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Introduction To explore the effect of elevated serum creatinine on the timing of surgery and prognosis in patients with progressive necrotizing enterocolitis. Methods A total of 367 children who underwent surgery for necrotizing enterocolitis(NEC) from May 2008 to April 2024 were collected, and 156 patients with incomplete data were excluded. Among the remaining 211 surgical cases, 168 patients (before August 14, 2019) were included in the statistical analysis, and 43 patients (after August 14, 2019) were used as the validation set. The basic data of the patients, including gender, gestational age, birth weight, age at onset, the length of ICU stay, cardiac ultrasound results, Bell’s stage, whether they were small for gestational age, urine volume in the 24 h before operation, preoperative blood routine (white blood cells, platelets), C-reactive protein (CRP), blood gas analysis, renal function (serum creatinine, blood urea nitrogen) and weight at the time of surgery were collected for statistical analysis. Results A total of 98 (26.7%) patients died among the 367 patients, of which 47 (48%) had acute kidney injury. Between the 211 patients included in the statistical analysis, 47 (22.3%) died, and among the 168 patients in the data set, 39 (23.2%) died. Of the 43 patients in the validation set, 8 (18.6%) died. There were statistically significant differences in birth weight, length of ICU stay, preoperative serum creatinine, urine volume, white blood cell count, lactate, HCO3-, heart malformations, and small for gestational age status in the collected data, p  < 0.05. After ROC-AUC analysis, it was found that when serum creatinine cutoff = 60.5ummol/L, the area under the curve AUC = 0.842, sensitivity = 0.795, specificity = 0.705, and after COX regression analysis, the serum creatinine HR value = 7.242, 95% CI [2.852–18.388]. Log Rank in the K-M curve of SGA = 42.958, p  < 0.001. Among the 43 cases in the validation set, 35 survived, sensitivity = 0.75, specificity = 0.771. Conclusion In addition to clinical manifestations, imaging, and infection indicators as factors for determining surgical indications in progressive NEC, more active intervention should be considered when serum creatinine begins to rise to 60.5ummol/L. Level of evidence Level III Retrospective Comparative Cohort Study.

Early NEC symptoms are non-specific and diagnostic tests lack discriminative power. Intestinal fatty acid-binding protein (I-FABP), mainly located in small bowel enterocytes, is released into the blood following NEC-associated enterocyte disruption. Aim of this prospective cohort trial was to determine the diagnostic value of I-FABP measured in plasma (I-FABPp) and urine (I-FABPu) for the presence of NEC, to evaluate I-FABP levels during NEC development, and to assess its prognostic value for the progression from suspected to complicated disease. Between 2010 and 2012 we prospectively enrolled neonates with suspected NEC. We measured I-FABP levels eight-hourly from onset of suspected NEC for at least 48 hours, or until surgery. NEC diagnosis was confirmed radiologically or during operation. We defined NEC as complicated if it resulted in surgery and/or death. We determined disease course and diagnostic I-FABP cut-off points. The study comprised 37 neonates (24M, 13F), gestational age 28 (24-36) weeks, birth weight 1190 (570-2,400) grams. We found significantly higher I-FABPp and I-FABPu levels in NEC patients (n = 22) than in patients with other diagnoses (n = 15). Cut-off values for diagnosing NEC were 9 ng/mL I-FABPp and 218 ng/mL I-FABPu, with corresponding likelihood ratios (LRs) of 5.6 (95% CI 0.89-35) and 5.1 (95% CI 0.73-36), respectively. I-FABP levels were highest in the first eight hours after symptom onset and gradually decreased over time. Cut-off values for complicated disease were 19 ng/mL I-FABPp and 232 ng/mL I-FABPu, with LRs of 10 (95% CI 1.6-70) and 11 (95% CI 1.6-81), respectively. Both plasma and urinary I-FABP levels specifically identify NEC in preterm infants prior to appearance of diagnostic radiological signs suggestive for NEC. Moreover, serial I-FABP measurements accurately predict development of complicated disease.

Necrotizing enterocolitis (NEC) is a life-threatening condition affecting preterm infants, sometimes necessitating surgical treatment. This study aimed to analyze differentially expressed proteins (DEPs) and access their biological and clinical significance in the plasma of neonates with NEC. Peripheral blood samples were collected from NEC infants at various time points, and plasma was separated. Data-independent acquisition (DIA) technology was utilized to identify DEPs among NEC patients at different stages. Bioinformatic analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, and protein-to-protein interaction analyses were performed on the DEPs. External datasets, along with receiver operating characteristic curves and gene set enrichment analysis, were used to clinically and biologically validate the findings. DEPs between the NEC and pre-NEC groups indicated reduced protein, heme, nitrogen, and purine nucleotide biosynthesis during NEC formation. In addition, enriched DEPs among the NEC groups at different time points suggested reconstructed extracellular matrix, aberrant B-lymphocyte immune responses, and decreased glycosaminoglycan levels during NEC progression. These findings were both clinically and biologically validated using external datasets. Our study highlights the clinical and biological relevance of proteomics in NEC patients. This study demonstrates key pathways involved in NEC pathogenesis and establishes DIA mass spectrometry as a powerful and noninvasive tool for evaluating and predicting NEC formation and progression. Graphical Abstract

Background Neonatal necrotizing enterocolitis (NEC) is a severe gastrointestinal emergency associated with high morbidity and mortality in neonates. Early identification of cases requiring surgical intervention is critical to improving outcomes. Objective To identify independent risk factors associated with surgical treatment in neonates with NEC and to develop a predictive model that supports timely surgical decision-making and enhances prognosis. Methods This retrospective study included 188 neonates diagnosed with NEC (Bell stage II or higher) at Liuzhou Hospital, Guangzhou Women and Children’s Medical Center between December 2018 and December 2024. Patients were categorized into a surgical treatment group ( n  = 70) and a conservative treatment group ( n  = 118). Least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression were used to identify independent risk factors. A nomogram was developed based on these factors. Model performance was assessed using receiver operating characteristic (ROC) curve analysis, calibration curve, and decision curve analysis (DCA). Results Among the 188 neonates, 70 (37.2%) underwent surgery. The mortality rate was significantly higher in the surgical group compared to the conservative group (17.1% vs. 1.1%). Multivariable analysis identified C-reactive protein (CRP), serum lactate, portal venous gas, reduced intestinal motility, white blood cell count, and absolute lymphocyte count as independent predictors of surgical intervention. The nomogram model demonstrated excellent discrimination (AUC = 0.946, 95% CI: 0.911–0.981), with a sensitivity of 0.914 and specificity of 0.890. Calibration and DCA confirmed strong clinical utility. Conclusion This study established a nomogram-based predictive model for surgical treatment in NEC, utilizing six indicators: CRP, serum lactate, portal venous gas, reduced intestinal motility, white blood cell count, and absolute lymphocyte count. The model shows high accuracy and clinical utility. It can assist clinicians in predicting the need for surgery at the early stages of NEC, optimizing treatment decisions, reducing mortality, and improving the prognosis of affected neonates.

Objective Neonatal necrotizing enterocolitis (NEC) is a serious intestinal inflammatory disease. We investigated intestinal fatty acid binding protein (I-FABP), I-FABP mRNA, and interleukin-6 (IL-6) as potential diagnostic biomarkers in NEC. Methods Forty mice were subjected to hypoxic-ischemic intestinal injury, and then serum I-FABP protein and mRNA levels were quantified. Ileal tissue pathological scores were determined by hematoxylin and eosin staining. I-FABP expression levels and translocation in these tissues were detected using western blotting and immunofluorescence, respectively. Samples from 30 human neonates with NEC and 30 healthy neonates had serum I-FABP protein/mRNA and IL-6 levels measured. Results The mouse ileal tissue pathological score and I-FABP levels, as well as serum I-FABP and I-FABP mRNA levels, were significantly higher in the model group than in the control group. Serum I-FABP, I-FABP mRNA, and IL-6 levels were significantly higher in human neonates with NEC than in the healthy group. Logistic regression and receiver operating curve analyses revealed that I-FABP protein/mRNA and IL-6 levels could be diagnostic biomarkers for NEC. Conclusions I-FABP protein/mRNA and IL-6 levels are useful biomarkers of intestinal ischemic injury in neonates with NEC. The combined detection of I-FABP protein/mRNA and IL-6 is recommended rather than using a single biomarker.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency in preterm infants and the clinical presentation of NEC may vary with gestational age. We lack reliable biomarkers for early diagnosis of NEC limiting timely intervention. Hematological changes in NEC are actively researched for their potential role as biomarkers. The pattern and severity of hematological abnormalities have been correlated with rapid progression, the need for surgery, increased risk of mortality, and morbidity. In this issue of Pediatric Research, Chong et al. report GA-specific hematological biomarkers in preterm infants with NEC that could predict the need for surgery. Thrombocytopenia at NEC onset was an independent predictor of surgical intervention in extremely preterm infants. Persistent thrombocytopenia and lymphopenia at 72 h and elevated C-reactive protein at 48 h after NEC onset, predicted surgery in infants of 28 to <32 weeks GA. Persistent thrombocytopenia at 24 h after the onset of NEC was predictive of mortality in infants who underwent surgery. Well-designed, prospective, multi-center studies are needed to confirm the role of hematological biomarkers in early diagnosis and prognostication in NEC.

Background This study aims to evaluate the role of C-reactive protein (CRP) in necrotizing enterocolitis (NEC) diagnosis and prognosis through a systematic review and meta-analysis. Methods A comprehensive search was conducted across PubMed, Cochrane Library, Embase, and Web of Science databases to identify relevant studies on CRP and NEC. Outcomes included correlations between CRP levels and NEC occurrence, surgical intervention, severity, and intestinal strictures. Results A total of 30 studies were included in the analysis. Data from categorical variables indicated a significant positive association between CRP and the incidence of NEC (OR: 3.5, 95% CI: 2.23–5.49), while continuous variables revealed a significant difference in CRP levels between the NEC and non-NEC groups (SMD: 2.61, 95% CI: 1.72–3.5). Elevated CRP levels were significantly correlated with an increased risk of surgery, with a notable difference in CRP levels between the surgical and non-surgical groups. CRP levels were also positively associated with the risk of NEC progression, and a significant difference was observed between the progression and non-progression groups. Besides, a significant difference in CRP levels was observed between the stricture and non-stricture groups. Subgroup analysis indicated that CRP has a higher predictive value in infants with NEC who had a gestational age greater than 28 weeks and a birth weight exceeding 1500 g. Conclusion CRP has significant clinical value in predicting the occurrence of NEC, disease progression, and the timing of surgical intervention.

Necrotizing enterocolitis is a significant cause of morbidity and mortality in premature infants. Various fecal, urinary, and serum biomarkers have all been investigated for their potential in the prediction and early detection of necrotizing enterocolitis. This pilot study aimed to explore the feasibility and clinical utility of measuring serum and fecal calprotectin levels in preterm infants with necrotizing enterocolitis. This prospective pilot study included preterm infants born at < 32 weeks’ gestation with a birth weight of ≤ 1500 g, consisting of patients diagnosed with necrotizing enterocolitis stage II or III and a randomly selected control group without necrotizing enterocolitis. The relationship between serum and fecal calprotectin concentrations and necrotizing enterocolitis severity, need for surgical intervention, and mortality was systematically analyzed. A total of 39 necrotizing enterocolitis patients (25 with stage II, 14 with stage III) and 20 randomly selected preterm infants were included as the control group. Serum and fecal calprotectin levels were significantly higher in necrotizing enterocolitis stage III and in infants who required surgery or died (p < 0.05), indicating their potential to predict disease severity and poor outcomes. This pilot study suggests that dual assessment of serum and fecal calprotectin may provide insight into necrotizing enterocolitis severity and outcomes. Larger studies are needed to validate these findings and determine clinical applicability. This study was registered with the ClinicalTrials.gov database under the registration number NCT06693154 on November 15, 2024.

Background Necrotizing enterocolitis (NEC) is a serious condition mainly affecting newborns, especially preterm or low birth weight ones, with a poor prognosis. The present study aimed to comprehensively evaluate the diagnostic value of intestinal-type fatty acid-binding protein (I-FABP) in NEC through meta-analysis. Methods Relevant documents on the diagnosis of I-FABP in neonatal NEC were retrieved from PubMed, ScienceDirect, Embase, Cochrane, Wanfang, and CNKI databases. Summary receiver operating characteristic curve (SROC), sensitivity, specificity, and likelihood ratio (LR) were constructed to evaluate the pooled diagnostic value. Meta-regression analysis was conducted to explore the sources of heterogeneity. Sensitivity analysis was performed to detect the robustness of current results. Results The present study encompassed 15 studies. I-FABP had a high diagnostic value for NEC, with a sensitivity at 0.78 (0.70–0.85), a specificity of 0.85 (0.78–0.90), and the area under the curve (AUC) value was 0.89 (0.86–0.91). The combined diagnostic odds ratio (DOR) was 20.33 (10.90–37.90) indicating a high diagnostic potential with strong discriminatory power. Sample source, detection method, and critical value might be the source of heterogeneity. There was no significant publication bias. Conclusion I-FABP played a crucial role in diagnosing NEC in premature infants.

BackgroundNecrotizing enterocolitis (NEC) is a life-threatening disease that affects premature infants. However, the role of inflammatory biomarkers in identifying surgical/death NEC without pneumoperitoneum remains elusive.PurposeWe aimed to verify the value of platelet-to-lymphocyte ratio (PLR) and the combination of white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil lymphocyte ratio (NLR), PLR, C reactive protein (CRP) and procalcitonin (PCT) in predicting the severity of NEC, and to construct a model to differ surgically NEC from non-surgically NEC.MethodsA retrospective analysis was performed on 191 premature infants with NEC. Based on the inclusion and exclusion criteria, 90 infants with Stage II and IIIA NEC were enrolled in this study, including surgical/death NEC (n = 38) and medical NEC (n = 52). The values of inflammatory biomarkers were collected within 24 h of onset.ResultsThe univariate analysis revealed that the values of WBC (p = 0.040), ANC (p = 0.048), PLR (p = 0.009), CRP (p = 0.016) and PCT (p < 0.01) in surgical/death NEC cohort were significantly higher than medical NEC cohort. Binary multivariate logistic regression analysis indicates that ANC, PLR, CRP, and PCT are capable of distinguishing infants with surgical/death NEC, and the AUC of the regression equation was 0.79 (95% CI 0.64–0.89; sensitivity 0.63; specificity 0.88), suggesting the equation has a good discrimination.Implications for practice and researchElevated PLR is associated with severe inflammation in surgical/death NEC patients. The prediction modelling of combination of ANC, PLR, CRP and PCT can differentiate surgical/death NEC from infants with medical NEC, which may improve risk awareness and facilitate effective communication between nurses and clinicians. However, multicentre research is needed to verify these findings for better clinical management of NEC.