Comparison of preoperative and intraoperative surgeon diagnosis and pathologic findings in spontaneous intestinal perforation vs necrotizing enterocolitis.

OBJECTIVE: To investigate the accuracy of preoperative and intraoperative diagnosis via comparison to pathologic diagnosis in spontaneous intestinal perforation (SIP) vs. necrotizing enterocolitis (NEC). STUDY DESIGN: A retrospective review of neonates <1500 g treated for pneumoperitoneum between 07/2004-09/2022 was conducted. Patients treated for NEC medically prior to diagnosis and those treated with drain only were excluded. Fleiss' Kappa analysis assessed agreement between all three diagnoses: preoperative, intraoperative, and pathologic. RESULT: Overall, 125 patients were included with mean birthweight 834.2 g (SD:259.2) and mean gestational age 25.8 weeks (SD:2.2). Preoperative and intraoperative diagnoses agreed in 90.3%, intraoperative and pathologic agreed in 71.1%, and preoperative and pathologic agreed in 75.2% of patients. Fleiss' Kappa was 0.55 (95% CI:0.43,0.68), indicating moderate agreement between the three diagnoses. CONCLUSION: Our study shows moderate agreement between preoperative, intraoperative, and pathologic diagnoses. Further studies investigating the clinical characteristics of SIP and NEC are needed to improve diagnostic accuracy and management.

Necrotizing enterocolitis: current understanding of the prevention and management.

Necrotizing enterocolitis (NEC) is one of the diseases in neonates, with a high morbidity and mortality rate, especially in preterm infants. This review aimed to briefly introduce the latest epidemiology, susceptibility factors, and clinical diagnosis and presentation of NEC. We also organized new prevention strategies by risk factors according to different pathogeneses and then discussed new treatment methods based on Bell's staging and complications, and the classification of mild to high severity based on clinical and imaging manifestations. Such a generalization will help clinicians and researchers to gain a deeper understanding of the disease and to conduct more targeted classification, grading prevention, and exploration. We focused on prevention and treatment of the early and suspected stages of NEC, including the discovery of novel biomarkers and drugs to control disease progression. At the same time, we discussed its clinical application, future development, and shortcomings.

Association of Early Postoperative Regional Oxygen Saturation Measures and Development of Necrotizing Enterocolitis in Neonates Following Cardiac Surgery.

Necrotizing enterocolitis (NEC) is a relatively common complication in neonates with single ventricle physiology following heart surgery. Near-infrared spectroscopy (NIRS) is used to measure regional oxygen saturations in neonates in the postoperative period. We sought to investigate the association of somatic regional oxygen saturation (srSO2) and cerebral regional oxygen saturation (crSO2) in the early postoperative period and the subsequent development of NEC. We performed a retrospective cohort study of neonates who underwent cardiac surgery with cardiopulmonary bypass from October 2017 to September 2021 at the University of Virginia Children's Hospital. Values of srSO2 and crSO2 were captured over the first 48 h following surgery. 166 neonates were included and the median age at time of surgery was 8 days. NEC was diagnosed in 18 neonates following heart surgery with a median interval from surgery to diagnosis of 7 days. Neonates with single ventricle physiology had lower average crSO2 (62% vs 78%, p < 0.001), average srSO2 (72% vs 86%, p < 0.001), average crSO2 to srSO2 ratio (0.874 vs 0.913, p < 0.001), and an increased average srSO2-crSO2 difference (10% vs 8%, p = 0.03). Adjusting for single ventricle physiology, lower average crSO2 was associated with the development of definite NEC (modified Bell's criteria stage IIa and higher) (OR = 0.86, 95% CI 0.78-0.96, p = 0.007). Lower crSO2 values in the early postoperative period in neonates following cardiac surgery was associated with an increased risk in the subsequent development of NEC.

Targeted LC-MS/MS profiling of bile acids reveals primary/secondary bile acid ratio as a novel biomarker for necrotizing enterocolitis.

Bile acids (BAs) are involved in the development of necrotizing enterocolitis (NEC), which mainly occurs in preterm infants. We aim to identify the change of BAs in preterm infants and validate its potential value in the detection of NEC. Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure the plasma BAs in healthy preterm infants and patients with NEC. By analyzing the level of BAs in healthy preterm infants, we found that the plasma concentrations of BAs were related to sex, gestational/postnatal age, birth weight, mode of birth, and feeding type after birth. The plasma levels of TCA, GCA, TCDCA, GCDCA, primary BAs, and total BAs and the primary/secondary BA ratio were decreased, while DCA, UDCA, and secondary BAs were increased in NEC. The primary/secondary BA ratio (cutoff point 62.9) can effectively differentiate NEC from healthy preterm infants, with an AUC of 0.9, a sensitivity of 94.5%, and a specificity of 78.1%. Combining the ratio with high-risk factors of NEC can better distinguish between NEC and control, with an AUC of 0.95. Importantly, significantly lower levels of primary/secondary BA ratio were found in infants with surgical NEC than in nonsurgical NEC cases. The cutoff point of 28.7 identified surgical NEC from nonsurgical NEC with sensitivity and specificity of 76.9% and 100%. Thus, our study identified that the primary/secondary BA ratio in the plasma can differentiate NEC from healthy preterm infants and effectively differentiate the surgical NEC from nonsurgical NEC. Therefore, LC-MS/MS was expected to be a novel measurement platform used to distinguish infants who are most in need of close monitoring or early surgical intervention.

Risk Factors for Adverse Outcomes in Term Infants with CHD and Definitive Necrotising Enterocolitis.

OBJECTIVES: To define the incidence of definitive necrotising enterocolitis in term infants with CHD and identify risk factors for morbidity/mortality. METHODS: We performed a 20-year (2000-2020) single-institution retrospective cohort study of term infants with CHD admitted to the Boston Children's Hospital cardiac ICU with necrotising enterocolitis (Bell's stage ≥ II). The primary outcome was a composite of in-hospital mortality and post-necrotising enterocolitis morbidity (need for extracorporeal membrane oxygenation, multisystem organ failure based on the paediatric sequential organ failure assessment score, and/or need for acute gastrointestinal intervention). Predictors included patient characteristics, cardiac diagnosis/interventions, feeding regimen, and severity measures. RESULTS: Of 3933 term infants with CHD, 2.1% (n = 82) developed necrotising enterocolitis, with 67% diagnosed post-cardiac intervention. Thirty (37%) met criteria for the primary outcome. In-hospital mortality occurred in 14 infants (17%), of which nine (11%) deaths were attributable to necrotising enterocolitis. Independent predictors of the primary outcome included moderate to severe systolic ventricular dysfunction (odds ratio 13.4,confidence intervals 1.13-159) and central line infections pre-necrotising enterocolitis diagnosis (odds ratio 17.7, confidence intervals 3.21-97.0) and mechanical ventilation post-necrotising enterocolitis diagnosis (odds ratio 13.5, confidence intervals 3.34-54.4). Single ventricle, ductal dependency, and feeding related factors were not independently associated with the primary outcome. CONCLUSIONS: The incidence of necrotising enterocolitis was 2.1% in term infants with CHD. Adverse outcomes occurred in greater than 30% of patients. Presence of systolic dysfunction and central line infections prior to diagnosis and need for mechanical ventilation after diagnosis of necrotising enterocolitis can inform risk triage and prognostic counseling for families.

Hyponatremia as a Marker for Predicting Surgical Intervention in Necrotizing Enterocolitis: A Retrospective Cohort Study.

INTRODUCTION: To investigate the predictive value of plasma sodium at the onset of necrotizing enterocolitis (NEC) diagnosis in distinguishing surgical NEC from medical NEC. METHODS: A retrospective review of all NEC neonates treated at our hospital between 2008 and 2022. Patients were divided into two groups based on treatment methods: surgical intervention and medical treatment. Patient demographics, laboratory parameters, and outcomes were all documented. The values of laboratory parameters were collected at the onset of NEC and after treatment. To identify potential predictors of surgical NEC, multivariate logistic regression analyses were used. The receiver operating characteristic curve was applied to determine predictive factors. RESULTS: Surgical treatment was performed in 111 infants (44.6%), and medical treatment in 138 cases (55.4%). Of 249 infants with NEC, 22 patients exhibited Bell stage I, 91 infants had Bell stage II, and 136 patients displayed Bell stage III. We discovered that white blood cell (WBC), C-reactive protein (CRP), fibrinogen, and sodium were independent predictors of NEC receiving surgery based on the results of the multivariate logistic regression analysis. Hyponatremia was found in 122 of the 249 patients (49%). At the onset of NEC diagnosis, hyponatremia was found in 83.8% of surgical intervention group and in 21.0% of medical treatment group (P < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for WBC, CRP, fibrinogen, and sodium were calculated. The cutoff values were determined using receiver operating characteristic analysis. The area under the curve of hyponatremia for surgical intervention was 0.875, with 84% sensitivity, 80% specificity, 77% positive predictive value, and 86% negative predictive value, which had a greater specificity (0.80) for predicting surgical intervention than WBC (0.67), CRP (0.50), and fibrinogen (0.70). CONCLUSIONS: When a surgical evaluation is necessary, hyponatremia can effectively distinguish surgical NEC from medical NEC. It could be used as a predictive marker to guide parental counseling for surgical intervention and rapid transfer of patients to tertiary centers when they have a surgical condition.

Clinical Decision Support for Improved Neonatal Care: The Development of a Machine Learning Model for the Prediction of Late-onset Sepsis and Necrotizing Enterocolitis.

OBJECTIVE: To develop an artificial intelligence-based software system for predicting late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in infants admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: Single-center, retrospective cohort study, conducted in the NICU of the Antwerp University Hospital. Continuous monitoring data of 865 preterm infants born at <32 weeks gestational age, admitted to the NICU in the first week of life, were used to train an XGBoost machine learning (ML) algorithm for LOS and NEC prediction in a cross-validated setup. Afterward, the model's performance was assessed on an independent test set of 148 patients (internal validation). RESULTS: The ML model delivered hourly risk predictions with an overall sensitivity of 69% (142/206) for all LOS/NEC episodes and 81% (67/83) for severe LOS/NEC episodes. The model showed a median time gain of ≤10 hours (IQR, 3.1-21.0 hours), compared with historical clinical diagnosis. On the complete retrospective dataset, the ML model made 721 069 predictions, of which 9805 (1.3%) depicted a LOS/NEC probability of ≥0.15, resulting in a total alarm rate of <1 patient alarm-day per week. The model reached a similar performance on the internal validation set. CONCLUSIONS: Artificial intelligence technology can assist clinicians in the early detection of LOS and NEC in the NICU, which potentially can result in clinical and socioeconomic benefits. Additional studies are required to quantify further the effect of combining artificial and human intelligence on patient outcomes in the NICU.

Neonatal perforated appendicitis: a presentation of necrotising enterocolitis?

In this case report, we present a late preterm growth-restricted neonate who developed signs of feeding intolerance on the second day of life, which progressed to frank peritonitis with perforation by the end of the second week of life. As necrotising enterocolitis was considered the most likely diagnosis, a glove drain was placed in the flanks. The neonate did not improve, and surgical exploration was done after medical stabilisation. On exploration, the neonate was found to have appendicular perforation and an appendicectomy was performed. During surgery, the rest of the gut was noted to be healthy. Histopathological examination of the appendix showed transmural inflammation, focal infarction and perforation. The postoperative period was uneventful, and the neonate showed rapid improvement and reached full enteral feeding in the next 5 days. Antibiotic therapy promptly resolved bacterial peritonitis, and the neonate was discharged successfully.

Postoperative Outcomes, and Growth and Brain Injury Outcomes in Spontaneous Intestinal Perforation vs Surgical Necrotizing Enterocolitis in Preterm Infants.

OBJECTIVE: To compare the clinical outcomes in preterm infants following surgical necrotizing enterocolitis (sNEC) and spontaneous intestinal perforation (SIP). METHODS: Retro-spective comparison of clinical information in preterm infants with sNEC and SIP admitted between January, 2013 and December 31, 2018. The clinical outcomes were compared in two groups, including postoperative and brain injury detected on brain magnetic resonance imaging (MRI) after clinical and histopathological confirmation of the SIP and the NEC diagnosis. RESULTS: 114 infants had sNEC, and 37 had SIP. Infants with SIP had lower median gestational age [25.1 weeks (23.5, 27.1) vs 26.6 (24.4, 31.0), P=0.03], an earlier mean (SD) age of disease onset [10.1 (11.3) days vs 19.6 (17.9); P<0.001] and lower maternal chorioamnionitis on placental pathology [4 (23.5%) vs 22 (68.8%); P=0.007), received more often Penrose drain therapy (54% vs 33%; P=0.03), had less median (IQR) bowel length loss [3.3 cm (1.72, 4.38) vs 21.4 (9.55, 35.3); P=<0.001] and had more often intact ileocecal valve (91.4% vs 65.7%; P=0.006] compared to those with sNEC. In addition, those with sNEC had lower median (IQR) weight z scores at the time of discharge [-1.88 (-2.80, -1.09) vs -1.14 (-2.22, -0.44); P=0.036] than SIP. There were no significant differences in postoperative ileus, duration of parenteral nutrition, surgical morbidity, length of stay, mortality, white matter, and grey matter injury on brain MRI at term equivalent age in preterm infants with SIP and sNEC. CONCLUSION: In our cohort, preterm infants with SIP and sNEC did not show significant differences in postoperative morbidity and brain MRI abnormalities at term equivalent age. sNEC had lower discharge weight z scores. Larger prospective studies are needed for confirmation of these findings.

Research Models to Mimic Necrotizing Enterocolitis and Inflammatory Bowel Diseases: Focus on Extracellular Vesicles Action.

This review focuses on the crucial role of the intestinal epithelium in maintaining intestinal homeostasis and its significance in the pathogenesis of necrotizing enterocolitis (NEC) and inflammatory bowel diseases (IBD). NEC is a devastating neonatal disease, while IBD represents a global healthcare problem with increasing incidence. The breakdown of the intestinal barrier in neonates is considered pivotal in the development and progression of both disorders. This review provides an overview of the current state of in vitro, ex vivo, and animal models to study epithelial injury in NEC and IBD, addressing pertinent questions that engage clinicians and researchers alike. Despite significant advancements in early recognition and aggressive treatment, no single therapy has been conclusively proven effective in reducing the severity of these disorders. Although early interventions have improved clinical outcomes, NEC and IBD continue to impose substantial morbidity, mortality, and economic burdens on affected individuals and society. Consequently, exploring alternative therapeutic options capable of preventing and treating the sequelae of NEC and IBD has become a pressing necessity. In recent decades, extracellular vehicles (EVs) have emerged as a potential solution to modulate the pathogenic mechanism in these multifactorial and complex disorders. Despite the diverse array of proposed models, a comprehensive model to investigate and decelerate the progression of NEC and IBD remains to be established. To bridge the translational gap between preclinical studies and clinical applications, enhancements in the technical development of gut-on-a-chip models and EVs hold considerable promise.

Risk factors associated with necrotizing enterocolitis in preterm infants: A case-control study.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal emergency in prematurity. The pathophysiology is multifactorial and remains incompletely understood. Early diagnosis and treatment could reduce the risk of mortality and morbidity. We aimed to identify factors associated with NEC in preterm newborns. METHOD: This case-control study included all preterm newborns presenting with NEC and managed between January 1, 2009 and December 31, 2018 in the neonatal intensive care unit of Nancy. For each case, two controls were matched according to three criteria: gestational age (WG), date of birth, and mode of delivery. Antenatal, peripartum, and postnatal risk factors prior to NEC were analyzed. RESULTS: A total of 292 infants were involved in the study, 113 of whom had NEC. Mean gestational age for newborns with NEC was 29 WG, and mean birth weight, 1340 g. Only early-onset infection was identified as a significant risk factor for NEC (15% vs. 6.6% for infection p<0.04, and 28.3% vs. 16.4% p<0.02 for infection and sepsis, NEC vs. controls, respectively). Late-onset feeding and initial continuous enteral feeding were significantly associated with the occurrence of more severe NEC (p<0.02 and p = 0.03, respectively). CONCLUSION: The results of this study are consistent with intestinal dysbiosis being a risk factor for NEC. Early-onset infection was found to be a significant risk factor. Enteral feeding practice may also be associated with NEC.

Plasma anti-myosin autoantibodies in the diagnosis of necrotizing enterocolitis.

We aimed to assess whether autoantibodies can be used as biomarkers for necrotizing enterocolitis (NEC) and applied for its early diagnosis. A prospective observational study was conducted in neonates with suspected NEC abdominal distension (the developmental study), which consisted of 50 neonates finally divided into NEC (n = 24) and non-NEC (n = 26) cohorts based on follow-up results. Serum samples were collected within 48 h of illness onset and used for screening NEC-associated plasma autoantibodies by autoantigen microarray. Additionally, we validated anti-myosin autoantibodies by enzyme-linked immunosorbent assay (ELISA) in an independent validation study, for which we selected plasma samples within 48 h of onset of NEC (n = 38) and samples of gestational age- and weight-matched controls (n = 13). Autoantigen microarray revealed that both IgG and IgM anti-myosin autoantibodies in plasma from neonates with NEC were significantly higher than those in neonates with other diagnoses. ELISA showed that plasma anti-myosin autoantibodies increased in the NEC cohort, with 1.5-fold higher levels than in the non-NEC cohort. Anti-myosin autoantibodies were able to distinguish NEC from non-NEC, achieving an area under the curve (AUC) of 0.8856 (95% confidence interval (CI): 0.7918-0.9795), with sensitivity of 81.58% and specificity of 76.93%. Plasma anti-myosin autoantibodies were significantly higher in all three subtypes of NEC (P < 0.0001 for NEC I; P = 0.0018 for NEC II; P = 0.0011 for NEC III), especially in NEC stage I than that in the non-NEC controls. CONCLUSION: Anti-myosin autoantibodies may be applied as a promising diagnostic marker for NEC, especially for NEC stage I. WHAT IS KNOWN: • Intestinal damage and self-antigen exposure may lead to increased autoantibodies, and they are widely used as biomarkers for diagnosing inflammatory bowel disease. • Necrotizing enterocolitis (NEC) is a devastating disease with overwhelming inflammation and immune dysregulation. WHAT IS NEW: • Increased autoantibodies were present in patients with NEC, even before typical X-ray manifestations. • Anti-myosin autoantibodies may be applied as a promising diagnostic marker for NEC.

Fatal Necrotizing Enterocolitis in Neonate Caused by Cronobacter sakazakii Sequence Type 64 Strain of CRISPR Sublineage b.

We report fatal neonatal necrotizing enterocolitis in China caused by Cronobacter sakazakii capsular profile K1:CA1, sequence type 64, and CRISPR type 197. Phylodynamic analyses indicated that the strain originated from the ancient, widespread, and antimicrobial drug-sensitive CRISPR sublineage b. Enhanced surveillance and pathogenesis research on this organism are required.

Fecal calprotectin as a non-invasive marker for the prediction of post-necrotizing enterocolitis stricture.

PURPOSE: This study aimed to evaluate the clinical utility of fecal calprotectin (FC) levels during the necrotizing enterocolitis (NEC) episode to predict the onset of post-NEC intestinal stricture. METHODS: The medical records of patients with NEC treated from April 2020 to April 2022 were recorded for this study. FC was quantified at the acute phase of NEC. FC levels were compared in patients with or without intestinal stricture. Receiver operating characteristics (ROC) analysis was constructed to determine optimal cut-offs of FC for post-NEC intestinal stricture. RESULTS: A total of 50 infants with NEC were enrolled in this study and 14 (28%) of them eventually developed intestinal stricture. All children with intestinal stricture underwent one-stage surgery and all made it through the follow-up period alive. The median FC level was 1237.55 (741.25, 1378.80) ug/g in patients with intestinal stricture and it was significantly higher than that in the non-stricture group [158.30 (76.23, 349.13) ug/g, P < 0.001]. FC had good diagnostic accuracy for predicting intestinal stricture, according to ROC curve analysis, with an AUC area of 0.911. At an optimal cut-off value of 664.2 ug/g, sensitivity and specificity were 85.71% and 91.67%, respectively. CONCLUSION: As a non-invasive parameter, FC has excellent efficacy and accuracy in predicting post-NEC intestinal stricture. Increased FC levels at the acute phase of NEC were associated with the development of intestinal stricture.

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Necrotizing enterocolitis (NEC), with the main manifestations of bloody stool, abdominal distension, and vomiting, is one of the leading causes of death in neonates, and early identification and diagnosis are crucial for the prognosis of NEC. The emergence and development of machine learning has provided the potential for early, rapid, and accurate identification of this disease. This article summarizes the algorithms of machine learning recently used in NEC, analyzes the high-risk predictive factors revealed by these algorithms, evaluates the ability and characteristics of machine learning in the etiology, definition, and diagnosis of NEC, and discusses the challenges and prospects for the future application of machine learning in NEC.

Neonatal complicated intraabdominal infection.

PURPOSE OF REVIEW: The purpose of this review is to summarize the treatment of complicated intraabdominal infections (cIAIs) in premature infants. RECENT FINDINGS: Recent work has continued to define the complex nature of cIAIs and necrotizing enterocolitis (NEC). This includes new findings on the microbiome, breast milk and risk factors associated with NEC. The treatment of cIAIs employs a combination of both surgical and medical treatment. Further look at what type and timing of surgical intervention is used as well as the ideal antibiotic regimen. Upcoming research is highlighted in future directions of NEC treatment. SUMMARY: cIAIs in premature infants is a challenging disease with more research needed to further delineate the pathophysiology and treatment options.

Current Practices, Challenges, and Recommendations in Enteral Nutrition After Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a neonatal disease with high mortality and morbidity. There is a lack of evidence-based recommendations on nutritional rehabilitation following NEC, and much of the current practice is guided by institutional policies and expert opinions. After a diagnosis of NEC, infants are exposed to an extended period of bowel rest and a prolonged course of antibiotics. Recognizing the patient characteristics that predict nutritional tolerance, early initiation of enteral nutrition, minimizing periods of bowel rest and antibiotic exposure, and standardization of dietary practices are the mainstay of post-NEC nutrition.

Clinical usefulness of splanchnic oxygenation in predicting necrotizing enterocolitis in extremely preterm infants: a cohort study.

BACKGROUND: Impaired intestinal microcirculation seems to play an important role in the pathogenesis of necrotizing enterocolitis (NEC). A previous study showed that a SrSO2 < 30% is associated with an increased risk of developing of NEC. We aimed to determine the clinical usefulness of the cut off < 30% for SrSO2 in predicting NEC in extremely preterm neonates. METHODS: This is a combined cohort observational study. We added a second cohort from another university hospital to the previous cohort of extremely preterm infants. SrSO2 was measured for 1-2 h at days 2-6 after birth. To determine clinical usefulness we assessed sensitivity, specificity, positive and negative predictive values for mean SrSO2 < 30. Odds ratio to develop NEC was assessed with generalized linear model analysis, adjusting for center. RESULTS: We included 86 extremely preterm infants, median gestational age 26.3 weeks (range 23.0-27.9). Seventeen infants developed NEC. A mean SrSO2 < 30% was found in 70.5% of infants who developed NEC compared to 33.3% of those who did not (p = 0.01). Positive and negative predictive values were 0.33 CI (0.24-0.44) and 0.90 CI (0.83-0.96), respectively. The odds of developing NEC were 4.5 (95% CI 1.4-14.3) times higher in infants with SrSO2 < 30% compared to those with SrSO2 ≥ 30%. CONCLUSIONS: A mean SrSO2 cut off ≥ 30% in extremely preterm infants between days 2-6 after birth may be useful in identifying infants who will not develop NEC.