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Streptococcus gallolyticus subspecies pasteurianus is a subtype of Streptococcus bovis (S. bovis) that has become increasingly recognized as a sepsis-causing pathogen in neonates. It is well documented that S. bovis species have a predilection to both cardiac and gastrointestinal tissue, and in adult populations, isolating these organisms in the bloodstream often triggers further evaluation for co-morbid complications such as colon cancer or endocarditis. However, no such guidance currently exists in neonatal literature. We present a case of a preterm infant with S. gallolyticus subsp. pasteurianus bacteremia presenting as necrotizing enterocolitis (NEC) not previously described in the literature. Furthermore, through a complete diagnostic evaluation, including an echocardiogram, our patient was found to have the rare complication of endocarditis. [ABSTRACT FROM AUTHOR]

Les infections bactériennes graves ont une incidence plus élevée dans la période néonatale qu'à tout autre âge pédiatrique et leur gravité est accrue en l'absence de diagnostic et de traitement précoces. L'incidence est encore plus importante chez les prématurés que chez les nouveau-nés à terme. Les signes cliniques induits sont peu spécifiques et parfois insignifiants, et les biomarqueurs sont peu performants au cours des 24 premières heures de l'infection. Pendant des décennies, cette situation a conduit à traiter trop d'enfants, pendant de longues périodes, avec des antibiotiques à large spectre. Aujourd'hui, le défi consiste à prescrire des traitements ciblés en identifiant les nouveau-nés réellement infectés. Au cours de ces dix dernières années, nous avons assisté à des changements de paradigme majeurs dont il est essentiel de tenir compte. En effet, la prise de conscience croissante de l'impact écologique de l'antibiothérapie précoce, notamment sa contribution à la résistance de certaines bactéries aux antibiotiques, implique de choisir l'antibiotique à spectre le plus étroit et des durées de traitement en adéquation réelle avec les signes d'infection. Parmi les tests biologiques, les plus importants sont les hémocultures. Au moins une hémoculture, réalisée dans des conditions d'asepsie, de volume suffisant (1 à 2 mL) et avec des flacons pédiatriques, doit être effectuée dès que la décision de traiter est prise, avant de débuter toute antibiothérapie. Les bactéries responsables des infections bactériennes néonatales précoces (IBPN) n'ont pas évolué de manière significative au cours des dernières années et restent dominées par les Streptocoques du groupe B et Escherichia coli , qui sont les principales cibles du traitement. Le SGB est largement prédominant chez les enfants nés à terme, mais la proportion d'infections dues à E. coli augmente avec la prématurité. Severe bacterial infections have a higher incidence in the neonatal period than at any other pediatric age. Incidence is even higher in premature babies than in term newborns, and severity is increased in the absence of early diagnosis and treatment. By contrast, clinical signs are nonspecific and sometimes trivial, and biomarkers perform poorly during the first 24 hours of infection. For decades, this has led to having too many children treated for extended periods with broad-spectrum antibiotics. Today, the challenge is to prescribe antibiotics in a targeted way, by identifying truly infected newborns. Over the last ten years, major paradigm shifts have occurred and should be taken into account, as a result of growing awareness of the ecological impact of early antibiotic therapy, notably antibiotic resistance, by choosing the narrowest spectrum antibiotic and stopping antibiotic therapy as soon as the diagnosis of infection has been reasonably ruled out. Among the biological tests, the most important are blood cultures. At least one blood culture, taken under aseptic conditions, of sufficient volume (1 to 2 mL), and using pediatric bottles must be taken as soon as the decision to treat has been made, before starting any antibiotic therapy. The bacteria responsible for early-onset bacterial neonatal infections (EBNI) have not changed significantly over recent years and remain dominated by Group B streptococcus and Escherichia coli , which are the main targets of treatment. GBS is largely predominant in full-term infants, but the proportion of infections due to E. coli increases with prematurity. [ABSTRACT FROM AUTHOR]

Early prediction of surgical necrotizing enterocolitis (sNEC) in preterm infants is important. However, owing to the complexity of the disease, identifying infants with NEC at a high risk for surgical intervention is difficult. We developed a machine learning (ML) algorithm to predict sNEC using perinatal factors obtained from the national cohort registry of very low birth weight (VLBW) infants. Data were collected from the medical records of 16,385 VLBW infants registered in the Korean Neonatal Network (KNN). Infants who underwent surgical intervention were identified with sNEC, and infants who received medical treatment, with medical NEC (mNEC). We used 38 variables, including maternal, prenatal, and postnatal factors that were obtained within 1 week of birth, for training. A total of 1085 patients had NEC (654 with sNEC and 431 with mNEC). VLBW infants showed a higher incidence of sNEC at a lower gestational age (GA) (p < 0.001). Our proposed ensemble model showed an area under the receiver operating characteristic curve of 0.721 for sNEC prediction. Conclusion: Proposed ensemble model may help predict which infants with NEC are likely to develop sNEC. Through early prediction and prompt intervention, prognosis of sNEC may be improved. What is Known: • Machine learning (ML)-based techniques have been employed in NEC research for prediction, diagnosis, and prognosis, with promising outcomes. • While most studies have utilized abdominal radiographs and clinical manifestations of NEC as data sources, and have demonstrated their usefulness, they may prove weak in terms of early prediction. What is New: • We analyzed the perinatal factors of VLBW infants acquired within 7 days of birth and used ML-based analysis to identify which infants with NEC are vulnerable to clinical deterioration and at high risk for surgical intervention using nationwide cohort data. [ABSTRACT FROM AUTHOR]

Background: Investigating the trend of changes in the occurrence of necrotizing enterocolitis (NEC) in preterm infants during 9 years and analyzing the risk factors of NEC with the purpose of providing reference for clinical diagnosis and treatment of NEC. Methods: Clinical data of NEC in preterm infants with Bell's stage ≥ II from January 2013 to December 2021 in the Neonatology Department of the Third Affiliated Hospital of Zunyi Medical University was retrospectively analyzed. Trends in the occurrence of NEC in preterm infants were analyzed by the trend chi-square test. Subsequently, the general data (sex, gestational age, singleton or multiple births, birth weight, serum albumin, alkaline phosphatase, sepsis, blood transfusion, mechanical ventilation, RDS, arterial catheterization) and perinatal data (intrauterine distress, turbid amniotic fluid, premature rupture of membranes, mode of delivery, fetal heart abnormalities, diabetes mellitus) were collected; then, the risk factors for NEC were analyzed by univariate and multivariate logistic-regression analysis. Results: In the past 9 years, 77 cases of NEC occurred, with the incidence rate of 1.95%, and the incidence of NEC in preterm infants has been increasing year by year (P < 0.05). The results of univariate analysis showed that the morbidity of NEC in preterm infants was associated with premature rupture of membranes, blood transfusion, sepsis, and the of serum albumin (P < 0.05). Multivariate logistic regression analysis revealed that blood transfusion (OR = 2.232, 95% CI: 1.012–4.923) and sepsis (OR = 0.899, 95% CI: 0.809–3.915) were independent risk factors of NEC in preterm infants, while high serum albumin (OR = 0.899, 95% CI: 0.809–3.915) was an independent protective factor of NEC in preterm infants. Conclusion: The morbidity of NEC is gradually increasing. Inhibition of infection and limitation of blood transfusion are effective measures to reduce the occurrence of NEC. Meanwhile, high serum albumin is a protective factor for NEC. [ABSTRACT FROM AUTHOR]

Introduction: The effect of the pandemic restrictions in the NICUs is not well studied. Necrotizing enterocolitis (NEC) is characterized by intestinal inflammation and bacterial invasion. This study aimed to investigate whether the incidence of NEC has changed during the COVID-19 pandemic in Sweden and whether it was associated with a change in the frequency of extremely preterm births. Methods: Data were retrieved from the Swedish Neonatal Quality Register (SNQ) for infants registered between January 2017 and December 2021 born below a gestational age of 35 weeks. The registry completeness is 98–99%. The diagnosis of NEC was the primary outcome. Generalized linear model analysis was used to calculate the risk ratio for NEC. Results: Totally 13,239 infants were included. 235 (1.8%) infants developed NEC, out of which 91 required surgical treatment. 8,967 infants were born before COVID-19 pandemic and 4,272 during. Median gestational age at birth was 32.8 weeks in both periods. The incidence of NEC was significantly lower during COVID-19 pandemic compared to the prior period (1.43 vs. 1.94%, p 0.037), but not the incidence of surgical NEC. The crude risk ratio of developing NEC during COVID-19 pandemic was 0.74 (95% CI: 0.55–0.98). The incidence of late-onset sepsis with positive culture was also declined during COVID-19 (3.21 vs. 4.15%, p value 0.008). Conclusion: While we found significant reduction in the incidence of NEC and culture-positive late-onset sepsis during the COVID-19 pandemic, the number of extremely preterm births was unchanged. [ABSTRACT FROM AUTHOR]

Background: To determine risk factors for surgical site infection (SSI) in infants after stoma closure, to identify at-risk patients, plan timing of surgery, and implement SSI-reduction strategies. Patients and Methods: A single center retrospective comparison study of all children less than one year of age who underwent enterostomy closure (2018–2020) with SSI diagnosed through a prospective surveillance program, using criteria from Public Health England (PHE). Demographics and risk factors, types of SSI, systemic sepsis, mortality and length of stay were compared between SSI and non-SSI. Significant factors associated with SSI were analyzed in a multivariate binomial logistic regression model. Results: Eighty-nine stoma closures were performed, most commonly for necrotizing enterocolitis (NEC) and anorectal malformation. Fourteen had SSI (16%): 12 superficial and two deep; three developed systemic sepsis, but no 30-day mortality. Surgical site infection was associated with NEC (12/14 vs. 32/75; p = 0.003), younger age (median 76 vs. 89 days; p = 0.014), lower corrected gestation (cutoff: 39 weeks gestation; 11/14 vs. 27/75; p = 0.004) and lower weight (cutoff: 2.2 kg; 7/14 vs. 16/75; p = 0.032), compared with non-SSI. After correcting for age, gestation, and weight, logistic regression showed NEC was an independent predictor for SSI (odds ratio [OR], 12; 95% confidence interval [CI],1.2–125). The at-risk cohort (n = 56; 63%) had seven-fold increased risk of SSI and four-fold longer hospital stay, which may be the target for SSI-reduction strategies. Conclusions: Necrotizing enterocolitis-related stoma closure is at increased risk for SSI. Considerations for delaying stoma closure until achieving 39 weeks gestation or 2.2 kg in weight may further reduce SSI. Targeting SSI-reduction strategies using these criteria may improve resource-rationalization. [ABSTRACT FROM AUTHOR]

Human milk contains extracellular vesicles (HMEVs). Pre‐clinical models suggest that HMEVs may enhance intestinal function and limit inflammation; however, it is unknown if HMEVs or their cargo survive neonatal human digestion. This limits the ability to leverage HMEV cargo as additives to infant nutrition or as therapeutics. This study aimed to develop an EV isolation pipeline from small volumes of human milk and neonatal intestinal contents after milk feeding (digesta) to address the hypothesis that HMEVs survive in vivo neonatal digestion to be taken up intestinal epithelial cells (IECs). Digesta was collected from nasoduodenal sampling tubes or ostomies. EVs were isolated from raw and pasteurized human milk and digesta by density‐gradient ultracentrifugation following two‐step skimming, acid precipitation of caseins, and multi‐step filtration. EVs were validated by electron microscopy, western blotting, nanoparticle tracking analysis, resistive pulse sensing, and super‐resolution microscopy. EV uptake was tested in human neonatal enteroids. HMEVs and digesta EVs (dEVs) show typical EV morphology and are enriched in CD81 and CD9, but depleted of β‐casein and lactalbumin. HMEV and some dEV fractions contain mammary gland‐derived protein BTN1A1. Neonatal human enteroids rapidly take up dEVs in part via clathrin‐mediated endocytosis. Our data suggest that EVs can be isolated from digestive fluid and that these dEVs can be absorbed by IECs. [ABSTRACT FROM AUTHOR]

The integrity of the intestinal mucus barrier is crucial for human health, as it serves as the body's first line of defense against pathogens. However, postnatal development of the mucus barrier and interactions between maturity and its ability to adapt to external challenges in neonatal infants remain unclear. In this study, we unveil a distinct developmental trajectory of the mucus barrier in preterm piglets, leading to enhanced mucus microstructure and reduced mucus diffusivity compared to term piglets. Notably, we found that necrotizing enterocolitis (NEC) is associated with increased mucus diffusivity of our large pathogen model compound, establishing a direct link between the NEC condition and the mucus barrier. Furthermore, we observed that addition of sodium decanoate had varying effects on mucus diffusivity depending on maturity and health state of the piglets. These findings demonstrate that regulatory mechanisms governing the neonatal mucosal barrier are highly complex and are influenced by age, maturity, and health conditions. Therefore, our results highlight the need for specific therapeutic strategies tailored to each neonatal period to ensure optimal gut health. [ABSTRACT FROM AUTHOR]

Purpose: To assess the predictive value of radiomics for surgical decision-making in neonatal necrotizing enterocolitis (NEC) when abdominal radiographs (ARs) do not suggest an absolute surgical indication for free pneumoperitoneum. Methods: In this retrospective study, we finally included 171 newborns with NEC and obtained their ARs and clinical data. The dataset was randomly divided into a training set (70%) and a test set (30%). We developed machine learning models for predicting surgical treatment using clinical features and radiomic features, respectively, and combined these features to build joint models. We assessed predictive performance of the different models by receiver operating characteristic curve (ROC) analysis and compared area under curve (AUC) using the Delong test. Decision curve analysis (DCA) was used to assess the potential clinical benefit of the models to patients. Results: There was no significant difference in AUC between the clinical model and the four radiomic models (P > 0.05). The XGBoost joint model had better predictive efficacy and stability (AUC, training set: 0.988, test set: 0.959). Its AUC in the test set was significantly higher than that of the clinical model (P < 0.05). DCA showed that the XGBoost joint model achieved higher net clinical benefit compared to the clinical model in the threshold probability range (0.2–0.6). Conclusion: Radiomic features based on AR are objective and reproducible. The joint model combining radiomic features and clinical signs has good surgical predictive efficacy and may be an important method to help primary neonatal surgeons assess the surgical risk of NEC neonates. [ABSTRACT FROM AUTHOR]

Chorioamnionitis is a risk factor for necrotizing enterocolitis (NEC). Ureaplasma parvum (UP) is clinically the most isolated microorganism in chorioamnionitis, but its pathogenicity remains debated. Chorioamnionitis is associated with ileal barrier changes, but colonic barrier alterations, including those of the mucus barrier, remain under-investigated, despite their importance in NEC pathophysiology. Therefore, in this study, the hypothesis that antenatal UP exposure disturbs colonic mucus barrier integrity, thereby potentially contributing to NEC pathogenesis, was investigated. In an established ovine chorioamnionitis model, lambs were intra-amniotically exposed to UP or saline for 7 d from 122 to 129 d gestational age. Thereafter, colonic mucus layer thickness and functional integrity, underlying mechanisms, including endoplasmic reticulum (ER) stress and redox status, and cellular morphology by transmission electron microscopy were studied. The clinical significance of the experimental findings was verified by examining colon samples from NEC patients and controls. UP-exposed lambs have a thicker but dysfunctional colonic mucus layer in which bacteria-sized beads reach the intestinal epithelium, indicating undesired bacterial contact with the epithelium. This is paralleled by disturbed goblet cell MUC2 folding, pro-apoptotic ER stress and signs of mitochondrial dysfunction in the colonic epithelium. Importantly, the colonic epithelium from human NEC patients showed comparable mitochondrial aberrations, indicating that NEC-associated intestinal barrier injury already occurs during chorioamnionitis. This study underlines the pathogenic potential of UP during pregnancy; it demonstrates that antenatal UP infection leads to severe colonic mucus barrier deficits, providing a mechanistic link between antenatal infections and postnatal NEC development. [ABSTRACT FROM AUTHOR]

Background and aim: 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. Materials and methods: 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 2 ml/kg EVOO with high phenolic content by gavage twice a day for 3 days. 3 cm of bowel including terminal ileum, cecum, and proximal colon was excised. Results: 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). Conclusion: Phenol-rich EVOO prevents intestinal damage caused by NEC by inhibiting inflammation, oxidative stress, apoptosis. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Introduction: Necrotizing enterocolitis (NEC) poses a significant threat to preterm infants, with nonspecific early manifestations complicating timely diagnosis. Therefore, this study aimed to develop a novel scoring system for early diagnosis of NEC, incorporating clinical and laboratory data with urinary caveolin-1 levels. Material and methods: A single-center prospective cohort study was conducted at a tertiary hospital in East Java, Indonesia. NEC diagnosis was established by Bell's criteria and proven gut dysbiosis. Urinary levels of claudin-2, caveolin-1, and epidermal growth factor (EGF) were assessed as potential indicators of tight junction disruption. The selected urine biomarker cutoff value was determined using symbolic classification analysis and combined with clinical and laboratory parameters from Bell's criteria to create an NEC scoring system, validated with the Aiken index. Sensitivity and specificity analyses were performed. Results: Thirty-four neonates, comprising NEC, preterm non-NEC, and term infants, were included. qPCR analysis highlighted elevated Klebsiella, Lactobacillus, Clostridium, and Bacteroides levels in NEC patients, indicating a gut dysbiosis trend. Among 3 biomarkers, caveolin-1 ≥ 17.81 ng/dl on day 3 demonstrated 72.86% negative predictive value and 87.50% positive predictive value. The combined scoring system which comprised abdominal cellulitis, distension, radiology, advanced resuscitation at birth, prematurity or low birthweight, platelet count, sepsis, orogastric retention, metabolic acidosis and caveolin-1 findings exhibited an AUC of 0.922 (95% CI: 0.81-1.00, p < 0.001), with ≥ 1.81 as the cutoff, offering 93% sensitivity and 94% specificity. Conclusions: Urine caveolin-1 on day 3 signifies enterocyte tight junction damage and the acute phase of NEC in premature infants. The proposed scoring system demonstrates good performance in predicting NEC incidence in preterm infants. [ABSTRACT FROM AUTHOR]

Multiple studies have documented the safety of intestinal anastomosis after resection for necrotizing enterocolitis (NEC). We sought to evaluate a large population of infants with surgical NEC and assess outcomes after primary anastomosis versus enterostomy. The Pediatric Health Information System database was used to identify infants with Bell Stage 3 NEC who underwent an intestinal resection for acute disease between 2016 and 2021. Demographics and preoperative physiology were assessed, and nutritional, infectious, and surgical outcomes were analyzed. Two hundred twenty-two infants at 38 children's hospitals were included. Thirty-five (15.8%) were managed with a primary anastomosis. Among infants who underwent a resection within 10 d of their first operative intervention and survived for at least 3 d, a primary anastomosis was used in 26 (13.7%). These patients were older but had similar weight and physiological status at the time of resection as those managed with an enterostomy. The incidence of wound and infectious complications, duration of parenteral nutrition and length of stay were similar after anastomosis or enterostomy. In a large, geographically heterogenous population of infants with NEC, only 15.8% were managed with a primary anastomosis after intestinal resection. Survivors who underwent resection within 10 d were demographically and physiologically comparable to those who underwent enterostomy and had similar surgical outcomes. While there are clearly indications for enterostomy in some infants with NEC, these data confirm the conclusions of smaller, single-center studies that a primary anastomosis should be considered more frequently. [ABSTRACT FROM AUTHOR]

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

Background: Necrotizing enterocolitis (NEC) is a major cause of morbidity in premature infants. However, effective treatment options for NEC are currently lacking. Purpose: This study aimed to determine the optimal dose of intraperitoneally administered bone marrow-derived mesenchymal stem cells (BM-MSCs) and investigate the therapeutic potential of orally administered BM-MSCs in NEC. Methods: Neonatal mice were fed maternal breast milk for the first 2 days of life. On day 3, the neonatal mice were randomly divided into control, negative control, and BM-MSC-treated groups. Lipopolysaccharide (LPS) was administered for 3 days, and cold stress (4°C, 10 minutes) was applied 3 times a day to induce NEC. High-dose (1x106 cells) or low-dose (1x105 cells) BM-MSCs were administered intraperitoneally 1 or 3 times between days 6 and 8 to treat the NEC. The orally administered group received a low dose of BM-MSCs on day 6. Fur thermore, except for the control group, intraepithelial cells (IECs) of the small intestine of neonatal mice were treated with LPS and exposed to 5% O2/95% N2 hypoxic stress for 2 hours. Thereafter, each was treated with BM-MSCs. Results: Tissue injury, apoptosis, and inflammatory marker levels were significantly reduced after BM-MSC administration. Oral administration was as effective as intraperitoneal administration, even at a low dose (1x105 cells) of BM-MSCs. The efficacy of high (1x106 cells) or multiple divided doses of BM-MSCs did not differ from that of low-dose treatment. Significantly improved wound healing was observed after BM-MSC administration to injured IECs. Conclusion: The oral administration of BM-MSCs is a promising treatment option for NEC in infants. Further human studies of BM-MSCs are necessary to determine the optimal dose required to achieve safe and effective outcomes. [ABSTRACT FROM AUTHOR]

Objective To explore the current status and hotpots of neonatal necrotizing enterocolitis (NEC) at home and abroad through bibliometric analysis. Methods The Chinese and English literature items were retrieved from the journal databases of China National Knowledge Infrastructure (CNKI), PubMed, Wan- fang and Web of Science (WOS). The retrieval period started from January 1, 1990 to June 20, 2023. Statistical analyses and comparisons were performed in terms of time distribution, journal distribution, country distribution and keyword of the included literature. Microsoft Excel and VOS viewer were utilized for integrating search re- sults. Results A total of 12 078 literature items related to NEC were included, including 1 060 Chinese and 11 018 English literature items. Among the English literature items, the United States had published the most literature; Chinese Journal of Pediatric Surgery and Pediatric Research were the journals with the highest num- ber of articles published in NEC journals at home and abroad respectively. In Chinese literature, the frequently appearing keywords were divided into three groups of "necrotizing enterocolitis" "risk factors" and "diagnosis and treatment". In English literature, the frequently appearing keywords were divided into four groups of "necro- tizing enterocolitis", "diagnosis", "neonatal outcome" and "treatment". Domestic and foreign research hotpots were generally consistent. Citation analysis indicated that, in recent 5 years, domestic and foreign researches fo- cused upon three aspects: "clinical value of laboratory parameters in NEC", "etiology of NEC" and "epidemiol- ogy and pathophysiology of NEC". Conclusions With some development prospect, NEC researches have at- tracted widespread attention both at home and abroad, and is a clinical difficulty and resarch hotpot. Chinese scholas should carry ont in-depth research to further improve the quality of NEC research in China. [ABSTRACT FROM AUTHOR]

BACKGROUND: We aim to determine clinical risk factors for postoperative complications in preterm infants with surgical necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP). METHODS: A retrospective cohort study of preterm infants with surgical NEC or SIP to compare clinical factors between those with and without postoperative complications. RESULTS: 78/109 (71.5%) infants had any complication following surgical NEC. Adhesions (20/35, 57.1%) and wound infection (6/35, 17.1%) were the most common single surgical complications. Patients with a single surgical complication (35/66, 53%) were significantly less likely to be exposed to antenatal steroids, more frequently had a jejunostomy, needed a central line longer, and had a longer length of stay than those without any surgical complication. Infants with > 1 surgical complication (43/71, 60.5%) included mainly females, and had AKI more frequently at NEC onset, lower weight z-scores and lower weight for length z- scores at 36 weeks PMA than those without any complications. On multinomial logistic regression, antenatal steroids exposure (OR 0.23 [CI 0.06, 0.84]; p = 0.027) was independently associated with lower risk and jejunostomy 4.81 (1.29, 17.9) was independently associated with higher risk of developing a single complication. AKI following disease onset (OR 5.33 (1.38, 20.6), P = 0.015) was independently associated with > 1 complication in surgical NEC/SIP infants. CONCLUSION: Infants with postoperative complications following surgical NEC were more likely to be female, have additional morbidities, and demonstrate growth failure at 36 weeks PMA than those without surgical complications. There was no difference in mortality between those with and without surgical complications. [ABSTRACT FROM AUTHOR]

Background Clostridium neonatale was isolated during an outbreak of neonatal necrotizing enterocolitis (NEC) in 2002. C. neonatale was validated as a new species within the genus Clostridium sensu stricto in 2018. In the present study, we evaluated the antimicrobial susceptibility, genetic determinants of resistance, and phylogenetic relationships of a collection of clinical isolates of C. neonatale. Methods C. neonatale strains (n = 68) were isolated from the stools of preterm neonates who either developed NEC or were asymptomatic carriers of C. neonatale in different periods and in different hospitals. Antimicrobial susceptibility was determined by the disc diffusion method. The MICs of clindamycin, cefotaxime and tetracycline were determined. Genetic determinants of resistance were screened by PCR (n = 68) and WGS (n = 35). Genotyping of the isolates was performed by MLST. Results Antimicrobial resistance was found to clindamycin (n = 24; 35%), cefotaxime (n = 7; 10%) and tetracycline (n = 1; 1%). One clindamycin-resistant isolate carried erm (B) by PCR. In addition, one isolate carrying tet (M) was tetracycline resistant (MIC = 16 mg/L) and 44 isolates carrying either tet (O), tet (32) or tet (M) were tetracycline susceptible (MICs < 16 mg/L). MLST showed that ST2 and ST15 were significantly associated with tet (32) (P < 0.0001) and tet (O) (P < 0.0001), respectively. From WGS, we identified aph(3′)-IIa and bla TEM-116 genes and a bla CBP-1-like gene. Conclusions C. neonatale is susceptible to anti-anaerobic molecules but resistant to clindamycin, cefotaxime and tetracycline. Genes encoding tetracycline ribosomal protection, macrolide-lincosamide-streptogramin B rRNA methyltransferase, aminoglycoside 3 '- phosphotransferase and β-lactamases have been identified in genomic regions flanked by mobile genetic elements. [ABSTRACT FROM AUTHOR]

Objective To summarize the clinical features of intestinal stricture after conservative measures for neonatal necrotizing enterocolitis (NEC) and compare the outcomes of single and multiple stricture groups. Methods From January 2014 to December 2020, retrospective review was performed for the relevant clinical data of 67 neonates operated for post-NEC intestinal strictures. Basic information, NEC onset time, Bell stage, radiographic studies, surgical approach postoperative complications were recorded. Then they were assigned into two groups of single stricture and multiple strictures and the prognosis between two groups were compared. Results Positive rate of preoperative contrast enema was 83.9%.Primary end-to-end anastomosis (n=60) and enterostomy (n=7) were performed at a median of 39 days after NEC with a median weight of 2.53 kg. Multiple strictures were detected in 33 neonates (49.3%) while the remainders had only 1 stricture. There were a total of 123 strictures. Except for 1 stricture spanning small intestine and colon (from terminal ileum to sigmoid colon), 65 strictures were present in small intestine, including terminal ileum (n=37) and colon (n=57)(ascending colon, n=27). Two cases underwent enterostomy later due to disease deterioration and 1 died at Month 2 after discharge. Another child accepted enterostomal closure 12 months later. Complications included intestinal prolapse (n=2) and adhesive intestinal obstruction (n=4). The long-term survival rate of intestinal strictures after conservative measures was 95.5%(64/67). Length of bowel resection (P < 0.001) and operative duration (P=0.008) were significantly longer in multiple-stricture group than those in single-stricture group. However, no significant inter-group difference existed in time to complete enteral feeding (P=0.862) or postoperative complications (P=0.347). Conclusions Despite a low incidence of intestinal strictures after conservative measures for NEC, multiple strictures account for a large proportion. The strictures occur predominantly in terminal ileum and colon. Contrast enema is valuable for preoperative examination. All intestinal segments should be carefully explored intraoperatively. And multiple strictures have no effect upon postoperative recovery and outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Necrotizing enterocolitis (NEC) is a severe intestinal disease primarily affecting premature infants, marked by impaired epithelial regeneration. Breastfed infants are less susceptible to NEC than formula-fed ones, and human milk oligosaccharides (HMO) found in breast milk have prebiotic properties that can protect against NEC. However, it is unclear how HMOs influence intestinal epithelium regeneration in relation to the gut microbiota. Methods: Broad-spectrum antibiotics were administered to pregnant dams to reduce the microbiota in offspring. NEC was induced through administration of hyperosmolar formula, lipopolysaccharide, and hypoxia from postnatal days (p) 5–9. Intestinal epithelial organoids were derived from p9 mice. HMOs were isolated from human donor breast milk and then solubilized in the formula for each feed or culture media for organoids. Results: HMOs did not alter the microbiota profile in the presence of a normal or reduced microbiota. In the reduced microbiota, HMO treatment decreased NEC intestinal injury, and increased proliferation and stem cell activity. Additionally, in the complete absence of the microbiota, HMOs stimulated intestinal organoid growth. Conclusion: This study demonstrates that HMOs promoted intestinal epithelial regeneration independent of the gut microbiota. These findings provide further insight into the various benefits HMOs may have in the protection against NEC. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature infants. Evidence indicates that bile acid homeostasis is disrupted during NEC: ileal bile acid levels are elevated in animals with experimental NEC, as is expression of the apical sodium-dependent bile acid transporter (Asbt). In addition, bile acids, which are synthesized in the liver, are extensively modified by the gut microbiome, including via the conversion of primary bile acids to more cytotoxic secondary forms. We hypothesized that the addition of bile acid-modifying bacteria would increase susceptibility to NEC in a neonatal rat model of the disease. The secondary bile acid-producing species Clostridium scindens exacerbated both incidence and severity of NEC. C. scindens upregulated the bile acid transporter Asbt and increased levels of intraenterocyte bile acids. Treatment with C. scindens also altered bile acid profiles and increased hydrophobicity of the ileal intracellular bile acid pool. The ability of C. scindens to enhance NEC requires bile acids, as pharmacological sequestration of ileal bile acids protects animals from developing disease. These findings indicate that bile acid-modifying bacteria can contribute to NEC pathology and provide additional evidence for the role of bile acids in the pathophysiology of experimental NEC. NEW & NOTEWORTHY: Necrotizing enterocolitis (NEC), a life-threatening gastrointestinal emergency in premature infants, is characterized by dysregulation of bile acid homeostasis. We demonstrate that administering the secondary bile acid-producing bacterium Clostridium scindens enhances NEC in a neonatal rat model of the disease. C. scindens-enhanced NEC is dependent on bile acids and driven by upregulation of the ileal bile acid transporter Asbt. This is the first report of bile acid-modifying bacteria exacerbating experimental NEC pathology. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is a critical gastrointestinal emergency with substantial morbidity and mortality risks, especially for very low-birth-weight (VLBW) infants, and unclear multifactorial pathophysiology. Whether common treatments for VLBW infants increase the NEC risk remains controversial. Indomethacin (utilized for patent ductus arteriosus) offers benefits but is concerning because of its vasoconstrictive impact on NEC susceptibility. Similarly, corticosteroids used to treat bronchopulmonary dysplasia may increase vulnerability to NEC by compromising immunity and altering the mesenteric blood flow. Histamine-2 receptor blockers (used to treat gastric bleeding) may inadvertently promote NEC by affecting bacterial colonization and translocation. Doxapram (used to treat apnea) poses a risk of gastrointestinal disturbance via gastric acid hypersecretion and circulatory changes. Glycerin enemas aid meconium evacuation but disrupt microbial equilibrium and trigger stress-related effects associated with the NEC risk. Prolonged antibiotic use may unintentionally increase the NEC risk. Blood transfusions for anemia can promote NEC via interactions between the immune response and ischemia–reperfusion injury. Probiotics for NEC prevention are associated with concerns regarding sepsis and bacteremia. Amid conflicting evidence, this review unveils NEC risk factors related to treatments for VLBW infants, offers a comprehensive overview of the current research, and guides personalized management strategies, thereby elucidating this clinical dilemma. [ABSTRACT FROM AUTHOR]

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

Abstract Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among neonates and low birth weight children in the United States. Current treatment options, such as antibiotics and intestinal resections, often result in complications related to pediatric nutrition and development. This systematic review aimed to identify alternative dietary bioactive compounds that have shown promising outcomes in ameliorating NEC in vivo studies conducted within the past six years. Following PRISMA guidelines and registering in PROSPERO (CRD42023330617), we conducted a comprehensive search of PubMed, Scopus, and Web of Science. Our analysis included 19 studies, predominantly involving in vivo models of rats (Rattus norvegicus) and mice (Mus musculus). The findings revealed that various types of compounds have demonstrated successful amelioration of NEC symptoms. Specifically, six studies employed plant phenolics, seven utilized plant metabolites/cytotoxic chemicals, three explored the efficacy of vitamins, and three investigated the potential of whole food extracts. Importantly, all administered compounds exhibited positive effects in mitigating the disease. These results highlight the potential of natural cytotoxic chemicals derived from medicinal plants in identifying and implementing powerful alternative drugs and therapies for NEC. Such approaches have the capacity to impact multiple pathways involved in the development and progression of NEC symptoms. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is the most common surgical disease in the neonatal period with a high mortality rate. To date, there is no consensus on the indications for surgery in the absence of pneumoperitoneum. This study aimed to determine the indications for surgery in pre-term infants with NEC and their mortality. Methods: We conducted a descriptive, observational, cross-sectional, and retrospective study including pre-term infants with NEC from two perinatal hospitals in Toluca, Mexico, between 2017 and 2022. Descriptive and inferential statistics and group comparisons were performed using Fisher and Kruskal-Wallis tests. Results: Of 236 patients with NEC, 52 (22%) required surgery; we analyzed 42 cases with complete clinical records. The indications for surgery were divided into (a) clinical deterioration (33.3%); (b) radiographic findings (31%); (c) laboratory alterations (19%); and (d) positive paracentesis (16.7%). The group of radiographic findings underwent surgery later, up to 2 days after the other groups. The mortality rate of surgical NEC was 42.9%. Conclusions: The most common indication for surgery in pre-term infants with NEC was clinical worsening despite optimal medical management; radiographic findings were the indication associated with the highest mortality. Laboratory abnormalities and positive paracentesis were the indications with the best outcomes but the least used. [ABSTRACT FROM AUTHOR]

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

OBJECTIVE Limited data exist comparing indomethacin and ibuprofen for the treatment of patent ductus arteriosus (PDA). The objective was to compare the safety and efficacy of indomethacin and ibuprofen for treatment of PDA closure. METHODS This single-center, pre-test/post-test quasi-experiment included preterm infants admitted to the neonatal intensive care unit who received indomethacin (July 1, 2013-September 30, 2015) or ibuprofen (December 1, 2015-July 31, 2019) for PDA. Patients were excluded if they were thrombocytopenic, had existing kidney injury, unresolved intraventricular hemorrhage (IVH) or necrotizing enterocolitis (NEC) at treatment initiation. Data were obtained from the electronic health record. Study outcomes were complete PDA closure, degree of PDA closure, resolution of symptoms, and new-onset acute kidney injury (AKI), IVH, or NEC. RESULTS A total of 114 patients were included: 44 (39%) received indomethacin and 70 (61%) received ibuprofen. Twenty-one (21%) patients experienced successful PDA closure within 1 week: 13 (32%) indomethacin patients and 8 (13%) ibuprofen patients (p = 0.023). PDA size reduction occurred in 43 (46%) patients with 29 (25%) experiencing complete symptom resolution. Significantly more indomethacin patients compared with ibuprofen patients experienced new-onset AKI (48% vs 17%; p < 0.001) and received concomitant nephrotoxins (68% vs 39%; p = 0.002). There were no significant differences in new-onset IVH or NEC. CONCLUSIONS Indomethacin administration successfully closed the PDA in more neonates than ibuprofen but resulted in higher rates of AKI. However, this was confounded by more frequent administration of concomitant nephrotoxins. Larger trials are needed to help elucidate the optimal drug for closure of the PDA in neonates. [ABSTRACT FROM AUTHOR]

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

Objective: To explore the effect of Xuebijing combine with ulinastatin on inflammatory response and myocardial protection of neonatus with necrotizing enterocolitis (NEC). Methods: 120 neonatus with NEC who were admitted to Guangdong Women and Children Hospital from May 2019 to May 2022 were selected. According to the random number table method, they were divided into control group (intravenous infusion of physiological saline before anesthesia induction), ulinastatin group (intravenous infusion of ulinastatin injection before anesthesia induction), Xuebijing group (intravenous infusion of Xuebijing injection before anesthesia induction), and combined group (intravenous infusion of ulinastatin injection and Xuebijing injection before anesthesia induction), with 30 cases of each group. The levels of mean arterial pressure (MAP), heart rate (HR), interleukin-17 (IL-17), C-reactive protein (CRP), tumor necrosis factor -α (TNF-α), cardiac troponin (cTnI), and B-type natriuretic peptide (BNP) were compared of four groups of neonatus, and the mortality and incidence of adverse reactions of four groups were recorded. Results: There was no statistically significant difference of HR between groups before surgery(P>0.05), ulinastatin group and Xuebijing group showed that decreased compared with control group after surgery and 1 d after surgery, and combined group showed that significant decreased after surgery and 1d after surgery compared with ulinastatin group and Xuebijing group(P<0.05). There was no statistically significant difference of MAP between groups before surgery(P>0.05), ulinastatin group and Xuebijing group showed that increased compared with control group after surgery and 1 d after surgery, and combined group showed that significant increased after surgery and 1 d after surgery compared with ulinastatin group and Xuebijing group(P<0.05). The CRP, IL-17, TNF-α of ulinastatin group, Xuebijing group, and combined group after surgery and 1 d after surgery were lower than those of control group at the same time point, and combined group were lower than those of ulinastatin group and Xuebijing group at the same time point(P<0.05). The cTnI and BNP of ulinastatin group, Xuebijing group, and combined group after surgery and 1 d after surgery were lower than those of control group at the same time point, and combined group were lower than those of ulinastatin group and Xuebijing group at the same time point(P<0.05). The mortality of combined group was lower than that of control group, ulinastatin group, and Xuebijing group. There was no statistically significant difference of the incidence of adverse reactions of four groups(P>0.05). Conclusion: Perioperative use of Xuebijing combine with ulinastatin of NEC, which is beneficial for the hemodynamic stability of neonatus, can alleviate the inflammatory response of neonatus, exert myocardial protection effect, and reduce clinical mortality. [ABSTRACT FROM AUTHOR]

Context Many preterm neonates often cannot be fed enterally and hence do not receive the benefits of colostrum. Oropharyngeal application of colostrum is a novel way of harnessing the immunological benefits of colostrum. Randomized controlled trials (RCTs) investigating the efficacy of this approach have shown variable results. Objective The aim of this systematic review was to synthesize available data on the effect of oropharyngeal application of colostrum or mother's own milk (CMOM) in preterm infants. Data Sources Six electronic databases (MEDLINE, Embase, CINAHL, Scopus, Web of Science, and Cochrane Library) were searched until January 13, 2022. Only RCTs comparing oral application of CMOM with placebo/routine care in preterm infants were eligible. Studies enrolling term neonates or administering enteral feeds were excluded. Data Extraction Two investigators independently extracted data using a structured proforma. Data Analysis The Cochrane Risk of Bias 2 tool was used to assess bias. Random-effects meta-analysis was undertaken using RevMan 5.4 software. From 2787 records identified, 17 RCTs enrolling 4106 preterm infants were included. There was no significant difference between groups in incidence of necrotizing enterocolitis (NEC) stage 2 or higher (RR = 0.65; 95%CI, 0.36–1.20; 1089 participants in 12 trials). Application of CMOM significantly reduced the incidence of sepsis (RR = 0.72; 95%CI, 0.56–0.92; 1511 participants in 15 studies) and any stage of NEC (RR = 0.58; 95%CI, 0.37–0.92; 1616 participants in 16 trials). The CMOM group achieved full enteral feeds 1.75 days sooner (95%CI, 0.3–3.2 days; 1580 participants in 14 studies) and had higher weight at discharge (MD = 43.9 g; 95%CI, 3–85 g; 569 participants in 3 studies). There were no statistically significant differences in other outcomes. Conclusions Evidence with low to very low certainty suggests CMOM has a beneficial effect on NEC (any stage), sepsis, and time to full enteral feeds. Given its low cost and minimal risk of harm, routine CMOM use may be considered in preterm neonates. Prospero Registration Number CRD42021262763 [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to investigate the clinical determinants of intestinal failure and death in preterm infants with surgical NEC. METHODS: Retrospective comparison of clinical information between Group A = intestinal failure (Parenteral nutrition (PN) >90 days) and death and Group B = survivors and with PN dependence < 90 days in preterm infants with surgical NEC. RESULTS: Group A (n = 99/143) had a lower mean gestational age (26.4 weeks [SD3.5] vs. 29.4 [SD 3.5]; p = 0.013), lower birth weight (873 gm [SD 427g] vs. 1425 gm [894g]; p = <0.001), later age of NEC onset (22 days [SD20] vs. 16 days [SD 17]; p = 0.128), received surgery later (276 hours [SD 544] vs. 117 hours [SD 267]; p = 0.032), had cholestasis, received dopamine (80.6% vs. 58.5%; p = 0.010) more frequently and had longer postoperative ileus time (19.8 days [SD 15.4] vs. 11.8 days [SD 6.5]; p = <0.001) and reached full feeds later (93 days [SD 45] vs. 44 [SD 22]; p = <0.001) than Group B. On multivariate logistic regression, higher birth weight was associated with lower risk (OR 0.35, 95% CI 0.15–0.82; p = 0.016) of TPN > 90 days or death. Longer length of bowel resected (OR 1.76, 95% CI 1.02–3.02; p = 0.039) and longer postoperative ileus (OR 2.87, 95% CI 1.26–6.53; p = 0.011) were also independently associated with TPN >90days or death adjusted for gestational age and antenatal steroid treatment. CONCLUSION: In preterm infants with surgical NEC, clinical factors such as lower birth weight, longer bowel loss, and postoperative ileus days were significantly and independently associated with TPN >90 days or death. [ABSTRACT FROM AUTHOR]

OBJECTIVE As broader spectrum antibiotics have been associated with adverse effects, our study evaluated whether the frequency of culture-positive late-onset sepsis (LOS) and multidrug resistant (MDR) infections were increased with the use of ceftazidime as compared with cefotaxime in the neonatal intensive care unit (NICU). METHODS This was a multihospital, retrospective chart review of patients who received at least 24 hours of ceftazidime or cefotaxime in the NICU between December 1, 2012 and August 31, 2021. Patients were excluded from analysis if they expired during the admission, had an incomplete history, positive cultures for an MDR infection prior to receiving either antibiotic, or received the alternate antibiotic within the same treatment course. RESULTS A total of 334 patients were included for analysis (ceftazidime, n = 147; cefotaxime, n = 187). The average birth weight was lower in the ceftazidime cohort compared with the cefotaxime cohort [1.46 kg (95% CI, 1.29-1.63 kg) versus 1.93 kg (95% CI, 1.75-2.11 kg), p = 0.0002] with a corresponding lower gestational age [28.9 weeks (95% CI, 28.0-29.9 weeks) versus 31.7 weeks (95% CI, 30.8-32.6 weeks), p = 0.0001]. Adjusting for baseline differences showed a protective effect for ceftazidime (OR = 0.32; 95% CI, 0.16-0.62; p = 0.0009). There was no statistically significant difference in the frequency of MDR infections between the cohorts (OR = 0.25; 95% CI, 0.053-1.14; p = 0.07), however this study was underpowered to detect the difference noted. CONCLUSIONS Ceftazidime appears to be a safe and effective alternative treatment option compared with cefotaxime in the NICU with no increase in the risk of culture-positive LOS or MDR infections. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the prevalence of abnormal vaginal colonization in women with cervical incompetence and to analyze its impact on obstetric and neonatal outcomes and placental inflammation. We included 138 pregnant women diagnosed with cervical incompetence and delivered in our hospital. Patients with major fetal anomaly or multifetal pregnancy were excluded. Upper vaginal culture was performed on the day of admission. A total of 60.9% (84/138) of cervical incompetence patients had abnormal bacterial colonization, and Escherichia coli (E. coli) was the most common colonized pathogen (33.3%, 46/138). The positive vaginal E. coli group had a higher rate of prior preterm birth (p = 0.021) and an earlier gestational age at which cervical incompetence was diagnosed (p < 0.01) than the negative group. The positive vaginal E. coli group had higher rates of clinical chorioamnionitis (p = 0.008) and subchorionic microabscess of the placenta (p = 0.012). Importantly, the positive vaginal E. coli group had significantly higher rates of proven early-onset neonatal sepsis (EONS) (p = 0.046), necrotizing enterocolitis (NEC) (p = 0.001), and neonatal mortality (p = 0.023). After adjusting for confounding variables, the positive vaginal E. coli group had significantly higher risk for proven EONS (OR: 3.853, 95% CI: 1.056–14.055) and NEC (OR: 12.410, 95% CI: 1.290–119.351). In conclusion, E. coli was the most common vaginal microorganism isolated from patients with cervical incompetence. Maternal vaginal E. coli colonization was associated with adverse neonatal outcomes including proven EONS and NEC and was characterized by a higher rate of placental subchorionic microabscess. [ABSTRACT FROM AUTHOR]

Internal hernias in preterm neonates, although rare, can arise due to various anatomical and physiological factors associated with prematurity. We report a case of a preterm infant with symptoms of suspected necrotizing enterocolitis (NEC) that turned out to be an internal hernia during surgical exploration. Given the overlapping symptoms, it is crucial to maintain a high index of suspicion and utilize the appropriate imaging techniques, such as ultrasound or radiographic studies, to aid in the differentiation between NEC and internal hernia, especially when responding to cases that do not improve with standard NEC management or exhibit atypical features. Early recognition and accurate differentiation are crucial for appropriate management and prevention of complications in affected neonates. [ABSTRACT FROM AUTHOR]

Background : Necrotizing enterocolitis (NEC) is a common gastrointestinal emergency among neonates which is characterized by acute intestinal inflammation and necrosis. The main risk factors for NEC are prematurity, low birth weight, and some preexisting health conditions such as congenital heart defects (CHDs). Investigation of the potential genetic predisposition to NEC is a promising approach that might provide new insights into its pathogenesis. One of the most important proteins that play a significant role in the pathogenesis of NEC is Toll-like receptor 4 (TLR4) which recognizes lipopolysaccharide found in Gram-negative bacteria. In intestinal epithelial cells, a protein encoded by the SIGIRR gene is a major inhibitor of TLR4 signaling. A few SIGIRR variants, including rare p.Y168X and p.S80Y, have already been identified in preterm infants with NEC, but their pathogenic significance remains unclear. This study aimed to investigate the spectrum of SIGIRR genetic variants in term newborns with CHD and to assess their potential association with NEC. Methods and Results: A total of 93 term newborns with critical CHD were enrolled in this study, 33 of them developed NEC. SIGIRR genetic variants were determined by Sanger sequencing of all exons. In total, eight SIGIRR genetic variants were identified, two of which were found only in newborns with NEC (P = 0.12). The rare missense p.S80Y (rs117739035) variant in exon 4 was found in two infants with NEC stage IIA. Two infants with NEC stage III and stage IB carried a novel duplication c. 102_121dup (rs552367848) variant in exon 10 that has not been previously associated with any clinical phenotype. Conclusions: The presence of both variants only in neonates who developed NEC, together with earlier published data, may suggest their potential contribution to the risk of developing NEC in term infants with CHD and allow planning larger cohort studies to clarify their relevance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The role of postnatal Doppler measurements of the superior mesenteric artery (SMA) in detecting neonates at risk of necrotizing enterocolitis (NEC) remains uncertain; therefore, we systematically reviewed and meta-analyzed the existing evidence regarding the usefulness of SMA Doppler measurements in detecting neonates at risk for NEC. We used the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, and we included studies which reported the following Doppler ultrasonography indices: peak systolic velocity, end-diastolic velocity, time average mean velocity, differential velocity, pulsatility index (PI) and resistive index. Eight studies were eligible for inclusion in the meta-analysis. Evidence suggested that, during the first postnatal day, neonates who developed NEC had a significantly higher peak systolic velocity (mean difference of 2.65 cm/s (95% confidence interval [CI] 1.23, 4.06, overall effect Z=3.66, P<0.001)), higher PI (mean difference of 1.52 (95% CI 0.00, 3.04, Z=1.96, P=0.05)) and higher resistive index (mean difference of 1.09 (95% CI 0.59, 1.60, Z=4.24, P<0.001)), compared to neonates who did not develop NEC. However, our findings do not support a strong association between the Doppler ultrasound indices and development of NEC at the time of disease onset. This meta-analysis suggests that first postnatal day SMA Doppler parameters, namely peak systolic velocity, PI and resistive index, are higher in neonates who develop NEC. On the other hand, the aforementioned indices are of uncertain significance once the diagnosis of NEC has been established. [ABSTRACT FROM AUTHOR]

1-propanesulfonic acid (DMPS) and continuous renal replacement therapy (CRRT) combined with CytoSorb. A 21-year-old woman was admitted to a hospital with abdominal pain, vomiting, and suspected gastrointestinal bleeding after taking 5000 mg of mercuric chloride for suicidal purposes. Due to the patient deteriorating general condition and multiple organ damage, on the third day she was transported to the Clinic of Anaesthesiology and Intensive Care (CAaIC), Łódź, Poland. Laboratory tests confirmed features of acute kidney injury and high mercury levels in the blood (1051 µg/l) and urine (22 960 µg/l) - DMPS therapy and CRRT combined with CytoSorb were instituted. Due to nervous system complaints (headache, dizziness), a lumbosacral puncture was performed - the mercury concentration in the cerebrospinal fluid (CSF) was 5.45 µg/l. During a colonoscopy, significant diagnostic abnormalities revealed features of colonic mucosal necrosis. The treatment resulted in a decrease in subjective complaints, decreased mercury levels in biological material, and improved parenchymal organ function. On the 15th day of therapy, the patient was transferred to the primary care center for further treatment. The case confirms the possibility of improvement of patient condition following ingestion of a potentially lethal dose (5 g) as a result of the initiation of appropriate therapy even on the third day. The presence of mercury in CSF confirms that inorganic mercury compounds (mercuric chloride) can pass through the blood-brain barrier after oral ingestion. [ABSTRACT FROM AUTHOR]

Objective Antenatal steroids are commonly used to stimulate fetal lung maturation, particularly in pregnancies at risk of early preterm labor. This study aimed to compare the effects of administering betamethasone at a 12- versus 24-hour interval on perinatal outcomes. Study Design This retrospective study included 423 early preterm births from 26 +0/7 to 33 +6/7 weeks of gestation. Patients received betamethasone at either a 12- or 24-hour dosing interval. Results When all patients in each group were evaluated together, there was no statistically significant difference between both groups for complications of prematurity, including respiratory distress syndrome (RDS). When the two groups were divided by gestational age (GA), the 32 +0/7 to 33 +6/7 -week group that received betamethasone at a 24-hour interval had statistically lower 1- and 5-minute APGAR scores (p = 0.06 and p = 0.02, respectively). They also had a greater need for neonatal intensive care unit (NICU), NICU length of stay, RDS, and need for surfactant (p = 0.20, p = 0.09, p = 0.27, and p = 0.23, respectively) than did the infants at 32 +0/7 to 33 +6/7 weeks, who received betamethasone at a 12-hour interval. In the group with GA between 28 +0/7 and 29 +6/7 weeks, the 1-minute APGAR score was lower (p = 0.22), and the durations of hospital stay, and mechanical ventilation were longer (p = 0.048, p = 0.21, respectively) in the 24-hour interval group. No statistically significant difference was observed for all parameters in other GA groups. Conclusion A 12-hour dosing interval for betamethasone appears to be more appropriate, as it results in a reduction in some neonatal complications and provides a short dose interval. Key Points RDS is reduced when betamethasone is used 12 hours apart. When betamethasone is used 12 hours apart, the need for surfactant is reduced. The use of betamethasone 12 hours apart is advantageous with its short dose interval. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) continues to be a devastating disease in preterm neonates and has a paucity of medical management options. Chondroitin sulfate (CS) is a naturally occurring glycosaminoglycan (GAG) in human breast milk (HM) and has been shown to reduce inflammation. We hypothesized that supplementation with CS in an experimental NEC model would alter microbial diversity, favorably alter the cytokine profile, and (like other sulfur compounds) improve outcomes in experimental NEC via the eNOS pathway. NEC was induced in 5‐day‐old pups. Six groups were studied (n = 9–15/group): (1) WT breastfed and (2) Formula fed controls, (3) WT NEC, (4) WT NEC + CS, (5) eNOS KO (knockout) NEC, and (6) eNOS KO NEC + CS. Pups were monitored for clinical sickness score and weights. On postnatal day 9, the pups were killed. Stool was collected from rectum and microbiome analysis was done with 16 s rRNA sequencing. Intestinal segments were examined histologically using a well‐established injury scoring system and segments were homogenized and analyzed for cytokine profile. Data were analyzed using GraphPad Prism with p < 0.05 considered significant. CS supplementation in formula improved experimental NEC outcomes when compared to NEC alone. CS supplementation resulted in similar improvement in NEC in both the WT and eNOS KO mice. CS supplementation did not result in microbial changes when compared to NEC alone. Our data suggest that although CS supplementation improved outcomes in NEC, this protection is not conferred via the eNOS pathway or alteration of microbial diversity. CS therapy in NEC does improve the intestinal cytokine profile and further experiments will explore the mechanistic role of CS in altering immune pathways in this disease. [ABSTRACT FROM AUTHOR]

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

Objective: To investigate and analysis the effects of cimetidine on inflammatory immune response and intestinal microorganism in mice with necrotizing enterocolitis (NEC). Methods: 36 cases of mice with necrotizing enterocolitis were randomly divided into three groups: model group, cimetidine group 1, and cimetidine group 2, with 12 mice in each group. The model group, cimetidine group 1, and cimetidine group 2 were orally administrated with 0.1 mL of normal saline, 0.1 mL of gastric cimetidine, and 0.2 mL of gastric cimetidine daily. After continuous application for 14 days, the inflammatory immune response and intestinal microbial changes of the mice were observed. Results: The body weight of cimetidine group 1 and cimetidine group 2 on the 7th and 14th day of treatment were significantly higher than that of the model group(P<0.05), and the body weight of cimetidine group 2 were significantly higher than that of cimetidine group 1(P<0.05). At the 14th day of treatment, the content of IL-2 in intestinal tissue of cimetidine group 1 and cimetidine group 2 were lower than that of model group (P<0.05), and the content of IL-10 were higher than that of model group(P<0.05). There were significant difference compared between cimetidine group 2 and cimetidine group 1 (P<0.05). At the 14th day of treatment, the relative expression levels of Bifidobacterium and Lactobacillus in the feces of cimetidine 1 and 2 groups were significantly higher than those of the model group(P<0.05), while the relative expression levels of Escherichia coli were significantly lower than those of the model group (P<0.05). There were significant difference compared between cimetidine 2 and cimetidine 1 groups (P<0.05). The relative expression levels of CaMKIV and CREM proteins in the intestinal tissue of cimetidine 1 and 2 groups were significantly lower than those of the model group on the 14th day of treatment(P<0.05), and cimetidine 2 group also significantly decreased compared with cimetidine 1 group (P<0.05). Conclusion: The application of cimetidine in mice with necrotizing enterocolitis can regulate the balance of inflammatory immune response, promote the recovery of mice weight to normal, and also reduce the relative expression level of CaMKIV and CREM proteins in intestinal tissue, thus improving the intestinal microbial status of mice, which is dose dependent. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to present the clinical and descriptive features of patients with portal vein thrombosis. Methods: The study was conducted in a tertiary neonatal intensive care unit in Istanbul, Turkey. We included the patients diagnosed with portal vein thrombosis hospitalized in our neonatal intensive care unit between January 2017 and December 2021, retrospectively. We investigated the birth history, anthropometric measurements, the postnatal day of portal vein thrombosis detected, and clinical history. Results: Nineteen patients (12 male) were eligible for the study. Portal vein thrombosis incidence was 3.9 per 1000 infants admitted to our neonatal intensive care unit. The mean gestational week was 35.1 ± 4.8 weeks. The median birth weight was 2835 g (1335-3250), and the median length was 47 cm (38-50). We detected portal vein thrombosis on median postnatal 13 days. Portal vein thrombosis was in the left portal vein in 84.2% (n = 16) and the main portal vein in 15.8% (n = 3) patients. About 68.4% (n = 12) of the patients had umbilical venous catheter, 47.4% (n = 9) had a history of perinatal asphyxia, 26.3% (n = 5) had necrotizing enterocolitis, 5.3% (n = 1) had tracheoesophageal fistula+anal atresia, and 5.3% (n = 1) had an omphalocele. In 15.7% (n = 3) of the patients, we detected portal vein thrombosis without any known clinical risk factor on the first postnatal day. About 26.3% (n = 5) of patients underwent anticoagulation treatment. All the thrombosis was re-canalized, except 1 patient. Conclusion: Portal vein thrombosis can be seen on the first postnatal day, even in babies with no perinatal problems. The cases had asphyxia and intra-abdominal operation/necrotizing enterocolitis as risk factors. Portal vein thrombosis incidence was 3.9 per 1000 neonatal intensive care unit admission. [ABSTRACT FROM AUTHOR]

Objective: To compare the probiotics with placebo in preventing the necrotizing enterocolitis (NEC) in preterm newborns. Study Design: Randomized Controlled Trial. Setting: Department of Pediatrics Unit-1, Bahawal Victoria Hospital, Bahawalpur, Pakistan. Period: May 2022 to April 2023. Material & Methods: A total of 92 pre-term neonates with gestational age between 28-32 weeks gestation were included. Patients were randomly assigned to either probiotics or placebo groups (46 in each group). In probiotics group, probiotics named Bifidobacteria (hiflora/gutcare one sachet daily) were given for 5 days while in placebo group, neonates were given placebo for 5 days. All neonates were observed for feeding intolerance, abdominal distension, grossly bloody stools (naked eye blood in stool) and change in colour of skin of abdomen (erythema). Patients having three or more of these features in first 7 days of life were labeled as having NEC. Results: In a total of 92 newborns, maternal age ranged between 18 to 40 years with mean age of 29.30±5.27 years. The mean gestational age was 30.88±2.08 weeks while the mean weight was 2.06±0.71 kg. The NEC was found in 3 (6.52%) neonates in probiotics groups versus 11 (23.9%) in placebo group (p=0.020). In the probiotics group, NEC was found to have significant association with gestational age between 31-32 weeks (p=0.012), spontaneous vaginal delivery (p=0.028) and maternal educational status as educated (p=0.006). In the placebo group, NEC had significant association with birth weight between 1-1.5 kg (p=0.007). Conclusion: This study concluded that probiotics are better in preventing NEC in preterm neonates than placebo. [ABSTRACT FROM AUTHOR]

Certain congenital cardiac lesions are at increased risk for the development of necrotizing enterocolitis (NEC). These patients are often reliant on pulmonary and systemic vasomodulators to maintain adequate perfusion and oxygenation. This study sought to determine whether pulmonary or systemic vasodilator treatment is protective against the development of NEC in this population. We utilized International Classification of Diseases (ICD) codes to identify high risk congenital cardiac disease patients ≤6 mo of age, cared for at a tertiary children's hospital between January 2011 and January 2021. Cardiac anomalies were stratified into ductal dependent (pulmonary DD-P or systemic DD-S) or independent lesions. The rate of NEC development in those who received vasodilators (inhaled nitric oxide [iNO], pulmonary vasodilators, systemic vasodilators) was compared to controls in a multivariate analysis. Of the 352 patients, who met inclusion criteria, 77.6% had ductal dependent lesions (DD-S 41.9%, DD-P 35.7%), 19.5% received iNO, and 37.5% received other vasodilatory drugs. The overall NEC rate was 15.1%. On univariate analysis, DD-S, iNO use, and systemic vasodilators was associated with a significantly higher risk of NEC, while DD-P was associated with lower NEC risk. On multivariate analysis, only iNO (odds ratio 2.725, confidence interval [1.36-5.44]) and DD-S (odds ratio 2.279, confidence interval [1.02-5.11]) were independent risk factors for NEC. In patients with at-risk congenital cardiac disease lesions, a ductus dependent systemic circulation or iNO treatment is associated with an increased risk of developing NEC. The presence of iNO or DD-S should be utilized as markers of increased risk both in the prevention and workup of suspected NEC. [ABSTRACT FROM AUTHOR]

Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly preterm infants. However, evidence about the outcomes associated with PTx and whether they provide clinical benefit or harm is lacking. The aim of this systematic review and meta-analysis is to assess the association between PTx in preterm infants and mortality, major bleeding, sepsis, and necrotizing enterocolitis (NEC) in comparison to not transfusing or using different platelet count thresholds for transfusion. A broad electronic search in three databases was performed in December 2022. We included randomized controlled trials, and cohort and case control studies of preterm infants with thrombocytopenia that (i) compared treatment with platelet transfusion vs. no platelet transfusion, (ii) assessed the platelet count threshold for PTx, or (iii) compared single to multiple PTx. We conducted a meta-analysis to assess the association between PTx and mortality, intraventricular hemorrhage (IVH), sepsis, and NEC and, in the presence of substantial heterogeneity, leave-one-out sensitivity analysis was performed. We screened 625 abstracts and 50 full texts and identified 18 reports of 13 eligible studies. The qualitative analysis of the included studies revealed controversial results as several studies showed an association between PTx in preterm infants and a higher risk of mortality, major bleeding, sepsis, and NEC, while others did not present a significant relationship. The meta-analysis results suggest a significant association between PTx and mortality (RR 2.4, 95% CI 1.8–3.4; p < 0.0001), as well as sepsis (RR 4.5, 95% CI 3.7–5.6; p < 0.0001), after a leave-one-out sensitivity analysis. There was also found a significant correlation between PTx and NEC (RR 5.2, 95% CI 3.3–8.3; p < 0.0001). As we were not able to reduce heterogeneity in the assessment of the relationship between PTx and IVH, no conclusion could be taken. Conclusion: Platelet transfusions in preterm infants are associated to a higher risk of death, sepsis, and NEC and, possibly, to a higher incidence of IVH. Further studies are needed to confirm these associations, namely between PTx and IVH, and to define the threshold from which PTx should be given with less harm effect. What is Known: • Platelet transfusions are given to preterm infants with thrombocytopenia either to treat bleeding or to prevent hemorrhage. • Lack of consensual criteria for transfusion. What is New: • A significant association between platelet transfusions and mortality, sepsis, and NEC. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis is a severe inflammatory disease of the intestine and is the main cause of death in infants, mostly occurring in premature infants. Intestinal obstruction may occur during the medical treatment of necrotizing enterocolitis. A common cause of intestinal obstruction is intestinal stricture, and entero-enteric fistulas may form in the proximal portion of the intestinal stricture. Several mechanisms may be suggested for the development of entero-enteric fistula. Intestinal ischemia and subsequent necrosis do not become intestinal perforation over time, causing an inflammatory reaction, and are attached to the adjacent intestine, forming a fistula. Alternatively, a subacute perforation may be sealed off by the adjacent intestine, resulting in fistula formation. Entero-enteric fistulas are closely related to distal stricture and occurs when there is a localized perforation rather than a generalized perforation. Fistulas can be diagnosed via contrast enema examination or distal loopogram, and surgical resection is required. Here, I report a case of a preterm infant with an entero-colonic fistula secondary to necrotizing enterocolitis. The patient had abdominal distention and bloody stool and was confirmed to have rotavius enteritis. Plain abdominal radiographs showed pneumatosis intestinalis. The patient received medical treatment for necrotizing enterocolitis. While the symptoms were improving, he vomited again, and intestinal obstruction was suspected. Gastrografin enema was performed due to intestinal obstruction, and an enterocolonic fistula was found. [ABSTRACT FROM AUTHOR]

Background: We have recently noted some sonographic features in necrotizing enterocolitis that have received little or no attention in the current literature. These include thickening of the mesentery, hyperechogenicity of intraluminal intestinal contents, abnormalities of the abdominal wall, and poor definition of the intestinal wall. It has been our impression that the above four sonographic findings are generally seen in neonates with more severe necrotizing enterocolitis and may be useful in predicting outcome. Objectives: The aim of this study is, firstly, to review a large series of neonates, known to have clinical NEC, to document how frequently the above four sonographic features occur in neonates with necrotizing enterocolitis and, secondly, to determine whether they are predictive of outcome. Materials and methods: We retrospectively analyzed the clinical, radiographic, sonographic, and surgical findings in neonates with necrotizing enterocolitis between 2018 and 2021. The neonates were categorized into two groups based on outcome. Group A included neonates with a favorable outcome defined as successful medical treatment with no surgical intervention. Group B included neonates with an unfavorable outcome defined as failed medical treatment requiring surgery (for acute complications or late strictures) or death because of necrotizing enterocolitis. The sonographic examinations were reviewed with attention to the features of mesenteric thickening, hyperechogenicity of intraluminal intestinal contents, abnormalities of the abdominal wall, and poor definition of the intestinal wall. We then determined the association of these four findings with the two groups. Results: We included 102 neonates with clinical necrotizing enterocolitis: 45 in group A and 57 in group B. Neonates in group B were born at a significantly earlier gestational age (median 25 weeks, range 22–38 weeks) and had a significantly lower birth weight (median 715.5 g, range 404–3120 g) than those in group A (median age 32 weeks, range 22–39 weeks, p = 0.003; median weight 1190 g, range 480–4500 g, p = 0.002). The four sonographic features were present in both study groups but with different frequency. More importantly, all four were statistically significantly more frequently present in neonates in group B compared to group A: (i) mesenteric thickening, A = 31 (69%), B = 52 (91%), p = 0.007; (ii) hyperechogenicity of intestinal contents, A = 16 (36%), B = 41 (72%), p = 0.0005; (iii) abnormalities of the abdominal wall, A = 11 (24%), B = 35 (61%), p = 0.0004; and (iv) poor definition of the intestinal wall, A = 7 (16%), B = 25 (44%), p = 0.005. Furthermore, the proportion of neonates with more than two signs was greater in group B compared to group A (Z test, p < 0.0001, 95% CI = 0.22–0.61). Conclusion: The four new sonographic features described were found to occur statistically significantly more frequently in those neonates with an unfavorable outcome (group B) than in those with a favorable outcome (group A). The presence or absence of these signs should be included in the sonographic report to convey the radiologists concern regarding the severity of the disease in every neonate, suspected or known to have necrotizing enterocolitis, as the findings may impact further medical or surgical management. [ABSTRACT FROM AUTHOR]

Objective The study aimed to determine the association of surgical necrotizing enterocolitis (NEC) and its timing, with the development and timing of retinopathy of prematurity (ROP). Study Design This was a secondary data analysis of 7,483 preterm infants from the Postnatal Growth and Retinopathy of Prematurity Study. Associations between infants with surgical NEC, early-onset surgical NEC (8–28 days), and late-onset surgical NEC (over 28 days) with ROP were evaluated by using multivariable logistic regression models, controlling for birth weight, gestational age, small for gestational age status, chronic lung disease, intraventricular hemorrhage, hydrocephalus, patent ductus arteriosus, and periventricular leukomalacia. Results Three hundred fifty-six (4.8%) infants had surgical NEC, with 56% having early surgical NEC. Infants with surgical NEC had a higher risk of any ROP and severe ROP (adjusted odds ratio [OR]: 2.7; 95% CI: 1.9–3.7) and 2.5 (95% CI: 1.9–3.3), respectively; p < 0.001) compared with infants without surgical NEC. Infants with early surgical NEC were at the highest risk of developing ROP and severe ROP (adjusted OR: 3.1 [95% CI: 2.1–4.8], and 3.3 [95% CI: 2.3–4.7] respectively, p < 0.001). Infants with late surgical NEC were also at increased risk of developing ROP and severe ROP (adjusted OR: 2.1 [95% CI: 1.3–3.4], and 1.9 [95% CI: 1.3–2.8] respectively, p < 0.001) compared with infants without surgical NEC. Conclusion Infants with surgical NEC, especially early surgical NEC, are at higher risk of ROP and severe ROP. Key Points Infants with surgical NEC are at higher risk of ROP and severe ROP than those without surgical NEC. Increased ROP risk is seen in infants with both early- or later onset surgical NEC. Early-onset surgical NEC is associated with a higher ROP risk compared with later onset surgical NEC. [ABSTRACT FROM AUTHOR]