% confidence interval: 0.867 to 0.998) with a sensitivity of 89.3%, a specificity of 88.2%, and a negative predictive value of 97.2% at the cut-off point of 23. Conclusions: The use of haematological parameters is feasible and can be performed rapidly. Neonatal sepsis showed a strong correlation with leukopenia, anaemia, thrombocytopenia, and an elevated MDW value. Moreover, the ROC curve analysis confirmed the high diagnostic ability of the MDW in neonatal sepsis prediction.

Diagnostic Value of PTX-3 Combined with PCT and CRP for Neonatal Sepsis

Aim: Neonatal sepsis is a critical illness among neonates and is the leading cause of neonatal death. In this study, we compared the changes in serum PTX-3 levels in neonates with sepsis and non-septicemia, as well as the diagnostic advantages and value of serum PTX-3 compared to traditional indicators such as WBC, CRP, and PCT. Methods: A total of 109 neonates were included in this study. Neonates were divided into three groups: 35 neonates were assigned to the sepsis group; 36 to the local infection group; and 38 assigned to the control group. Blood was collected to measure complete blood counts, CRP, PCT, liver and kidney function, lactate, and PTX-3 levels. Results: CRP, PCT, and PTX-3 in the sepsis group were significantly higher compared to the local infection group and non-infection group (P<0.01 or P>0.05). PCT and PTX-3 levels in the local infection group were significantly higher compared to the non-infection group (P>0.05). The combination of WBC+CRP+PCT+PTX-3 was more sensitive for the diagnosis of neonatal infection. For the diagnosis of neonatal sepsis, CRP was the most sensitive index, with PTX-3 having the best specificity. The combination of WBC+CRP+PTX-3 was found to significantly improve the sensitivity and specificity of diagnosis. Conclusion: PTX-3 could be used as a new biomarker for neonatal sepsis, while the combination with WBC, CRP, and PCT could significantly improve the sensitivity and specificity for sepsis diagnosis.

Systematic review and meta-analysis of the diagnostic value of four biomarkers in detecting neonatal sepsis in low- and middle-income countries

BackgroundBiomarkers may enhance diagnostic capability for common paediatric infections, especially in low- and middle-income countries (LMICs) where standard diagnostic modalities are frequently unavailable, but disease burden is high. A comprehensive...

Identification of key biomarkers in neonatal sepsis by integrated bioinformatics analysis and clinical validation

BackgroundNeonatal sepsis (NS) is a systemic inflammatory response to severe pathogenic infections, and is a major cause of high morbidity and mortality in newborns. Currently, there is a lack of efficient diagnostic technology to accurately and rapidly diagnose NS, and the precise pathogenesis of NS has yet to be fully elucidated. The present study aimed to identify the optimal biomarkers in the progression of NS. MethodsThe differentially expressed genes (DEGs) between NS and controls in the discovery datasets were screened. Gene set variation analysis (GSVA) was used to enrich the changes in biological functions and pathways in sepsis patients compared to healthy individuals. The differences in immune cell infiltration between these two groups were assessed using CIBERSORT. Furthermore, LASSO algorithm and ROC analysis were performed to identify and evaluate the gene signature. ResultsA total of 85 upregulated and 40 downregulated overlapping DEGs were screened in sepsis samples. The GSVA results indicated that DEGs largely contributed to upregulated inflammation and metabolism-related processes, and suppressed adaptive immune responses in NS. Markedly lower infiltration of most types of immune cell was observed in sepsis patients, except for some innate immune cells. Moreover, 57 genes with AUC >0.9 in both discovery sets were selected and applied to a LASSO model. Using this model, a seven-gene signature was acquired, which was validated in the discovery and independent validation sets. Five genes among the gene signatures with optimal diagnostic performance were obtained and further validated in clinical samples using RT-qPCR. Finally, three genes SLC2A3, OSCAR, and CD3G were identified as key biomarkers for NS. ConclusionsOur findings will provide novel insights into the pathogenesis of NS, and the potential biomarkers may have promising application values for its early detection and therapeutic intervention.

Diagnostic Value of Biomarkers in Neonatal Sepsis at Neonatal Intensive Care Unit at Minia University Hospitals

Diagnostic Value of Biomarkers in Neonatal Sepsis at Neonatal Intensive Care Unit at Minia University Hospitals

Is it possible to use the Toll-like receptors as biomarkers for neonatal sepsis? Review of the recent literature

Background. Sepsis continues to be one of the main death causes in the neonate population. The toll-like receptors are molecules that express in the plasma or endosomal membrane and recognize endosomal or microorganism components. While aiming at the identification of new neonatal sepsis biomarkers, the toll-like receptors (TLR) have been considered that some of them overexpress in contact with the bacterial components. Methods. Research in the PubMed database has been made by the following criteria: Inclusion criteria (PubMed database, Period 2005-2022, English & Humans, generated 29, Meta-Analysis - 0, Review - 6, Systematic Review - 0), Exclusion criteria (Studies on animal models, Articles with merely didactical content, Articles regarding only one of the words researched either only neonatal sepsis or TLR in another context than together, Articles that are not directly connected with the topic). Based on the above-mentioned criteria 13 articles were consulted, of which 7 articles included in vivo studies, 6 with in vitro studies. Conclusions. The data of the present review and the current diagnostic method point at the fact that TLRs increase in the conditions of the presence of the inflammatory syndrome. Their dosing during in the neonatal sepsis is possible, but the non-specific overexpression is not a diagnostic.

Diagnostic and prognostic predictive values of triggering receptor expressed on myeloid cell-1 expression in neonatal sepsis: A meta-analysis and systematic review

ObjectiveThe purpose of this systematic review was to explore the value of the expression level of the triggering receptor expressed on myeloid cell-1 (TREM-1) in the diagnosis and prognosis of neonatal sepsis.MethodsA comprehensive search was performed to identify the diagnostic and prognostic predictive values of the TREM-1 expression level in neonatal sepsis. Based on the retrieval strategy, Cochrane Library, Embase, Ovid, ProQuest, PubMed, Scopus, and Web of Science databases were searched from inception to February 2022. Studies were included if they assessed the accuracy of TREM-1 expression in the diagnosis of neonatal sepsis and distinguished survival and death in neonatal sepsis. Two authors independently evaluated the study and extracted the data, including the first author of the literature, country, total study population, basic population characteristics of the study group and the control group, study design (observational studies), type of sample, sepsis onset, type of biomarker, assay method, cut-off, sensitivity, specificity, true positives (TP), false positives (FP), false negatives (FN), and true negatives (TN). A third party will be consulted if disputed. The accuracy of TREM-1 expression in the diagnosis and prognostic prediction of neonatal sepsis was evaluated by a bivariate mixed-effects model. The source of heterogeneity was explored through meta-regression analysis.ResultsThirteen articles that met the research criteria were included in qualitative analysis, and 11 of them were included in quantitative analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operator characteristic (SROC) curve of soluble TREM-1 (sTREM-1) were 0.94 (95% CI: 0.82, 0.98), 0.87 (95% CI: 0.70, 0.95), 7.36 (95% CI: 2.75, 19.74), 0.07 (95% CI: 0.02, 0.24), 111.71 (95% CI: 13.24, 942.92), and 0.96 (95% CI: 0.94, 0.98), respectively. Meta-regression and subgroup analysis were used to investigate the heterogeneity, owing to non-threshold effects caused by types of test sample and research design. sTREM-1 as a biomarker for distinguishing survival and death in neonates with sepsis had pooled sensitivity, specificity, area under the SROC curve, PLR, NLR, and DOR of 0.95 (95% CI: 0.83, 0.99), 0.98 (95% CI: 0.68, 1.00), 0.99 (95% CI: 0.97, 0.99), 39.28 (95% CI: 2.13, 723.99), 0.05 (95% CI: 0.01, 0.19), and 789.61 (95% CI: 17.53, 35,560.72), respectively.ConclusionThe study showed that TREM-1 was a potential biomarker for the diagnosis and prognosis of neonatal sepsis. The biggest advantage of this study is that it is the first to comprehensively explore the role of TREM-1 expression in the diagnosis and prognosis of neonatal sepsis. However, there are some limitations in this study, such as the reduced number of clinical studies on TREM-1 expression as a biomarker of neonatal sepsis, regional bias, and differences in detection methods. Hence, more large-scale and high-quality studies are needed to improve diagnostic accuracy.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022338041.

Serum miR-34a-5p and miR-199a-3p as new biomarkers of neonatal sepsis.

BackgroundNeonatal sepsis is a serious condition. Recent clinical studies have indicated that microRNAs (miRNAs) are key players in the pathogenesis of sepsis, which could be used as biomarkers for this condition.Patients and methodsA total of 90 neonates with sepsis and 90 healthy neonates were enrolled in this study. qRT-PCR was performed to measure the expression levels of serum miR-34a-5p and miR-199a-3p.ResultsmiR-34a-5p and miR-199a-3p serum levels were significantly reduced in neonates with sepsis compared with those in healthy neonates (P = 0.006 and P = 0.001, respectively). Significant correlations of miR-34a-5p and miR-199a-3p with each of TLC, RDW, RBS, and C-reactive protein (CRP) as well as SNAPII were observed, indicating their associations with the severity of neonatal sepsis.ConclusionmiR-34a-5p and miR-199a-3p may be useful as novel biomarkers in neonatal sepsis and may provide a new direction for its treatment.

DNA Methylation Pattern Of Cpg Site In The Promoter Region Of CALCA-Alpha Gene As A Putative Epigenetic Biomarker In Neonatal Sepsis- A Prospective Observational Study In South India

Background: Recently, several studies have been reported on epigenetic modifications of DNA as a predisposing factor for several diseases among neonates and adults. Here we aimed to study the changes in the DNA methylation pattern in the promoter region of the CALCA gene among the neonates suspected to have sepsis in a tertiary care hospital.

Identification of Key Biomarkers in Neonatal Sepsis by Integrated Bioinformatics Analysis and Clinical Validation

Identification of Key Biomarkers in Neonatal Sepsis by Integrated Bioinformatics Analysis and Clinical Validation

Fabrication of a sensing platform for identification of tumor necrosis factor-alpha: a biomarker for neonatal sepsis.

Neonatal sepsis is a prime cause of neonatal deaths across the globe. Presently, various medical tests and biodevices are available in neonatal care. These diagnosis platforms possess several limitations such as being highly expensive, time-consuming, or requiring skilled professionals for operation. These limitations can be overcome through biosensor development. This work discusses the assembling of an electrochemical sensing platform that is designed to detect the level of tumor necrosis factor-alpha (TNF-α). The sensing platform was moderated with nanomaterials molybdenum disulfide nanosheets (MoS2NSs) and silicon dioxide-modified iron oxide nanoparticles (Fe3O4@SiO2NPs). The integration of nanomaterials helps in accomplishing the improved characteristics of the biosensor in terms of conductivity, selectivity, and sensitivity. Further, the molecularly imprinted polymer (MIP) approach was incorporated for sensing the presence of TNF-α on the surface of the working electrode. The electrochemical response of the electrode was recorded at different conditions. A broad concentration range was selected to optimize the biosensor from 0.01pM to 100nM. The sensitivity of the biosensor was higher and it exhibits a lower detection limit (0.01pM).

Electrochemical Based C-Reactive Protein (CRP) Sensing Through Molecularly Imprinted Polymer (MIP) Pore Structure Coupled with Bi-Metallic Tuned Screen-Printed Electrode

Neonatal sepsis is a serious and potentially life-threatening condition and a major cause of higher mortality and morbidity in the infant population. At present, the available for neonatal sepsis detection is conventional microbial testing. However, this method has various constraints, including being expensive, requiring qualified individuals, large sample volume needed for testing, and time-consuming process. The emergence of biosensors facilitates advantages over these constraints. The presented work describes the development of an electrochemical biosensor detecting C-reactive protein, a biomarker for neonatal sepsis, utilizing molecularly imprinted polymer fabricated on an electrode surface. Gold-platinum bimetallic nanomaterials were coated on the screen-printed carbon electrode to enhance the sensor's surface area and catalytic property. The C-reactive protein imprinted polymer was then deposited on the surface of the electrode. Further, the electrochemical technique was applied to measure the response of the developed electrode. It was observed that the sensing matrix was able to detect C-reactive protein and can be operated in a wide detection range and exhibits a lower detection limit as 0.1 nM with higher sensitivity (0.14 μA/nM). The developed sensing platform can provide a user-friendly approach and rapid detection results.

Diagnosis of neonatal sepsis: the past, present and future.

Sepsis remains a significant cause of neonatal mortality and morbidity, especially in low and middle-income countries. Neonatal sepsis presents with nonspecific signs and symptoms that necessitate tests to confirm the diagnosis. Early and accurate diagnosis of infection will improve clinical outcomes and decrease overuse of antibiotics. Current diagnostic methods rely on conventional culture methods, which is time-consuming and may delay critical therapeutic decisions. Nonculture-based techniques including molecular methods and mass spectrometry may overcome some of the limitations seen with culture-based techniques. Biomarkers including hematological indices, cell adhesion molecules, interleukins and acute phase reactants have been used for diagnosis of neonatal sepsis. In this review, we examine past and current microbiological techniques, hematological indices and inflammatory biomarkers that may aid sepsis diagnosis. The search for an ideal biomarker that has adequate diagnostic accuracy, early in sepsis is still ongoing. We discuss promising strategies for the future that are being developed and tested that may help us diagnose sepsis early and improve clinical outcomes.

DNA Methylation Analysis to Unravel Altered Genetic Pathways Underlying Early Onset and Late Onset Neonatal Sepsis. A Pilot Study.

Background: Neonatal sepsis is a systemic condition widely affecting preterm infants and characterized by pro-inflammatory and anti-inflammatory responses. However, its pathophysiology is not yet fully understood. Epigenetics regulates the immune system, and its alteration leads to the impaired immune response underlying sepsis. DNA methylation may contribute to sepsis-induced immunosuppression which, if persistent, will cause long-term adverse effects in neonates.Objective: To analyze the methylome of preterm infants in order to determine whether there are DNA methylation marks that may shed light on the pathophysiology of neonatal sepsis.Design: Prospective observational cohort study performed in the neonatal intensive care unit (NICU) of a tertiary care center.Patients: Eligible infants were premature ≤32 weeks admitted to the NICU with clinical suspicion of sepsis. The methylome analysis was performed in DNA from blood using Infinium Human Methylation EPIC microarrays to uncover methylation marks.Results: Methylation differential analysis revealed an alteration of methylation levels in genomic regions involved in inflammatory pathways which participate in both the innate and the adaptive immune response. Moreover, differences between early and late onset sepsis as compared to normal controls were assessed.Conclusions: DNA methylation marks can serve as a biomarker for neonatal sepsis and even contribute to differentiating between early and late onset sepsis.

Directed Transport of CRP Across In Vitro Models of the Blood-Saliva Barrier Strengthens the Feasibility of Salivary CRP as Biomarker for Neonatal Sepsis.

C-reactive protein (CRP) is a commonly used serum biomarker for detecting sepsis in neonates. After the onset of sepsis, serial measurements are necessary to monitor disease progression; therefore, a non-invasive detection method is beneficial for neonatal well-being. While some studies have shown a correlation between serum and salivary CRP levels in septic neonates, the causal link behind this correlation remains unclear. To investigate this relationship, CRP was examined in serum and saliva samples from 18 septic neonates and compared with saliva samples from 22 healthy neonates. While the measured blood and saliva concentrations of the septic neonates varied individually, a correlation of CRP levels between serum and saliva samples was observed over time. To clarify the presence of active transport of CRP across the blood–salivary barrier (BSB), transport studies were performed with CRP using in vitro models of oral mucosa and submandibular salivary gland epithelium. The results showed enhanced transport toward saliva in both models, supporting the clinical relevance for salivary CRP as a biomarker. Furthermore, CRP regulated the expression of the receptor for advanced glycation end products (RAGE) and the addition of soluble RAGE during the transport studies indicated a RAGE-dependent transport process for CRP from blood to saliva.

Downregulation of miR-1184 serves as a diagnostic biomarker in neonatal sepsis and regulates LPS-induced inflammatory response by inhibiting IL-16 in monocytes.

Neonatal sepsis (NS) remains a global problem. In the present study, abnormal expression of microRNA-1184 (miR-1184) was detected in neonates with NS and it was endeavored to investigate the diagnostic value of miR-1184, as well as its regulatory role in lipopolysaccharide (LPS)-induced inflammatory response in vitro. Furthermore, the correlation between interleukin-16 (IL-16) and miR-1184 was investigated to elucidate the pathological mechanisms of NS development. Reverse transcription-quantitative PCR was used to detect the expression of miR-1184. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of miR-1184 in NS. Furthermore, a sepsis cell model was established by using LPS-induced monocytes to explore the effect of miR-1184 on the inflammatory response. The levels of inflammatory cytokines were determined by ELISA. A luciferase reporter assay was used to investigate the direct targeting interaction between miR-1184 and IL-16. The results indicated that the serum levels of miR-1184 in neonates with sepsis were decreased and miR-1184 had a high diagnostic value when differentiating NS from respiratory conditions in neonates. In vitro, the expression of miR-1184 in monocytes was inhibited by LPS and overexpression of miR-1184 reversed the effect of LPS to stimulate the inflammatory response. IL-16 was demonstrated to be a target of miR-1184 and a negative correlation between them was identified in patients with NS. The inflammatory response inhibited by miR-1184 mimics was enhanced by overexpression of IL-16 in LPS-induced monocytes. In conclusion, decreased levels of serum miR-1184 may be a potential diagnostic biomarker for NS. In addition, miR-1184 inhibited the LPS-induced inflammatory response by targeting IL-16 in monocytes, suggesting that the miR-1184/IL-16 axis may be a potential therapeutic target for NS.

Biochemical and molecular study on serum miRNA-16a and miRNA- 451 as neonatal sepsis biomarkers

BackgroundSepsis is the serious cause of fatality in the unit of medical-intensive care (ICU). Non-coding RNA transcripts are microRNA that control gene expression by repressing translation or degrading mRNA. There are several reports discussing the concept of using miRNAs as sepsis a biomarkers by profiling miRNA dysregulation in sepsis patients' blood samples. ObjectivesThe research was aimed at exploring the clinical utility of miRNA-16a and miRNA- 451 for diagnosis of neonatal sepsis. Subjectsand methods: This research was conducted on 50 full term neonates, 25 neonates with suspected or proven sepsis and 25 clinically healthy sex and age matched neonates with no evidence of sepsis. All newborns have been exposed to clinical review, history taking and laboratory investigations including total & differential count of blood cells, C-reactive protein, blood culture. Serum miRNA-16a and miRNA-451 levels have been assessed using Real Time polymerase chain reaction (Real Time PCR) technique. ResultsNeonates with sepsis had considerably higher levels of miRNA-16a and miRNA- 451 than the healthy neonates (p ≤ 0.001). Receiver operating curve (ROC) showed that serum miRNA-16a was superior to miRNA-451 for diagnosis of sepsis with neonatal origin; it had sensitivity and specificity of 88% and 98% versus 64% and 61% respectively. Cut off point for miRNA-16a to diagnose neonatal sepsis was above or equal 3.16. Also, cut off point for miRNA-451 was above or equal 1.26. miRNA-16 a and miRNA 451 expression was significantly correlated with respiratory rate, WBCs, and CRP. ConclusionBoth miRNA −16a and miRNA-451 are detected in higher levels in newborn with sepsis compared to controls. MiRNA- 16a could be considered as promising biomarkers for diagnosis of neonatal sepsis.