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High concentrations of immunoglobulins, bioactive peptides, and growth factors are found in bovine colostrum (BC), the milk produced by cows in the first few days after parturition. Various biological functions make it increasingly used to provide nutritional support and immune protection to the offspring of many species, including humans. These biological functions include cell growth stimulation, anti-infection, and immunomodulation. The primary components and biological functions of colostrum were reviewed in the literature, and the authors also looked at its latent effects on the growth and development of neonates as well as on conditions such as infections, necrotizing enterocolitis, short bowel syndrome, and feeding intolerance. The importance of BC in neonatal nutrition, immune support, growth and development, and gut health has been demonstrated in a number of experimental and animal studies. BC has also been shown to be safe at low doses without adverse effects in newborns. BC supplementation has been shown to be efficient in preventing several disorders, including rotavirus diarrhea, necrotizing enterocolitis, and sepsis in animal models of prematurity and some newborn studies. Therefore, BC supplementation should be considered in cases where maternal milk is insufficient or donor milk is unavailable. The optimal age, timing, dosage, and form of BC administration still require further investigation. [ABSTRACT FROM AUTHOR]

This retrospective study aims to analyze the baseline characteristics and factors associated with poor outcomes in patients with necrotizing enterocolitis (NEC) complicating respiratory syncytial virus (RSV) infection. Using the Virtual Pediatric Systems data registry, patients under 2 years admitted to the pediatric intensive care unit (PICU) were screened. Patients with documented RSV infection and NEC, intestinal perforation, noninfectious gastroenteritis/colitis, or pneumatosis intestinalis occurring around the timing of RSV bronchiolitis diagnosis were included. Out of the screened patients, 41 were analyzed. Most patients (93%) were aged 30 days to 2 years, one-third had baseline anatomical cardiac defects, and 20% history of prematurity. Median PICU length of stay was 11.7 days. Seven patients died before hospital discharge. While not statistically significant, nonsurvivors tended to exhibit higher PRISM-3 scores, more acidemia, and lower systolic blood pressure. These findings emphasize the need for cautious assessment of gastrointestinal symptoms in critically ill patients with RSV infection. [ABSTRACT FROM AUTHOR]

Purpose: The STAT trial is a multicenter randomized controlled trial in 12 centers worldwide aiming to determine the most effective operation for neonates with necrotizing enterocolitis (NEC) requiring intestinal resection: stoma formation (ST) or primary anastomosis (PA). Methods: Infants having a primary laparotomy for NEC were randomized intraoperatively to PA or ST if the operating surgeon thought that both were viable treatment options for that patient. The primary outcome (duration of parenteral nutrition [PN]) was evaluated by Cox regression. Results: Eighty patients were recruited from 2010 to 2019. Infants undergoing anastomosis finished PN significantly earlier than patients undergoing stoma (hazard ratio PA vs. ST 2.38, 95% CI 1.36–4.12 p = 0.004). There was no difference in mortality between the two groups (PA 4/35 vs. ST 8/38 p = 0.35) or in the rate of complications requiring further unplanned operations (p = n.s.). Multiple intestinal complications were more frequent in the stoma group compared to the anastomosis group (ST 12/26 vs. PA 5/31, p = 0.02, Fisher's Exact test). Conclusion: At laparotomy for NEC, when there is no disease distal to resected intestine, primary anastomosis should be performed as it enhances the recovery from NEC, reduces the risk of multiple intestinal complications and does not increase adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal (GI) emergency in preterm neonates. Untargeted metabolomics may allow the identification of biomarkers involved in NEC pathophysiology. Methods: We conducted a prospective study including preterm infants born at < 34 gestational weeks (GWs) whose urine was longitudinally collected at birth (< 48 h, T0) and at 14 (T1) and 28 days (T2). Neonates were followed for their development of NEC, spontaneous intestinal perforation (SIP), or other GI conditions and compared to those of matched healthy controls. Urine samples were investigated by untargeted metabolomic analysis based on mass-spectrometry. Results: Thirty-five patients with NEC, 5 patients with SIP, 14 patients with other GI diseases and 113 controls were enrolled and selected for metabolomic analysis on the basis of their clinical characteristics and available samples. Considering urine samples at T0, the one-class classification approach was able to correctly classify 16/20 subjects (80%) who developed NEC, 3/3 (100%) who developed SIP and 5/7 subjects (71.4%) with other GI pathologies as not belonging to the control group. Neonates with surgical NEC had higher N-acetylaspartic acid, butyrylcarnitine and propionylcarnitine levels than did those with medical NEC. Considering the time evolution of the urinary metabolome, the NEC and control groups showed differences independently of the time point. Conclusions: The urinary metabolome is closely associated with the underlying GI disease from birth. Urinary metabolic features characterize NEC patients from healthy controls until 28 days of life. The early urinary metabolome has the potential to predict surgical NEC. Future studies are needed to validate our results. [ABSTRACT FROM AUTHOR]

To study the methodology and results of studies assessing the relationship between fetal heart rate and specified neonatal outcomes including, heart rate, infection, necrotizing enterocolitis, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, and seizure.Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and CINAHL were searched from inception to October 5, 2023.Forty-two studies were included, encompassing 57,232 cases that underwent fetal monitoring and were evaluated for neonatal outcome. Heterogeneity was observed in the timing and duration of fetal heart rate assessment, classification guidelines used, number of assessors, and definition and timing of neonatal outcome assessment. Nonreassuring fetal heart rate was linked to lower neonatal heart rate variability. A significant increase in abnormal fetal heart rate patterns were reported in neonates with hypoxic-ischemic encephalopathy, but the predictive ability was found to be limited. Conflicting results were reported regarding sepsis, seizure and intraventricular hemorrhage. No association was found between necrotizing enterocolitis rate and fetal heart rate.There is great heterogeneity in the methodology used in studies evaluating the association between fetal heart rate and aforementioned neonatal outcomes. Hypoxic-ischemic encephalopathy was associated with increased abnormal fetal heart rate patterns, although the predictive ability was low. Further research on developing and evaluating an automated early warning system that integrates computerized cardiotocography with a perinatal health parameter database to provide objective alerts for patients at-risk is recommended. [ABSTRACT FROM AUTHOR]

Several perinatal factors influence the intestinal microbiome of newborns during the first days of life, whether during delivery or even in utero. These factors may increase the risk of developing necrotizing enterocolitis (NEC) by causing dysbiosis linked to a NEC-associated microbiota, which may also be associated with other gastrointestinal problems. The objective of our study was to evaluate the potential risks associated with microbial shifts in newborns with gastrointestinal symptoms and identify the intestinal microbiota of neonates at risk for NEC.During the study period, 310 preterm and term newborns' first passed meconium occurring within 72 h of birth were collected, and the microbiome was analyzed. We identified the risk factors in the NEC/FI group. Regarding microbiota, we compared the bacterial abundance between the NEC/FI group at the phylum and genus levels and explored the differences in the microbial composition of the 1st stool samples. A total of 14.8% (n = 46) of the infants were diagnosed with NEC or FI. In univariate analysis, the mean gestational age and birth weight were significantly lower in the NEC/FI group (p < 0.001). Prolonged rupture of membranes (PROM) > 18 h, chorioamnionitis, and histology were significantly higher in the NEC/FI group (p < 0.001). Multivariate analysis showed that gestational age (GA), prolonged membrane rupture (> 18 h), and early onset sepsis were consistently associated with an increased risk of NEC/FI. Infants diagnosed with NEC/FI exhibited a significantly lower abundance of Actinobacteria at the phylum level than the control group (p < 0.001). At the genus level, a significantly lower abundance of Streptococcus and Bifidobacterium which belong to the Actinobacteria phylum, was observed in the NEC/FI group (p < 0.001). Furthermore, the NEC/FI had significantly lower alpha diversities (Shannon Index,3.39 vs. 3.12; P = 0.044, respectively). Our study revealed that newborns with lower diversity and dysbiosis in their initial gut microbiota had an increased risk of developing NEC, with microbiota differences appearing to be associated with NEC/FI. Dysbiosis could potentially serve as a predictive marker for NEC- or GI-related symptoms. [ABSTRACT FROM AUTHOR]

There is little research concerning the role of stem cells in necrotizing enterocolitis (NEC). Bone marrow-derived mesenchymal stem cells (BMDSC) and amniotic fluid-derived stem cells significantly reduced the amount and severity of NEC in the animal models. ADSCs share similar surface markers and differentiation potential with BMDSCs. Their potential role in the setting of NEC has not been researched before. The hypothesis of the study was that prophylactic intraperitoneal administration of ADSCs before the onset of the disease will result in limiting the inflammatory response, effecting a lower incidence of NEC. On a molecular level, this should result in lowering the levels of inflammatory cytokines IL-1 and IL-6. The local ethical committee for animal experiments approval was acquired (WAW2/093/2021). We utilized a self-modified rat NEC model based on single exposure to hypothermia, hypoxia, and formula feeding. One hundred and twenty-eight rat puppies were divided into two groups—prophylaxis (ADSC-NEC, n = 66) and control group (NEC-PLCB, n = 62)—to measure the influence of ADSCs administration on the inflammatory changes in NEC, the level of cell engraftment, and the histopathology of the disease. The analysis did not show a significant effect on histopathology between groups, H(2) = 2.12; p = 0.347; η²H = 0.00. The intensity of the NEC variable results was similar across the analyzed groups (NEC-PLCB and ADSC-NEC). For IL-1 and IL-6, the difference between the NEC-PLCB group and the ADSC-NEC group was statistically significant, p = 0.002 and p < 0.001, respectively. To conclude, administration of adipose tissue-derived stem cells before the onset of the disease lowers the levels of inflammatory cytokines IL-1 and IL-6 but does not affect the histopathological results in the rat model of NEC. [ABSTRACT FROM AUTHOR]

Microbiota and feeding modes influence the susceptibility of premature newborns to necrotizing enterocolitis (NEC) through mechanisms that remain unknown. Here, we show that microbiota colonization facilitated by breastmilk feeding promotes NOD-like receptor family CARD domain containing 5 (Nlrc5) gene expression in mouse intestinal epithelial cells (IECs). Notably, inducible knockout of the Nlrc5 gene in IECs predisposes neonatal mice to NEC-like injury in the small intestine upon viral inflammation in an NK1.1+ cell-dependent manner. By contrast, formula feeding enhances neonatal gut colonization with environment-derived tilivalline-producing Klebsiella spp. Remarkably, tilivalline disrupts microbiota-activated STAT1 signaling that controls Nlrc5 gene expression in IECs through a PPAR-γ-mediated mechanism. Consequently, this dysregulation hinders the resistance of neonatal intestinal epithelium to self-NK1.1+ cell cytotoxicity upon virus infection/colonization, promoting NEC development. Together, we discover the underappreciated role of intestinal microbiota colonization in shaping a disease tolerance program to viral inflammation and elucidate the mechanisms impacting NEC development in neonates. [Display omitted] • Breastmilk-fed gut microbiota sparks STAT1 to shift IECs into an NLRC5highTAP1high state • Formula feeding enhances tilivalline (TV)-producing Klebsiella spp. colonization • TV confers IECs with an NLRC5lowTAP1low state via PPAR-γ-mediated STAT1 inhibition • NLRC5lowTAP1low IECs are killed by self-NK cells upon viral inflammation, leading to NEC Subramanian, Geng, and colleagues discover that formula-feeding facilitates neonatal gut colonization with environment-derived tilivalline-producing Klebsiella spp., which impedes STAT1-NLRC5 axis maturation in intestinal epithelial cells through tilivalline-induced PPAR-γ activation. This dysregulation causes the epithelium to lose resistance to autologous NK cell cytotoxicity, leading to necrotizing enterocolitis (NEC) during virus colonization/infection. [ABSTRACT FROM AUTHOR]

Aberrant preterm infant gut microbiota assembly predisposes to early-life disorders and persistent health problems. Here, we characterize gut microbiome dynamics over the first 3 months of life in 236 preterm infants hospitalized in three neonatal intensive care units using shotgun metagenomics of 2,512 stools and metatranscriptomics of 1,381 stools. Strain tracking, taxonomic and functional profiling, and comprehensive clinical metadata identify Enterobacteriaceae , enterococci, and staphylococci as primarily exploiting available niches to populate the gut microbiome. Clostridioides difficile lineages persist between individuals in single centers, and Staphylococcus epidermidis lineages persist within and, unexpectedly, between centers. Collectively, antibiotic and non-antibiotic medications influence gut microbiome composition to greater extents than maternal or baseline variables. Finally, we identify a persistent low-diversity gut microbiome in neonates who develop necrotizing enterocolitis after day of life 40. Overall, we comprehensively describe gut microbiome dynamics in response to medical interventions in preterm, hospitalized neonates. [Display omitted] • Antibiotics and non-antibiotic drugs govern infant gut microbiome development • Antibiotic-associated microbial shifts introduce pathogens and resistance • Hospitalized preterm infants share isogenic C. difficile and S. epidermidis • Microbial development stagnates before late-onset necrotizing enterocolitis Preterm neonates undergo numerous interventions. Thänert, Schwartz, Keen, et al. use multi-omics to show that antibiotics and other drugs alter gut microbiome development, but prenatal factors do not. Microbiome development stagnates before necrotizing enterocolitis ensues, but only among infants who experience this devastating complication after 40 days of life. [ABSTRACT FROM AUTHOR]

Background: Gastroschisis is a rare congenital anomaly in which abdominal organs herniate through a defect in the abdominal wall. Managing gastroschisis in extremely low birth weight (ELBW) infants presents significant challenges because of their immature physiologies and increased risk of complications. Case presentation: This report discusses the case of a female ELBW infant born via an emergency cesarean section at 29 weeks of gestation, weighing 768 g, who had a prenatal diagnosis of gastroschisis. Postnatal management included immediate surgical intervention using a hand-made silo manufactured from expanded polytetrafluoroethylene (ePTFE) sheets that were sutured to the patient's abdominal wall to accommodate her small abdominal cavity and preserve mesenteric blood flow. Necrotizing enterocolitis with bowel perforation emerged as a complication, which led to the excision of a 10 cm segment of the ileum and the creation of an ileostomy. The infant experienced insufficient weight gain and liver dysfunction. However, she was eventually discharged on day 142 of life, weighing 2774 g, on oral feeding, without significant complications. Conclusions: This case emphasizes how prematurity significantly affected the patient's clinical outcomes, and highlights the importance of individualized management strategies. Our experience demonstrates that custom silo placement allows for the size to be adapted to the abdominal defect, and highlights the critical need to prioritize postnatal bowel perfusion in ELBW infants with gastroschisis. [ABSTRACT FROM AUTHOR]

Neonatal necrotizing enterocolitis (NEC) is a critical digestive disorder frequently affecting premature infants. Characterized by intestinal inflammation caused by activated M1 macrophages, modulation of macrophage polarization is considered a promising therapeutic strategy for NEC. It has been demonstrated that the growth factor‐like protein progranulin (PGRN), which plays roles in a number of physiological and pathological processes, can influence macrophage polarization and exhibit anti‐inflammatory characteristics in a number of illnesses. However, its role in NEC is yet to be investigated. Our research showed that the levels of PGRN were markedly elevated in both human and animal models of NEC. PGRN deletion in mice worsens NEC by encouraging M1 polarization of macrophages and escalating intestinal damage and inflammation. Intravenous administration of recombinant PGRN to NEC mice showed significant survival benefits and protective effects, likely due to PGRN's ability to inhibit M1 polarization and reduce the release of pro‐inflammatory factors. Our findings shed new light on PGRN's biological role in NEC and demonstrate its potential as a therapeutic target for the disease. [ABSTRACT FROM AUTHOR]

Surfactant administration significantly improves respiratory outcomes in preterm infants with respiratory distress syndrome (RDS). However, surfactant administration may lead to hemodynamic alterations, particularly in the heart, affecting the patent ductus arteriosus (PDA), the consequences of which are not fully understood. This prospective observational study took place in an Indian neonatal care unit from July 2019 to November 2020, enrolling preterm neonates (26–34 weeks' gestation) with RDS needing non-invasive positive pressure ventilation. They were divided into two groups: those who received surfactant while on respiratory support and those who did not. All newborns in the study had an initial echocardiogram within 24 h to detect PDA flow. Subsequent echocardiograms were conducted between 48 and 72 h or earlier based on symptoms. Of 220 infants requiring respiratory support, 84 were enrolled, with 42 in each group. While demographic variables were similar, the surfactant group had a lower median gestational age (29.0 vs. 31.0 weeks). In the surfactant group, a significantly higher percentage of neonates had hemodynamically significant PDA (hsPDA) compared to the non-surfactant group (54.76% vs. 26.19%, P -value =.008). Multiple logistic regression found no significant association between gestation, birth weight, or shock and hsPDA occurrence. Pulmonary hemorrhage occurred more often in the surfactant group. Bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) > grade 2, and necrotizing enterocolitis (NEC) ≥ grade 2 did not differ significantly between the groups. Surfactant therapy via the less invasive surfactant administration technique was associated with a higher incidence of hsPDA. While surfactant is crucial for neonatal respiratory care, its potential hemodynamic effects, including hsPDA, should be considered. [ABSTRACT FROM AUTHOR]

Enteral feeds are often withheld from neonates with ductal dependent cardiac lesions who are receiving prostaglandins. This is despite positive benefits of enteral feeding. We describe a multicenter cohort of these neonates who were fed pre-operatively. We also give a granular description of vital sign measurements and other risk factors prior to feeding. A retrospective chart review was performed at seven centers. Inclusion criteria were full-term neonates under one month of age with ductal dependent lesions receiving prostaglandins. These neonates were fed for at least 24 h during the pre-operative period. Premature neonates were excluded. Using the inclusion criteria, 127 neonates were identified. While being fed, 20.5% of the neonates were intubated, 10.2% were on inotropes, and 55.9% had an umbilical arterial catheter in place. Median oxygen saturations in the six hours prior to feeding were 92.5% in patients with cyanotic lesions, median diastolic blood pressure was 38 mmHg and median somatic NIRS were 66.5%. The median peak daily feeding volume reached was 29 ml/kg/day (IQ range 15.5–96.8 ml/kg/day). One patient developed suspected necrotizing enterocolitis (NEC) in this cohort. Only one adverse event occurred, which was an aspiration thought to be related to feeding, but did not result in intubation or cessation of feeds. NEC was rare among neonates with ductal dependent lesions while receiving enteral nutrition pre-operatively. Umbilical arterial catheters were in place in the majority of these patients. Hemodynamic measures demonstrated a high median oxygen saturation prior to initiation of feeds. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis is the most severe life-threatening acquired gastrointestinal disorder among preterm neonates. We describe here an outbreak of Clostridium butyricum- related necrotizing enterocolitis in preterm neonates that occurred in three different neonatal centres, in southeast France. We defined a confirmed case of C. butyricum -related necrotizing enterocolitis in preterm neonates by the presence of clinical signs according to modified Bell criteria and C. butyricum identified from stool samples using real-time polymerase chain reaction or culture. A phylogenetic analysis of the isolated strains by whole-genome sequencing was also performed. Between 5th and 27th January 2022, we identified 10 confirmed cases of C. butyricum- related necrotizing enterocolitis , including five from Neonatal Centre 1, four from Neonatal Centre 2, and one from Neonatal Centre 3. The attack rate of necrotizing enterocolitis in Neonatal Centre 1 was 7.1% (5/70). The positivity rate of C. butyricum detected from stool samples was higher during the outbreak period (37/276; 13.4%) than outside this period (7/369; 1.9%), while systematic screening was maintained (P <0.001). Phylogenetic analysis showed a clonality between strains inside four clusters. Two clusters included neonates hospitalized in different neonatal centres, suggesting the transmission of C. butyricum strains during the transfer of neonates between neonatal centres. This outbreak of C. butyricum- related necrotizing enterocolitis confirms a cross-transmission between preterm neonates, including twin or triplet siblings, and involving necrotizing enterocolitis cases together with asymptomatic carriers. After three months of follow-up, no further cases were identified following the implementation of contact precautions with sporicidal agents. [ABSTRACT FROM AUTHOR]

Short bowel syndrome is the most common reversible cause of intestinal failure. Most of the children are started on parenteral nutrition (PN) after surgery to enable growth and allow time for intestinal adaptation. This is a process whereby the shorter length of bowel is able to achieve complete function as if the entire length of bowel is present. With management advances, most children with short bowel syndrome can discontinue PN and establish full enteral feeds. This article mainly focuses on the complications of short bowel syndrome that need to be avoided for the child to achieve intestinal adaptation, establish on enteral feeds/oral diet and achieve enteral autonomy. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is common in preterm infants, especially infants less than 32 weeks gestation. Mortality from NEC is 7% and occurs in 1 out of 1000 preterm infants. Studies have shown the efficacy of an exclusive milk from mother diet in decreasing rates of NEC and associated mortality. Purpose: To evaluate the effectiveness of an existing exclusive human milk diet (EHMD) protocol on the incidence of NEC in extremely premature infants. EHMD, for the purposes of this project is defined as breast milk of mother, with or without human milk-based fortifier. Methods: A single-center retrospective quasi-experimental study. The sample included 201 infants born less than 32 weeks gestation, weighing less than 1250 grams, small for gestational age (SGA) and with low Apgar scores. Outcomes measured included incidences of NEC, mortality, and co-morbidities in infants pre- and postinitiation of an EHMD protocol. Results: Just 4.8% of the EHMD group had a NEC diagnosis compared to 10.5% of the bovine-based (BOV) group. There was a 1% mortality rate of the EHMD group as compared to 6% in the BOV group. The EHMD group had a statistically significant greater weight gain during hospitalization as compared to infants fed BOV (P = < .05). Implications for Practice and Research: Neonatal intensive care units should consider EHMDs for use in this infant population. Future research is needed to support dissemination of the use of EHMD as standard of practice. [ABSTRACT FROM AUTHOR]

Background/Objectives: Very low birth weight (VLBW) infants may require enhanced nutrition, even during complementary feeding. However, there are limited data on macronutrient intake during this period, particularly concerning the individual timing of the introduction of solid foods in a representative VLBW infant population. Methods: This prospective observational study analyzed macronutrient intake in VLBW infants with a gestational age < 32 weeks based on whether solid foods were introduced early (<17 weeks corrected age (CA)) or late (≥17 weeks corrected age) Nutritional intake was analyzed using a 24 h recall at 6 weeks CA and 3-day dietary records at 12 weeks, 6, 9, and 12 months CA. Results: In total, 115 infants were assigned to the early and 82 to the late group. The timing of solid food introduction did not affect macronutrient intake, except for a lower fat and higher carbohydrate intake (% of energy) in the early group at 12 weeks and 6 months CA: early vs. late, fat—12 weeks: 47.0% vs. 49.0%, 6 months: 39.2% vs. 43.3%; carbohydrates—12 weeks: 44.9% vs. 43.2%, 6 months: 51.3% vs. 48.0%. Apart from docosahexaenoic acid (DHA) and arachidonic acid (AA), dietary intake recommendations were met in both groups. While nutrient intakes varied significantly between breastfed and formula-fed infants, those with comorbidities exhibited similar nutrient intake levels compared to those without. Conclusions: Our findings suggest adequate macronutrient intakes in VLBW infants irrespective of the timing of solid introduction. However, there is a notable need to enhance dietary intakes of DHA and AA. Future research is crucial to assess whether current nutrient intakes are sufficient for VLBW infants with comorbidities. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease characterized by intestinal inflammation and injury, with high mortality risk. Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently discovered damage-associated molecular pattern that propagates inflammation and tissue injury; however, the role of eCIRP in NEC remains unknown. We hypothesize that eCIRP exacerbates NEC pathogenesis and the novel eCIRP-scavenging peptide, milk fat globule-epidermal growth factor-factor VIII (MFG-E8)-derived oligopeptide 3 (MOP3), attenuates NEC severity, serving as a new therapeutic strategy to treat NEC. Methods: Stool samples from premature neonates were collected prospectively and eCIRP levels were measured. Wild-type (WT) and CIRP−/− mouse pups were subjected to NEC utilizing a combination of hypoxia and hypercaloric formula orogastric gavage with lipopolysaccharide supplementation. In parallel, WT pups were treated with MOP3 or vehicle. Endpoints including NEC severity, intestinal injury, barrier dysfunction, lung injury, and overall survival were determined. Results: Stool samples from NEC neonates had elevated eCIRP levels compared to healthy age-matched controls (p < 0.05). CIRP−/− pups were significantly protected from NEC severity, intestinal injury, bowel inflammation, intestinal barrier dysfunction, lung injury, and systemic inflammation. NEC survival was 100% for CIRP−/− pups compared to 65% for WT (p < 0.05). MOP3 treatment recapitulated the benefits afforded by CIRP-knockdown, preventing NEC severity, improving inflammatory profiles, and attenuating organ injury. MOP3 treatment improved NEC survival to 80% compared to 50% for vehicle treatment (p < 0.05). Conclusions: eCIRP exacerbates NEC evidenced by protection with CIRP-deficiency and administration of MOP3, a CIRP-directed therapeutic, in a murine model. Thus, eCIRP is a novel target with human relevance, and MOP3 is a promising treatment for lethal NEC. [ABSTRACT FROM AUTHOR]

Background/aim: Necrotizing enterocolitis (NEC) is a serious condition that predominantly affects premature infants and involves an aberrant immune response and inflammatory cytokine release resulting in intestinal epithelial damage. The current study investigated the immunoregulatory effects of vitamin D3 on the maturation and activation of dendritic cells (DCs) and the antiinflammatory impact on the intestines in a neonatal rat model of NEC. Materials and methods: Inflammatory damage to intestinal tissue was assessed via morphological changes and apoptosis and DC expression of costimulatory molecules, inflammatory factors, and immunoregulatory factors by immunohistochemical staining, quantitative real-time PCR, and immunofluorescence. The fluorescein isothiocyanate-ovalbumin (FITC-OVA) uptake assay was used to analyze DC endocytosis. Results: Vitamin D3 administration attenuated intestinal damage and apoptosis, inhibiting CD86 and increasing CD80 expression. Lipopolysaccharide (LPS)-challenged DC2.4 cells in vitro showed upregulated CD86, tumor necrosis factor-a (TNF-a), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase 1 (IDO-1) expression, which were all reduced by vitamin D3, except for IDO-1. LPS inhibited CD80 expression, which was restored by vitamin D3 treatment, and endocytic capacity was improved. Vitamin D3 ameliorated intestinal damage in neonatal rats with NEC and exerted antiinflammatory and immunomodulatory effects on DCs. Conclusion: Vitamin D3 has potential as a supplementary treatment for NEC patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: The high morbidity of necrotizing enterocolitis (NEC) in very low birth weight infants (<1500 grams) (VLBW) requires the search for prevention strategies that are more effective than treatment. Current evidence supports the use of probiotics as protective factors. OBJECTIVES: To determine if probiotic supplementation in VLBW infants represents a preventive factor for the development of NEC. METHODS: Retrospective cohort study conducted in 145 VLBW infants, where the presence of NEC was evaluated in populations supplemented with L. reuteri, B. lactis or not supplemented. The comparison among groups was performed with the chi-square test for maximum likelihood-ratio. RESULTS: Of 66 supplemented patients, 86.4% did not present NEC (RR 0.23 [95% Ci: 0.12-0.43]; p<0.0001). In those not supplemented, the incidence of NEC was 59.5%. An NNT of 1.7 to 3.1 was obtained. CONCLUSIONS: Despite the heterogeneity in clinical studies of probiotic supplementation, the evidence is strongly in favor of probiotic treatment for the prevention of NEC. This study found that supplementation from the first days of life at doses of 600 million CFUs/ day was more effective in preventing the presentation of NEC than higher doses. [ABSTRACT FROM AUTHOR]

Background: Surgeons often encounter patients with intestinal failure due to inadequate intestinal length ("short bowel syndrome"/SBS). Treatment in these patients remains challenging and the process of physiologic adaptation may take years to complete, which frequently requires parenteral nutrition. We propose a proof-of-concept mechanical bowel elongation approach using a self-expanding prototype of an intestinal expansion sleeve (IES) for use in SBS to accelerate the adaptation process. Methods: IESs were deployed in the small intestines of Sprague Dawley rats. Mechanical characterization of these prototypes was performed. IES length–tension relationships and post-implant bowel expansion were measured ex vivo. Bowel histology before and after implantation was evaluated. Results: IES mechanical studies demonstrated decreasing expansive force with elongation. The deployment of IES devices produced an immediate 21 ± 8% increase in bowel length (p < 0.001, n = 11). Mechanical load testing data showed that the IESs expressed maximum expansive forces at 50% compression of the initial pre-contracted length. The small-intestine failure load in the rats was 1.88 ± 21 N. Intestinal histology post deployment of the IES showed significant expansive changes compared to unstretched bowel tissue. Conclusions: IES devices were scalable to the rat intestinal model in our study. The failure load of the rat small intestine was many times higher than the force exerted by the contraction of the IES. Histology demonstrated preservation of intestinal structure with some mucosal erosion. Future in vivo rat studies on distraction enterogenesis with this IES should help to define this organogenesis phenomenon. [ABSTRACT FROM AUTHOR]

Immune factors are important antecedents in the pathophysiology of necrotizing enterocolitis (NEC). However, studies on the peripheral blood lymphocyte subsets changes in NEC patients among different Bell stages and in patients requiring surgery are scarce. 34 infants with NEC and 33 age-matched controls were included. Peripheral blood was collected within 48 h after NEC diagnosis. Peripheral blood B and T lymphocytes subsets were detected by 12-color flow cytometry. Cell ratios were calculated, and their relationship to disease severity and their roles as indicators for surgery were assessed. NEC patients showed elevated percentages of unSwB cells (CD27+IgD+ unswitched memory/activated B cells)/B cells, SwB cells (CD27+IgD-switched memory B cells)/B cells, CD8+ T (CD3+CD8+ T cells)/T cells, Tem (CD45RA-CCR7-effector memory T cells)/CD4+ T cells, Tem/CD8+ T cells and decreased Bn (CD27-IgD+ naïve B cells)/B cells, CD4+T (CD3+CD4+ T cells)/T cells, CD45RA+ CCR7+ naïve T cells (CD45RA+CCR7+ naïve T cells)/CD8+T cells. Compared to NEC patients at BELL stage I + II, patients at BELL stage III showed increased percentages of SwB cells/B cells, antibody secreting cell (ASC, CD3-CD20-CD27high CD38high ASCs)/B cells and Tem/CD4+ T cells, and decreased percentages of CD45RA+CCR7+ naïve T cells/CD4+ T cells. The Receiver Operating Characteristic Curve analysis showed that the sensitivity of ASC/B cells ratio (0.52%) is 86.67% and the specificity of Tem/CD4+T ratio (5.22%) is 100%, indicating that NEC patients required surgery. The severity of NEC exhibits codirectional changes with the maturation of B and T lymphocytes, especially CD4+ T cells. The increased ASC/B and Tem/CD4+ T cells could serve as potential indicators for NEC patients requiring surgery. [ABSTRACT FROM AUTHOR]

Purpose: Weight thresholds have historically determined timing of enterostomy closure (EC) in premature neonates. Recent evidence suggests that neonates less than 2 kg (L2K) can safely undergo EC. We evaluate our single-center experience with performing EC in preterm neonates at L2K versus greater than 2 kg (G2K) at time of EC. Methods: A retrospective review of neonates who underwent EC from January 2018 to 2020 was performed. Neonates who were greater than 90 days at initial operation were excluded. Demographics, clinical characteristics including gestational age (GA) and birth weight (BW), operative reports, and outcomes were reviewed. We compared 30-day complications between neonates who underwent EC at L2K and G2K. We also compared time to full feeds (FF) and postoperative length of stay (LOS). Results: Twenty-four neonates were included: 11 L2K and 13 G2K. The median GA and BW was 25.9 weeks (IQR 2.89) and 805 g (IQR 327), respectively. The most common intraoperative diagnosis during index operation was spontaneous perforation (70%), followed by necrotizing enterocolitis (8.69%). There were no significant differences in GA, BW, or diagnosis, between the L2K versus G2K cohort. We found no difference in complication rates, time to FF (12 days versus 10 days, P =.89), or postoperative LOS (31 days versus 36.5 days, P =.76) between patients who underwent EC at L2K versus G2K, respectively. Conclusion: Although weight gain may be an important indicator of perioperative nutrition status, this study shows that weight alone should not preclude otherwise appropriate patients from undergoing EC. [ABSTRACT FROM AUTHOR]

Purpose: The primary objective was to evaluate the impact of necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP) on mortality and neurodevelopmental outcomes at 2 years' corrected age (CA) in infants born before 32 weeks' gestation (WG). Methods: We studied neurodevelopment at 2 years' CA of infants with NEC or SIP who were born before 32 WG from the EPIPAGE-2 cohort study. The primary outcome was death or the presence of moderate-to-severe motor or sensory disability defined by moderate-to-severe cerebral palsy or hearing or visual disability. The secondary outcome was developmental delay defined by a score < 2 SDs below the mean for any of the five domains of the Ages and Stages Questionnaire. Results: At 2 years' CA, 46% of infants with SIP, 34% of infants with NEC, and 14% of control infants died or had a moderate-to-severe sensorimotor disability (p < 0.01). This difference was mainly due to an increase in in-hospital mortality in the infants with SIP or NEC. Developmental delay at 2 years' CA was more frequent for infants with SIP than controls (70.8% vs 44.0%, p = 0.02) but was similar for infants with NEC and controls (49.3% vs 44.0%, p = 0.5). On multivariate analysis, the likelihood of developmental delay was associated with SIP (adjusted odds ratio = 3.0, 95% CI 1.0–9.1) but not NEC as compared with controls. Conclusion: NEC and SIP significantly increased the risk of death or sensorimotor disability at 2 years' CA. SIP was also associated with risk of developmental delay at 2 years' CA. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine the incidence of growth failure in infants with necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP) and whether initial laparotomy versus peritoneal drainage (PD) impacted the likelihood of growth failure. Summary Background Data: Infants with surgical NEC and SIP have high mortality, and most have neurodevelopmental impairment and poor growth. Existing literature on growth outcomes for these infants is limited. Methods: This is a preplanned secondary study of the Necrotizing Enterocolitis Surgery Trial dataset. The primary outcome was growth failure (Z-score for weight < -2.0) at 18 to 22 months. We used logistic regression, including diagnosis and treatment, as covariates. Secondary outcomes were analyzed using the Fisher exact or Pearson χ² test for categorical variables and the Wilcoxon rank sum test or one-way ANOVA for continuous variables. Results: Among 217 survivors, 207 infants (95%) had primary outcome data. Growth failure at 18 to 22 months occurred in 24/50 (48%) of NEC infants versus 65/157 (42%) SIP (P=0.4). The mean weight-for-age Z-score at 18 to 22 months in NEC infants was -2.05±0.99 versus -1.84±1.09 SIP (P= 0.2), and the predicted mean weight-for-age Z-score SIP (Beta -0.27; 95% CI: -0.53, -0.01; P=0.041). Median declines in weight-for-age Z-score between birth and 18 to 22 months were significant in all infants but most severe (>2) in NEC infants (P=0.2). Conclusions: This first ever prospective study of growth outcomes in infants with surgical NEC or SIP demonstrates that growth failure is very common, especially in infants with NEC, and persists at 18-22 months. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) affect 6–8% of extremely low birth weight (ELBW) infants. SIP has lower mortality than NEC, but with similar short-term morbidity in length of stay, growth failure, and supplemental oxygen requirements. Comparative long-term neurodevelopmental outcomes have not been clarified. Data were prospectively collected from 59 North American neonatal units, regarding ELBW infants (401–1000 g or 22–27 weeks gestational age) born between 2011 and 2018 and evaluated again at 16–26 months corrected age. Outcomes were collected from infants with laparotomy-confirmed NEC, laparotomy-confirmed SIP, and those without NEC or SIP. The primary outcome was severe neurodevelopmental disability. Secondary outcomes were weight <10th percentile, medical readmission, post-discharge surgery and medical support at home. Adjusted risk ratios (ARR) were calculated. Of 13,673 ELBW infants, 6391 (47%) were followed including 93 of 232 (40%) with NEC and 100 of 235 (42%) with SIP. There were no statistically significant differences in adjusted risk of any outcomes when directly comparing NEC to SIP (ARR 2.35; 95% CI 0.89, 6.26). However, infants with NEC had greater risk of severe neurodevelopmental disability (ARR 1.43; 1.09–1.86), rehospitalization (ARR 1.46; 1.17–1.82), and post-discharge surgery (ARR 1.82; 1.48–2.23) compared to infants without NEC or SIP. Infants with SIP only had greater risk of post-discharge surgery (ARR 1.64; 1.34–2.00) compared to infants without NEC or SIP. ELBW infants with NEC had significantly increased risk of severe neurodevelopmental disability and post-discharge healthcare needs, consistent with prior literature. We now know infants with SIP also have increased healthcare needs. Level II. • What is currently known about this topic? SIP has decreased risk of mortality compared to NEC, with similar short-term morbidity. NEC has increased risk of long-term morbidity. Limited data exists in SIP. • What new information is contained in this article? ELBW NEC infants had increased risk of neurodevelopmental disability and post-discharge healthcare needs. SIP infants also have increased healthcare needs. [ABSTRACT FROM AUTHOR]

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Abstract Background Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal (GI) emergency in preterm neonates. Untargeted metabolomics may allow the identification of biomarkers involved in NEC pathophysiology. Methods We conducted a prospective study including preterm infants born at

Abstract Several perinatal factors influence the intestinal microbiome of newborns during the first days of life, whether during delivery or even in utero. These factors may increase the risk of developing necrotizing enterocolitis (NEC) by causing dysbiosis linked to a NEC-associated microbiota, which may also be associated with other gastrointestinal problems. The objective of our study was to evaluate the potential risks associated with microbial shifts in newborns with gastrointestinal symptoms and identify the intestinal microbiota of neonates at risk for NEC.During the study period, 310 preterm and term newborns’ first passed meconium occurring within 72 h of birth were collected, and the microbiome was analyzed. We identified the risk factors in the NEC/FI group. Regarding microbiota, we compared the bacterial abundance between the NEC/FI group at the phylum and genus levels and explored the differences in the microbial composition of the 1st stool samples. A total of 14.8% (n = 46) of the infants were diagnosed with NEC or FI. In univariate analysis, the mean gestational age and birth weight were significantly lower in the NEC/FI group (p 18 h, chorioamnionitis, and histology were significantly higher in the NEC/FI group (p 18 h), and early onset sepsis were consistently associated with an increased risk of NEC/FI. Infants diagnosed with NEC/FI exhibited a significantly lower abundance of Actinobacteria at the phylum level than the control group (p

Abstract Background Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease characterized by intestinal inflammation and injury, with high mortality risk. Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently discovered damage-associated molecular pattern that propagates inflammation and tissue injury; however, the role of eCIRP in NEC remains unknown. We hypothesize that eCIRP exacerbates NEC pathogenesis and the novel eCIRP-scavenging peptide, milk fat globule-epidermal growth factor-factor VIII (MFG-E8)-derived oligopeptide 3 (MOP3), attenuates NEC severity, serving as a new therapeutic strategy to treat NEC. Methods Stool samples from premature neonates were collected prospectively and eCIRP levels were measured. Wild-type (WT) and CIRP−/− mouse pups were subjected to NEC utilizing a combination of hypoxia and hypercaloric formula orogastric gavage with lipopolysaccharide supplementation. In parallel, WT pups were treated with MOP3 or vehicle. Endpoints including NEC severity, intestinal injury, barrier dysfunction, lung injury, and overall survival were determined. Results Stool samples from NEC neonates had elevated eCIRP levels compared to healthy age-matched controls (p

Abstract 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

Abstract Background Colony stimulating factor 1 (CSF1) is generally expressed by immune cells in response to pro-inflammatory stimuli. The CSF1 receptor (CSFR) is activated by CSF1, and plays a key role in macrophage homeostasis. Furthermore, the CSF1R+ macrophages maintain homeostasis in the intestinal epithelium. The aim of this study was to explore the functions of CSF1-expressing and CSF1R+ macrophages in necrotizing enterocolitis (NEC), which commonly affects the ileum of neonates. Methods In-situ CSF1 expression in the intestines of neonates with NEC or intestinal atresia (n = 4 each) was detected by immunofluorescence staining. The CSF1 levels in the intestinal crypt-derived organoid cultures were measured by ELISA. Peripheral blood monocyte-derived Mφ macrophages were co-cultured with the organoids and stimulated with lipopolysaccharide (LPS) to mimic the inflamed state of the ileum in NEC patients. Results CSF1 was expressed in the intestinal epithelial cells of the fetal and neonatal samples, but suppressed in the NEC samples. Furthermore, CSF1 expression was downregulated in the intestinal crypt-derived organoids by LPS. CSF1R+ macrophages were detected near the intestinal crypts in the non-inflamed intestines but were absent in tissues obtained from pediatric NEC patients. Peripheral blood monocyte-derived macrophages promoted intestinal organoid proliferation in vitro following CSF1 stimulation. Finally, low concentrations of LPS slightly enhanced the proliferation of organoids co-cultured with the macrophages, whereas higher doses had a significant inhibitory effect. Conclusions Intestinal epithelial cells express CSF1 to regulate the resident macrophages, maintain epithelial homeostasis, and resist infection. The abundant CSF1R+ macrophages in the fetal intestine may overexpress TNF-α upon activation of the TLR4/NF-κB pathway, resulting in epithelial damage and NEC induction.

BACKGROUND: Bowel ultrasound (US) is one of the methods used to enhance diagnostic accuracy of necrotizing enterocolitis (NEC) and its associated complications in premature newborns. AIM: To explore the diagnostic accuracy of bowel US in extremely low birth weight (ELBW) infants with NEC. METHODS: A single-center retrospective case-control study included 84 extremely low birth weight (ELBW) infants. The infants were divided into three groups: Group 1 –infants with NEC (n = 26); Group 2 –infants with feeding problems (n = 28); Group 3 –control group (n = 30). RESULTS: The specific bowel US findings in premature newborns with NEC (stage 3) included bowel wall thinning, complex (echogenic) ascites, and pneumoperitoneum, p < 0.05. The diagnostic effectiveness of these sonographic signs was 96.8% (sensitivity 75.0% and specificity 97.6%), p < 0.05. These findings with high specificity were associated with the need for surgical intervention, poor outcomes, or increased mortality. Stage 2 NEC which did not require surgery showed impaired differentiation of the bowel wall layers, absent or decreased bowel peristalsis, pneumatosis intestinalis, portal venous gas, or simple ascites, with a diagnostic accuracy of 82.9% (sensitivity 55.6%, specificity 91.4%, p < 0.05). CONCLUSIONS: Bowel US can be used as an adjunct to abdominal radiography to aid in the diagnosis of infants with suspected NEC by providing more detailed evaluation of the intestine. [ABSTRACT FROM AUTHOR]

Abstract Background Necrotizing enterocolitis (NEC) is a complex disease characterized by gastrointestinal inflammation and is one of the most common gastrointestinal emergencies in neonates. Mild to moderate cases of NEC require medical treatment, whereas severe cases necessitate surgical intervention. However, evidence for surgical indications is limited and largely dependent on the surgeon’s experience, leading to variability in outcomes. The primary aim of this study is to identify the risk factors for surgical intervention in neonatal NEC, which will aid in predicting the optimal timing for surgical intervention. Methods A literature search was conducted in PubMed, Embase, and Web of Science databases for case-control studies exploring risk factors for NEC requiring surgical intervention. The search was completed on June 16, 2024, and data analysis was performed using R Studio 4.3.2. Results 18 studies were included, comprising 1,104 cases in the surgery group and 1,686 in the medical treatment group. The meta-analysis indicated that high C-reactive protein (CRP) levels [OR = 1.42, 95% CI (1.01, 1.99)], lower gestational age [OR = 0.52, 95% CI (0.3, 0.91)], sepsis [OR = 2.94, 95% CI (1.87, 4.60)], coagulation disorder [OR = 3.45, 95% CI (1.81, 6.58)], lack of enteral feeding [OR = 3.18, 95% CI (1.37, 7.35)], and hyponatremia [OR = 1.22, 95% CI (1.07, 1.39)] are significant risk factors for surgical treatment in neonatal NEC. Conclusions High CRP levels, coagulation disorders, sepsis, lower gestational age, lack of enteral feeding, and hyponatremia are significant risk factors for surgical intervention in neonatal NEC. These findings have potential clinical significance for predicting surgical risk.

Nowadays, an urgent problem of pediatric gastroenterology is the study of inflammatory bowel diseases with very early onset (VEO-IBD), which have unique genetic, clinical, immunological, morphological, and laboratory sings. Early VEO-IBD is usually considered as monogenic disease, especially in combination with congenital immune defects, which leads to difficulties in diagnosis and management this pathology. Despite this, systematization of information about this group of nosological forms of IBD is practically not carried out. This article presents a review of the available information on etiological factors, course variants, and therapeutic options for VEO-IBD.

Background: Surgeons often encounter patients with intestinal failure due to inadequate intestinal length (“short bowel syndrome”/SBS). Treatment in these patients remains challenging and the process of physiologic adaptation may take years to complete, which frequently requires parenteral nutrition. We propose a proof-of-concept mechanical bowel elongation approach using a self-expanding prototype of an intestinal expansion sleeve (IES) for use in SBS to accelerate the adaptation process. Methods: IESs were deployed in the small intestines of Sprague Dawley rats. Mechanical characterization of these prototypes was performed. IES length–tension relationships and post-implant bowel expansion were measured ex vivo. Bowel histology before and after implantation was evaluated. Results: IES mechanical studies demonstrated decreasing expansive force with elongation. The deployment of IES devices produced an immediate 21 ± 8% increase in bowel length (p < 0.001, n = 11). Mechanical load testing data showed that the IESs expressed maximum expansive forces at 50% compression of the initial pre-contracted length. The small-intestine failure load in the rats was 1.88 ± 21 N. Intestinal histology post deployment of the IES showed significant expansive changes compared to unstretched bowel tissue. Conclusions: IES devices were scalable to the rat intestinal model in our study. The failure load of the rat small intestine was many times higher than the force exerted by the contraction of the IES. Histology demonstrated preservation of intestinal structure with some mucosal erosion. Future in vivo rat studies on distraction enterogenesis with this IES should help to define this organogenesis phenomenon.

Yunhan Zhang,1,&ast; Yuyun Chen,2,&ast; Jilin Lv,1 Xiao Xiang,1 Peiyao Wang,1 Wei Feng,1 Zhenhua Guo1 1Department of Neonatal Surgery, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, People’s Republic of China; 2Fujian Children’s Hospital, Fujian Branch of Shanghai Children’s Medical Center, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Zhenhua Guo, Department of neonatal surgery, Children’s Hospital of Chongqing Medical University, 20 Jinyu Road, Yubei District, Chongqing, 400025, People’s Republic of China, Tel +86-23-68370286, Email zhguo@cqmu.edu.cnBackground: This study aims to investigate the potential significance of mean platelet volume (MPV) and platelet distribution width (PDW) in predicting surgical neonatal necrotizing enterocolitis (NEC) and establish the correlation between MPV/PDW levels and the severity/prognosis of NEC.Methods: A retrospective study was conducted on a cohort of 372 patients diagnosed with NEC. The patients were categorized into two groups based on whether they underwent surgical therapy. Univariate /multivariate analysis were employed to compare the MPV and PDW between the two groups. Moreover, patients in surgical group were categorized into multiple subgroups based on intraoperative findings and postoperative prognosis, and the levels of MPV and PDW were compared among these subgroups.Results: Of the 372 patients, the operative group exhibited significantly higher levels of MPV and PDW than the nonoperative group (P < 0.05). Logistic regression analysis revealed that MPV (OR = 4.895, P < 0.001) and PDW (OR = 1.476, P < 0.001) independently associated with surgical NEC. The analysis of the receiver operating characteristic (ROC) curve revealed that the area under the curve (AUC) was 0.706 for MPV alone, with a cut-off value of 11.8 fL. Similarly, the AUC was 0.728 for PDW alone, with a cut-off value of 16%. However, when MPV and PDW were combined, the AUC increased to 0.906 for predicting surgical NEC. In accordance with the intraoperative findings, the levels of MPV and PDW were found to be higher in the large area necrosis group than in the partial or mild necrosis group (P < 0.01). Furthermore, the MPV and PDW values in the death group were significantly greater than those in the survival group (P =0.040, P =0.008).Conclusion: MPV and PDW may serve as potentially valuable indicators for determining the need for surgical intervention and predicting the prognosis of patients with NEC.Keywords: mean platelet volume, platelet distribution width, necrotizing enterocolitis, neonatal

Objective To investigate the mechanism of autoinducer-2(AI-2) in relieving intestinal injury in neonatal mouse model of necrotizing enterocolitis (NEC). Methods Thirty-six 7-day-old C57BL/6J mice were randomly divided into Control group (fed by mother mice), NEC group (NEC model induced by formula+lipopolysaccharide administration, hypoxia and cold stress), and NEC+AI-2 group (AI-2 solution added to the modeled formula milk), with 12 mice in each group.The body weight and survival rate of each group were recorded during the modeling period.In 3 d after modeling, the mice were euthanized, and the histopathological changes in the terminal ileum were observed using HE staining.The mRNA expression levels of aryl hydrocarbon receptor (AHR), cytochrome P450 1A1(CYP1A1), TNF-α, IL-6 and IL-22 in intestinal tissue were detected with RT-qPCR.The protein levels of AHR and CYP1A1 in intestinal tissues were measured with Western blotting.The contents of TNF-α, IL-6 and IL-22 in intestinal tissues were detected using enzyme-linked immunosorbent assay (ELISA). Results The survival rate of neonatal rats was significantly higher in the NEC+AI-2 group than the NEC group (91.7%vs 66.7%, P < 0.05).The NEC+AI-2 group had obviously lower intestinal pathological injury score (1.33±0.21 vs 2.67±0.33, P < 0.05), increased mRNA and protein levels of AHR and CYP1A1 in intestinal tissues (P < 0.05), decreased expression levels of pro-inflammatory factors TNF-α and IL-6 in intestinal tissues (P < 0.05), while increased expression level of anti-inflammatory factor IL-22(P < 0.05) when compared with the NEC group.Furthermore, the expression and activation of intestinal AHR were negatively correlated with the intestinal pathological injury score (P < 0.001). Conclusion AI-2 alleviates intestinal injury in neonatal mice with NEC by activating AHR to regulate inflammatory response.

Abstract Background Necrotizing enterocolitis (NEC) and intracranial hemorrhage are severe emergencies in the neonatal period. The two do not appear to be correlated. However, our report suggests that parenchymal brain hemorrhage in full-term newborns may put patients at risk for NEC by altering intestinal function through the brain-gut axis. Case presentation We present a case of spontaneous parenchymal cerebral hemorrhage in a full-term newborn who developed early-stage NEC on Day 15. Conclusions It is possible to consider brain parenchymal hemorrhage as a risk factor for the appearance of NEC. Clinicians should be highly cautious about NEC in infants who have experienced parenchymal hemorrhage. This article is the first to discuss the relationship between parenchymal hemorrhage and NEC in full-term newborns.

Background: Necrotizing enterocolitis (NEC) is a complex disease characterized by gastrointestinal inflammation and is one of the most common gastrointestinal emergencies in neonates. Mild to moderate cases of NEC require medical treatment, whereas severe cases necessitate surgical intervention. However, evidence for surgical indications is limited and largely dependent on the surgeon's experience, leading to variability in outcomes. The primary aim of this study is to identify the risk factors for surgical intervention in neonatal NEC, which will aid in predicting the optimal timing for surgical intervention. Methods: A literature search was conducted in PubMed, Embase, and Web of Science databases for case-control studies exploring risk factors for NEC requiring surgical intervention. The search was completed on June 16, 2024, and data analysis was performed using R Studio 4.3.2. Results: 18 studies were included, comprising 1,104 cases in the surgery group and 1,686 in the medical treatment group. The meta-analysis indicated that high C-reactive protein (CRP) levels [OR = 1.42, 95% CI (1.01, 1.99)], lower gestational age [OR = 0.52, 95% CI (0.3, 0.91)], sepsis [OR = 2.94, 95% CI (1.87, 4.60)], coagulation disorder [OR = 3.45, 95% CI (1.81, 6.58)], lack of enteral feeding [OR = 3.18, 95% CI (1.37, 7.35)], and hyponatremia [OR = 1.22, 95% CI (1.07, 1.39)] are significant risk factors for surgical treatment in neonatal NEC. Conclusions: High CRP levels, coagulation disorders, sepsis, lower gestational age, lack of enteral feeding, and hyponatremia are significant risk factors for surgical intervention in neonatal NEC. These findings have potential clinical significance for predicting surgical risk. [ABSTRACT FROM AUTHOR]

Introduction: Optimal oxygen saturation targets remain unknown for extremely preterm infants. Methods: Cohort analysis of eligible preterm infants born <29 weeks’ gestation admitted between 2011 and 2018 to centers submitting data to the Canadian Neonatal Network (CNN) database. Site questionnaires to determine saturation targets, alarm settings, and date of change, allowed assignation of centers to intermediate (88–93%) or high (90–95%) saturation targets. A 6-month washout period was applied to sites which switched targets during the study period. Our primary outcome was survival free of major morbidity. Secondary outcomes were death, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity, and evidence of brain injury during admission. Generalized estimating equations were applied to compensate for demographic differences and site practices. Results: There were 2,739 infants in the high (mean gestational age [GA] 26 ± 1.6 weeks) and 6,813 infants in the intermediate (mean GA 26.2 ± 1.6 weeks) saturation target group. Survival without morbidity was higher in the intermediate target group (adjusted odds ratio [aOR] 1.59; 95% CI: 1.04, 2.45). There was no difference in mortality between groups (aOR 0.81; 95% CI: 0.59, 1.11), in NEC, treated retinopathy, or brain injury. On subgroup analysis, restricting data to sites which switched targets during the study, intermediate saturation targets were associated with lower rates of BPD (aOR 0.45; 95% CI: 0.28, 0.72). Conclusion: For neonates <29 weeks’ gestation, intermediate saturation target was associated with higher odds of survival without major morbidity compared to higher oxygen saturation target. [ABSTRACT FROM AUTHOR]

We describe cases of three infants who developed acquired colonic atresia presumed secondary to significant systemic cardiovascular compromise and in the absence of necrotizing enterocolitis. An acquired colonic atresia may present as feed intolerance and should be investigated with a lower gastrointestinal contrast study. We would also recommend routine lower gastrointestinal contrast study prior to stoma closure in an infant with history of significant cardiovascular compromise, even in the absence of significant widespread colonic inflammation such as necrotizing enterocolitis. [ABSTRACT FROM AUTHOR]

Introduction: Necrotizing enterocolitis (NEC) is a severe gastrointestinal problem that predominantly affects premature babies. The aim of this retrospective study was to evaluate patients who underwent surgical treatment for NEC and newborns who initially recovered with medical treatment but later developed a stricture and required surgery. Materials and Methods: We analyzed patients diagnosed with NEC between January 2009 and December 2021. Our study included patients who developed strictures after initially receiving medical treatment for NEC and subsequently underwent surgery. Demographic findings, mother's age, gestational weeks, birth weight, type of birth, postnatal age at NEC diagnosis, pH, first C-reactive protein (CRP) after onset of symptoms, leukocytes, hemoglobin and thrombocytes at the onset of NEC, echocardiography results, age at surgery, blood values before surgery, surgery technique, and outcomes were retrospectively analyzed. Results: Out of 40 patients who underwent primary surgery for NEC during the newborn period, 6 patients underwent surgery after initially receiving medical treatment. The female-to-male ratio was 15/31, and the median gestational age was 29 weeks. The median mother's age was 30 years, and the median birth weight was 1097g. The median postnatal age at NEC onset was 6 days (range 2-39). Echocardiography was performed in 43 patients, with 6 showing normal results and 28 having congenital cardiac anomalies. The median surgery day for patients who underwent primary surgery for NEC was 19 days (range 2-90). Ileostomy was performed in 26 patients, colostomy in 8 patients, and ileostomy plus colostomy in 1 patient. Surgery was conducted in 6 out of 392 patients who developed post- NEC strictures after initial medical treatment. Comparison between post-NEC stricture patients and those who underwent surgery for NEC revealed significant differences only in the age at surgery (p=0.024). Conclusion: Patients who clinically experience NEC should be considered for the development of strictures, especially in cases of prolonged feeding intolerance, distention, gastric residual, and rectal bleeding. Therefore, close follow-up and multidisciplinary approaches are crucial, and contrast barium radiography should be the initial diagnostic step. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6 weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41–2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82–1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31–4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16–2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20–3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17–1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC. Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: • CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. • NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: • CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. • Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes. [ABSTRACT FROM AUTHOR]

While neonatal necrotising enterocolitis (NEC) is associated with high mortality rates in newborns, survivors can face long-term sequelae. However, the relationship between NEC and neurodevelopmental impairment (NDI) in preterm infants remains unclear. To explore the relationship between neonatal NEC and neurodevelopmental outcomes in preterm infants, we searched PubMed, EMBASE, and the Cochrane Library from their inception to February 2024 for relevant studies. Studies included were cohort or case–control studies reporting neurodevelopmental outcomes of NEC in preterm infants. Two independent investigators extracted data regarding brain damage and neurodevelopmental outcomes in these infants at a corrected age exceeding 12 months. Odds ratios (ORs) were pooled using a random effects model. We included 15 cohort studies and 18 case–control studies, encompassing 60,346 infants. Meta-analysis of unadjusted and adjusted ORs demonstrated a significant association between NEC and increased odds of NDI (OR 2.15, 95% CI 1.9–2.44; aOR 1.89, 95% CI 1.46–2.46). Regarding brain injury, pooled crude ORs indicated an association of NEC with severe intraventricular haemorrhage (IVH) (OR 1.42, 95% CI 1.06–1.92) and periventricular leucomalacia (PVL) (OR 2.55, 95% CI 1.76–3.69). When compared with conservatively treated NEC, surgical NEC potentially carries a higher risk of NDI (OR 1.78, 95% CI 1.09–2.93) and severe IVH (OR 1.57, 95% CI 1.20–2.06). However, the risk of PVL did not show a significant difference (OR 1.60, 95% CI 0.47–5.40). Conclusions: Our meta-analysis provides evidence suggesting an association between NEC and NDI. Additionally, the severity of intestinal lesions appears to correlate with a higher risk of NDI. Further high-quality studies with comprehensive adjustments for potential confounding factors are required to definitively establish whether the association with NDI is causal. What is Known: • NEC is a serious intestinal disease in the neonatal period with a high mortality rate, and surviving children may have digestive system sequelae. • Compared with non-NEC preterm infants, the reported incidences of brain injury and neurodevelopmental disorders in NEC preterm infants are not the same. What is New: • The risk of neonatal brain injury and neurodevelopmental disorders in preterm infants with NEC is higher than that in non-NEC infants, and the risk of NDI in surgical NEC infants is higher than that in the conservative treatment group. • NEC may increase the risk of motor, cognitive, language development delays, and attention deficits in children. [ABSTRACT FROM AUTHOR]

Reduction–oxidation (redox) chemistry plays a vital role in human homeostasis. These reactions play critical roles in energy generation, as part of innate immunity, and in the generation of secondary messengers with various functions such as cell cycle progression or the release of neurotransmitters. Despite this cornerstone role, if left unchecked, the body can overproduce reactive oxygen species (ROS) or reactive nitrogen species (RNS). When these overwhelm endogenous antioxidant systems, oxidative stress (OS) occurs. In neonates, OS has been associated with retinopathy of prematurity (ROP), leukomalacia, and bronchopulmonary dysplasia (BPD). Given its broad spectrum of effects, research has started to examine whether OS plays a role in necrotizing enterocolitis (NEC). In this paper, we will discuss the basics of redox chemistry and how the human body keeps these in check. We will then discuss what happens when these go awry, focusing mostly on NEC in neonates. [ABSTRACT FROM AUTHOR]

Objective Necrotizing enterocolitis (NEC) primarily affects preterm, especially small for gestational age (SGA), infants. This study was designed to (1) describe frequency and timing of NEC in SGA versus non-SGA infants and (2) assess whether NEC is independently associated with the severity of intrauterine growth failure. Study Design Retrospective cohort study of infants without severe congenital malformations born <33 weeks' gestational age (GA) carried out from 2009 to 2021. The frequency and time of NEC were compared between SGA and non-SGA infants. Multivariate logistic regression was used to assess whether NEC was independently associated with intrauterine growth restriction. Severe growth restriction was defined as birth weight Z -score < −2. Results Among 2,940 infants, the frequency of NEC was higher in SGA than in non-SGA infants (25/268 [9.3%] vs. 110/2,672 [4.1%], respectively, p < 0.001). NEC developed 2 weeks later in SGA than non-SGA infants. In multivariate analysis, the adjusted odds of NEC increased with extreme prematurity (<28 weeks' GA) and with severe but not moderate growth restriction. The adjusted odds of NEC increased with urinary tract infection or sepsis within a week prior to NEC, were lower in infants fed their mother's own milk until discharge, and did not change over five epochs. NEC was independently associated with antenatal steroid (ANS) exposure in infants with birth weight (BW) Z -score < 0. Conclusion NEC was more frequent in SGA than in non-SGA infants and developed 2 weeks later in SGA infants. NEC was independently associated with severe intrauterine growth failure and with ANS exposure in infants with BW Z -score < 0. Key Points We studied 2,940 infants <33 weeks' GA. We assessed NEC. NEC was more frequent in SGA infants. NEC occurred 2 weeks later in SGA infants. NEC was associated with severe growth restriction. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is one of the most devasting diseases affecting preterm neonates. However, despite a lot of research, NEC's pathogenesis remains unclear. It is known that the pathogenesis is a multifactorial process, including (1) a pathological microbiome with abnormal bacterial colonization, (2) an immature immune system, (3) enteral feeding, (3) an impairment of microcirculation, and (4) possibly ischemia-reperfusion damage to the intestine. Overall, the immaturity of the mucosal barrier and the increased expression of Toll-like receptor 4 (TLR4) within the intestinal epithelium result in an intestinal hyperinflammation reaction. Concurrently, a deficiency in counter-regulatory mediators can be seen. The sum of these processes can ultimately result in intestinal necrosis leading to very high mortality rates of the affected neonates. In the last decade no substantial advances in the treatment of NEC have been made. Thus, NEC animal models as well as in vitro models have been employed to better understand NEC's pathogenesis on a cellular and molecular level. This review will highlight the different models currently in use to study immunological aspects of NEC. [ABSTRACT FROM AUTHOR]