Does serum albumin at the onset of necrotising enterocolitis predict severe disease in preterm infants?

OBJECTIVE: To investigate whether laboratory markers obtained at the onset of necrotising enterocolitis (NEC) predict the severity of the disease in preterm infants. METHODS: Prospective cohort study conducted in a tertiary referance hospital. A total of 88 preterm infants were included in the study. Of those, 60 infants had the diagnosis of severe NEC, while the remaining 28 infants constituted the non-severe NEC group. Severe NEC was defined as surgical NEC or NEC-related mortality. Infants with and without severe NEC were compared in terms of demographic, clinical and laboratory characteristics. RESULTS: At the onset of disease, infants with severe NEC noted to have lower platelet count and serum ALB levels (p = 0.011, p = 0.004; respectively), whereas higher CRP, and serum lactate levels (p = 0.009, p = 0.008; respectively). Multiple binary logistic regression analyses showed that CRP (1.03(1.01-1.05), p = 0.024) and serum albumin level (0.16(0.04-0.64), p = 0.010) were statistically significant independent risk factors for severe NEC. The optimal cut-off value for the serum ALB level was found to be 23 g/L with 52% sensitivity (95%CI: 37-68%) and 84% specificity (95%CI: 60-97%) (AUC 0.727; p = 0.002). CONCLUSION: Serum ALB level at NEC onset might be a reliable biomarker for severe disease in preterm infants.

Acute mesenteric ischaemia: a rare complication mimicking necrotising enterocolitis in a premature infant.

Acute mesenteric ischaemia (AMI) is a life-threatening gastrointestinal complication uncommonly described in premature infants. The diagnosis of AMI is challenging and may be delayed due to the limitation of accurate diagnostic imaging and non-specific clinical signs. Furthermore, AMI can be misdiagnosed as necrotising enterocolitis (NEC) due to the overlapping clinical and radiological features. Though known to be associated with high mortality rates, early recognition and intervention can improve the survival rates in infants with AMI. We describe a case of a premature infant who presented with an acute abdomen and haemodynamic collapse, initially treated for NEC but later diagnosed with AMI intraoperatively. Due to the extensive bowel necrosis, surgical intervention was rendered futile and the infant finally succumbed to the disease.

Surgery for intestinal injuries in very preterm infants: a Norwegian population-based study with a new approach to disease classification.

OBJECTIVE: To evaluate population-based data on very preterm infants (<32 weeks gestation) operated for intestinal injuries, focusing on necrotising enterocolitis (NEC) and focal intestinal perforation (FIP). DESIGN: Nationwide, population-based registry cohort study. SETTING: All 21 neonatal units in Norway. PARTICIPANTS: All very preterm infants born from 2014 through 2021 and admitted to a neonatal unit. MAIN OUTCOME MEASURES: Incidence of surgery for subgroups of intestinal injuries, medical record data on laboratory-radiology results, anatomical location of affected bowel, length of resections, number of re-operations, morbidities of prematurity and/or death before discharge. RESULTS: Abdominal surgery was performed in 124/4009 (3.1%) very preterm infants and in 97/1300 (7.5%) extremely preterm infants <28 weeks. The main intestinal injuries operated were NEC (85/124; 69%), FIP (26/124; 21%) and 'other abdominal pathologies' (13/124; 10%). NEC cases were divided in (i) acute NEC, extensive disease (n=18), (ii) non-extensive disease (n=53) and (iii) NEC with surgery >3 days after disease onset (n=14). High lactate values immediately prior to surgery was predominantly seen in acute NEC-extensive disease and associated with high mortality. Other laboratory values could not discriminate between acute NEC and FIP. Timing of surgery for acute NEC and FIP overlapped. Radiological absence of portal venous gas was typical in FIP. Most infants (62.5%) underwent a stoma formation at initial surgery. The overall survival rate was 67% for NEC and 77% for FIP. CONCLUSION: NEC cases have different presentation and prognosis depending on the extent of bowel affected. Revised classifications for intestinal injuries in preterm infants may improve prognostication and better guide therapy.

Acute myeloid leukemia-M1 in a horse with neurologic signs and necrotizing enterocolitis.

An 18-y-old American Saddlebred mare was admitted with fever and acute onset of neurologic signs including grade 3 of 5 ataxia, difficulty in prehension, and dull mentation. Because of financial restraints, desired testing could not be performed; the horse's condition declined despite supportive treatment, and euthanasia was elected. Postmortem examination revealed petechiae and ecchymoses in the meninges and neuroparenchyma of the encephalon. Blast-like neoplastic round cells were identified within the vasculature and areas of hemorrhage in the neuroparenchyma, the intestinal submucosa, and other organs, including the liver, kidney, lung, and mesenteric lymph node. Necrotizing enterocolitis and acute fibrinonecrotizing bacterial pneumonia were also noted. Of the atypical round cells in the encephalon, >70% expressed ionized calcium-binding adapter molecule 1 (Iba1), 10-20% expressed myeloperoxidase (MPO), and <10% expressed PAX5, CD3, CD20, CD79a, or MUM1. The bone marrow was diffusely effaced by neoplastic round cells expressing Iba1, and ~70% of these cells expressed MPO with no expression of CD3 or CD20. CD172a also immunolabeled a portion of the neoplastic cells. These findings were consistent with the diagnosis of acute myeloid leukemia-M1 with an unusual neurologic presentation.

Clinical value of prokineticin 2 in the diagnosis of neonatal necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is an inflammatory and necrotizing intestinal emergency that occurs in preterm infants and low birth weight newborns; however, no specific serum biomarkers for the diagnosis of NEC has been identified so far. METHODS: Serum samples were collected from healthy neonatal controls and patients with NEC newly admitted to the Children's Hospital of Chongqing Medical University. ELISA was used to measure serum PK2 levels, and ROC curve analysis was sued to evaluate the diagnostic efficacy of PK2 and other clinical biomarkers. RESULTS: Serum PK2 levels in the NEC group (n = 53) were significantly lower than those in the control group (n = 18), but increased to near-normal levels after the postoperative recovery period. The NLR value of NEC group was higher than that of control group (P < 0.05). There was no significant difference in WBC and PLT count between NEC group and control group (P > 0.05). Serum CRP and PCT levels in NEC group were significantly higher than those in control group (P < 0.001 for CRP and P < 0.05 for PCT, respectively). After surgery, serum CRP, NLR and PCT levels were lower than before surgery, while serum PK2 levels were higher than before surgery (P < 0.05). The areas under the ROC curve (AUC) of PK2, PCT and CRP for the diagnosis of NEC were 0.837, 0.662 and 0.552, respectively. The AUC of PK2 combined with PCT, PK2 combined with CRP, and PK2 combined with PCT and CRP were 0.908, 0.854 and 0.981, respectively. PK2 exhibited the highest diagnostic efficacy for NEC. CONCLUSION: PK2 has higher diagnostic efficacy than PCT and CRP in the diagnosis of NEC; the combination of PK2 and PCT or CRP can significantly improve its diagnostic efficiency, especially when the three are combined at the same time.

Clinical Predictors of Spontaneous Intestinal Perforation vs Necrotizing Enterocolitis in Extremely and Very Low Birth Weight Neonates.

PURPOSE: Spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) are distinct disease processes associated with significant morbidity and mortality. Initial treatment, laparotomy (LP) versus peritoneal drainage (PD), is disease specific however it can be difficult to distinguish these diagnoses preoperatively. We investigated clinical characteristics associated with each diagnosis and constructed a scoring algorithm for accurate preoperative diagnosis. METHODS: A cohort of extreme and very low birth weight (<1500 g) neonates surgically treated for SIP or NEC between 07/2004-09/2022 were reviewed. Clinical characteristics included gestational age (GA), birth weight (BW), feeding history, physical exam, and laboratory/radiological findings. Intraoperative diagnosis was used to determine SIP vs NEC. Pre-drain diagnosis was used for patients treated with PD only. RESULTS: 338 neonates were managed for SIP (n = 269, 79.6%) vs NEC (n = 69, 20.4%). PD was definitive treatment in 146 (43.2%) patients and 75 (22.2%) patients were treated with upfront LP. Characteristics associated with SIP included younger GA, younger age at initial laparotomy or drainage (ALD), and history of trophic or no feeds. Multivariate logistic regression determined pneumatosis, abdominal wall erythema, higher ALD and history of feeds to be highly predictive of NEC. A 0-8-point scale was designed based on these characteristics with the area under the receiver operating characteristic curve of 0.819 (95% CI 0.756-0.882) for the diagnosis of NEC. A threshold score of 1.5 had a 95.2% specificity for NEC. CONCLUSION: Utilizing clinical characteristics associated with SIP & NEC we developed a scoring system designed to assist surgeons accurately distinguish SIP vs NEC in neonates. TYPE OF STUDY: Retrospective Chart Review. LEVEL OF EVIDENCE: Level III.

Assessment of inflammatory biomarkers to identify surgical/death necrotizing enterocolitis in preterm infants without pneumoperitoneum.

BACKGROUND: Necrotizing 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. PURPOSE: We 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. METHODS: A 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. RESULTS: The 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 RESEARCH: Elevated 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.

I-FABP protein/mRNA and IL-6 as biomarkers of intestinal barrier dysfunction in neonates with necrotizing enterocolitis and SPF BALB/c mouse models.

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.

Receptor-interacting protein kinase-3 (RIPK3): a new biomarker for necrotising enterocolitis in preterm infants.

OBJECTIVE: This study aimed to evaluate the role of receptor-interacting protein kinase-3 (RIPK3) in the diagnosis, estimation of disease severity, and prognosis of premature infants with necrotising enterocolitis (NEC). METHODS: RIPK3, lactic acid (LA), and C-reactive protein (CRP) levels were measured in the peripheral blood of 108 premature infants between 2019 and 2023, including 24 with stage II NEC, 18 with stage III NEC and 66 controls. Diagnostic values of the indicators for NEC were evaluated via receiver operating characteristic (ROC) curve analysis. RESULTS: Plasma RIPK3 and LA levels upon NEC suspicion in neonates with stage III NEC were 32.37 ± 16.20 ng/mL. The ROC curve for the combination of RIPK3, LA, CRP for NEC diagnosis were 0.925. The time to full enteral feeding (FEFt) after recovery from NEC was different between two expression groups of plasma RIPK3 (RIPK3 < 20.06 ng/mL and RIPK3 ≥ 20.06 ng/mL). CONCLUSION: Plasma RIPK3 can be used as a promising marker for the diagnosis and estimation of disease severity of premature infants with NEC and for the guidance on proper feeding strategies after recovery from NEC.

An investigation into augmentation and preprocessing for optimising X-ray classification in limited datasets: a case study on necrotising enterocolitis.

PURPOSE: Obtaining large volumes of medical images, required for deep learning development, can be challenging in rare pathologies. Image augmentation and preprocessing offer viable solutions. This work explores the case of necrotising enterocolitis (NEC), a rare but life-threatening condition affecting premature neonates, with challenging radiological diagnosis. We investigate data augmentation and preprocessing techniques and propose two optimised pipelines for developing reliable computer-aided diagnosis models on a limited NEC dataset. METHODS: We present a NEC dataset of 1090 Abdominal X-rays (AXRs) from 364 patients and investigate the effect of geometric augmentations, colour scheme augmentations and their combination for NEC classification based on the ResNet-50 backbone. We introduce two pipelines based on colour contrast and edge enhancement, to increase the visibility of subtle, difficult-to-identify, critical NEC findings on AXRs and achieve robust accuracy in a challenging three-class NEC classification task. RESULTS: Our results show that geometric augmentations improve performance, with Translation achieving +6.2%, while Flipping and Occlusion decrease performance. Colour augmentations, like Equalisation, yield modest improvements. The proposed Pr-1 and Pr-2 pipelines enhance model accuracy by +2.4% and +1.7%, respectively. Combining Pr-1/Pr-2 with geometric augmentation, we achieve a maximum performance increase of 7.1%, achieving robust NEC classification. CONCLUSION: Based on an extensive validation of preprocessing and augmentation techniques, our work showcases the previously unreported potential of image preprocessing in AXR classification tasks with limited datasets. Our findings can be extended to other medical tasks for designing reliable classifier models with limited X-ray datasets. Ultimately, we also provide a benchmark for automated NEC detection and classification from AXRs.

Do hematological biomarkers predict surgical necrotizing enterocolitis?

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.

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.

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.

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.

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.

What animal model should I use to study necrotizing enterocolitis?

Unfortunately, we are all too familiar with the statement: "Necrotizing enterocolitis remains the leading cause of gastrointestinal surgical emergency in preterm neonates". It's been five decades since the first animal models of necrotizing enterocolitis (NEC) were described. There remains much investigative work to be done on identifying various aspects of NEC, ranging from the underlying mechanisms to treatment modalities. Experimental NEC is mainly focused on a rat, mouse, and piglet models. Our aim is to not only highlight the pros and cons of these three main models, but to also present some of the less-used animal models that have contributed to the body of knowledge about NEC. Choosing an appropriate model is essential to conducting effective research and answering the questions asked. As such, this paper reviews some of the variations that come with each model.