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.

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.

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.

Cord Blood Low-Density Granulocytes Correspond to an Immature Granulocytic Subset with Low Expression of S100A12.

Although substantial progress has been achieved concerning neonatal sepsis, its lethality remains considerably high, and further insights into peculiarities and malfunctions of neonatal immunity are needed. This study aims to contribute to a better understanding of the role of human neonatal granulocyte subpopulations and calgranulin C (S100A12). For this purpose, we gathered 136 human cord blood (CB) samples. CD66b+ CB low-density granulocytes (LDG) and CB normal-density granulocytes were isolated and functionally and phenotypically compared with healthy adult control granulocytes. We could identify CB-LDG as CD66bbright CD64high CD16low CD35low CD10low S100A12med-low and, based on these markers, recovered in whole CB stainings. Consistent with flow cytometric findings, microscopic imaging supported an immature phenotype of CB-LDG with decreased S100A12 expression. In CB serum of healthy neonates, S100A12 was found to be higher in female newborns when compared with males. Additionally, S100A12 levels correlated positively with gestational age independently from sex. We could solidify functional deficits of CB-LDG concerning phagocytosis and generation of neutrophil extracellular traps. Our study reveals that previously described suppressive effects of CB-LDG on CD4+ T cell proliferation are exclusively due to phagocytosis of stimulation beads used in cocultures and absent when using soluble or coated Abs. In conclusion, we characterize CB-LDG as immature neutrophils with functional deficits and decreased expression and storage of S100A12. Concerning their cross-talk with the adaptive immunity, we found no direct inhibitory effect of LDG. Neonatal LDG may thus represent a distinct population that differs from LDG populations found in adults.

Serum amyloid A - A prime candidate for identification of neonatal sepsis.

Neonatal sepsis is common, lethal, and hard to diagnose. In combination with clinical findings and blood culture, biomarkers are crucial to make the correct diagnose. A Swedish national inquiry indicated that neonatologists were not quite satisfied with the available biomarkers. We assessed the kinetics of 15 biomarkers simultaneously: ferritin, fibrinogen, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ, interleukin (IL)-1ß, -6, -8, -10, macrophage inflammatory protein (MIP)-1ß, procalcitonin, resistin, serum amyloid A (SAA), tumor necrosis factor (TNF)-α, tissue plasminogen activator-3 and visfatin. The goal was to observe how quickly they rise in response to infection, and for how long they remain elevated. From a neonatal intensive care unit, newborns ≥28 weeks gestational age were recruited. Sixty-eight newborns were recruited to the study group (SG), and fifty-one to the control group (CG). The study group subjects were divided into three subgroups depending on clinical findings: confirmed sepsis (CSG), suspected sepsis (SSG) and no sepsis. CSG and SSG were also merged into an entire sepsis group (ESG) for sub-analysis. Blood samples were collected at three time-points; 0 h, 12-24 h and 48-72 h, in order to mimic a "clinical setting". At 0 h, visfatin was elevated in SSG compared to CG; G-CSF, IFN-γ, IL-1ß, -8 and - 10 were elevated in SSG and ESG compared to CG, whereas IL-6 and SAA were elevated in all groups compared to CG. At 12-24 h, IL-8 was elevated in ESG compared to CG, visfatin was elevated in ESG and SSG compared to CG, and SAA was elevated in all three groups compared to CG. At 48-72 h, fibrinogen was elevated in ESG compared to CG, IFN-γ and IL-1ß were elevated in SSG and ESG compared to CG, whereas IL-8 and SAA were elevated in all three groups compared to CG. A function of time-formula is introduced as a tool for theoretical prediction of biomarker levels at any time-point. We conclude that SAA has the most favorable kinetics regarding diagnosing neonatal sepsis, of the biomarkers studied. It is also readily available methodologically, making it a prime candidate for clinical use.

Neonatal blood culture inoculant volume: feasibility and challenges.

BACKGROUND: Clinicians often express concerns about poor sensitivity of blood cultures in neonates resulting from inadequate inoculant volumes. Our objective was to determine the inoculant volume sent for neonatal sepsis evaluations and identify areas of improvement. METHODS: Single-center prospective observational study of infants undergoing sepsis evaluation. Blood volume was determined by clinician documentation over 21 months, and additionally by weighing culture bottles during 12 months. Adequate volume was defined as ≥1 mL total inoculant per evaluation. For first-time evaluations, local guidelines recommend sending an aerobic-anaerobic pair with 1 mL inoculant in each. RESULTS: There were 987 evaluations in 788 infants. Clinicians reported ≥1 mL total inoculant in 96.9% evaluations. Among 544 evaluations where bottles were weighed, 93.4% had ≥1 mL total inoculant. Very low birth weight infants undergoing evaluations >7 days after birth had the highest proportion of inadequate inoculants (14.4%). Only 3/544 evaluations and 26/1011 bottles had total inoculant <0.5 mL. Ninety evaluations had <1 mL in both aerobic and anaerobic bottles despite a total inoculant volume that allowed inoculation of ≥1 mL in one of the bottles. CONCLUSIONS: Obtaining recommended inoculant volumes is feasible in majority of neonates. Measuring inoculant volumes can focus improvement efforts and improve test reliability. IMPACT: Clinicians express concern about the unreliability of neonatal blood cultures because of inadequate inoculant volume. We investigated over 900 evaluations and found >90% of evaluations have ≥1 mL inoculant. Monitoring adequacy of blood culture technique can identify areas of improvement and may allay concerns about blood culture reliability. Current recommendations for adequate inoculant volume for blood cultures are met in a majority of neonates. Areas of improvement include preterm late-onset sepsis evaluations and distribution techniques during inoculation.

C-reactive protein and the neonatal early-onset sepsis calculator for the diagnosis of neonatal sepsis.

Our aim was to evaluate the utility of the neonatal early-onset sepsis risk calculator (NEOSC) to the utility of C-reactive protein (CRP) for diagnosing neonatal EOS. This retrospective study reviewed the records of neonates who underwent sepsis workups due to equivocal symptoms and compared their CRP values to the calculator's recommendations and their cultures. A total of 382 newborns who underwent sepsis work-up due to equivocal symptoms were included in our study. The calculator's recommendations would have reduced the number of newborns who underwent sepsis workups by 82.5% and antibiotic treatment by 83.4% (n = 315). Considering that 373 of 382 (97.6%) ultimately had no sepsis, the calculator's specificity was higher than that of CRP (83.9% versus 76.1%). When comparing the maximal CRP value with the risk according to the neonatal sepsis calculator, a significant correlation was found between them (P < 0.01), but the relationship was not strong (Pearson's correlation = 0.27). We found a significant correlation between the risk of sepsis according to the NEOSC and the CRP values, although the correlation was not strong. The calculator's high specificity enables safe avoidance of multiple blood tests and antibiotic treatments for suspected neonates who are not infected. CRP tests can reduce the number of infected newborns the calculator may miss, at the cost of unnecessary blood tests and antibiotic therapy to many newborns.

Elevated Red Cell Distribution Width as a Useful Marker in Neonatal Sepsis.

Neonatal sepsis is an important cause of neonatal morbidity and mortality in the neonatal intensive care unit. Red blood cell distribution width (RDW) is an important and independent prognostic factor in several diseases. The objective of this study was to evaluate the diagnostic value of RDW in neonatal sepsis. An observational, retrospective cohort study was conducted on newborns admitted to the neonatal intensive care unit in a Tertiary Care University Hospital between 2016 and 2019. Patients were classified into sepsis and control groups. Demographic characteristics and laboratory findings including RDW were analyzed. RDW was significantly higher in the sepsis group than in the control group (P=0.001). RDW had an area under the receiver operating characteristic curve of 0.799 for the diagnosis of sepsis. The sensitivity and specificity of an RDW value of 17.4% were found to be 60% and 88.3%, respectively (P=0.001). Multivariable logistic regression analysis showed a positive association of RDW with sepsis (odds ratio: 2.71; 95% confidence interval: 2.19-3.36; P=0.001). RDW value was significantly higher in neonatal sepsis and could be used as a useful alternative to other assessment tools as a readily available biomarker.

Interleukin-6 as a Biomarker of Early-Onset Neonatal Sepsis.

OBJECTIVE: The aim of this study is to determine the utility of C reactive protein (CRP) and interleukin (IL)-6 in the diagnosis of neonatal sepsis (NS) in a neonatal intensive care unit (NICU) in the south of Colombia. STUDY DESIGN: A nonmatched case-control study was conducted. Convenience sampling was performed. Data were obtained from clinical records. IL-6 levels were determined using enzyme-linked immunosorbent assay. Receiver operator characteristic (ROC) curve analysis and Youden's index were used to determine the optimal cutoffs for CRP and IL-6 levels in diagnosing NS, early-onset NS (EONS), and late-onset NS (LONS). RESULTS: Data from 31 cases and 62 controls were included. History of chorioamnionitis (infinite odds ratio [OR] [3.07-infinity]), and the presence of meconium-stained amniotic fluid during birth (OR: 9.04 [1.35-112]) were identified as risk factors for NS. Differences in CRP (p < 0.0001) and IL-6 (p < 0.0485) levels were also found, more significantly for LONS and EONS patients, respectively. In the diagnosis of LONS using CRP levels, the area under the ROC curve (AUC) was 0.8371 (p < 0.0001). The optimal cutoff was 0.53 mg/dL. For EONS diagnosis using IL-6, the AUC was 0.6869 (p = 0.0315) and the optimal cutoff was 17.75 pg/mL. CONCLUSION: Differences between CRP and IL-6 levels were found between control and NS groups. Furthermore, CRP showed greater potential diagnostic utility in the LONS group, whereas IL-6 showed greater potential utility in the EONS group. KEY POINTS: · NS is a major morbimortality cause worldwide. · CRP and IL-6 levels may be useful NS biomarkers. · No biomarker alone is enough for the diagnosis of NS.

The Emerging Role of Presepsin (P-SEP) in the Diagnosis of Sepsis in the Critically Ill Infant: A Literature Review.

Sepsis causes high rates of morbidity and mortality in NICUs. The estimated incidence varies between 5 and 170 per 1000 births, depending on the social context. In very low birth-weight neonates, the level of mortality increases with the duration of hospitalization, reaching 36% among infants aged 8-14 days and 52% among infants aged 15-28 days. Early diagnosis is the only tool to improve the poor prognosis of neonatal sepsis. Blood culture, the gold standard for diagnosis, is time-consuming and poorly sensitive. C-reactive protein and procalcitonin, currently used as sepsis biomarkers, are influenced by several maternal and fetal pro-inflammatory conditions in the perinatal age. Presepsin is the N-terminal fragment of soluble CD14 subtype (sCD14-ST): it is released in the bloodstream by monocytes and macrophages, in response to bacterial invasion. Presepsin seems to be a new, promising biomarker for the early diagnosis of sepsis in neonates as it is not modified by perinatal confounding inflammatory factors. The aim of the present review is to collect current knowledge about the role of presepsin in critically ill neonates.

miRNA-23b as a biomarker of culture-positive neonatal sepsis.

BACKGROUND: Neonatal sepsis remains an important cause of morbidity and mortality. The ability to quickly and accurately diagnose neonatal sepsis based on clinical assessments and laboratory blood tests remains difficult, where haemoculture is the gold standard for detecting bacterial sepsis in blood culture. It is also very difficult to study because neonatal samples are lacking. METHODS: Forty-eight newborns suspected of sepsis admitted to the Neonatology Department of the Mother-Child Specialized Hospital of Tlemcen. From each newborn, a minimum of 1-2 ml of blood was drawn by standard sterile procedures for blood culture. The miRNA-23b level in haemoculture was evaluated by RT-qPCR. RESULTS: miR-23b levels increased in premature and full-term newborns in early onset sepsis (p < 0.001 and p < 0.005 respectively), but lowered in late onset sepsis in full-term neonates (p < 0.05) compared to the respective negative controls. miR-23b levels also increased in late sepsis in the negative versus early sepsis negative controls (p < 0.05). miR-23b levels significantly lowered in the newborns who died from both sepsis types (p < 0.0001 and p < 0.05 respectively). In early sepsis, miR-23b and death strongly and negatively correlated (correlation coefficient = - 0.96, p = 0.0019). In late sepsis, miRNA-23b and number of survivors (correlation coefficient = 0.70, p = 0.506) positively correlated. CONCLUSIONS: Lowering miR-23b levels is an important factor that favours sepsis development, which would confirm their vital protective role, and strongly suggest that they act as a good marker in molecular diagnosis and patient monitoring.

Progranulin as a novel biomarker in diagnosis of early-onset neonatal sepsis.

BACKGROUND: Infections are leading causes of morbidity and mortality in neonates and may also have severe long-term consequences. As early diagnosis of neonatal sepsis improves prognosis, identification of new or complementary biomarkers is of great importance. In this study, we have evaluated the diagnostic value of progranulin (PGRN) in early-onset neonatal sepsis (EOS) and compare its effectiveness with other commonly used biomarkers, such as procalcitonin (PCT) and C-reactive protein (CRP). METHODS: A total of 121 infants with gestational age of >34 weeks admitted with suspected EOS were included in this study. Before initiating therapy, blood samples for whole blood count, CRP, PCT and PGRN were obtained from all neonates. Receiver-operating characteristic (ROC) curve and multivariate logistic regression analyses were performed. RESULTS: Serum PGRN level of infected group was significantly higher than uninfected group (median 47.72 vs. 37.86 ng/ml, respectively; Mann-Whitney p < 0.0001). The ROC area under the curve (AUC) was 0.786 [95% confidence interval (CI) 0.706-0.867; p < 0.0001] for PGRN, 0.699 (95% CI 0.601-0.797; p = 0.0001) for age adjusted PCT, and 0.673 (95% CI 0.573-0.773; p = 0.0007) for CRP. With a cut-off value of 37.89 ng/ml, the diagnostic sensitivity and negative predictive value of PGRN were 94.34% and 91.7%, respectively. PGRN could significantly predict EOS independently of PCT (p < 0.0001), and the combined use of PGRN and PCT could significantly improve diagnostic performance for EOS (0.806; 95% CI 0.73-0.88; p < 0.0001), with a specificity of 89.06% and a positive predictive value of 81.10%. CONCLUSIONS: PGRN may be used as a promising biomarker for the diagnosis of EOS, and the combined use of PGRN and PCT could improve the diagnosis of sepsis.

Challenges in developing a consensus definition of neonatal sepsis.

Sepsis remains a leading cause of morbidity and mortality in the neonatal population, and at present, there is no unified definition of neonatal sepsis. Existing consensus sepsis definitions within paediatrics are not suited for use in the NICU and do not address sepsis in the premature population. Many neonatal research and surveillance networks have criteria for the definition of sepsis within their publications though these vary greatly and there is typically a heavy emphasis on microbiological culture. The concept of organ dysfunction as a diagnostic criterion for sepsis is rarely considered in neonatal literature, and it remains unclear how to most accurately screen neonates for organ dysfunction. Accurately defining and screening for sepsis is important for clinical management, health service design and future research. The progress made by the Sepsis-3 group provides a roadmap of how definitions and screening criteria may be developed. Similar initiatives in neonatology are likely to be more challenging and would need to account for the unique presentation of sepsis in term and premature neonates. The outputs of similar consensus work within neonatology should be twofold: a validated definition of neonatal sepsis and screening criteria to identify at-risk patients earlier in their clinical course. IMPACT: There is currently no consensus definition of neonatal sepsis and the definitions that are currently in use are varied.A consensus definition of neonatal sepsis would benefit clinicians, patients and researchers.Recent progress in adults with publication of Sepsis-3 provides guidance on how a consensus definition and screening criteria for sepsis could be produced in neonatology.We discuss common themes and potential shortcomings in sepsis definitions within neonatology.We highlight the need for a consensus definition of neonatal sepsis and the challenges that this task poses.

Identification of progranulin as a novel diagnostic biomarker for early-onset sepsis in neonates.

Neonatal early-onset sepsis (EOS) is associated with high morbidity and mortality. Accurate early diagnosis is crucial for prompt treatment and a better clinical outcome. We aimed to identify new biomarkers for the diagnosis of EOS. A total of 152 neonates with a risk of EOS were divided into an EOS group and a non-EOS group according to the conventional diagnostic criteria. Blood samples were collected within 0-24, 24-48, and 48-72 h after birth. Serum levels of progranulin (PGRN), interleukin (IL)-33, IL-17a, IL-23, IL-6, tumor necrosis factors α (TNF-α), interferon γ (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), procalcitonin (PCT), and C-reactive protein (CRP) were determined. PGRN levels were significantly elevated in the EOS neonates compared with the levels in the non-EOS neonates (1.53 vs. 0.77 ng/ml (median), P < 0.001), with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.76 (P < 0.001). Compared with PGRN, IL-33, IL-17a, IL-23, IL-6, PCT, and CRP showed significant (AUC > 0.70) but slightly less predictive power for EOS within the same time range. Stepwise multivariate regression analysis identified PGRN, IL-33, and PCT as independent predictors of EOS. In addition, the combined measurements of PGRN, IL-33, and PCT showed significantly higher predictive power for EOS than any of the three markers alone. PGRN showed greater efficacy for predicting EOS than the traditional markers PCT and CRP as well as other potential markers tested in this study. PGRN may serve as an effective biomarker for the early diagnosis of EOS.

Efficacy of cefotaxime combined with gamma globulins on C-reactive protein and procalcitonin in neonatal sepsis.

C-reactive protein (CRP) is encoded by CRP or PTX1 gene and procalcitonin (PCT) is produced by the CALC-1 gene induction. Both PCT and CRP are known as valued biomarkers markers in prediction of Serious Bacterial Infections (SBI) in children. This experiment carried out to analyze the efficacy of cefotaxime combined with gamma globulins on neonatal sepsis and the effect on CRP and PCT. For this purpose, a total of 120 sepsis children were selected and randomly divided into observation and control groups. Children in the control group were treated with cefotaxime, while children in the observation group were treated with cefotaxime combined with gamma globulins. The two groups were compared in terms of the relative measures of efficacy, the total effective rate of treatment, the incidence of complications and serum CRP and PCT levels before and after treatment. The clinical measures of the observation group were all lower than those of the control group, and the total effective rate of the treatment was higher than that of the control group, while the incidence of complications was lower than that of the control group. In addition, before treatment, there was no difference in CRP and PCT between the two groups; after treatment, the above measures in the observation group were lower than those in the control group. It is concluded that Cefotaxime combined with gamma globulins in the treatment of neonatal sepsis has significant efficacy and is clinically more effective than cefotaxime monotherapy. This combination can shorten clinical symptom remission time and hospital stay, improve serum CRP and PCT levels and promote the recovery of children, worthy of promotion.

Low vasopressin and progression of neonatal sepsis to septic shock: a prospective cohort study.

The study objective was to analyze the association between low plasma vasopressin and progression of sepsis to septic shock in neonates < 34 weeks gestation. Septic neonates of < 34 weeks gestation were consecutively enrolled; moribund neonates and those with major malformations were excluded. Subjects were monitored for progression of sepsis to septic shock over the first 7 days from enrolment. Plasma vasopressin levels and inducible nitric oxide synthase levels were measured at the onset of sepsis (T0), severe sepsis (T1), and septic shock (T2). Primary outcome was plasma vasopressin levels at the point of sepsis in those who progressed to septic shock in comparison with matched nested controls in the non-progression group. Forty-nine (47%) enrolled subjects developed severe sepsis or septic shock. Plasma vasopressin levels (pg/ml) at the onset of sepsis were significantly low in those who progressed to septic shock (median (IQR), 31 (2.5-80) versus 100 (12-156); p = 0.02). After adjusting for confounders, vasopressin levels were independently associated with progression to septic shock (adjusted OR (95% CI), 0.97 (0.96, 0.99); p = 0.01).Conclusion: Preterm septic neonates who progressed to septic shock had suppressed vasopressin levels before the onset of shock. Low vasopressin levels were independently associated with progression to septic shock.What is known:• In animal sepsis models and adult septic patients, exuberant production of nitric oxide metabolites and low vasopressin levels have been reportedly associated with progression to septic shock.• Vasopressin levels have been variably reported as low as well as elevated in children with septic shock.What is New:• Preterm neonates who progressed from sepsis to septic shock had significantly lower levels of vasopressin before the onset of shock in comparison with those who did not progress.• Low vasopressin levels independently predicted the progression from sepsis to septic shock in this population.

Prognostic Value of Ionized Calcium Levels in Neonatal Sepsis.

BACKGROUND: Despite recent advances in the treatment of neonatal infection, mortality rates and comorbidities associated with neonatal sepsis remain high. Hypocalcemia has been reported in critically ill patients, especially in as-sociation with sepsis. However, the importance of hypo-calcemia in neonatal sepsis has not been explored in detail. OBJECTIVES: The purpose of this study was to evaluate the prognostic value of hypocalcemia in neonatal sepsis patients and to identify the risk factors associated with sepsis-related mortality. METHODS: This retrospective study examined perinatal data from patients in a level IV neonatal in-tensive care unit between January 2010 and June 2016. Univariate analysis was performed to understand the differences in clinical and laboratory characteristics between patients with and without neonatal sepsis. Neonates with sepsis were further stratified as having ionized hypocalcemia (if serum ionized calcium [iCa] <1.0 mmol/L) or not. Uni- and multivariate logistic regression analyses were utilized to evaluate the predictive potential of iCa for identifying sepsis-related mortality. RESULTS: A total of 472 neonates were enrolled in this study, including 169 neonates diagnosed with culture-proven sepsis and 303 neonates without infection (control group). The comparison of neonates with and without sepsis highlighted significant differences in levels of iCa (0.97 ± 0.26 vs. 1.12 ± 0.25 mmol/L), magnesium (0.75 ± 0.22 vs. 0.89 ± 0.12 mmol/L), and phosphate (2.26 ± 1.08 vs. 1.65 ± 0.85 mmol/L; all p < 0.001). When neonates with sepsis were stratified into 2 subgroups based on serum iCa, neonates with hypocalcemia showed higher rates of organ dysfunction than those with normal iCa, as well as higher rates of cardiovascular system dysfunction (37.35 vs. 17.44%), renal dysfunction (34.94 vs. 30.95%), disseminated intravascular coagulation (26.51 vs. 11.63%), and seizure (16.04 vs. 5.8%; all p < 0.05). Among all neonates who had sepsis, the mortality rate was 13.61%, and this rate was higher among neonates with hypocalcemia than among those with normal iCa (20.48 vs. 6.98%, p < 0.05). Uni- and multivariate analyses showed that acidosis, hypoalbuminemia, hypocalcemia, and hyperphosphatemia were independent prognostic markers of sepsis-related mortality. In receiver-operating characteristic curve analysis, the areas under the curve were 0.70 (95% CI 0.624-0.768; p = 0.0004), 0.74 (95% CI 0.671-0.808; p < 0.0001), 0.73 (95% CI 0.653-0.792; p = 0.0002), and 0.67 (95% CI 0.59-0.737; p = 0.0154) for serum albumin, iCa, phosphate, and acidosis, respectively. Based on these findings, we developed a nomogram to predict sepsis-related mortality. CONCLUSIONS: Hypocalcemia is common in neonates with sepsis and is significantly associated with organ dysfunction and sepsis-related mortality.

Clinical effect and safety of continuous renal replacement therapy in the treatment of neonatal sepsis-related acute kidney injury.

BACKGROUND: Sepsis is the leading cause of acute kidney injury (AKI) in the neonatal intensive care unit (NICU). The aim of the study is to explore the efficacy and security of continuous renal replacement therapy (CRRT) in the treatment of neonatal sepsis-related AKI. METHOD: Totally12 sepsis-related AKI neonates treated with CRRT were hospitalized in the NICU of Shanghai Children's Hospital between November 2012 and November 2019, and the clinical data of these 12 cases were retrospectively analyzed. Renal function, acid-base balance, electrolytes, blood pressure and hemodynamics indexes were recorded before CRRT initiation, 12/24/48 h after CRRT initiation and at the end of CRRT respectively. The efficacy of CRRT was evaluated and the clinical outcome was observed in these 12 sepsis-related AKI neonates. Repeated measurement analysis of variance was used for statistical analysis of the data. RESULT: (1) Continuous veno-venous hemodialysis filtration (CVVHDF) was used in 12 cases of sepsis-related AKI neonates. There were 6 cases with oliguria, 3 cases with fluid overload (FO), 3 cases with septic shock. The duration of CRRT was 49 ~ 110 h, average (76.2 ± 23.5) h. (2) The blood pressure (BP) of 12 sepsis -related AKI neonates could reach the normal level (40-60 mmHg) 12 h after CRRT initiation, and the normal BP level could be maintained during the CRRT treatment. After 12 h CRRT, the blood pH value increased to the normal range (7.35 ~ 7.45). After 12 h CRRT treatment, the oxygenation index of 12sepsis-related AKI neonates could reach 200 mmHg. After 24 h CRRT treatment, it could rise to more than 300 mmHg. Serum potassium, serum urea nitrogen and serum creatinine levels decreased significantly 12 h after CRRT initiation, and reached the normal range 24 h after CRRT initiation. The urine volume significantly increased 24 h after CRRT initiation. (3) Venous catheterization was performed successfully in all sepsis-related AKI neonates. We observed 2 cases of thrombocytopenia, 1 case of obstruction and 1 case of hypotension in the course of CRRT. There were no complications such as hypothermia, hemorrhage, thrombosis and infection.11 neonates were cured and discharged. One neonate was treated with CRRT and passed through the oliguria stage of AKI, but died after the parents gave up the treatment. CONCLUSIONS: It is safe and effective to treat neonatal sepsis-related AKI with CRRT, which should be an effective measure for the treatment of sepsis-related AKI neonates.

Red cell distribution width as a predictor of late-onset Gram-negative sepsis.

BACKGROUND: Late-onset sepsis (LOS) remains an important cause of morbidity and mortality in preterm infants. In this study, our aim was to investigate the red-cell distribution width (RDW) levels during a LOS episode, and its association with the type of growing microorganism and mortality. METHODS: Preterm infants with culture-proven sepsis during their neonatal intensive care unit stay were enrolled. Red-cell distribution width levels were obtained in the first 4 h of postnatal life and at the onset of the LOS episode, and compared for these time frames. The study cohort was divided into two groups according to the type of the growing microorganism. The RDW levels were then assessed in intra- and inter-group analyses. RESULTS: Eighty-six infants were included in the final analysis. RDW levels were increased in the study cohort after a LOS attack (P < 0.001). Infants with Gram-negative sepsis showed a significant increase in their RDW levels, but they remained unchanged in infants with Gram-positive sepsis (P < 0.001 and P = 0.4, respectively). An RDW cut-off of >19.50% was related with a sensitivity of 87% and a specificity of 81% for predicting late-onset Gram-negative sepsis (P < 0.001). Logistic regression analysis showed a positive association of RDW with mortality when adjusted for covariants (adjusted odds ratio: 1.40; 95% confidence interval: 1.02-1.80; P = 0.03). CONCLUSIONS: Our findings show that RDW levels increased during a LOS episode in preterm infants, which was especially evident in Gram-negative infections. We believe that these findings may be of importance in the early diagnosis and prognosis of LOS in preterm infants.

C-reactive protein as a predictor of meningitis in early onset neonatal sepsis: a single unit experience.

Objectives To determine whether there is a cut off value of serum C-reactive protein (CRP) associated with a higher risk of meningitis in suspected early onset sepsis (EOS) (onset birth to 7 days of life). Methods A retrospective cohort study on neonates admitted in neonatal intensive care unit at McMaster Children's Hospital from January 2010 to 2017 and had lumbar puncture (LP) and CRP for workup of EOS. Included subjects had either (a) non-traumatic LP or (b) traumatic LP with cerebral spinal fluid (CSF) polymerase chain reaction or gram stain or culture-positive or had received antimicrobials for 21 days. Excluded were CSF done for metabolic errors, before cytomegalovirus (CMV) treatment; from ventriculo-peritoneal (VP) shunts; missing data and contamination. Neonates were classified into definite and probable meningitis and on the range of CRP. We calculated sensitivity, specificity, and likelihood ratios for CRP values; and area under the receiver operating characteristic (AUROC) curve. Results Out of 609 CSF samples, 184 were eligible (28 cases of definite or probable meningitis and 156 controls). Sensitivity, specificity, predictive values, likelihood ratios, and AUROC were too low to be of clinical significance to predict meningitis in EOS. Conclusions Serum CRP values have poor discriminatory power to distinguish between subjects with and without meningitis, in symptomatic EOS.