Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in diagnosing neonatal sepsis.

Clinical manifestations of neonatal sepsis are often unspecified. Therefore, sepsis biomarkers could be used to support diagnosis while waiting for blood culture results, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). The aim of this study was to evaluate the role of NLR and PLR as diagnostic markers in neonatal sepsis. A cross-sectional study was conducted at Haji Adam Malik General Hospital, Medan, Indonesia, from April to October 2019. This study included neonates aged less than 28 days, diagnosed with suspected sepsis, and had no previous history of antibiotics administration. Patients underwent clinical assessment, laboratory examination, and blood culture. Patients were grouped into sepsis and non-sepsis based on the blood culture results. The median hematological examination and the range of NLR and PLR in both the sepsis and non-sepsis groups were subjected to analysis using the Mann-Whitney U test to assess differences. NLR and PLR optimal cut-off values were determined using a receiver operator curve (ROC) with a confidence interval of 95%. A total of 137 neonates were enrolled, of which 49 were classified as sepsis and 89 as non-sepsis based on blood culture results. The optimal cutoff values for NLR and PLR were 2.75 and 11.73. Using those cutoff values, NLR and PLR could predict neonatal sepsis with sensitivities of 52.1% and 47.9%, specificities of 50.6% and 47.2%, area under the curve (AUC) of 0.46 and 0.47, with p=0.525 and p=0.662, respectively. Further investigation is warranted to refine the NLR and PLR utility and enhance diagnostic accuracy in clinical practices.

Assessment of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and systemic immune-inflammatory index, as diagnostic markers for neonatal sepsis.

OBJECTIVE: To assess the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII), as diagnostic markers for neonatal sepsis. METHODS: This retrospective study involve neonates with sepsis and healthy neonates as controls. NLR, PLR, and SII were compared between groups. RESULT: In total, 60 neonates with sepsis and 60 healthy controls were involved in the study. Compared with controls, the sepsis group had higher values for NLR, PLR and SII. Logistic regression analysis suggested that the NLR, PLR and SII were independent risk factors for neonatal sepsis. In addition, receiver operating characteristic (ROC) curve analysis indicated that the NLR, PLR and SII were reliable predictors of neonatal sepsis and SII had the best predictive value. CONCLUSIONS: NLR, PLR and SII appear to be useful indicators for predicting neonatal sepsis.

Loop-mediated isothermal amplification (LAMP) assay for early on-site detection of Group B Streptococcus infection in neonatal sepsis blood sample.

BACKGROUND: Neonatal sepsis, often attributed to Group B Streptococcus (GBS) infection, poses a critical health risk to infants, demanding rapid and accurate diagnostic approaches. Existing diagnostic approaches are dependent on traditional culture methods, a process that requires substantial time and has the potential to delay crucial therapeutic assessments. METHODS: This study introduces an innovative Loop-Mediated Isothermal Amplification (LAMP) assay for the early on-site detection of GBS infection from neonatal sepsis blood samples. To develop a LAMP assay, the primers are designed for the selective targeting of a highly conserved segment within the cfb gene encoding the CAMP factor in Streptococcus agalactiae ensuring high specificity. RESULTS: Rigorous optimization of reaction conditions, including temperature and incubation time, enhances the efficiency of the LAMP assay, enabling rapid and reliable GBS detection within a short timeframe. The diagnostic efficacy of the LAMP assay was evaluated using spiked blood samples by eliminating the DNA extraction step. The simplified colorimetric LAMP assay has the capability to detect S. agalactiae in a neonatal blood sample containing 2 CFU/mL during sepsis. Additionally, the LAMP assay effectively detected S. agalactiae in both the standard and spiked blood samples, with no detectable interference with blood. CONCLUSION: This optimised LAMP assay emerges as a promising tool for early GBS detection, offering a rapid and accurate on-site solution that has the potential to inform timely interventions and improve outcomes in neonatal sepsis cases.

Trends in C-Reactive Protein Use in Early-onset Sepsis Evaluations and Associated Antibiotic Use.

OBJECTIVE: To determine the prevalence of C-reactive protein (CRP) use in early-onset sepsis (EOS) evaluations in neonatal intensive care units (NICUs) across the US over time and to determine the association between CRP use and antibiotic use. STUDY DESIGN: A retrospective cohort study of NICUs contributing data to Premier Healthcare Database from 2009 through 2021. EOS evaluation was defined as a blood culture charge ≤ 3 days after birth. CRP use for each NICU was calculated as the proportion of infants with a CRP test obtained ≤ 3 days after birth among those undergoing an EOS evaluation and categorized as, low (<25%); medium-low (25 to < 50%), medium-high (50 to < 75%), and high (≥75%). Outcomes included antibiotic use and mortality ≤ 7 days after birth. RESULTS: Among 572 NICUs, CRP use varied widely and was associated with time. The proportion of NICUs with high CRP use decreased from 2009 to 2021 (24.7% vs 17.4%, P < .001), and those with low CRP use increased (47.9% vs 64.8%, P < .001). Compared with low-use NICUs, high-use NICUs more frequently continued antibiotics > 3 days (10% vs 25%, P < .001). This association persisted in multivariable-adjusted regression analyses (adjusted risk ratio 1.95, 95%CI 1.54, 2.48). Risk of mortality was not different in high-use NICUs (adjusted risk difference -0.02%, 95%CI -0.04%, 0.0008%). CONCLUSIONS: CRP use in EOS evaluations varied widely across NICUs. High CRP use was associated with prolonged antibiotic therapy but not mortality ≤ 7 days after birth. Reducing routine CRP use in EOS evaluations may be a target for neonatal antibiotic stewardship efforts.

Diagnostic capacity of miRNAs in neonatal sepsis: a systematic review and meta-analysis.

BACKGROUND: Neonatal sepsis is the third leading cause of mortality during the neonatal period, with manifestations atypical and obscure. But the gold standard-blood culture test, requiring 3-5 days, makes it difficult to unveil the final pathogen and leads to the increasing ratio of false-negative results. The empirical method is consulting traditional biomarkers, such as procalcitonin (PCT), C-reactive protein (CRP), and white blood cell count. However, they are not specific for neonate in diagnostic capacity, especially for infants within three days after delivery, so more novel biomarkers are urgently needed to assist diagnosing neonatal sepsis. microRNAs (miRNAs) have been widely studied in recent years for their diagnostic and prognostic values in different diseases and we conducted a meta-analysis of miRNAs on the topic that whether they are potentially novel biomarkers in early detection of neonatal sepsis. OBJECTIVES: The purpose of the study was to assess whether circulating miRNAs could be used as potential biomarkers for neonatal sepsis, including early and late-onset neonatal sepsis, then calculate their overall accuracy (OA) via meta-analysis. METHODS: PubMed, Cochrane Library, Embase, Web of Science, Scopus, and Ovid databases were retrieved; data cutoff for this analysis was 15 January 2023. Methodological quality assessment of included studies was performed through the Quality in Prognostic Studies tool. Corresponding 95% confidence interval (95%CI) was calculated to present miRNAs' diagnostic value including the pooled sensitivity (Sen), specificity (Spe), positive or negative likelihood ratios (PLR or NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). Differences in OA between the septic group and non-septic group were compared using Chi-square test. RESULTS: After identification, 16 records out of 11 selected articles were eligible for systematic review of miRNAs and four records for PCT; the case group for miRNAs included 945 neonatal sepsis cases; contrast group included 190 respiratory tract infections or pneumonia cases, 60 systemic inflammatory response syndrome (SIRS) cases and 559 healthy neonates. The pooled Sen, Spe, and DOR of miRNAs were 0.87 (95%CI 0.81-0.91), 0.79 (95%CI 0.71-0.85), and 24 (95%CI 12-50), respectively. The pooled Sen, Spe, and DOR of PCT were 0.92 (95%CI 0.83-0.96), 0.64 (95%CI 0.56-0.70), and 20 (95%CI, 7-56), respectively. The OA value of miRNAs was 80.38% and that of PCT was 77.36%, which were not statistically significant difference (p = .13) after the Chi-square test. In addition, no significant publication bias was indicated (p = .92). CONCLUSIONS: Circulating miRNA levels could be applied as diagnostic biomarkers in neonatal sepsis.

Association of low vitamin D level and full-term early-onset neonatal sepsis; a case-control study.

BACKGROUND: Sepsis is one of the main causes of death in newborns worldwide. Vitamin D levels during fetal and neonatal periods have a significant role in the development of the immunological system. The study aims to evaluate the association between vitamin D levels and the risk of early-onset neonatal sepsis in full-term neonates in a developing country. METHODS: This case-control study was conducted at the Neonatal Intensive Care Units (NICUs) of Kasr Alainy Hospital, Cairo, Egypt. The study was composed of two groups; the sepsis group involved full-term neonates appropriate for gestational age with sepsis-related clinical signs. The control group included newborns with no signs of clinical/laboratory infection within 72 h of life. Blood samples were collected on admission during the first three days of life in both groups for the measurement of 25-hydroxyvitamin D levels, Complete Blood Count (CBC), C reactive protein (CRP), and blood culture. RESULTS: Forty-five newborns with clinical and laboratory findings of early-onset neonatal sepsis within 72 h of life were enrolled, and the control group included forty-five newborns with no evidence of sepsis. Vitamin D levels in the sepsis group were significantly lower than in the control group. Apgar score at the first minute was significantly lower in the sepsis group. 57.8% of neonates with sepsis had positive blood cultures. There was a statistical difference between deficient, insufficient, and sufficient vitamin D levels regarding the duration of the NICU stay, which was longer in neonates with deficient vitamin D levels. CRP was significantly higher in neonates with deficient vitamin D levels. The area under the receiver operating characteristic curve for serum vitamin D in the prediction of neonatal sepsis was 0.76 at a cutoff < 19.7(ng/ml). CONCLUSION: In the current study, full-term newborns with EOS had considerably lower vitamin D levels than healthy controls. Through appropriate vitamin supplementation of the mothers during pregnancy, it could be possible to ensure adequate vitamin D levels for newborns. This may contribute to the reduction of the risk of EOS, together with the other well-known preventive measures (i.e. breastfeeding and intrapartum antibiotic prophylaxis).

Syndecan-1 Level, a Marker of Endothelial Glycocalyx Degradation, Is Associated With Fetal Exposure to Chorioamnionitis and Is a Potential Biomarker for Early-Onset Neonatal Sepsis.

The goal of this investigation was to identify the association between Syndecan-1 (S1) serum levels in preterm newborns exposed to chorioamnionitis (CA) in utero and the potential of S1 as a biomarker of early-onset neonatal sepsis. A cohort of preterm newborns born <33 weeks gestational age was recruited. Within 48 hours of birth, 0.5 mL of blood was drawn to obtain S1 levels, measured via ELISA. Placentas were examined and classified as having (1) no CA, (2) CA without umbilical cord involvement, or (3) CA with inflammation of the umbilical cord (funisitis). S1 levels were compared between preterm newborns without exposure to CA verus newborns with exposure to CA (including with and without funisitis). Preterm newborns exposed to CA were found to have significantly elevated S1 levels compared to those unexposed. Although S1 levels could not differentiate fetal exposure to CA from exposure to CA with funisitis, the combined CA groups had significantly higher S1 levels compared to those not exposed to CA. S1 level has the potential to become a clinically useful biomarker that could assist in the management of mothers and preterm newborns with CA and funisitis. Furthermore, S1 level could aid in the diagnosis and treatment of early-onset neonatal sepsis.

DEVELOPMENT AND VALIDATION OF A MODEL FOR PREDICTION OF SEPTIC SHOCK IN NEONATES WITH SEPSIS.

ABSTRACT: Purpose: This study aimed to develop and validate a model for prediction of septic shock in neonates with sepsis. Materials and methods: This retrospective study included early-onset septic neonates in the Renmin Hospital of Wuhan University between January 2017 and June 2021. The neonates were divided into the training set and the validation set in a ratio of 7:3 and further categorized into septic shock group and none-shock group according to presence or absence of shock symptoms. Results: A total of 406 septic neonates were enrolled, including 217 in septic shock group. Sex (odds ratio [OR] = 0.092, 95% confidence interval [CI]: 0.012 to 0.683, P = 0.020), C-reactive protein at 6 h (OR = 8.475, 95% CI: 3.154 to 22.774, P < 0.001), serum amyloid A at 6 h (OR = 1.179, 95% CI: 1.094 to 1.269, P < 0.01), white blood cells at 6 h (OR = 0.173, 95% CI: 0.092 to 0.326, P < 0.001), platelets at 6 h (OR = 0.985, 95% CI: 0.975 to 0.995, P < 0.001), and Ca 2+ at 6 h (OR = 1.44 × 10 11 , 95% CI: 2.70 × 10 6 to 7.70 × 10 15 , P < 0.001) were identified as independent risk factors for septic shock and were further included in the nomogram. The areas under the receiver operator characteristic curve were 0.873 and 0.920 in training and validation sets, respectively. Conclusions: A predictive model for early diagnosis of septic shock in neonates was developed and initially validated in this study, allowing for timely intervention.

Evaluation of systemic inflammatory indices in the diagnosis of early onset neonatal sepsis in very low birth weight infants.

BACKGROUND: Previously, not six systemic inflammatory indices were evaluated in the diagnosis of early onset sepsis (EOS) in very low birth weight (VLBW, <1500g) premature infants. OBJECTIVES: We evaluated the effectiveness of systemic inflammatory indices in the diagnosis of EOS in VLBW infants. METHODS: Premature infants with birth weight <1500 g were included in the study. Six systemic inflammatory indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and systemic inflammation response index (SIRI) were compared in patients with EOS (treatment group) and without EOS (control group). RESULTS: Of 917 infants enrolled, 204 infants were in the EOS group and 713 infants comprised the control group. NLR, MLR and SIRI values were significantly higher in the EOS group than in the control group (p < 0.001). The AUC value of SIRI for the predictivity of EOS was 0.803. CONCLUSIONS: The SIRI can be used together with other parameters as both an easily accessible and the reliable systemic inflammatory indices in the diagnosis of EOS in VLBW preterm infants.

Diagnostic value of maternal, cord blood and neonatal biomarkers for early-onset sepsis: a systematic review and meta-analysis.

BACKGROUND: An accurate diagnosis of early-onset sepsis (EOS) is challenging because of subtle symptoms and the lack of a good diagnostic tool, resulting in considerable antibiotic overtreatment. A biomarker, discriminating between infected and non-infected newborns at an early stage of the disease, could improve EOS prediction. Numerous biomarkers have been tested, but have never been compared directly. OBJECTIVES: We aimed to provide a comprehensive overview of early biomarkers and their diagnostic value in maternal samples, umbilical cord blood, and neonatal serum. DATA SOURCES: PubMed-Medline, EMBASE, The Cochrane Library, and Web of Science were searched up to 1 March 2023, without restrictions on publication date, population, or language. STUDY ELIGIBILITY CRITERIA: Articles describing the diagnostic value of at least one biomarker in the detection of EOS in neonates, independent of gestational age, were included. ASSESSMENT OF RISK OF BIAS: The QUADAS-2 tool was used to assess study quality. METHODS OF DATA SYNTHESIS: Three independent researchers assessed the articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was performed with all manuscripts describing diagnostic accuracy using a random-effects model. RESULTS: Of 2296 identified articles, 171 reports were included in the systematic review and 69 in the meta-analysis. Literature showed mixed and inconsistent evidence for most biomarkers and sample types, because of a lack of a uniform EOS case definition, small sample sizes, and large heterogeneity between studies. Interesting markers were procalcitonin (pooled sensitivity 79%, 95% CI 71-84%; specificity 91%, 95% CI 83-96%, n = 11) and interleukin (IL)-6 (pooled sensitivity 83%, 95% CI 71-90%; specificity 87%, 95% CI 78-93%, n = 8) in umbilical cord blood and presepsin (pooled sensitivity 82%, 95% CI 62-93%; specificity 86%, 95% CI 73-93%, n = 3) and serum amyloid A (pooled sensitivity 92%, 95% CI 75-98%; specificity 96%, 95% CI 78-99%, n = 4) in neonatal serum. Studies on the combination of biomarkers were scarce. CONCLUSIONS: A biomarker stand-alone test is currently not reliable for direct antibiotic stewardship in newborns, although several biomarkers show promising initial results. Further research into biomarker combinations could lead to an improved EOS diagnosis, reduce antibiotic overtreatment, and prevent associated health-related problems.

Diagnostic Accuracy of Point-of-Care Testing of C-Reactive Protein, Interleukin-6, and Procalcitonin in Neonates with Clinically Suspected Sepsis: A Prospective Observational Study.

OBJECTIVE: Sepsis often prompts clinicians to start empirical antibiotics in suspected neonates while awaiting diagnosis. The next-generation testing with point-of-care (POC) techniques offers a lead-time advantage that could bridge the gap by providing a timely diagnosis. MATERIALS AND METHODS: We conducted a prospective diagnostic study in 82 neonates enrolled between May and October 2022 in a level III neonatal intensive care unit. All neonates with a new episode of clinically suspected sepsis were included. Diagnostic accuracy of POC testing of C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) with standard laboratory methods was performed. RESULTS: The mean gestation age and birth weight of the neonates were 33.17 ± 4.25 weeks and 1,695.4 ± 700.74 grams, respectively. Most neonates were preterm (75%) with nearly equal proportions of early (51.22%) and late-onset (48.78%) sepsis. The POC CRP correlated well with standard CRP (r = 0.8001, 95% CI: 0.706-0.867, p < 0.0001). Among the three biomarkers, CRP had the maximum diagnostic accuracy (area under the curve [AUC] - 0.73) followed by PCT (AUC - 0.65) and IL-6 (0.55). There was no significant difference in the diagnostic accuracy of CRP (p = 0.46), PCT (p = 0.29), and IL-6 (p = 0.60) in early- and late-onset sepsis. The mean time for POC estimation of IL-6, PCT, and CRP was 12 ± 3 min which was significantly less compared to 366 ± 61 min for standard techniques (p < 0.001). CONCLUSION: POC CRP correlates well with standard techniques of estimation, and CRP alone and in combination with PCT has good diagnostic accuracy in neonatal sepsis.

Cord blood presepsin as a predictor of early-onset neonatal sepsis in term and preterm newborns.

BACKGROUND: To date, no studies on presepsin values in cord blood of term infants with risk factors for early-onset sepsis (EOS) are available, whereas only one study reported presepsin values in cord blood of preterm infants at risk. In this study, we investigated the presepsin values in cord blood of term and preterm infants with documented risk factors for EOS. METHODS: In this single-center prospective pilot study, we enrolled neonates presenting with documented risk factors for EOS. P-SEP levels were assessed in a blood sample collected from the clamped umbilical cord after the delivery in 93 neonates, using a point-of-care device. The primary outcome of our study was to evaluate the role of cord blood P-SEP in predicting clinical EOS in term and preterm infants. RESULTS: During the study period, we enrolled 93 neonates with risk factors for EOS with a gestational age ranging between 24.6 and 41.6 weeks (median 38.0). The median P-SEP value in all infants was 491 pg/ml (IQR 377 - 729). Median cord P-SEP values were significantly higher in infants with clinical sepsis (909 pg/ml, IQR 586 - 1307) rather than in infants without (467 pg/ml, IQR 369 - 635) (p = 0.010). We found a statistically significant correlation between cord P-SEP value at birth and the later diagnosis of clinical sepsis (Kendall's τ coefficient 0.222, p = 0.002). We identified the maximum Youden's Index (best cut-off point) at 579 pg/ml, corresponding to a sensitivity of 87.5% and a specificity of 71.8% in predicting clinical sepsis. CONCLUSIONS: Maximum Youden's index was 579 pg/ml for clinical EOS using cord P-SEP values. This could be the starting point to realize multicenter studies, confirming the feasibility of dosing P-SEP in cord blood of infants with risk factors of EOS to discriminate those who could develop clinical sepsis and spare the inappropriate use of antibiotics.

Sepsis neonatal precoz: recomendaciones para su abordaje en la práctica clínica / Early neonatal sepsis: recommendations for approach in clinical practice / Sepse neonatal precoce: recomendações para sua abordagem na prática clínica

La sepsis neonatal precoz se define como la que se manifiesta en las primeras 72 horas de vida. Es una importante causa de morbilidad y mortalidad neonatal. Su incidencia es inversamente proporcional a la edad gestacional. Los microorganismos considerados como frecuentes son Streptoccocus del grupo B, Escherichia coli y Listeria monocytogenes. El diagnóstico de sepsis precoz se basa principalmente en la presencia de factores de riesgo como la corioamnionitis y la edad gestacional. Los signos clínicos son inespecíficos y los exámenes paraclínicos disponibles actualmente, como los reactantes de fase aguda (proteína C reactiva y procalcitonia) tienen escaso valor predictivo positivo. Se realizó una revisión bibliográfica de las últimas publicaciones disponibles sobre sepsis neonatal precoz en recién nacidos, en cuanto a su sospecha, confirmación diagnóstica y tratamiento. A partir de las últimas publicaciones se confeccionó una guía para el manejo clínico de los recién nacidos con sospecha de sepsis precoz.

Early neonatal sepsis is defined as that type of sepsis with an onset within the first 72 hours of life and that is a major cause of neonatal morbidity and mortality. Its incidence is inversely proportional to its gestational age. Frequent microorganisms are group B Streptococcus, Escherichia coli and Listeria monocytogenes. Early sepsis diagnosis is mainly based on the presence of risk factors such as chorioamnionitis and gestational age. Clinical signs are non-specific and currently available paraclinical tests such as acute phase reactants (C-reactive protein and procalcitonin) have little positive predictive value. A bibliographic review of the suspicion, diagnostic confirmation and treatment on Early Neonatal Sepsis in newborns in the latest papers and guidelines were prepared for the clinical treatment of newborns with suspected early sepsis.

A sepse neonatal precoce é definida como aquela que se manifesta nas primeiras 72 horas de vida e que é uma das principais causas de morbidade e mortalidade neonatal. Sua incidência é inversamente proporcional à idade gestacional. Os microrganismos considerados frequentes são o Streptococcus grupo B, Escherichia coli e Listeria monocytogenes. O diagnóstico de sepse precoce baseia-se principalmente na presença de fatores de risco como a coioamnionite e a idade gestacional. Os sinais clínicos são inespecíficos e os testes para-clínicos atualmente disponíveis, como reagentes de fase aguda (proteína C-reativa e procalcitonia) têm pouco valor preditivo positivo. Fizemos uma revisão bibliográfica das últimas publicações disponíveis sobre sepse neonatal precoce em recém-nascidos em termos de suspeita e confirmação diagnóstica e tratamento. Com base nas últimas publicações, elaboramos um guia para o manejo clínico de recém-nascidos com suspeita de sepse precoce.

Delivery Characteristics and the Risk of Early-Onset Neonatal Sepsis.

BACKGROUND AND OBJECTIVES: Multiple strategies are used to identify newborn infants at high risk of culture-confirmed early-onset sepsis (EOS). Delivery characteristics have been used to identify preterm infants at lowest risk of infection to guide initiation of empirical antibiotics. Our objectives were to identify term and preterm infants at lowest risk of EOS using delivery characteristics and to determine antibiotic use among them. METHODS: This was a retrospective cohort study of term and preterm infants born January 1, 2009 to December 31, 2014, with blood culture with or without cerebrospinal fluid culture obtained ≤72 hours after birth. Criteria for determining low EOS risk included: cesarean delivery, without labor or membrane rupture before delivery, and no antepartum concern for intraamniotic infection or nonreassuring fetal status. We determined the association between these characteristics, incidence of EOS, and antibiotic duration among infants without EOS. RESULTS: Among 53 575 births, 7549 infants (14.1%) were evaluated and 41 (0.5%) of those evaluated had EOS. Low-risk delivery characteristics were present for 1121 (14.8%) evaluated infants, and none had EOS. Whereas antibiotics were initiated in a lower proportion of these infants (80.4% vs 91.0%, P < .001), duration of antibiotics administered to infants born with and without low-risk characteristics was not different (adjusted difference 0.6 hours, 95% CI [-3.8, 5.1]). CONCLUSIONS: Risk of EOS among infants with low-risk delivery characteristics is extremely low. Despite this, a substantial proportion of these infants are administered antibiotics. Delivery characteristics should inform empirical antibiotic management decisions among infants born at all gestational ages.

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

BACKGROUND: Neonatal 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 METHODS: A 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. RESULTS: miR-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. CONCLUSION: miR-34a-5p and miR-199a-3p may be useful as novel biomarkers in neonatal sepsis and may provide a new direction for its treatment.

Paediatric and neonatal sepsis and inflammation.

Sepsis has a huge impact on global mortality and has been declared as a priority by the World Health organisation the WHO.1 Children have a high incidence of sepsis especially in the neonatal with an estimated 3 million babies affected worldwide and mortality ranges from 11 to 19%.2 In addition, long-term neurodevelopmental outcomes are affected but this is largely unquantified. However, challenges remain in the early recognition, diagnosis and standardised management of sepsis. This series on Sepsis and inflammation in children reviews the conundrums of diagnostic criteria, biomarkers, management and future strategies to improve outcomes.

Molecular imprinting based electrochemical biosensor for identification of serum amyloid A (SAA), a neonatal sepsis biomarker.

Neonatal septicemia is a bacterial infection in newborns. It is caused by bacteria including Escherichia coli and Group B Streptococcus (GBS). Neonatal septicemia is divided into early-onset and late-onset sepsis. The diagnosis of neonatal septicemia is a challenging task because of the presence of nonspecific symptoms. Biomarkers such as C-reactive protein (CRP), procalcitonin (PCT), and serum amyloid A (SAA) can help in the detection of sepsis at early stages. The level of biomarkers is elevated once sepsis occurs in the body. This study presents the development of an electrochemical biosensor based on nanomaterials integrated molecularly imprinted polymer technique. To obtain the synergistic effect and high conductivity, multi-walled carbon nanotubes (MWCNTs), manganese oxide nanospheres (MnO2NSs), and cobalt oxide nanoparticles (Co3O4NPs) were coated over the screen-printed electrode (SPE). A further modification was done by polymerizing molecularly imprinted polymer (MIP) specifically synthesized for SAA onto modified SPE. The performance of the designed platform was evaluated through electrochemical techniques. The operating range of the developed sensor was found to be 0.01 pM to 1 µM and 0.01 pM as the lower detection limit.

Noninfectious influencers of early-onset sepsis biomarkers.

Diagnostic tests for sepsis aim to either detect the infectious agent (such as microbiological cultures) or detect host markers that commonly change in response to an infection (such as C-reactive protein). The latter category of tests has advantages compared to culture-based methods, including a quick turnaround time and in some cases lower requirements for blood samples. They also provide information on the immune response of the host, a critical determinant of clinical outcome. However, they do not always differentiate nonspecific host inflammation from true infection and can inadvertently lead to antibiotic overuse. Multiple noninfectious conditions unique to neonates in the first days after birth can lead to inflammatory marker profiles that mimic those seen among infected infants. Our goal was to review noninfectious conditions and patient characteristics that alter host inflammatory markers commonly used for the diagnosis of early-onset sepsis. Recognizing these conditions can focus the use of biomarkers on patients most likely to benefit while avoiding scenarios that promote false positives. We highlight approaches that may improve biomarker performance and emphasize the need to use patient outcomes, in addition to conventional diagnostic performance analysis, to establish clinical utility.

Aberrant long non-coding RNA cancer susceptibility 15 (CASC15) plays a diagnostic biomarker and regulates inflammatory reaction in neonatal sepsis.

Neonatal sepsis (NS) is one of the important causes of neonatal death. There are many studies to confirm the role of long non-coding RNA (lncRNA) in neonatal infectious diseases. This study aimed to explore the level of cancer susceptibility 15 (CASC15) and its effect on inflammatory response in NS. Seventy-nine neonatal pneumonia (NP) patients and 80 NS patients were enrolled in this study. Reverse Transcription-quantitative PCR (RT-qPCR) was used to determine the expression levels of CASC15 and miR-144-3p. Receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic value of CASC15 in NS. RAW264.7 cells were stimulated with LPS to simulate the inflammatory response in NS patients, and the regulation and mechanism of CASC15 on the inflammatory response were explored in this in vitro cell model. Serum CASC15 was upregulated in NS patients, and it had the ability to distinguish NS patients from NP patients. LPS stimulation increased the expression of CASC15 and simultaneously stimulated the secretion of inflammatory cytokines, while the knockdown of CASC15 alleviated the inflammatory response induced by LPS stimulation. Besides, serum miR-144-3p was reduced in NS patients, and luciferase reporter genes showed that miR-144-3p was a direct target of CASC15. Overexpression of CASC15 may promote the inflammatory response of NS by targeted regulating the expression of miR-144-3p, which may provide us with new insights in the treatment of NS.