Piezo1-mediated endoplasmic reticulum stress-dependent apoptosis exacerbates intestinal epithelial barrier disruption in necrotizing enterocolitis.

Gut microbiota as a risk and protective factor in neonatal necrotizing enterocolitis: An integrative review.

Early necrotizing enterocolitis in a 2-day-old term neonate: A case report

BackgroundNeonatal necrotizing enterocolitis (NEC) is prevalent among preterm neonates and is associated with high morbidity and mortality. While surgical intervention remains essential for advanced NEC, postoperative neonates exhibit an elevated risk of brain injury. However, which surgery-related factors exacerbate neonatal brain damage remains insufficiently investigated. This study aimed to identify risk factors for brain injury in neonates with surgical NEC and establish a predictive model to facilitate early identification and intervention, which may ultimately decrease neurodevelopmental impairment rates.MethodsThis study analyzed 181 consecutive NEC surgical cases at our tertiary referral center (2017–2023). Brain injury was confirmed by cranial MRI. Primary analysis was used to compare groups via Student's t test for normally distributed data and the Mann‒Whitney U/χ2 test for nonparametric variables. Significant predictors (p < 0.05) were incorporated into multivariate logistic regression, with model performance validated by receiver operating characteristic (ROC) analysis.ResultsMultivariate analysis revealed six independent risk factors (all p < 0.05): lower gestational age (GA) (OR 0.85 [95% CI: 0.73–0.98]; p = 0.028), higher procalcitonin (PCT) levels at surgery (OR 1.03 [95% CI: 1.01–1.06]; p = 0.017), postoperative sepsis (OR 3.46 [95% CI: 1.36–8.76]; p = 0.009), transmural necrosis with perforation (OR 3.03 [95% CI: 1.18–7.78]; p = 0.021), longer diagnosis-to-surgery intervals (> 24 h) (OR 3.52 [95% CI: 1.23–10.08]; p = 0.019), and retention of the necrotic bowel (OR 4.88 [95% CI: 1.50–15.91]; p = 0.009). The ROC analysis revealed an area under the curve (AUC) of 0.86 for the prediction model.ConclusionThe incidence of brain injury in neonates with surgical NEC is independently associated with elevated PCT levels at surgery, the presence of sepsis, and the occurrence of transmural necrosis with perforation. Conversely, increased GA, early surgical recognition and intervention, and complete resection of the necrotic bowel may serve as potential protective factors against brain injury. The predictive model constructed on the basis of these findings demonstrated strong discriminative ability and we propose immediate neuroprotective intervention when model-predicted risk exceeds the 53% threshold.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12887-025-06324-x.

To reduce necrotizing enterocolitis (NEC) in infants born <32 weeks or <1500 g by implementing probiotics protocol using quality improvement (QI) methodology. Probiotics were discontinued following the FDA warning. Multidisciplinary team developed an evidence-based protocol and identified key drivers for implementation. Protocol compliance was the process measure. NEC rate was the outcome measure tracked at baseline, during the QI initiative, and after the FDA warning. Death and sepsis were the balancing measures. Protocol compliance was 84.5%. The baseline NEC rate was 4.6%, decreased in the post-implementation group to 0.6%, then increased following the FDA warning to 3.8% (p = 0.045). Two special cause variations were observed in relation to implementing and discontinuing probiotics. None of the infants who received probiotics died or developed probiotics associated sepsis. QI initiative safely implemented probiotics and reduced NEC. The regulatory ban of probiotics was associated with a rebound in NEC rate.

To investigate the effect of Infant-Driven Feeding (IDF) on feeding outcomes and growth among preterm infants with a gestational age of 32 to 37weeks at birth in the neonatal intensive care unit (NICU). An interventional study was conducted to evaluate the effectiveness of an IDF protocol compared to a standard feeding regimen. The control group (N=88) received the standard feeding protocol, while the experimental group (N=92) received the IDF protocol. Data were collected between January 1 and December 31, 2022. The experimental group exhibited a higher average oral milk intake per minute than the control group (t =-7.762, P <.001). Additionally, the experimental group achieved full oral feeding in a significantly shorter time (t =4.434, P <.001) compared to the control group. The experimental group also had a shorter nasogastric tube indwelling time (t =4.372, P <.001) and length of hospital stay (t=3.682, P <.001) compared to the control group. During the first week of life, the experimental group showed no significant differences in length (t=-1.475, P =.142), head circumference (t=-0.410, P =.683); however, weight gain on the 7th day was greater in the experimental group (t=-2.260, P =.025) when compared to the control group. The experimental group had a significantly lower incidence of vomiting (χ2=5.327, P =.021), oxygen desaturations (χ2=5.715, P =.017), and milk choking (χ2=6.105, P =.013) as compared to control group. There were no significant differences in the incidence of necrotizing enterocolitis (NEC) between the 2 groups (χ2=-1.071, P =.284). The implementation of IDF protocol in preterm infants with a gestational age of 32 to 37weeks at birth in the NICU improved feeding outcomes, expedited the feeding process, and reduced complications associated with poor feeding. Moreover, it did not adversely affect the growth and development of these infants and enhanced their feeding safety.

To investigate the risk factors for white matter damage (WMD) in preterm infants with necrotizing enterocolitis (NEC). A retrospective analysis was conducted on the clinical data of 249 preterm infants with NEC admitted to Children's Hospital of Fudan University between January 2021 and December 2023. Based on brain magnetic resonance imaging (MRI) white matter scores, the infants were categorized into a WMD group (≥7 points) and a non-injury group (<7 points). A multivariable logistic regression analysis was performed to identify risk factors for WMD. Compared with the non-injury group, the WMD group had significantly higher rates of Gram-negative bacterial infection (43.1% vs 28.2%), surgical treatment (47.2% vs 23.2%), and moderate-to-severe abnormalities on video electroencephalography (VEEG) (51.4% vs 11.9%) (all P<0.05). The multivariable logistic regression analysis showed that surgical treatment (OR=1.822, 95%CI: 1.199-2.777), longer hospital stay (OR=1.041, 95%CI: 1.004-1.080), and moderate-to-severe VEEG abnormalities (OR=7.045, 95%CI: 3.349-14.855) were independent risk factors for WMD (all P<0.05). Surgical treatment, prolonged hospitalization, and moderate-to-severe VEEG abnormalities are independent risk factors for WMD in preterm infants with NEC, providing a basis for early clinical identification and intervention to improve neurological outcomes.

Background: Intestinal perforation (IP) is one of the most critical surgical emergencies in neonates. It most often occurs in premature infants, with necrotizing enterocolitis (NEC) as the leading cause. Hirschsprung's disease (HD) is another important etiology. In this study, we aimed to investigate the frequency of HD among neonates with non-NEC IP and assessed the value of performing rectal biopsy in these patients. Methods: Neonates who were treated for non-NEC IPs between 2005 and 2021 were evaluated retrospectively. Demographic data, clinical features, operative details, and rectal biopsy results were collected. These features were compared according to the histopathological results of rectal biopsy (aganglionic versus ganglionic). Results: Rectal biopsies were performed in 48 neonates with non-NEC IP (33 preterm [68.8%], 15 term [31.2%]). The most common perforation site was the ileum (52.4%). Rectal biopsy revealed aganglionosis in 12.5% of the patients. Gestational age was higher in aganglionic than ganglionic cases (36.7 versus 32.5 weeks; P = .026). The perforations were colonic in all aganglionic cases (n = 6) and 47.6% (n = 20) of the ganglionic cases (P = .025). Conclusion: This study highlights the importance of considering HD in the differential diagnosis of neonatal IPs. Rectal biopsy should be considered in non-NEC perforations; particularly in term (or near-term) neonates and in cases of colonic perforation, to help identify underlying aganglionosis and guide timely management. Level of Evidence: Level 3 b.

Background Necrotizing enterocolitis (NEC) is a devastating intestinal disorder in premature infants, characterized by inflammation and tissue injury. Identifying key regulatory pathways contributing to NEC pathogenesis is essential for developing targeted therapeutic strategies. Methods Transcriptomic analysis of NEC and control samples identified a core regulatory module comprising AHSG, BHMT2, and MAT1A. Their expression and functional roles were investigated in human primary intestinal epithelial cells (HPIECs), a transwell co-culture system with THP-1 macrophages, and a mouse model of NEC. Molecular techniques, including RT-qPCR, Western blotting, ELISA, chromatin immunoprecipitation, and flow cytometry were employed to decipher the functional mechanism of this regulatory module. Results AHSG, BHMT2, and MAT1A were upregulated in NEC samples and LPS-stimulated HPIECs. BHMT2 and MAT1A regulated AHSG expression through S-adenosylmethionine production and histone methylation. In the co-culture system, silencing BHMT2, MAT1A, or AHSG in LPS-stimulated HPIECs attenuated M1 macrophage polarization, inflammatory cytokine production, and invasive capacity of THP-1 cells. Conversely, overexpressing these genes in HPIECs promoted M1 macrophage activation. In the NEC mouse model, targeting BHMT2, MAT1A, or AHSG alleviated intestinal tissue damage, inflammation, and M1 macrophage polarization. Conclusion The BHMT2/MAT1A/AHSG axis in intestinal epithelial cells orchestrates M1 macrophage activation and contributes to the exacerbation of NEC. Targeting this pathway may represent a potential therapeutic strategy for NEC management. Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-22915-1.

Necrotising enterocolitis (NEC) is a significant complication for very preterm infants (VPIs). The role of genetic predisposition in the development of NEC among VPIs has not been firmly established. This study aimed to explore the heritability factors in NEC among VPIs. A retrospective cohort study was conducted on 4138 infants from 2069 twin pairs. Twins were categorised based on chorionicity.Chi-square analyses were conducted to compare the incidence of NEC between monochorionic and dichorionic twin pairs. The Pearson chi-square test and ACE modelling appropriate for analysing twin cohorts were utilised. Stratified analyses were conducted for early-onset and late-onset NEC, surgical NEC, and NEC in different gestational age groups. The overall incidence of NEC was 5%. No significant difference was observed between monochorionic and dichorionic twins. ACE modelling revealed no contribution of heritability to NEC risk (% A = 0.00%, 95% CI [0.00%, 0.07%]). Stratified analyses for early-onset and late-onset NEC, surgical NEC, and NEC in different gestational age groups (GA < 28 weeks and 28+0-31+6 weeks) also revealed no significant heritability. Our findings suggest that, under the current conditions of medical practice, heritability does not play a major role in the development of NEC. NEC is a significant and potentially life-threatening complication in very preterm infants (VPIs). Previous studies have suggested a potential genetic susceptibility to NEC, although the evidence has been inconsistent. Genetic heritability does not play a major role in the development of NEC. Stratified analyses for early-onset and late-onset NEC, surgical NEC, and different gestational age groups also confirmed the lack of significant genetic influence. Our findings suggest that attention should be given to the risk factors contributing to the occurrence of NEC and that efforts should be made to improve the level of clinical treatment.

Necrotizing enterocolitis (NEC) is an acute, life-threatening intestinal disorder in neonates, associated with notably high mortality. It is characterized by insidious and non-specific early clinical manifestations, a rapid disease progression course, and often results in long-term sequelae in affected infants, such as short bowel syndrome and neurodevelopmental impairments. The pathogenesis of NEC remains complex and not fully elucidated; thus, the screening and validation of biomarkers with high specificity, high sensitivity, and clinical applicability constitutes a core strategy to enhance the efficacy of early diagnosis and accuracy of prognostic assessment for this disease. This article aims to systematically synthesize the current clinical dilemmas in the field of NEC and the update status of relevant clinical guidelines, with a focus on reviewing the research advances of both traditional and emerging biomarkers in the contexts of NEC early diagnosis, disease staging, severity stratification, prediction of surgical intervention requirements, and prognostic evaluation. Additionally, it analyzes the consistencies and discrepancies between cutting-edge research findings and clinical guidelines, and prospects the future development direction of precision diagnosis and treatment for NEC.

Background Necrotizing enterocolitis (NEC) remains a major challenge in neonatology, particularly affecting premature infants and those with very low birth weight. This study analyzes trends in NEC incidence in Kazakhstan from 2020 to 2024, highlighting regional disparities and comparing them with international benchmarks. Data from perinatal centers and neonatal intensive care units (NICUs) indicate a significant increase in NEC cases, particularly in urban areas. Key recommendations include improving early diagnosis, standardizing feeding protocols, and promoting the use of breast milk to reduce NEC incidence and associated mortality rates. Objective The aim of this study was to examine surgical necrotizing enterocolitis in newborns. Materials and Methods This retrospective study analyzed data on NEC cases from neonatal intensive care units (NICUs) and perinatal centers across Kazakhstan from 2020 to 2024. Cases were categorized by region and year, with additional analysis focusing on neonatal characteristics such as birth weight and gestational age. Comparative analysis with international data was conducted to contextualize findings and identify potential areas for improvement in neonatal care practices. Results The analysis revealed a significant increase in NEC incidence in Kazakhstan, particularly in urban regions such as Almaty and Almaty Region. The number of cases peaked in 2023, with a 1.7-fold increase compared to 2020. Regional disparities were evident, with higher incidence rates in areas with better healthcare infrastructure. In less developed regions, such as Akmola and Turkestan, the growth was less pronounced but still present. Conclusion This study underscores the rising trend of NEC in Kazakhstan and the associated regional disparities. Adopting evidence-based preventive measures, enhancing healthcare infrastructure, and standardizing neonatal care protocols are essential for reducing NEC incidence and improving outcomes for this vulnerable population. BJMS, Vol. 24 No. 04 October’25 Page : 1119-1123

Empowering parents in neonatal decision making using Q-methodology: Development of a decision guidance framework for necrotizing enterocolitis.

Bovine colostrum stands out as a natural supplement with rich bioactive components that attract attention for its therapeutic potential in the maintenance and improvement of gastrointestinal (GI) health. The major bioactive components of bovine colostrum include immunoglobulin (Ig) (especially immunoglobulin G), lactoferrin (LF), growth Factors (IGF-I, TGF-β, EGF), oligosaccharides (OS), and bioactive peptides. These components play a role in epithelial repair, suppression of inflammation, balancing the microbiota, and enhancing the mucosal barrier. Various animal models and recent human studies show that bovine colostrum has various positive effects against gastrointestinal tract diseases such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), non-steroidal anti-Inflammatory drug (NSAID)-induced enteropathy, and necrotizing enterocolitis (NEC). These effects include preservation of epithelial integrity, reduction of inflammatory markers, and improvement of intestinal permeability. Studies on the tolerability and efficacy profiles of various bovine colostrum formulations for oral, oropharyngeal, and enteral administration are increasing. In this review, the multifaceted effects of bovine colostrum on the gastrointestinal tract are explained at a mechanistic level, and potential areas of study for clinical translation are presented. Bovine Colostrum stands out as a promising natural biotherapeutic agent for both preventive and therapeutic approaches.

ObjectiveDeficiency of pulmonary surfactant (PS) induces the onset of neonatal respiratory distress syndrome (RDS), which can lead to progressively worsening respiratory failure and even death. However, studies on improving lung function via the use of vibrating mesh nebulizer (VMN) technology to deliver PS to premature infants with RDS are limited.MethodsThis prospective multicenter, open-label, exploratory, randomized clinical trial, including 2 parallel groups and a 1:1 allocation, was conducted in 7 hospitals from Jan. 1, 2023, to Dec. 31, 2024. Premature infants born at less than 32 weeks of gestation and weighing less than 1500 g who presented after birth with RDS with the need for noninvasive ventilatory support as initial treatment were eligible for inclusion.ResultsOf the 49 eligible premature infants, 25 were randomized to the VMN group, and 24 to the less invasive surfactant administration (LISA) group. We did not find a difference in the need for mechanical ventilation via an endotracheal tube (MVET) within 72 h between the VMN and LISA groups (3 [12.00%] vs. 5 [20.80%]; odds ratio, 0.52; 95% confidence intervals (CI), 0.11–2.46; P = 0.653). Comparing the LISA group, the incidence of apnea of prematurity and transient decrease in oxygen saturation was lower in the VMN group (2[8.00%] vs. 10 [41.67%]; odds ratio [OR], 0.10; 95% CI 0.02–0.54, P = 0.003; 3[12.00%] vs. 16[66.67%]; OR, 0.10; 95% CI 0.02–0.30, P < 0.001). However, there was no difference in the bronchopulmonary dysplasia (BPD), death in hospital, pneumothorax, periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), periventricular–intraventricular hemorrhage (PIVH), and application of PS again between the two groups (all P > 0.05).ConclusionIn this exploratory clinical trial, compared with LISA, the noninvasive VMN technique may be a safe and well-tolerated approach for PS delivery in preterm infants with RDS.Trial registration: ChiCTR2300072262 (https://www.chictr.org.cn).“Supplementary InformationThe online version contains supplementary material available at 10.1186/s40001-025-03316-6.

Allicin attenuates necrotizing enterocolitis via PINK1/Parkin-mediated mitophagy to suppress pyroptosis.

We intend to investigate the risk factors of the necrotizing enterocolitis (NEC)-associated bloodstream infection (BSI) in neonates with NEC. This analysis included a multi-centered retrospective case-control study in 4 newborn intensive care units (NICUs) from 2015 to 2024. The factors involved in the NEC-associated BSI were investigated using univariate and multivariate analyses. The majority of NEC-associated BSIs were caused by Klebsiella spp. (23%). Compared with those without BSI, the neonates with BSI had significantly lower gestational age and birth weight (BW), had a higher incidence rate of NEC of stage III (P = .048) and surgical NEC. The independent risk factors of concurrent BSI were BW and first white blood cell (WBC) count. And BSI, vasopressor use at enrollment, and respiratory support were independent risk factors of the NEC-attributable mortality. The BSI following NEC was associated with low BW and high WBC, which might be helpful for the optimization of treatment planning.

Gastric pneumatosis is a condition defined as air within the wall of the stomach, however, is an extremely rare sign during neonatal period. Due to an association of this entity with Necrotizing enterocolitis (NEC) which is a fulminant condition with high morbidity and mortality in neonates, finding gastric pneumatosis especially in a premature neonate should alert the clinician. Other causes have also been identified like gastric outlet obstruction or displaced nasogastric or orogastric tube in stomach wall. This entity should not be confused with free air in abdomen and can be managed conservatively. We herein present a case of a premature neonate with a finding of gastric pneumatosis and culture-proven sepsis who was managed conservatively.

Background Necrotizing enterocolitis (NEC) lacks useful biomarkers for early risk stratification. Despite evidence of lactate metabolism and immune dysregulation in NEC pathogenesis, their synergistic diagnostic potential remains underexplored. Method This retrospective cohort study analyzed 118 neonates with NEC (2017–2022), stratified into two subgroups: mild NEC (Bell’s stage ≤ IIa, n = 59) and severe NEC (Bell’s stage ≥ IIb, n = 59). Threshold effects, multivariable logistic regression, and mediation analysis were employed to assess nonlinear relationships and biomarker interaction. Results Severe NEC exhibited significantly lower lymphocytes (1.58 vs. 3.71 × 109/L, p < 0.001), increased mechanical ventilation requirements (89.8% vs. 39.0%, p < 0.001), and elevated lactate levels (6.4 mmol/L vs. 2.8 mmol/L, p < 0.001). Multivariable regression identified lactate (OR 3.84, p < 0.001) and lymphocytes (OR 0.33, p = 0.021) as independent severity predictors. Threshold analysis showed nonlinear correlations of lactate with NEC severity, surgical intervention, and mortality (turning point: 6.1, 6.4, and 5.4 mmol/L), each 1 mmol/L lactate increase above threshold raised mortality risk 1.7-fold (OR 1.70, p = 0.022). Lymphocytes exhibited significant indirect mediation in combined lactate-NEC evaluation (7.79%, p = 0.008). The lactate-lymphocyte combination achieved useful prognostic accuracy (AUC = 0.96, sensitivity = 89.8%, specificity = 89.8%), outperforming lactate alone (AUC = 0.93, sensitivity = 91.5%, specificity = 81.4%; p < 0.001). Conclusion Combined lactate and lymphocytes enhance risk stratification and prognostic accuracy in NEC, bridge metabolic and immune pathways, and offer clinical utility for guiding early interventions in high-risk neonates with NEC.

Patients with CHD are at risk for developing necrotising enterocolitis. Currently, no standardised approaches for identification, diagnosis, and treatment of necrotising enterocolitis exists, and there are varying rates and management strategies of necrotising enterocolitis across centres. We used the Paediatric Cardiac Critical Care Consortium to identify high- and low-performing centres based on necrotising enterocolitis rates and convened a necrotising enterocolitis working group. The aims of the group were to understand why variability exists, identify risk factors, and create a foundation for a prospective improvement project. Nine centres participated, and collaborative learning sessions were held with multidisciplinary input. REDCap surveys were disseminated to centres to create consensus among site practices and recommendations. The following topics were discussed: diagnosis, risk factors, and management. Diagnosis consensus suggests (1) Diagnosis would benefit from a comprehensive scoring tool, and (2) ultrasound may serve as a highly sensitive diagnostic tool for those at high risk with the absence of other radiologic findings of necrotising enterocolitis. Risk factor consensus suggests (1) those with ductal-dependent systemic blood flow are the highest risk, and (2) vasopressors with splanchnic constriction should be used with caution. Management consensus suggests (1) breastmilk be used first-line for feeding, 2) resume feeds 24-48 hours after a necrotising enterocolitis rule-out, and 3) surgical deference to physical examination and laboratory evaluation above radiographic findings. Variability exists in diagnosing necrotising enterocolitis and feeding approaches for at-risk patients. Opportunities exist for collaboration to standardise definitions, compare outcomes, identify risk factors, and create consensus on the management of necrotising enterocolitis.