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Objective: Necrotizing enterocolitis (NEC) is characterized by a rich infiltration of macrophages in the intestines, which is derived from monocytes in the blood. The authors aimed to explore the changing trend of absolute monocyte counts (AMC) over time in NEC infants and to verify whether the reduction of AMC correlates with the severity of NEC and whether it can be used to identify infants who need surgery. Method: The authors collected the clinical data of 66 control and 222 NEC infants. The NEC infants were divided into medical NEC (M-NEC) and surgical NEC (S-NEC). The counting of monocyte and their percentage change were compared at the time of birth, before NEC (baseline), the onset of NEC and after NEC (recovery). In addition, the same comparison was made among stages 1, 2 and 3 of Bell's staging, respectively. Results: The authors found that the AMC in NEC infants decreased sharply at the onset. Further comparison was made between 172 cases of M-NEC and 50 cases of S-NEC. It was discovered that the AMC reduced more in S-NEC infants at onset, but it increased more at recovery. In addition, the authors found that among stage 1,2 and 3, stage 3 had the lowest AMC and the largest percentage decrease at the onset. Conclusion: The AMC decreases sharply in NEC infants at onset, and the degree of decline is associated with the severity of NEC. AMC is expected to be a marker of NEC and provide a reference for clinicians in the diagnosis and treatment of NEC.

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.

The aim of this study was to investigate whether age at introduction of solid foods in preterm infants influences growth in the first year of life. This was a prospective observational study in very low birth weight infants stratified to an early (

Background: The patent ductus arteriosus (PDA) treatment in very preterm infants is controversial. This study focused on preterm infants born at 28–32 weeks of gestation and analyzed the association between various PDA treatments and clinical outcomes. Methods: We conducted a retrospective cohort study of infants born at 28–32 weeks of gestation between 2016 and 2019 at 22 hospitals in the Taiwan Premature Infant Follow-up Network. We categorized the infants into four groups according to treatment strategies: medication, primary surgery, medication plus surgery, or conservative treatment. Results: A total of 1244 infants presented with PDA, and 761 (61.1%) were treated. Medication was the predominant treatment (50.0%), followed by conservative treatment (38.9%), medication plus surgery (7.6%), and primary surgery (3.5%). The risk of mortality was not reduced in the active treatment group compared to the conservative treatment group. There was a higher prevalence of severe intraventricular hemorrhage, necrotizing enterocolitis (NEC), and any degree of bronchopulmonary dysplasia (BPD) in both the primary surgery and medication plus surgery groups than in the conservative treatment group. After adjustment, both the primary surgery and medication plus surgery groups still had higher odds ratios for the occurrence of NEC and any degree of BPD. Conclusions: Compared with active PDA treatment, conservative treatment for PDA did not increase the risk of mortality and morbidity in very preterm infants born at 28–32 weeks of gestation. The risks and benefits of surgery (PDA ligation) in these infants must be considered cautiously.

Objective To explore the effect of sodium butyrate on brain injury in mice with necrotizing enterocolitis (NEC). Methods A total of 137 3-day-old C57BL/6 mice were randomly divided into Control group (CON group, n=40, without maternal separation), NEC+PBS group (NP group, n=57) and NEC+butyrate group (NB group, n=40). The mice from the NP and NB groups were separated maternally and given either PBS or sodium butyrate by gavage from postnatal day 3 for 7 consecutive days, then a NEC model was established by formula feeding combined with hypoxia and hypothermia for 3 consecutive days. Survival rate, histopathological injury of the intestine, mRNA expression of TNF-α and IL-6 in the brain, and number of activated microglia and astrocytes were observed and detected. Morris water maze and transmission electron microscopy were employed to observe the long-term cognitive impairment and microstructure of myelin, respectively, for the adult mice (4 weeks old). Western blotting was used to measure the protein level of HMGB1 in the intestine and TLR4 as well as NF-κB in the brain. Results Compared with the CON group, the mice of the NP group showed increased mRNA expression of TNF-α(1.51± 0.20 vs 0.67±0.14) and IL-6 (2.03±0.39 vs 1.01±0.17) in the brain (both P < 0.05), raised number of activated microglia (751.00±82.35 vs 284.70±52.01, P < 0.05) and astrocytes (P < 0.05) in the hippocampus, and elevated protein levels of HMGB1 (1.76±0.19 vs 0.73±0.06) in the intestine as well as TLR4 (1.14±0.16 vs 0.81±0.01) and NF-κB (1.21±0.19 vs 0.60±0.15) in the brain (all P < 0.05). In addition, the adult mice in the NP group demonstrated the prolonged escape latency and decreased crossing-platform times, and increased G-ratio (all P < 0.05). After the administration of sodium butyrate, the mRNA expression levels of TNF-α(0.81±0.12 vs 1.51±0.20) and IL-6 (0.93±0.38 vs 2.03±0.39) in the brain were decreased, the activation of microglia was inhibited (468.00±99.59 vs 751.00±82.35), and the number of astrocytes was reduced (all P < 0.05). The decreased expression levels of HMGB1 (1.22±0.11 vs 1.76±0.19) in the intestine and TLR4 (0.88±0.06 vs 1.14±0.16) and NF-κB (0.70±0.19 vs 1.21±0.19) in the brain were also marked in the NB group (all P < 0.05). The adult mice of the NB group showed shortened escape latency, and increased crossing-platform times and myelin thickness (all P < 0.05). Conclusion Sodium butyrate alleviates the neuroinflammation by inhibiting the activation of TLR4-NF-κB signal pathway in the NEC brain, and thus exerts protective effect against NEC-associated brain injury.

Abstract Background Impaired intestinal microcirculation seems to play an important role in the pathogenesis of necrotizing enterocolitis (NEC). A previous study showed that a SrSO2

Necrotizing enterocolitis is an inflammatory disease caused by infection and hypoxic–ischemic damage of the intestinal mucosa, which leads to generalization with the development of a systemic inflammatory response. The pathogenetic mechanisms leading to intestinal wall damage are ischemia and pain. Therefore, the use of central neuraxial blocks, which provide the analgesic effect and preganglionic blockade of the sympathetic nervous system, is pathogenetically justified. The aim of the work is to acquaint practitioners with the case of successful comprehensive treatment using neuraxial blocks in a newborn with necrotizing enterocolitis. Materials and methods. The child was treated at the Department of Anesthesiology and Intensive Care for Newborns of Zaporizhzhia City Pediatric Hospital No. 5. He underwent clinical and biochemical blood tests, microbiological, radiological and ultrasound examinations using hospital equipment. Results. A child was operated due to suspected intestinal perforation and pneumoperitoneum. It was found that throughout the small and large intestines had multiple hemorrhages and air bubbles in the subserosa, but no perforation sites were found. Subsequently, the child underwent conservative treatment with antibacterial therapy according to the de-escalation principle, antifungal therapy, intravenous immunoglobulins, total parenteral nutrition. In addition to this standard treatment, the child underwent caudal-epidural blocks twice a day for a week in the postoperative period for effective analgesia, improvement of microcirculation and splanchnic blood flow. Conclusions. Surgical intervention performed on a newborn child with the second stage of necrotizing enterocolitis (intestinal pneumatosis), when its perforation could not be excluded, did not significantly affect the course of the disease, so the positive outcome can be considered the result of successful comprehensive intensive care. In our opinion, the decisive factor that influenced the positive treatment outcomes (prevention of perforation and peritonitis) was the effect of neuraxial caudal epidural blocks, which contributed to the improvement of microcirculation in the splanchnic area, elimination of intestinal ischemia and effective anesthesia.

Abstract Aim Necrotizing enterocolitis (NEC) is the most lethal disease of the gastrointestinal tract of preterm infants. New and existing management strategies need clinical evaluation. Large heterogeneity exists in the selection, measurement, and reporting of outcome measures in NEC intervention studies. This hampers meta-analyses and the development of evidence-based management guidelines. We aim to develop a Core Outcome Set (COS) for NEC that includes the most relevant outcomes for patients and physicians, from moment of diagnosis into adulthood. This COS is designed for use in NEC treatment trials, in infants with confirmed NEC. Methods This study is designed according to COS-STAD (Core Outcome Set-STAndards for Development) recommendations and the COMET (Core Outcome Measures in Effectiveness Trials) Initiative Handbook. We obtained a waiver from the Ethics Review Board and prospectively registered this study with COMET (Study 1920). We will approach 125 clinicians and/or researchers from low-middle and high-income countries based on their scientific output (using SCIVAL, a bibliometric tool). Patients and parents will be approached through local patient organisations. Participants will be separated into three panels, to assess differences in priorities between former patients and parents (1. lay panel), clinicians and researchers involved in the neonatal period (2. neonatal panel) and after the neonatal period (3. post-neonatal panel). They will be presented with outcomes currently used in NEC research, identified through a systematic review, in a Delphi process. Eligible outcome domains are also identified from the patients and parents’ perspectives. Using a consensus process, including three online Delphi rounds and a final face-to-face consensus meeting, the COS will be finalised and include outcomes deemed essential to all stakeholders: health care professionals, parents and patients’ representatives. The final COS will be reported in accordance with the COS-Standards for reporting (COS-STAR) statement. Conclusions Development of an international COS will help to improve homogeneity of outcome measure reporting in NEC, will enable adequate and efficient comparison of treatment strategies, and will help the interpretation and implementation of clinical trial results. This will contribute to high-quality evidence regarding the best treatment strategy for NEC in preterm infants.

Abstract Background Human milk–based human milk fortifier (HMB-HMF) makes it possible to provide an exclusive human milk diet (EHMD) to very low birth weight (VLBW) infants in neonatal intensive care units (NICUs). Before the introduction of HMB-HMF in 2006, NICUs relied on bovine milk–based human milk fortifiers (BMB-HMFs) when mother's own milk (MOM) or pasteurized donor human milk (PDHM) could not provide adequate nutrition. Despite evidence supporting the clinical benefits of an EHMD (such as reducing the frequency of morbidities), barriers prevent its widespread adoption, including limited health economics and outcomes data, cost concerns, and lack of standardized feeding guidelines. Methods Nine experts from seven institutions gathered for a virtual roundtable discussion in October 2020 to discuss the benefits and challenges to implementing an EHMD program in the NICU environment. Each center provided a review of the process of starting their program and also presented data on various neonatal and financial metrics associated with the program. Data gathered were either from their own Vermont Oxford Network outcomes or an institutional clinical database. As each center utilizes their EHMD program in slightly different populations and over different time periods, data presented was center-specific. After all presentations, the experts discussed issues within the field of neonatology that need to be addressed with regards to the utilization of an EHMD in the NICU population. Results Implementation of an EHMD program faces many barriers, no matter the NICU size, patient population or geographic location. Successful implementation requires a team approach (including finance and IT support) with a NICU champion. Having pre-specified target populations as well as data tracking is also helpful. Real-world experiences of NICUs with established EHMD programs show reductions in comorbidities, regardless of the institution’s size or level of care. EHMD programs also proved to be cost effective. For the NICUs that had necrotizing enterocolitis (NEC) data available, EHMD programs resulted in either a decrease or change in total (medical + surgical) NEC rate and reductions in surgical NEC. Institutions that provided cost and complications data all reported a substantial cost avoidance after EHMD implementation, ranging between $515,113 and $3,369,515 annually per institution. Conclusions The data provided support the initiation of EHMD programs in NICUs for very preterm infants, but there are still methodologic issues to be addressed so that guidelines can be created and all NICUs, regardless of size, can provide standardized care that benefits VLBW infants.

Objective: Acute kidney injury (AKI) in the neonatal period is associated with worst outcomes as increased mortality and increased length of hospital stay. Very low birth weight (VLBW) newborns are at higher risk for developing several other conditions that are associated with worst outcomes. Understanding the risk factors for AKI may help to prevent this condition and improve neonatal care for this population. Methods: This retrospective cohort study included 155 very low birth weight newborns admitted between 2015 and 2017. The authors compared the newborns who developed neonatal AKI with the non-AKI group and analyzed the main risk factors for developing AKI in the population. The authors also performed an analysis of the main outcomes defined as the duration of mechanical ventilation, length of stay, and death. Results: From the cohort, a total of 61 (39.4%) patients had AKI. The main risk factors associated with Neonatal AKI were necrotizing enterocolitis (aOR 7.61 [1.69 – 34.37]; p = 0.008), neonatal sepsis (aOR 2.91 [1.17 – 7.24], p = 0.021), and hemodynamic instability (aOR 2.99 [1.35 – 6.64]; p = 0.007). Neonatal AKI was also associated with an increase in the duration of mechanical ventilation in 9.4 days (p = 0.026) and in an increase in mortality 4 times (p = 0.009), after adjusting for the other variables. Conclusion: The present results highlight the importance of minimizing sepsis and necrotizing enterocolitis, as well as the importance of identifying hemodynamic instability, to prevent AKI and diminish the burden of morbimortality in VLBW newborns.

IntroductionNecrotizing enterocolitis (NEC) is a serious intestinal condition characterized by ischemic necrosis of the intestinal mucosa, inflammation, and invasion by gas-forming organisms, posing a significant threat to neonatal health. Necrotizing enterocolitis remains a significant cause of neonatal morbidity and mortality, particularly in developing countries. Due to limited research conducted in Ethiopia and the study area, there is a lack of information regarding the risk factors associated with necrotizing enterocolitis. Therefore, the goal of this study is to fill the aforementioned gap.ObjectiveThis study aims to identify the risk factors of necrotizing enterocolitis among neonates admitted to the neonatal intensive care unit (NICU) at selected general and referral hospitals in southern Ethiopia in the year 2023.Methods and materialsA facility-based unmatched case–control study was conducted. All neonates admitted to the NICU and diagnosed with necrotizing enterocolitis by the attending physician during the data collection period were considered as cases, whereas neonates admitted to the NICU but not diagnosed with necrotizing enterocolitis during the data collection period were considered as controls. Data were collected through face-to-face interviews and record reviews using the Kobo toolbox platform. The binary logistic regression method was used to determine the relationship between a dependent variable and independent variables. Finally, a p-value of

Neutrophils, the most abundant type of white blood cells, are pivotal in fighting bacterial infections due to their immunological and anti-infection capabilities. In recent years, scientists have discovered a novel mechanism known as neutrophil extracellular traps, which are fibrous networks primarily released by neutrophils that combat bacterial infections. There is a growing interest in studying NETs and their role in human infectious diseases, particularly in neonates susceptible to bacterial infections. NETs and their components have been found in various samples from neonatal-infected patients, providing a new route for early diagnosis of neonatal infectious diseases. This paper aims to summarize the studies on NETs in adult diseases and mainly discuss NETs in neonatal sepsis, necrotizing enterocolitis, and purulent meningitis, to provide scientific evidence for early monitoring, diagnosis, and treatment of neonatal infections.

ABSTRACT Necrotizing enterocolitis (NEC) is a challenging gastrointestinal disease that disproportionately affects premature neonates, with high incidence and case-fatality rates. Despite extensive research efforts, the pathogenesis and mechanisms of NEC remain unclear, making it difficult to effectively eradicate. However, it has been established that dysbiosis of gut microbes occurs before the onset of NEC, providing compelling evidence for the potential use of probiotic therapy. As such, we have focused our attention on two probiotics in particular: Clostridium butyricum and Clostridium tyrobutyricum, especially in light of recent breakthroughs that have linked several Clostridia species with NEC. To determine whether C. butyricum and C. tyrobutyricum are pathogenic or probiotic, we conducted a comparison of the phenotypic traits of NEC mice treated with each bacterium. Our results confirm that treatment with C. tyrobutyricum restores intestinal barrier integrity and alleviates inflammatory immune responses associated with NEC. In contrast, treatment with C. butyricum exacerbates intestinal barrier damage and promotes immune disorder, including increased numbers of macrophages, monocytes, and neutrophils in the intestinal lamina propria. Further analysis of the gut microbiome suggests that the positive effects of C. tyrobutyricum treatment are associated with an increase in Akkermansia muciniphila, while C. butyricum treatment decreases the level of A. muciniphila, which accounts for its negative effect on NEC. This study sheds light on the fact that treatment with C. tyrobutyricum, but not C. butyricum, has the potential to protect against NEC development. The opposite effects of these two probiotics on NEC may result from their different modulation of the level of A. muciniphila, a gut microbe that is closely associated with intestinal homeostasis. In summary, by improving the abundance of A. muciniphila to alleviate intestinal inflammation and enhance intestinal barrier integrity, supplementation with C. tyrobutyricum may become a promising therapy for NEC.IMPORTANCEThis study sheds light on that treatment with Clostridium tyrobutyricum but not Clostridium butyricum is entitled to protect against necrotizing enterocolitis (NEC) development potentially. The mechanisms behind the opposite effect on NEC may result in different modulation on the level of Akkermansia muciniphila, which is deeply associated with intestinal homoeostasis. Briefly, through improving the abundance of A. muciniphila to alleviate intestinal inflammation and enhance intestinal barrier integrity, C. tyrobutyricum supplement may become a promising therapy for NEC.

IntroductionAcute intestinal diseases (AID), including necrotizing enterocolitis and spontaneous intestinal perforation, are a group of conditions that typically present in preterm infants, and are associated with an elevated mortality and morbidity rate. The risk factors for these diseases remain largely unknown. The aim of the study is to identify the correlation between twinning and the development of AID.MethodsA single-center retrospective case–control study was conducted. We recruited all infants with a diagnosis of AID, confirmed by anatomopathology, recovered in NICU between 2010 and 2020. Considering the rarity of the outcome, 4 matched controls for each subject were randomly chosen from the overall population of newborns. Odds Ratio (OR) and 95% Confidence Interval (CI) were calculated using a conditional logistic regression model and a multivariate model by the creation of a Directed Acyclic Graph (www.dagitty.net).ResultsThe study population resulted in 65 cases and 260 controls. The two groups present similar median gestational age and mean birthweight in grams. The cases have a higher frequency of neonatal pathology (defined as at least one of patent ductus arteriosus, early or late sepsis, severe respiratory distress) (84.6% vs. 51.9%), medically assisted procreation (33.8% vs. 18.8%) and periventricular leukomalacia (10.8% vs. 2.7%), and a lower frequency of steroids prophylaxis (67.7% vs. 86.9%). About 50% of cases needed surgery. The OR for the direct effect were difference from one using logistic regression booth without and with repeated measures statements: from 1.14 to 4.21 (p = .019) and from 1.16 to 4.29 (p = .016), respectively.ConclusionsOur study suggests that twinning may be a risk factor for the development of AID. Due to the small number of cases observed, further studies on larger populations are needed.

ABSTRACT Clostridium neonatale was described as a new species within the Clostridium genus cluster I sensu stricto. It was recovered from the gut microbiota of infants and has been associated with necrotizing enterocolitis (NEC), a severe gastrointestinal disease affecting preterm neonates. In the absence of molecular typing methods, we developed a core (cg)-genome multilocus sequence typing (MLST) scheme based on 48 newly sequenced and 12 publicly available genomes of C. neonatale. Using the ChewBBACA algorithm, a stable MLST scheme consisting of 2,350 target genes (with genomes having ≥95% cgMLST targets) is proposed. The strains are distributed among five clades, and while some are clonality related within clades, the C. neonatale strain distribution is independent of geographic or temporal clustering. When considering strains isolated from patients with and without NEC, there were no observable differences in clustering. When compared to a core-single nucleotide polymorphism (SNP) analysis approach (31,248 positions), we showed that both cgMLST and cgSNP have comparable genetic discrimination of strains. In this study, we validated the use of cgMLST and cgSNP-based typing methods for the genetic comparison of clinical isolates of C. neonatale, which will allow for future surveillance and epidemiological clinical investigations of this potential opportunistic pathogen. IMPORTANCE Clostridium neonatale has been isolated from the fecal samples of asymptomatic neonates and cases of necrotizing enterocolitis (NEC). Taking advantage of a large collection of independent strains isolated from different spatio-temporal settings, we developed and established a cgMLST scheme for the molecular typing of C. neonatale. Both the cgMLST and cgSNP methods demonstrate comparable discrimination power. Results indicate geographic- and temporal- independent clustering of C. neonatale NEC-associated strains. No specific cgMLST clade of C. neonatale was genetically associated with NEC.

Introduction: Neonatal appendicitis is extremely rare and lacks specific clinical signs. Given its rarity, lack of specific physical signs and the subsequent low index of suspicion; diagnosis and surgical intervention are often delayed in neonates resulting in significant morbidity and mortality. Case presentation: We describe the case of a premature twin male born via spontaneous vaginal delivery at 22 weeks of gestation. Due to hypoxic respiratory failure and sepsis at birth, he required prolonged ventilator support and intermittent vasopressor support. On the 26th day of life, he developed feeding intolerance with hypotension and was found to have abdominal distension and significant pneumoperitoneum on plain radiograph without signs of peritonitis on physical exam. During an emergent laparotomy with ileocecectomy, he was found to have acute gangrenous appendicitis with large perforation at the base. Pathology examination demonstrated transmural necrosis of the appendix with perforation and an abundance of ganglion cells throughout the length of the examined bowel, excluding the possibility of Hirschsprung's disease. Conclusion: While neonatal appendicitis is historically considered rare, given improved survival of premature babies due to medical advances in perinatal care, it is expected that the incidence of neonatal appendicitis will continue to rise. Our case report describes the unusual presentation of neonatal appendicitis without peritonitis despite significant pneumoperitoneum and it highlights the importance of having a thorough understanding of the nonspecific signs of neonatal appendicitis and a higher index of suspicion with a comprehensive differential diagnosis to facilitate a timely diagnosis and initiate urgent surgical intervention.

Introduction: A boy with chronic intestinal dysmotility and severe abdominal distention developed complete intestinal obstruction by age three. We present a unique case of acquired Type IIIa colonic atresia, likely as a progressive sequela from necrotizing enterocolitis (NEC). Case presentation: Born with suspected prune belly syndrome (PBS) and severe ileus, he was treated for NEC at one month of age. Prior to age three, he was hospitalized over 20 times for abdominal distention, vomiting and electrolyte derangements and treated with rehydration and stomach decompression. He passed stool infrequently and tolerated small amounts of formula by mouth for months at a time. A dysmotility workup at 23 months showed gastroparesis with abnormal antroduodenal motility and normal anorectal motility. Imaging at birth showed dilated bowel without obstruction. Radiographic imaging showed progression from ileus to stricture to obstruction over a 3-year period. At age three, exploratory laparotomy revealed Type IIIa colonic atresia in the transverse colon with complete mesenteric separation. The massive right colon was resected, and a diverting ileostomy created. He continues to have oral aversion, gastroparesis, and malabsorption due to pseudo-obstruction. Conclusion: The absence of a distal microcolon and the patent bowel on imaging done early in life, are compatible with acquired, instead of congenital, Type IIIa colonic atresia. Previously reported cases of acquired colonic atresia associated with NEC have been type I and found in infancy. An acquired colonic atresia with complete mesenteric separation is highly unusual. This is the first report of such a finding in a three-year-old child.

ABSTRACTMicrobiome-targeting therapies have received great attention as approaches to prevent disease in infants born preterm, but their safety and efficacy remain uncertain. Here we summarize the existing literature, focusing on recent meta-analyses and systematic reviews that evaluate the performance of probiotics, prebiotics, and/or synbiotics in clinical trials and studies, emphasizing interventions for which the primary or secondary outcomes were prevention of necrotizing enterocolitis, late-onset sepsis, feeding intolerance, and/or reduction in hospitalization length or all-cause mortality. Current evidence suggests that probiotics and prebiotics are largely safe but conclusions regarding their effectiveness in the neonatal intensive care unit have been mixed. To address this ambiguity, we evaluated publications that collectively support benefits of probiotics with moderate to high certainty evidence in a recent comprehensive network meta-analysis, highlighting limitations in these trials that make it difficult to support with confidence the routine, universal administration of probiotics to preterm infants.

ABSTRACTBacterial colonization in the gut plays a pivotal role in neonatal necrotizing enterocolitis (NEC) development, but the relationship between bacteria and NEC remains unclear. In this study, we aimed to elucidate whether bacterial butyrate end-fermentation metabolites participate in the development of NEC lesions and confirm the enteropathogenicity of Clostridium butyricum and Clostridium neonatale in NEC. First, we produced C.butyricum and C.neonatale strains impaired in butyrate production by genetically inactivating the hbd gene encoding β-hydroxybutyryl-CoA dehydrogenase that produces end-fermentation metabolites. Second, we evaluated the enteropathogenicty of the hbd-knockout strains in a gnotobiotic quail model of NEC. The analyses showed that animals harboring these strains had significantly fewer and less intense intestinal lesions than those harboring the respective wild-type strains. In the absence of specific biological markers of NEC, the data provide original and new mechanistic insights into the disease pathophysiology, a necessary step for developing potential novel therapies.

Background: Neonatal gastric perforation (NGP) is an uncommon but fatal condition. The exact cause of NGP remains unclear, although some cases have been linked to medical interventions. NGP is rarely reported in twins. Case Presentation: Herein we report two cases of gastric perforation in twins. The first baby was one of the 34-week preterm twins that developed abdominal distension and respiratory distress on the third day of life. While the other baby was one of the 32-week preterm twins that too developed abdominal distension and respiratory distress. Both had gastric perforations that needed surgical repair. One baby died of sepsis while the other neonate had a stormy postoperative course, which was managed with meticulous monitoring and multidisciplinary management, and discharged in good clinical condition. Conclusion: Clinical cases demonstrate that successful management of NGP requires a multidisciplinary approach, including timely surgical intervention, meticulous postoperative care, and close monitoring of complications.

Introduction: There is no adequate and easily reproducible model of complicated necrotizing enterocolitis (NEC) that allows to study its etiopathogenesis and test various surgical treatment options in an experiment.Objective: To devise a method for in vivo modeling of complicated NEC using laparoscopy.Materials and methods: Our study was conducted at the premises of the Laboratory of Experimental Surgery and Oncology (Scientific Research Institute of Experimental Medicine, Kursk State Medical University) in compliance with international ethical standards and guidelines for humane animal treatment. Fifteen immature male rabbits underwent laparoscopy under inhalation anesthesia and then subserosal injection of damaging solutions (33% H2O2, 10% CaCl2, 4% KCl, 70% C2H5OH, 10% CH2O) into the intestinal wall. In 24 hours, we performed laparotomy, assessed pathological changes visually, and resected the section of the intestinal tube at the injection site. Then we performed a single­layer end­to­end intestinal anastomosis. Histological samples were made from a biopsy specimen. Morphological assessment of the changes was performed.Results: The most pronounced macro­ and microscopic changes were found in the animals injected with hydrogen peroxide. We assessed changes in the abdominal cavity 24 hours since the start of modeling and observed a pattern of partial intestinal obstruction and serous peritonitis. The morphological pattern was characterized by acute circulatory disorder in the intestinal wall with ulcerative necrotic defects and perforations.Conclusions: Based on morphological manifestations we devised a method for modeling complicated NEC using laparoscopy. It is easily reproducible in an in vivo experiment, close to the clinical situation, and allows to simulate typical morphological changes during severe NEC.

ObjectivePatients with necrotizing enterocolitis display severe gastrointestinal complications of prematurity, but the mechanism driving this clinical profile remains unknown. We used mass cytometry time-of-flight to characterize and compare immune cell populations in the blood and intestine tissue from patients with and without (controls) necrotizing enterocolitis at single-cell resolution.MethodsWe completed a deep mapping of the immune system of the peripheral blood mononuclear cells and intestinal mucosa tissue using mass cytometry to evaluate immune cell types, which revealed global immune dysregulation characteristics underlying necrotizing enterocolitis.ResultsCompared with controls, natural killer cells display signs of heightened activation and increased cytotoxic potential in the peripheral blood and mucosa of patients with necrotizing enterocolitis. Furthermore, CD4+ T effector memory cells, non-classical monocytes, active dendritic cells, and neutrophils were specifically enriched in the mucosa, suggesting trafficking from the periphery to areas of inflammation. Moreover, we mapped the systemic and local distinct immune signatures suggesting patterns of cell localization in necrotizing enterocolitis.ConclusionWe used mass cytometry time-of-flight technology to identify immune cell populations specific to the peripheral blood and intestinal mucosa tissue from patients with necrotizing enterocolitis and controls. This information might be used to develop precise diagnosis and therapies that target specific cell populations in patients with necrotizing enterocolitis.

A broad range of allergic disorders and intolerance are associated with cow's milk protein in the infant diet. Allergy and intolerance to cow's milk proteins are commonly recognized in the healthy term infant, and the prevalence cow's milk protein intolerance (CMPI) varies widely but 5 challenge confirmed studies free from selection bias ranged from 1.9%-4.9%. These disorders are classified by the presence of IgE, non-IgE or T-cell-mediated signaling. Additionally, the severity of these adverse food reactions can range from mild gastrointestinal symptoms to severe sepsis-like episodes, as in the case of food protein-induced enterocolitis syndrome (FPIES). Food protein-induced intolerance in the healthy young infant lies in stark contrast to enterocolitis that typically occurs in the preterm neonate. Necrotizing enterocolitis (NEC) is a distinct progressive disease process, usually characterized by a high mortality rate, with a risk of death from 30% to 50%. While its exact etiology is unclear, its main triggers include formula (cow's milk protein), hypoxia, perfusion-related issues, and unregulated inflammation in the premature intestine. The distinction between NEC and cow's milk protein intolerance is difficult to discern in some cases. In the late preterm population, infants with colitis can have both NEC and cow's milk intolerance on the differential. In infants with multiple episodes of mild NEC, cow's milk protein intolerance may be the underlying diagnosis. In this review, we compare the pathophysiological characteristics, diagnosis and treatment of disorders of cow's milk protein intolerance with the entity of preterm NEC. This review highlights similarities in both entities and may inspire future cross-disciplinary research.

Introduction: Upon birth, a hitherto naïve immune system is confronted with a plethora of microbial antigens due to intestinal bacterial colonization. To prevent excessive inflammation and disruption of the epithelial barrier, physiological mechanisms must promote immune-anergy within the neonatal gut. As high concentrations of human lactoferrin (hLF), a transferrin glycoprotein shown to modulate macrophage function, are frequently encountered in colostrum, its direct interaction with intestinal macrophages may satisfy this physiological need. Thus, the primary objective of this study was to investigate transcriptional changes induced by human lactoferrin in neonatal monocyte-derivedmacrophages. Methods: Cord blood-derivedmonocytesweredifferentiatedwithM-CSF in presence or absence of 500 μg/mL hLF for 7 days and afterwards stimulatedwith 1 ng/mL LPS or left untreated. RNA was then isolated and subjected tomicroarray analysis. Results: Differentiation of cord blood-derived monocytes in presence of hLF induced a distinct transcriptional program defined by cell cycle arrest in the G2/M phase, induction of IL-4/IL-13-like signaling, altered extracellular matrix interaction, and enhanced propensity for cell-cell interaction. Moreover, nearcomplete abrogation of transcriptional changes induced by TLR4 engagement with LPS was observed in hLF-treated samples. Discussion: The global transition towards an M2-like homeostatic phenotype and the acquisition of quiescence elegantly demonstrate theontogenetical relevanceof hLF in attenuating pro-inflammatory signaling within the developing neonatal intestine. The marked anergy towards proinflammatory stimuli such as LPS further underlines the glycoprotein's potential therapeutic relevance. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is an inflammatory intestinal disease that profoundly affects preterm infants. Currently, the pathogenesis of NEC remains controversial, resulting in limited treatment strategies. The preterm infants are thought to be susceptible to gut inflammatory disorders because of their immature immune system. In early life, intestinal macrophages (IMjs), crucial components of innate immunity, demonstrate functional plasticity and diversity in intestinal development, resistance to pathogens, maintenance of the intestinal barrier, and regulation of gut microbiota. When the stimulations of environmental, dietary, and bacterial factors interrupt the homeostatic processes of IMjs, they will lead to intestinal disease, such as NEC. This review focuses on the IMjs related pathogenesis in NEC, discusses the multi-functional roles and relevant molecular mechanisms of IMjs in preterm infants, and explores promising therapeutic application for NEC. [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]

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]

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]

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: 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]

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]

Antibiotic overutilization in the neonatal intensive care unit (NICU) has many adverse effects, and necrotizing enterocolitis (NEC) is one of the most common indications for antibiotics in premature infants. Evidence for a preferred antibiotic regimen for NEC is lacking. This project aims to reduce piperacillin-tazobactam use and overall antibiotic duration in neonates with NEC through the implementation of an antibiotic stewardship pathway based on the modified Bell stage classification system. A multidisciplinary team consisting of neonatology, pharmacy, infectious disease, and surgery developed an antibiotic protocol for the management of NEC based on Bell stage. Recommendations included 48 h of ampicillin/gentamicin (AG) for stage I, 5–10 days of AG for stage II, the addition of metronidazole for stage IIIA, and 7–14 days of piperacillin-tazobactam (PT) for stage IIIB. We evaluated overall antibiotic and PT exposure, progression to surgical NEC, NEC recurrence, antibiotic resistance, bacteremia/fungemia, and mortality 1 year pre- and post-protocol implementation. 27 patients pre-intervention and 44 post-intervention were analyzed. Antibiotic exposure was reduced from a median 119.19 to 80.65 days of therapy (DOT) per 1000 patient days (p = 0.11). PT exposure decreased after protocol implementation (median 68.78 vs. 7.97 DOT per 1000 patient days, p = 0.002). There were no significant differences in morbidity or mortality outcomes. Antibiotic stewardship strategies can be implemented in the NICU without compromising outcomes in patients with NEC. Bell stage stratification appears to be an effective method for antibiotic selection. Further studies are needed in a larger population to optimize regimens and ensure safety. Retrospective comparative study. Level III. [ABSTRACT FROM AUTHOR]

Maturational changes in the gut start in utero and rapidly progress after birth, with some functions becoming fully developed several months or years post birth including the acquisition of a full gut microbiome, which is made up of trillions of bacteria of thousands of species. Many factors influence the normal development of the neonatal and infantile microbiome, resulting in dysbiosis, which is associated with various interventions used for neonatal morbidities and survival. Extremely low gestational age neonates (<28 weeks' gestation) frequently experience recurring arterial oxygen desaturations, or apneas, during the first few weeks of life. Apnea, or the cessation of breathing lasting 15–20 s or more, occurs due to immature respiratory control and is commonly associated with intermittent hypoxia (IH). Chronic IH induces oxygen radical diseases of the neonate, including necrotizing enterocolitis (NEC), the most common and devastating gastrointestinal disease in preterm infants. NEC is associated with an immature intestinal structure and function and involves dysbiosis of the gut microbiome, inflammation, and necrosis of the intestinal mucosal layer. This review describes the factors that influence the neonatal gut microbiome and dysbiosis, which predispose preterm infants to NEC. Current and future management and therapies, including the avoidance of dysbiosis, the use of a human milk diet, probiotics, prebiotics, synbiotics, restricted antibiotics, and fecal transplantation, for the prevention of NEC and the promotion of a healthy gut microbiome are also reviewed. Interventions directed at boosting endogenous and/or exogenous antioxidant supplementation may not only help with prevention, but may also lessen the severity or shorten the course of the disease. [ABSTRACT FROM AUTHOR]

Early-life gut dysbiosis has been associated with an increased risk of inflammatory, metabolic, and immune diseases later in life. Data on gut microbiota changes in infants undergoing intestinal surgery requiring enterostomy are scarce. This prospective cohort study examined the enterostomy effluent of 29 infants who underwent intestinal surgery due to congenital malformations of the gastrointestinal tract, necrotizing enterocolitis, or spontaneous intestinal perforation. Initial effluent samples were collected immediately after surgery and final effluent samples were collected three weeks later. Gut microbiota composition was analysed using real-time PCR and 16S rRNA gene sequencing. Three weeks after surgery, an increase in total bacteria number (+21%, p = 0.026), a decrease in Staphylococcus (−21%, p = 0.002) and Candida spp. (−16%, p = 0.045), and an increase in Lactobacillus (+3%, p = 0.045) and in less abundant genera belonging to the Enterobacteriales family were found. An increase in alpha diversity (Shannon's and Simpson's indexes) and significant alterations in beta diversity were observed. A correlation of necrotizing enterocolitis with higher Staphylococcus abundance and higher alpha diversity was also observed. H2-blockers and/or proton pump inhibitor therapy were positively correlated with a higher total bacteria number. In conclusion, these results suggest that positive changes occur in the gut microbiota profile of infants three weeks after intestinal surgery. [ABSTRACT FROM AUTHOR]

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

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]

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]

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]

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]

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]

Prematurity is the leading cause of early neonatal death and child morbidity. Numerous attempts to prevent premature births have not led to a significant decrease in their rate in the world, therefore it is important to organize the medical care for premature babies during childbirth and in the first minutes of life. Kyiv Perinatal Center has many years of experience in providing care to premature newborns, which is implemented in cooperation with obstetrician-gynecologists and neonatologists. The objective: to assess the dynamics of neonatal indicators in the Kyiv Perinatal Center for 2012–2022. Materials and methods. The dynamics of neonatal indicators (early neonatal mortality, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), leukomalacia) were assessed quarterly in newborns with a gestational age of 22–34 weeks for 2012–2022 using the linear regression method. The impact of implemented technologies – intranatal magnesium therapy in 2014 and the method of stabilizing a newborn on a pulsating umbilical cord in 2016 on the indicated indicators was also studied. Therefore, 3 time periods were formed – 2012–2013, 2014–2015, and 2016–2022 years. For quantitative indicators, the median and interquartile range were calculated. The Kruskal–Wallis test was used for comparison. Aposteriori comparisons were made according to Dunn’s test. Results. During 10 years of work at the Perinatal Center, a decreased rate of early neonatal mortality among premature newborns was determined from 12.7±2.5% to 1.7±0.9% (р<0.05), while the rate of the second period was significantly different from the first one, and the second period – from the third one, that is, it was influenced by the wide implementation of both intranatal magnesium therapy and stabilization on an intact umbilical cord. A tendency towards a decrease in the frequency of IVH was established during the second period – from 12.0±3.1% to 5.6±1.5%, during the third one – to 2.0±1.3% (p<0.05), i.e. both interventions had a positive effect on this indicator. A similar pattern was found for NEC and leukomalacia, the frequency of which decreased from 9.3±1.7% to 2.0±0.9% (p<0.05) and from 3.6±1.3% to 0.1±0.2% (p<0.05), respectively. Instead, a decrease in the frequency of BPD and the need for invasive ventilation was found only for the third time interval – from 4.0±0.9% to 1.1±0.7% (p<0.05) and 13.8±2.8% to 6.5±2.0% (p<0.05), respectively. To prevent these complications, the technique of stabilizing the newborn on an intact umbilical cord is effective. Conclusions. In the process of activity of the Kyiv Perinatal Center, a statistically significant decrease in the rate of early neonatal mortality in premature births was found (from 12.7±2.5% in 2012 to 1.7±0.9% in 2022), as well as the frequency of the main complications of prematurity – intraventricular hemorrhages, necrotizing enterocolitis, bronchoalveolar dysplasia, leukomalacia. A decrease in the frequency of invasive pulmonary ventilation of premature newborns was also determined. According to the linear regression method, a significant effect of the widespread introduction of magnesium therapy on the rate of early neonatal mortality, the frequency of intraventricular hemorrhages, necrotizing enterocolitis, and leukomalacia was demonstrated, as well as the significant importance of the widespread implementation of the technology of stabilizing the newborn on an intact umbilical cord on the indicator of early neonatal mortality, the frequency of necrotizing enterocolitis, leukomalacia and bronchopulmonary dysplasia. [ABSTRACT FROM AUTHOR]

Human milk (HM) has been associated with a lower risk of necrotizing enterocolitis (NEC). However, the association of precise HM proportion with the outcome of NEC remains unclear. A total of 77 cases and 154 matched controls were included in this study. The samples were divided into three groups based on the HM proportion of the total enteral intake before NEC onset: ≥70% (HHM), <70% (LHM), and 0% (NHM). The study cohort did not show a significant association between different HM proportions and NEC risk. The adjusted odds ratio (OR) for the highest versus the lowest intake was 0.599. In the prognosis of NEC, different HM proportions significantly affected weight gain, the timing of NEC onset, diagnosis time, hospitalization cost, and the severity of NEC (p < 0.05). Our findings support the beneficial effects of HM on reducing NEC in preterm infants, particularly when a greater proportion of HM of the total enteral intake is included in their feeding. Additionally, the study indicates that preterm infants fed with lower proportions of HM of the total enteral feeding are more prone to experiencing severe cases of NEC. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is the leading cause of intestinal morbidity and mortality in neonates. A large body of work exists; however, the pathogenesis of NEC remains poorly understood. Numerous predictors have been implicated in the development of NEC, with relatively less emphasis on maternal factors. Utilizing human tissue plays a crucial role in enhancing our comprehension of the underlying mechanisms accountable for this devastating disease. In this review, we will discuss how maternal stress affects the pathogenesis of NEC and how changes in the intestinal microbiome can influence the development of NEC. We will also discuss the results of transcriptomics-based studies and analyze the gene expression changes in NEC tissues and other molecular targets associated with the pathogenesis of NEC. [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]

With the development and progress of medical technology, the survival rate of premature and low-birth-weight infants has increased, as has the incidence of a variety of neonatal diseases, such as hypoxic–ischemic encephalopathy, intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, and retinopathy of prematurity. These diseases cause severe health conditions with poor prognoses, and existing control methods are ineffective for such diseases. Stem cells are a special type of cells with self-renewal and differentiation potential, and their mechanisms mainly include anti-inflammatory and anti-apoptotic properties, reducing oxidative stress, and boosting regeneration. Their paracrine effects can affect the microenvironment in which they survive, thereby affecting the biological characteristics of other cells. Due to their unique abilities, stem cells have been used in treating various diseases. Therefore, stem cell therapy may open up the possibility of treating such neonatal diseases. This review summarizes the research progress on stem cells and exosomes derived from stem cells in neonatal refractory diseases to provide new insights for most researchers and clinicians regarding future treatments. In addition, the current challenges and perspectives in stem cell therapy are discussed. [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]