Necrotizing Enterocolitis Group Research Articles

Abstract 4136819: Necrotizing Enterocolitis is More Common After Hybrid Stage 1 Palliation Than Norwood Without Clear Risk Factors

Background: Infants with congenital heart disease are at high risk of developing necrotizing enterocolitis (NEC), with increased morbidity and mortality compared to infants without heart disease who develop NEC. Shunted single ventricle patients are at even higher risk. The hybrid stage 1 palliation (HS1P) is an alternative to the Norwood procedure for high-risk single ventricle patients or as initial palliation for patients with future two ventricle repair, as bridge to transplant, or as destination therapy. Few small studies have shown similar or slightly higher rates of NEC after HS1P compared to after Norwood. Aims: To evaluate the incidence, risk factors, and outcomes of NEC in HS1P versus Norwood patients. Methods: This is a single-center retrospective cohort study of all neonates who underwent HS1P or Norwood procedure from 2011-2022. Demographic data and episodes of NEC (defined using modified Bell’s criteria) were collected. NEC incidences and risk factors were compared between HS1P and Norwood patients using Chi-square test. For HS1P patients, more extensive data were collected including planned and final physiologic outcomes (single ventricle palliation, biventricular repair, transplant, and destination) and primary patient risk factors that led to HS1P. Risk factors and clinical outcomes of HS1P patients with and without NEC were compared using standard univariate tests. Results: The cumulative incidence of NEC in the HS1P group was 53% versus 37% in the Norwood group (p=0.01) and HS1P patients had more NEC episodes than the Norwood group (median 2 vs 1, p=0.03). Suspected NEC (stage 1A/1B) accounted for 70-75% of NEC cases in both groups. Only two infants, both in the HS1P group, had surgical (stage 3B) NEC. We found no differences in baseline demographics between patients with and without NEC in both HS1P and Norwood groups. In the HS1P group, NEC was associated with longer hospital length of stay (LOS), (median 49 days vs 23 days, p<0.0001) and greater need for tube feeds at 1 year (32% of the NEC group exclusively orally fed versus 43% of the non-NEC group, p=0.03). Final physiologic outcome was not associated with development of NEC in the HS1P group (p=0.38). Conclusions: While the exact risk factors or predictors are not clear, NEC is more common after HS1P compared to Norwoods and is associated with longer hospital LOS and late feeding difficulty. Further studies to better understand the physiologic causes of NEC in the HS1P population are needed.

Risk of neurodevelopmental impairment in Swedish preterm children treated for necrotizing enterocolitis: retrospective cohort study.

As the survival of preterm infants has increased, the management of long-term complications, especially neurodevelopmental impairment, becomes increasingly important. The aim of this study was to investigate the risk of neurodevelopmental disorders in preterm babies receiving medical or surgical treatment for necrotizing enterocolitis, compared with other preterm babies and preterm babies who received abdominal surgery for other indications. In this nationwide Swedish cohort study, including all liveborn preterm babies born between 1998 and 2019, the risk of attention deficit (and hyperactivity) disorder, autism spectrum disorders, cerebral palsy and intellectual disability was assessed by multivariable Cox regression, expressed as hazard ratios and 95% confidence intervals (c.i.). Of the surgically (n = 384) and medically (n = 709) treated preterm infants with necrotizing enterocolitis, neurodevelopmental disorders were present in 32% (HR 2.24, 95% c.i. 1.86 to 2.69) and 22% respectively (HR 1.40, 95% c.i. 1.19 to 1.65), compared with 21% (HR 1.63, 95% c.i. 1.40 to 1.91) in the abdominal surgery group (n = 844) and 13% (reference) among other preterm infants (n = 78 972). The highest relative increases were for intellectual disability (HR 3.60, 95% c.i. 2.65 to 4.89) in the surgical necrotizing enterocolitis group and abdominal surgery group (HR 2.84, 95% c.i. 2.12 to 3.80) compared with the control preterm group, and for cerebral palsy (respectively HR 2.74, 95% c.i. 2.04 to 3.68 and HR 2.54, 95% c.i. 1.87 to 3.44). Medically treated necrotizing enterocolitis was associated with autism (HR 1.67, 95% c.i. 1.34 to 2.08), without significant increases for the other specific outcomes. Both surgically treated groups were also strongly associated with both attention deficit (and hyperactivity) disorder and autism. Surgically treated necrotizing enterocolitis, medically treated necrotizing enterocolitis and abdominal surgery for other indications in preterm infants were all associated with an increased risk of impaired neurodevelopmental outcomes, compared with other preterm infants.

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

To investigate whether laboratory markers obtained at the onset of necrotising enterocolitis (NEC) predict the severity of the disease in preterm infants. 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. 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 23g/L with 52% sensitivity (95%CI: 37-68%) and 84% specificity (95%CI: 60-97%) (AUC 0.727; p = 0.002). Serum ALB level at NEC onset might be a reliable biomarker for severe disease in preterm infants.

The clinical characteristics and risk factors analysis within one week before the onset of necrotizing enterocolitis

There are considerable researches on risk factors for necrotizing enterocolitis (NEC), focusing primarily on the entire course before onset. However, fewer studies address risk factors within the brief period before NEC occurrence. The current study aims to retrospectively analyze the clinical data of NEC patients while focusing on relevant risk factors in the preceding week of NEC onset. Infants born between January 2019 and December 2021 at Suzhou Municipal Hospital and Suzhou University Children’s Hospital with a birth weight < 1500 g or a gestational age < 32 weeks were included. Around 54 NEC patients and 180 controls were recruited in the study. NEC patients satisfying the inclusion criteria formed the case group, while a 1:4 matching principle helped select the control group based on gestational age and birth weight. A statistically significant difference was observed between groups when red blood cell transfusions were compared the week before NEC onset (adjusted OR and 95% CI 2.16 (1.10, 4.24)). Broad-spectrum antibiotic usage before NEC occurrence was significantly lower in the NEC group than in the control group (adjusted OR and 95% CI 0.95 (0.91, 0.99)). A statistically significant difference was observed between groups while comparing patent ductus arteriosus (PDA) (adjusted OR and 95% CI 2.45 (1.23, 4.91)). The indication for packed red blood cell transfusion should be strictly controlled. Moreover, close monitoring of the patient’s condition for NEC occurrence should be conducted within one-week post-transfusion. Accurately identifying infections and using broad-spectrum antibiotics can reduce the incidence of NEC.

Risk factors for necrotizing enterocolitis in small-for-gestational-age infants: a matched case–control study

Few studies have focused on the risk factors for necrotizing enterocolitis (NEC) in small for gestational age (SGA) infants. The aim of this study was to identify the risk factors for NEC in SGA newborns. This study included consecutive SGA neonates admitted to a tertiary hospital in Jiangxi Province, China from Jan 2008 to Dec 2022. Patients with NEC (Bell’s stage ≥ II) were assigned to the NEC group. Gestational age- and birth weight-matched non-NEC infants born during the same period at the same hospital were assigned to the control group. The risk factors associated with NEC were analyzed with univariate and logistic regression models. During the study period, 2,912 SGA infants were enrolled, 150 (5.15%) of whom developed NEC. In total, 143 patients and 143 controls were included in the NEC and control groups, respectively. Logistic regression analysis revealed that sepsis (OR 2.399, 95% CI 1.271–4.527, P = 0.007) and anemia (OR 2.214, 95% CI 1.166–4.204, P = 0.015) might increase the incidence of NEC in SGA infants and that prophylactic administration of probiotics (OR 0.492, 95% CI 0.303–0.799, P = 0.004) was a protective factor against NEC. Therefore, sepsis, anemia and a lack of probiotic use are independent risk factors for NEC in SGA infants.

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.

Reduced Expression of REG4 as a Sign of Altered Goblet Cell Function in Necrotizing Enterocolitis.

Defective Goblet cells have been proposed to be involved in necrotizing enterocolitis (NEC). The aim was to study the expression of the Goblet cell marker REG4 and its potential involvement in NEC in preterm infants with and without NEC. Seventy histologically intact intestinal biopsies were studied: 43 were collected during surgery due to NEC (NEC group: 26.5 ± 3.0 weeks' gestational age [wGA]), and 27 from individuals who underwent surgery due to other conditions (Control group; 36.1 ± 4.5 wGA). The tissue samples were immunohistochemically stained for REG4. REG4 expression was quantified with a semiautomated digital image analysis and with clinical data compared between the groups. REG4 expression was lower in the NEC group than in the Control group (p = 0.035). Low REG4 expression correlated to the risk of NEC (p = 0.023). In a multivariable logistic regression analysis including GA and REG4 expression for NEC risk, only GA (p < 0.001) and not REG4 expression (p = 0.206) was associated with NEC risk. This study concludes that Goblet cell dysfunction may be involved in NEC development, as low expression of the Goblet cell marker REG4 was related to an increased NEC risk in preterm infants. Maturity could however not be excluded as a potential confounder for REG4 expression. · REG4 is a specific Goblet cell marker not yet studied in NEC.. · REG4 was quantified in intestinal biopsies from infants with and without NEC.. · REG4 expression was lower in infants with NEC, and expression seems to be maturity dependent..

Advancing necrotizing enterocolitis prediction through iterative monitoring.

Necrotizing enterocolitis (NEC) is a severe inflammatory intestinal disease in preterm infants, marked by heightened morbidity and mortality. Timely prediction of NEC is significant in the management of critical neonates. However, it is difficult to predict NEC accurately because of the multi-factorial pathogenesis. This study aimed to develop a prediction model through repeated measurement data to further improve the accuracy of prediction in NEC. We retrospectively collected clinical data of premature infants admitted to the Neonatology Department of the First Affiliated Hospital of Anhui Medical University from January 2016 to December 2023. The infants were categorized into the NEC group (Bell's stage ≥ II) (n=150) and the non-NEC group (n=150). The clinical baseline data of the NEC and non-NEC groups were matched. Laboratory examination indicators were collected on the 1st day, the 7th day after birth, and the day of NEC onset. Univariate and multivariate logistic regression analyses were conducted to identify independent factors influencing NEC. A nomogram was constructed based on these factors to predict NEC. The concordance index and calibration plot were used to assess the efficiency of the nomogram in the training and validation cohorts. This study demonstrated that antenatal steroids, antenatal antibiotics, probiotics treatment before NEC, anion gap (AG, day 7), and mean corpuscular volume (MCV, day 7) were independent risk factors which combined to accurately predict NEC. A nomogram of NEC was created utilizing these five predictors. With an area under the receiver operator characteristic (ROC) curve of 0.835 [95% confidence interval (CI): 0.785-0.884]. Concordance index for the training and validation groups were 0.835 and 0.848, respectively. As the calibration plots indicate, the predicted probability of NEC is highly consistent with the actual observation. The risk estimation nomogram for NEC offers clinical value by guiding early prediction, targeted prevention, and early intervention strategies for NEC.

Risk factors of necrotizing enterocolitis in twin preterm infants

PurposeThis study was aimed to investigate the risk factors of necrotizing enterocolitis (NEC) in twin preterm infants.MethodsThe clinical data of 67 pairs of twin preterm infants admitted to the neonatal department of our hospital from January 2010 to December 2021 were retrospectively collected. One of the twins had NEC (Bell II and above) and the other twin without NEC. They were divided into NEC group and control group according to whether NEC occurred or not.ResultsUnivariate analysis showed that NEC was associated with congenital heart disease, small for gestational age, mild asphyxia at birth and feeding intolerance (P < 0.05).ConclusionOccurrence of NEC was associated with congenital heart disease, small for gestational age, and asphyxia at birth. For twin preterm infants with congenital heart disease, small for gestational age, or asphyxia at birth, special attention should be paid to the occurrence of NEC to minimize and avoid the occurrence of NEC.

Evaluation of the protective and therapeutic effects of extra virgin olive oil rich in phenol in experimental model of neonatal necrotizing enterocolitis by clinical disease score, ınflammation, apoptosis, and oxidative stress markers.

Necrotizing Enterocolitis (NEC) is an inflammation-associated ischemic necrosis of the intestine. To investigate the effects of extra virgin olive oil (EVOO) on inflammation, oxidative stress, apoptosis, and histological changes in NEC-induced newborn rats. 24 rats were randomly divided into three groups: control, NEC and NEC + EVOO. NEC induction was performed using hypoxia-hyperoxia, formula feeding, and cold stress. The NEC + EVOO group received 2ml/kg EVOO with high phenolic content by gavage twice a day for 3days. 3cm of bowel including terminal ileum, cecum, and proximal colon was excised. Weight gain and clinical disease scores were significantly higher in the NEC + EVOO group than in the NEC group (p < 0.001). EVOO treatment caused significant decreases in IL1β, IL6 levels (p = 0.016, p = 0.029 respectively) and EGF, MDA levels (p = 0.032, p = 0.013 respectively) compared to NEC group. Significant decreases were observed in IL6 gene expression in the NEC + EVOO group compared to the NEC group (p = 0.002). In the group NEC + EVOO, the number of Caspase-3 positive cells was found to be significantly reduced (p < 0.001) and histopathological examination revealed minimal changes and significantly lower histopathological scores (p < 0.001). Phenol-rich EVOO prevents intestinal damage caused by NEC by inhibiting inflammation, oxidative stress, apoptosis.

MiR-375-3p targets YWHAB to attenuate intestine injury in neonatal necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a significant contributor to neonatal mortality. This study aimed to investigate the role of high levels of miR-375-3p in breast milk in the development of NEC and elucidate its mechanism. Differential expression of miR-375-3p in the intestines of breast-fed and formula-fed mice was confirmed using real-time polymerase chain reaction (RT-PCR). NEC mice models were established, and intestinal injury was assessed using HE staining. RT-PCR and Western blot were conducted to examine the expression of miR-375-3p, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein β (YWHAB), as well as the inflammatory in IEC-6 cells, and intestinal tissues obtained from NEC mice and patients. Flow cytometry and cell counting kit-8 (CCK-8) were employed to elucidate the impact of miR-375-3p and YWHAB on cell apoptosis and proliferation. Breastfeeding increases miR-375-3p expression in the intestines. The expression of miR-375-3p in NEC intestinal tissues exhibited a significant decrease compared to the healthy group. Additionally, the expression of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) was higher in the NEC group compared to the control group. Down-regulation of miR-375-3p inhibited IEC-6 cell proliferation, increased apoptosis, and elevated secretion of inflammatory factors. Bioinformatics revealed that YWHAB may be a target of miR-375-3p. RT-PCR and Western blot indicated a down-regulation of YWHAB expression in intestines of NEC patients and mice. Furthermore, YWHAB was found to be positively connected with miR-375-3p. Knockdown miR-375-3p down-regulated YWHAB expression in cells. Inhibition of YWHAB exhibited similar effects to miR-375-3p in IEC-6 cells. YWHAB plasmid partially reverse cellular functional impairment induced by miR-375-3p knockdown. Breastfeeding elevated miR-375-3p expression in intestines in neonatal mice. MiR-375-3p leads to a decrease in apoptosis of intestinal epithelial cells, an increase in cell proliferation, and a concomitant reduction in the expression of inflammatory factors partly through targeting YWHAB.

Clinical characteristics of postoperative necrotizing enterocolitis in patients with congenital jejunoileal atresia and its risk factors

ObjectiveTo review postoperative necrotizing enterocolitis (NEC) in patients with jejunoileal atresia (JIA) and to explore the potential risk factors related to the concurrence of NEC.MethodsPatients diagnosed with JIA who received...

Biomarkers in the Severity of Necrotizing Enterocolitis in Preterm Infants: A Pilot Study.

The occurrence of necrotizing enterocolitis (NEC) is a common and severe disease of the digestive system in neonates. This study aims to assess the value of the intestinal tissue oxygen saturation (rintSO2) combined with the levels of procalcitonin (PCT) and mean platelet volume (MPV) in predicting the severity of NEC in preterm infants. This experiment was a retrospective cohort study conducted in the Department of Pediatrics, Hongqi Hospital Affiliated to Mudanjiang Medical University between January 2017 and July 2022. Premature neonates with NEC were enrolled and divided into mild-moderate NEC group and severe NEC group according to Bell's stage. The general information data, rintSO2 and blood parameters such as the white blood cell (WBC) count, platelet count (PLT), PCT, MPV, red blood cell distribution width (RDW), hemoglobin (Hb), C-reactive protein (CRP) were compared between the two groups. A total of 122 patients were enrolled, including 79 mild-moderate NEC and 43 severe NEC. The rintSO2 was lower in severe group than in mild-moderate group (P = 0.042), the PCT and MPV were both higher in severe group than in mild-moderate group (P = 0.048, P = 0.049). The results of logistic regression suggested that the rintSO2 (OR = 1.491, P = 0.003), PCT (OR = 3.071, P = 0.001) and MPV (OR = 4.027, P = 0.015) were independent predictive factors for severity of NEC. The area under the curve (AUC) of the rintSO2 combined with PCT and MPV showed good diagnostic ability in the severity of NEC. The rintSO2 combined with PCT and MPV may be considered as the early biomarkers in the severity of NEC and could help us to diagnose the case early with early treatment with better prognosis.

Dried blood spots-based metabolomic analysis in preterm infants with necrotizing enterocolitis

Objective Necrotizing enterocolitis (NEC) is the leading cause of death among premature infants, and there is a lack of specific early diagnostic markers. Blood sampling is expected to better reflect pathophysiological and metabolic changes in systematic illness, but there is a risk of iatrogenic anemia, especially in premature infants. Dried blood spots technique seems to have important advantages compared to whole blood sampling as it requires only 12–15 μL as sample volume. This study aimed to investigate the special metabolomics of preterm neonates at high risk of NEC using dried blood spots. Methods Cases and controls were strictly matched 1:1. Dried blood spots (n = 32, 16 cases–16 controls) from newborn screening were subjected to LC–MS/MS. Metabolomic data were analyzed by orthogonal partial least squares-discriminant analysis (OPLS-DA) and univariate/multivariate statistical analysis. Results Compared to the control group, the NEC group had a significant reduction in seven amino acids (glycine, alanine, threonine, proline, ornithine, lysine, and asparagine). Conclusions The metabolic profile of neonates with NEC differs significantly from that of controls, making possible their separation with the use of targeted (LC–MS/MS) dried blood spots-based metabolomic analysis. Seven specific markers were identified for early detection and intervention.

Active polypeptide MDANP protect against necrotizing enterocolitis (NEC) by regulating the PERK-eIF2ɑ-QRICH1 axis

The effect of MDANP effects on ER stress signalling not well known or elucidated. Endoplasmic reticulum (ER) stress plays a critical role in necrotizing enterocolitis (NEC) pathogenesis through the PERK-eIF2ɑ-QRICH1 axis. The present study aimed to explore the protective effects of MDANP in NEC development. Firstly, a function screening was designed to identify the candidate peptides in human milk, and then the identified peptides were validated in NEC patients. In vivo, NEC was induced in mice pups and divided into four groups: (1) control group, (2) NEC group, (3) MDANP + NEC group, and (4) NS + NEC group. In vitro, lentivirus-mediated QRICH1 silencing, was used to transfect NCM460 cell lines, then stimulated with LPS. After LPS stimulation, cells were treated with chemically synthesized MDANP, and the essential proteins in the QRICH1 signalling pathway in cells were tested and compared. After the small-scale screening, a peptide (SKSKKFRRPDIQYPDATDED) named MDANP was determined as the principal peptide. Its protective effect against NEC through inhibiting the expression of ERS key proteins and impeding the intestinal cells’ apoptosis was observed in the animal models. Furthermore, the inhibitive effect of MDANP on apoptosis of intestinal epithelial cells through modulating the PERK-eIF2ɑ-QRICH1 ERS pathway was also confirmed in vitro. Taken together, our data suggest that MDANP effectively ameliorates apoptosis in NEC through attenuating PERK-eIF2ɑ-QRICH1.

Occurrence of Neonatal Necrotizing Enterocolitis in Premature Neonates and Gut Microbiota: A Case-Control Prospective Multicenter Study.

Necrotizing enterocolitis (NEC) is still one of the leading causes of neonatal death. The present study reports the data from a French case-control prospective multicenter study. A total of 146 preterm neonates (PNs) with or without NEC were included. Bacterial 16S rRNA gene sequencing was performed on stool samples (n = 103). Specific culture media were used to isolate Escherichia coli, Clostridium butyricum, and Clostridium neonatale, and strains were phenotypically characterized. The gut microbiota of PNs was dominated by Firmicutes and Proteobacteria, and five enterotypes were identified. The microbiota composition was similar between NEC cases and PN controls. However, differences were observed in the relative abundance of Lactobacillus genus, which was significantly lower in the NEC group, whereas that of the Clostridium cluster III was significantly higher (p < 0.05). Within enterotypes, several phylotypes were significantly more abundant in NEC cases (p < 0.05). Regarding perinatal factors, a statistical association was found between the gut microbiota and cesarean delivery and antifungal therapy. In NEC cases and PN controls, the carriage rates and virulence genes of uropathogenic E. coli were equivalent based on culture. No correlation was found between E. coli, C. butyricum, and C. neonatale carriages, beta-lactam resistance, and antibiotic treatment. At disease onset, our data support a microbiota dysbiosis between NEC and control infants at the genus level. In addition, it provides valuable information on bacterial antimicrobial susceptibility.

Effect of gut microbiota homeostasis on hematopoiesis in a neonatal rat model of necrotizing enterocolitis

To study the effect of gut microbiota on hematopoiesis in a neonatal rat model of necrotizing enterocolitis (NEC). Neonatal Sprague-Dawley rats were randomly divided into a control group and a model group (NEC group), with 6 rats in each group. Formula milk combined with hypoxia and cold stimulation was used to establish a neonatal rat model of NEC. Hematoxylin and eosin staining was used to observe the pathological changes of intestinal tissue and hematopoiesis-related organs. Routine blood tests were conducted for each group. Immunohistochemistry was used to observe the changes in specific cells in hematopoiesis-related organs. Flow cytometry was used to measure the changes in specific cells in bone marrow. 16S rDNA sequencing was used to observe the composition and abundance of gut microbiota. Compared with the control group, the NEC group had intestinal congestion and necrosis, damage, atrophy, and shedding of intestinal villi, and a significant increase in NEC histological score. Compared with the control group, the NEC group had significantly lower numbers of peripheral blood leukocytes and lymphocytes (P<0.05), nucleated cells in the spleen, thymus, and bone marrow, and small cell aggregates with basophilic nuclei in the liver (P<0.05). The NEC group had significant reductions in CD71+ erythroid progenitor cells in the liver, CD45+ lymphocytes in the spleen and bone marrow, CD3+ T lymphocytes in thymus, and the proportion of CD45+CD3-CD43+SSChi neutrophils in bone marrow (P<0.05). There was a significant difference in the composition of gut microbiota between the NEC and control groups, and the NEC group had a significant reduction in the abundance of Ligilactobacillus and a significant increase in the abundance of Escherichia-Shigella (P<0.05), which replaced Ligilactobacillus and became the dominant flora. Multi-lineage hematopoietic disorder may be observed in a neonatal rat model of NEC, which may be associated with gut microbiota dysbiosis and abnormal multiplication of the pathogenic bacteria Escherichia-Shigella.

Deciphering the role of TNF‑α‑induced protein8‑like2 in the pathogenesis of necrotizing enterocolitis in neonatal rats.

Neonatal necrotizing enterocolitis (NNEC) is a disease characterized by intestinal inflammation and ischemic necrosis. Despite progress having been made during decades of research, details regarding its pathophysiology remain to be elucidated. It is known that abnormal expressions of TNF-α-induced protein 8-like 2 (TIPE2) can be observed in several diseases. However, the expression of TIPE2 in necrotizing enterocolitis (NEC) rats has not been examined before. The present study aimed to describe the expression pattern of TIPE2 and its role in NNEC pathogenesis. An NEC rat model was generated and used in the present study. All rats were sacrificed when the phenotype developed and the intestine between the lower end of the duodenum and the ileocecal were collected for further study. Hematoxylin and eosin, and immunohistochemical staining, reverse transcription-quantitative PCR and western blotting analysis were used to examine the expression of TIPE2. The results showed that the average body weight was significantly decreased in the NEC group compared with the control group along with a significant decrease of TIPE2 expression. However, the expressions of phosphatidylinositol-3-kinase (PI3K) and serine/threonine kinase AKT were significantly increased in NEC rats. The correlation analysis showed that the expressions of TIPE2 and PI3K were negatively correlated with a correlation coefficient of -0.797. To further determine the association between TIPE2 and PI3K/AKT pathway, two groups of wild type Sprague Dawley rats were infected with recombinant adenovirus Ad-V and Ad-TIPE2 respectively. The results showed that the expression of TIPE2 was significantly increased among rats in the Ad-TIPE2-infected group (OE group) compared to the ones from the Ad-V-infected group (NC group). However, the mRNA and protein expressions of PI3K and AKT were significantly decreased in Ad-TIPE2-infected rates. The difference of each index between OE and NC groups was statistically significant. The present study showed that the expression of TIPE2 was downregulated in NEC rats. TIPE2 might be involved in the pathogenesis of NEC by activating the PI3K/Akt signaling pathway.

Patent ductus arterious and increased conjugated bilirubin in the second week after birth are independent risk factors for necrotizing enterocolitis in preterm infants: an observational study

BackgroundNeonatal necrotizing enterocolitis (NEC) is a common critical illness of the gastrointestinal system in neonatal intensive care units with complex causes. We want to explore effects of serum-conjugated bilirubin on the occurrence of NEC in preterm infants.MethodsA retrospective study of clinical case data of premature infants from 2017 to 2020 in the Department of pediatrics of the First Affiliated Hospital of Nanjing Medical University was conducted. Among these, 41 were diagnosed with NEC. After screening, 2 cases were excluded because of incomplete data. Propensity-matching score (PSM) was performed according to the ratio of 1:2(2 preterm infants in the NEC group were not matched), and finally, 37 cases were in the NEC group (average time to diagnosis was 18.9 days), and 74 cases in the non-NEC group. We compared the difference between the NEC and non-NEC groups in early serum-conjugated bilirubin and total bilirubin levels (time points: the first day of birth, 1 week after birth, 2 weeks after birth).Results(1) The changing trend of conjugated bilirubin was different between the two groups(F = 4.085, P = 0.019). The NEC group’s serum-conjugated bilirubin levels gradually increased (bar x ± s:12.64±2.68; 17.11±4.48; 19.25±11.63), while the non-NEC group did not show a continuous upward trend (bar x ± s:13.39±2.87; 15.63±3.75; 15.47±4.12). (2) Multiple analyses showed that patent ductus arteriosus(PDA) (odds ratio[OR] = 5.958, 95%confidence interval[CI] = 2.102 ~ 16.882) and increased conjugated bilirubin in the 2nd week (OR = 1.105, 95%CI = 1.013 ~ 1.206) after birth were independent risk factors for NEC.ConclusionsThe body had already experienced an elevation of conjugated bilirubin before the occurrence of NEC. The change of early conjugated bilirubin may be an important factor in the occurrence of NEC.

Time to first passage of meconium and defecation frequency preceding necrotizing enterocolitis in preterm infants: a case–control study

Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality in preterm infants. Early recognition and treatment of NEC are critical to improving outcomes. Enteric nervous system (ENS) immaturity has been proposed as a key factor in NEC pathophysiology. Gastrointestinal dysmotility is associated with ENS immaturity and may serve as a predictive factor for the development of NEC. In this case–control study, preterm infants (gestational age (GA) < 30 weeks) were included in two level-IV neonatal intensive care units. Infants with NEC in the first month of life were 1:3 matched to controls based on GA (± 3 days). Odds ratios for NEC development were analyzed by logistic regression for time to first passage of meconium (TFPM), duration of meconial stool, and mean daily defecation frequency over the 72 h preceding clinical NEC onset (DF < T0). A total of 39 NEC cases and 117 matched controls (median GA 27 + 4 weeks) were included. Median TFPM was comparable in cases and controls (36 h [IQR 13–65] vs. 30 h [IQR 9–66], p = 0.83). In 21% of both cases and controls, TFPM was ≥ 72 h (p = 0.87). Duration of meconial stool and DF < T0 were comparable in the NEC and control group (median 4 and 3, resp. in both groups). Odds of NEC were not significantly associated with TFPM, duration of meconial stools, and DF < T0 (adjusted odds ratio [95% confidence interval]: 1.00 [0.99–1.03], 1.16 [0.86–1.55] and 0.97 [0.72–1.31], resp.).Conclusion: In this cohort, no association was found between TFPM, duration of meconium stool, and DF < T0 and the development of NEC.What is Known:• Necrotizing enterocolitis (NEC) is a life-threatening acute intestinal inflammatory disease of the young preterm infant. Early clinical risk factors for NEC have been investigated in order to facilitate early diagnosis and treatment.• Signs of disrupted gastrointestinal mobility, such as gastric retention and paralytic ileus, have been established to support the diagnosis of NEC. Nevertheless, defecation patterns have insufficiently been studied in relation to the disease.What is New:• Defecation patterns in the three days preceding NEC did not differ from gestational age-matched controls of corresponding postnatal age. Additionally, the first passage of meconium and the duration of meconium passage were comparable between cases and controls. Currently, defecation patterns are not useful as early warning signs for NEC. It remains to be elucidated whether these parameters are different based on the location of intestinal necrosis.