Necrotizing Enterocolitis Research Articles

Probiotics to prevent necrotizing enterocolitis and reduce mortality in neonates: A meta-analysis.

Probiotics are gradually being used as a supplementation to prevent necrotizing enterocolitis (NEC) and reduce mortality in neonates. We performed an updated meta-analysis to systematically evaluate the efficacy and safety of prophylactic probiotic supplementation for preventing NEC. The databases including PubMed, Embase, Scopus, Web of Science, and China National Knowledge Infrastructure were used to search the relevant articles. The latest retrieval date was up to December 2021. The meta-analysis was performed using Stata version 10.0. Finally, a total of 70 studies containing 8319 cases and 9283 controls were included. The strength of the association between the supplementation of probiotics and NEC was measured by risk ratios (RRs) with 95% confidence intervals (CIs). Pooled effect sizes across studies were performed by a random effect model. The results showed that the probiotics could significantly reduce the incidence of NEC (stage II or more) (RR = 0.436, 95% CI = 0.357-0.531, P < .001), the overall mortality (RR = 0.651, 95% CI = 0.506-0.836, P < .001), and NEC-related mortality (RR = 0.639, 95% CI = 0.423-0.966, P = .034). Due to the lack of sufficient sample size, we did not perform the subgroup analysis by types of probiotic strain. This meta-analysis indicates that the use of probiotics can effectively reduce the occurrence of NEC and mortality in neonates.

Molecular Mechanisms of Hyperoxia-Induced Neonatal Intestinal Injury

Oxygen therapy is important for newborns. However, hyperoxia can cause intestinal inflammation and injury. Hyperoxia-induced oxidative stress is mediated by multiple molecular factors and leads to intestinal damage. Histological changes include ileal mucosal thickness, intestinal barrier damage, and fewer Paneth cells, goblet cells, and villi, effects which decrease the protection from pathogens and increase the risk of necrotizing enterocolitis (NEC). It also causes vascular changes with microbiota influence. Hyperoxia-induced intestinal injuries are influenced by several molecular factors, including excessive nitric oxide, the nuclear factor-κB (NF-κB) pathway, reactive oxygen species, toll-like receptor-4, CXC motif ligand-1, and interleukin-6. Nuclear factor erythroid 2-related factor 2 (Nrf2) pathways and some antioxidant cytokines or molecules including interleukin-17D, n-acetylcysteine, arginyl-glutamine, deoxyribonucleic acid, cathelicidin, and health microbiota play a role in preventing cell apoptosis and tissue inflammation from oxidative stress. NF-κB and Nrf2 pathways are essential to maintain the balance of oxidative stress and antioxidants and prevent cell apoptosis and tissue inflammation. Intestinal inflammation can lead to intestinal damage and death of the intestinal tissue, such as in NEC. This review focuses on histologic changes and molecular pathways of hyperoxia-induced intestinal injuries to establish a framework for potential interventions.

Outcome of infants with necrotising enterocolitis at Charlotte Maxeke Johannesburg Academic Hospital, South Africa

Background. Necrotising enterocolitis (NEC) is an inflammatory disease almost exclusively affecting preterm infants. Previous research has presented a higher mortality rate in infants requiring surgical treatment compared with infants receiving medical treatment. However, the knowledge of mortality and morbidity of the disease in low- and middle-income countries is still limited.Objectives. To review infants with NEC admitted to the neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH),determine a potential difference in mortality between medically and surgically treated infants, and to identify characteristics and factors associated with mortality among these infants.Methods. This retrospective study described infants with NEC born between 1 January 2016 and 31 December 2018 who were admittedto the neonatal unit. The characteristics and survival of these infants were compared using univariate and multivariate analyses.Results. During the study period, 5 061 infants were admitted to the neonatal unit, of which 218 infants were diagnosed with NEC.The period prevalence of NEC was 4.3% among all neonatal infants and 11.0% among very-low-birthweight (VLBW) infants. Mortalitywas significantly higher among surgically treated infants with NEC compared with medically treated infants (p=0.025, odds ratio 1.888(95% confidence interval 1.082 - 3.296)). Late-onset sepsis was significantly more common among VLBW infants with NEC (71.3%)compared with VLBW infants without NEC (27.1%). Among infants with late-onset sepsis, Gram-negative bacteria, multidrug-resistantbacteria and fungal sepsis was significantly more common in the group of infants with NEC.Conclusions. Infants with NEC treated surgically at CMJAH have an increased risk of dying compared with those receiving medicaltreatment, likely due to the severity of disease. Furthermore, this study emphasised the burden of sepsis among infants with NEC and may contribute to a better knowledge of NEC in South Africa.

Neonatal necrotizing enterocolitis: Clostridium butyricum and Clostridium neonatale fermentation metabolism and enteropathogenicity

ABSTRACT Bacterial 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.

Screening inflammatory protein biomarkers on premature infants with necrotizing enterocolitis

ObjectiveThis study aimed to explore potential inflammatory biomarkers for early prediction of necrotizing enterocolitis (NEC) in premature infants.MethodsPlasma samples were collected from premature infants with NEC (n = 30), sepsis (n = 29), and controls without infection (n = 29). The 92 inflammatory-related proteins were assessed via high-throughput OLINK proteomics platform.ResultsThere were 11 inflammatory proteins that significate differences (p < 0.05) among NEC, sepsis and control preterm infants, which include IL-8, TRAIL, IL-24, MMP-10, CCL20, CXCL1, OPG, TSLP, MCP-4, TNFSF14 and LIF. A combination of these 11 proteins could serve as differential diagnosis between NEC and control infants (AUC = 0.972), or between NEC and sepsis infants (AUC = 0.881). Furthermore, the combination of IL-8, OPG, MCP-4, IL-24, LIF and CCL20 could distinguish Stage II and III of NEC (AUC = 0.977). Further analysis showed the combination of IL-8, IL-24 and CCL20 have the best prediction value for NEC and control (AUC = 0.947), NEC and sepsis (AUC = 0.838) and different severity of NEC (AUC = 0.842).ConclusionInflammatory proteins were different expressed in premature infants with NEC compared with controls or sepsis. Combining these proteins provide a higher diagnostic potential for preterm NEC infants.

ПРЕДИКТОРЫ НЕКРОТИЗИРУЮЩЕГО ЭНТЕРОКОЛИТА У НЕДОНОШЕННЫХ НОВОРОЖДЕННЫХ С ГЕСТАЦИОННЫМ ВОЗРАСТОМ МЕНЕЕ 32 НЕДЕЛЬ

Necrotizing enterocolitis (NEC) is a serious gastrointestinal problem in premature newborns that can often lead to a poor outcome. Physicians’ knowledge of the earliest predictors of NEC will reduce the likelihood of its development. The purpose of the research was to seek for the earliest predictors of NEC development in the neonatal period in surviving premature newborns with the gestational age (GA) at birth of less than 32 weeks. Materials and methods used: a single-center retrospective cohort study. The analysis of 167 medical records in the Moscow Oblast Regional Perinatal Center (MOPC, located in Balashikha, Moscow Oblast, Russia) was carried out. Inclusion criteria: 1) newborns with GA of less than 32 weeks; 2) information corresponding to the primary variables of this research in the patient's medical records; 3) patients were treated during the period from Apr. 22 to Dec. 24, 2021. Exclusion criteria: 1) lethal outcome, 2) congenital malformations affecting the outcome, 3) chromosomal and/or genetic abnormalities. Two groups: G1 (“NEC”) of 35 patients with NEC; G2 (“without NEC”) of 132 without NEC. Results: NEC incidence was 8.3% (35/167). Prenatal factors that are statistically significantly more common in the NEC group: an increase in the level of C-reactive protein (CRP) in the mother's blood prior to the delivery (p=0.003), an increase in pathogenic microflora during pregnancy (p=0.010), detection of Enterococcus faecalis during pregnancy (p=0.016), delivery by the C-section (p=0.028) and the C-section due to fetal deterioration (p=0.001). In premature newborns from the NEC group, a decrease in serum albumin (SA) concentration was statistically significantly more common in the first 30 hours of life (p&lt;0.001). The use of dexamethasone in the first 168 hours of life (p=0.003) and for the prevention of bronchopulmonary dysplasia (p=0.010) was statistically significantly more common in patients with NEC. Conclusion: the earliest prenatal predictors of NEC in surviving premature newborns with the GA at birth of less than 32 weeks are as follows: an increase in the level of CRP in the mother's blood prior to the delivery, the growth of pathogenic microflora during pregnancy, esp. of the fecal Enterococcus, the C-section, esp. due to the deterioration of the fetus; and the postnatal predictors of NEC are as follows: lower concentration of SA in premature infants in the first 30 hours of life, the use of dexamethasone in the neonatal period.

Dynamic changes of the gut microbial colonization in preterm infants with different time points after birth.

Risks associated with preterm birth are unevenly distributed across all gestations. At earlier gestational ages, complications such as necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) conditions are significantly more common and are associated with a shift in the composition of the gut microbiome. Conventional bacterial culture techniques demonstrate that the colonization of the gut microbiota of preterm infants differs significantly from that of healthy-term infants. The current study aimed to investigate the impact of preterm infancy on the dynamic changes of fecal microbiota in preterm infants at different time points (1, 7, 14, 21, 28, and 42 days) after birth. We selected 12 preterm infants hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2017. A total of 130 fecal specimens from preterm infants were analyzed using 16S rRNA gene sequencing. We found that the colonization process of fecal microbiota in preterm infants is highly dynamic at different time points after birth, i.e., Exiguobacterium, Acinetobacter, and Citrobacter showed a declining abundance pattern with the advancement of age, while the bacterial groups of Enterococcus (Klebsiella and Escherichia coli) gradually grew and became the main microbiota during the development of fecal microbiota in preterm infants at the age of 42 days. Furthermore, the colonization of intestinal Bifidobacteria in preterm infants was relatively late and did not rapidly become the predominant microbiota. Moreover, the results also showed the presence of Chryseobacterium bacterial group, whose colonization was different in different time point groups. Conclusively, our findings deepen our comprehension and offer new perspectives on targeting particular bacteria in the treatment of preterm infants at different time points after birth.

Therapeutic Potential of Gut Microbiota and Its Metabolite Short-Chain Fatty Acids in Neonatal Necrotizing Enterocolitis

Short chain fatty acids (SCFAs), the principle end-products produced by the anaerobic gut microbial fermentation of complex carbohydrates (CHO) in the colon perform beneficial roles in metabolic health. Butyrate, acetate and propionate are the main SCFA metabolites, which maintain gut homeostasis and host immune responses, enhance gut barrier integrity and reduce gut inflammation via a range of epigenetic modifications in DNA/histone methylation underlying these effects. The infant gut microbiota composition is characterized by higher abundances of SCFA-producing bacteria. A large number of in vitro/vivo studies have demonstrated the therapeutic implications of SCFA-producing bacteria in infant inflammatory diseases, such as obesity and asthma, but the application of gut microbiota and its metabolite SCFAs to necrotizing enterocolitis (NEC), an acute inflammatory necrosis of the distal small intestine/colon affecting premature newborns, is scarce. Indeed, the beneficial health effects attributed to SCFAs and SCFA-producing bacteria in neonatal NEC are still to be understood. Thus, this literature review aims to summarize the available evidence on the therapeutic potential of gut microbiota and its metabolite SCFAs in neonatal NEC using the PubMed/MEDLINE database.

Clinical characteristics and risk factors for early-onset necrotizing enterocolitis in preterm infants with very/extremely low birth weight

To investigate the clinical characteristics and risk factors for early-onset necrotizing enterocolitis (NEC) in preterm infants with very/extremely low birth weight (VLBW/ELBW). A retrospective analysis was performed on the medical data of 194 VLBW/ELBW preterm infants with NEC who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. These infants were divided into early-onset group (onset in the first two weeks of life; n=62) and late-onset group (onset two weeks after birth; n=132) based on their onset time. The two groups were compared in terms of perinatal conditions, clinical characteristics, laboratory examination results, and clinical outcomes. Sixty-two non-NEC infants with similar gestational age and birth weight who were hospitalized at the same period as these NEC preterm infants were selected as the control group. The risk factors for the development of early-onset NEC were identified using multivariate logistic regression analysis. Compared with the late-onset group, the early-onset group had significantly higher proportions of infants with 1-minute Apgar score ≤3, stage III NEC, surgical intervention, grade ≥3 intraventricular hemorrhage, apnea, and fever or hypothermia (P<0.05). The multivariate logistic regression analysis showed that feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, and hemodynamically significant patent ductus arteriosus were independent risk factors for the development of early-onset NEC in VLBW/ELBW preterm infants (P<0.05). VLBW/ELBW preterm infants with early-onset NEC have more severe conditions compared with those with late-onset NEC. Neonates with feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, or hemodynamically significant patent ductus arteriosus have a higher risk of early-onset NEC.

Association between gastrointestinal perforation and patent ductus arteriosus in extremely-low-birth-weight infants: a retrospective study of our decade-long experience.

Management of persistently patent ductus arteriosus (PDA) in extremely low-birth-weight infants (ELBWIs) requires attention due to the risk of tissue hypoperfusion. We investigated the association between PDA and gastrointestinal perforation. We performed a retrospective chart review from 2012 to 2021. Preterm (≤ 32weeks) ELBWIs with PDA after birth who developed necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and idiopathic gastric perforation were included; ELBWIs with congenital heart disease were excluded. Data were analyzed using chi-squared tests with Yates; correction, and Student's t test. Five hundred thirty-five preterm ELBWIs were analyzed, including 20 with NEC, 22 with FIP, and 1 with gastric perforation. In NEC and FIP, the ductus arteriosus remained open in 40% (4/10) and 63.6% (14/22) of cases, respectively, and cyclo-oxygenase inhibitor treatment showed poor efficacy (p = 0.492 and 0.240). The incidence of perforation in NEC (4/9 vs. 6/11, p = 0.653), mortality in NEC (3/4 vs. 3/6, p = 0.895) and FIP (6/14 vs. 3/8, p = 0.838) did not differ according to whether the PDA persisted or resolved. The presentation of PDA did not affect the mortality or morbidity of ELBWIs. However, it is essential to consider the possibility of gastrointestinal perforation due to decreased organ blood flow caused by ductal steal.

Gut-Brain cross talk: The pathogenesis of neurodevelopmental impairment in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating condition of multi-factorial origin that affects the intestine of premature infants and results in high morbidity and mortality. Infants that survive contend with several long-term sequelae including neurodevelopmental impairment (NDI)-which encompasses cognitive and psychosocial deficits as well as motor, vision, and hearing impairment. Alterations in the gut-brain axis (GBA) homeostasis have been implicated in the pathogenesis of NEC and the development of NDI. The crosstalk along the GBA suggests that microbial dysbiosis and subsequent bowel injury can initiate systemic inflammation which is followed by pathogenic signaling cascades with multiple pathways that ultimately lead to the brain. These signals reach the brain and activate an inflammatory cascade in the brain resulting in white matter injury, impaired myelination, delayed head growth, and eventual downstream NDI. The purpose of this review is to summarize the NDI seen in NEC, discuss what is known about the GBA, explore the relationship between the GBA and perinatal brain injury in the setting of NEC, and finally, highlight the existing research into possible therapies to help prevent these deleterious outcomes.

Early antibiotics and risk for necrotizing enterocolitis in premature infants: A narrative review.

While prompt initiation of antibiotics at birth due to concerns for early onset sepsis is common, it often leads to many preterm infants being exposed to treatment despite negative blood cultures. Such exposure to early antibiotics can impact the developing gut microbiome putting infants at increased risk of several diseases. Necrotizing enterocolitis (NEC), a devastating inflammatory bowel disease that affects preterm infants, is among the most widely studied neonatal disease that has been linked to early antibiotics. While some studies have demonstrated an increased risk of NEC, other studies have demonstrated seemingly contrary findings of decreased NEC with early antibiotics. Studies using animal models have also yielded differing findings of benefit vs. harm of early antibiotic exposure on subsequent NEC susceptibility. We thus sought to conduct this narrative review to help clarify the relationship between early antibiotics exposure and future risk of NEC in preterm infants. Our objectives are to: (1) summarize findings from human and animal studies that investigated the relationship between early antibiotics and NEC, (2) highlight important limitations of these studies, (3) explore potential mechanisms that can explain why early antibiotics may increase or decrease NEC risk, and (4) identify future directions for research.

Effects of Hesperidin and Diosmin on Necrotizing Enterocolitis: An Experimental Study

Background: Necrotizing enterocolitis (NEC) is a serious intestinal illness in newborns. Objectives: We aimed to investigate the potential protective effects of hesperidin (Hsd) and diosmin on NEC. Methods: Thirty newborn rats were divided into 3 groups: The control group (n = 10), the NEC group (n = 10), and the treatment group (n = 10). The treatment group was given 100 mg/kg of the flavonoid by oral gavage twice daily. On day 5 of the study, animals were sacrificed under anesthesia. After laparotomy, the tissue samples were obtained from the stomach, cecum, and ileum. NEC scoring was performed histopathologically. Apoptotic changes were evaluated by TUNEL (terminal deoxynucleotidyl transferase–mediated biotin–deoxyuridine triphosphate nick-end labeling) staining. Furthermore, levels of oxidants and antioxidants were determined by biochemical analyzes of the tissues. Results: Glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) levels were significantly higher in the NEC group than in the control group in all gastrointestinal tract regions examined. Similar to the control group, GSH-Px and MDA were found to be low only in the cecum in the group treated with flavonoids. NEC damage score and apoptotic index in all 3 regions examined were significantly higher in the NEC group than in the control and treatment groups. The apoptotic index values in the treatment group were similar in the stomach and cecum, and the NEC damage score was similar to those in the control group only in the cecum. Conclusions: Hsd and diosmin treatment significantly reduces the severity of NEC-induced damage and apoptotic cell death, especially in the cecum.

Association of Early Postoperative Regional Oxygen Saturation Measures and Development of Necrotizing Enterocolitis in Neonates Following Cardiac Surgery.

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 48h following surgery. 166 neonates were included and the median age at time of surgery was 8days. NEC was diagnosed in 18 neonates following heart surgery with a median interval from surgery to diagnosis of 7days. 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.

The correlation between levels of vitamin D (25(HD)D) and the occurrence of necrotizing enterocolitis (NEC) in preterm infants

The correlation between levels of vitamin D (25(HD)D) and the occurrence of necrotizing enterocolitis (NEC) in preterm infants

Does protocol miconazole administration improve mortality and morbidity on surgical necrotizing enterocolitis?

Our previous clinical pilot study reported that miconazole (MCZ) prevented morbidity from surgical necrotizing enterocolitis (NEC). The present study re-investigated this effect in a long-term cohort over 20years. We conducted a retrospective cohort study from April 1998 to March 2020. A total of 1169 extremely low-birth-weight infants (ELBWIs) admitted to our neonatal intensive care unit, including 45 with NEC (3.8%), underwent surgery. Since 2002, protocol MCZ administration for 3weeks has been applied for neonates born before 26weeks' gestation or weighing under 1000g. We compared the background characteristics and clinical outcomes between patients with and without MCZ administration. The morbidity rate decreased after applying the MCZ protocol, but no improvement in mortality was seen. A propensity score-matched analysis indicated that treated patients by MCZ showed a delay in developing surgical NEC by 12days. The MCZ protocol also helped increase body weight at surgery. Prophylactic MCZ administration did not improve the neurological development of the language-social and postural-motor domains in the surgical NEC patients. But cognitive-adaptive domain caught up by a chronological age of 3years old. Revising the protocol to extend the dosing period may improve the outcomes of surgical NEC after the onset.

Long-Term Complications of Neonatal Necrotic Enterocolitis: Twisting of Stenosed Small Intestine

Neonatal necrotic enterocolitis (NEC) is a nonspecific inflammatory disease of unknown etiology with multifactorial pathogenesis, which development is explained as a result of hypoperfusion of the immature intestinal mucosa of a newborn who has undergone perinatal hypoxia and, as a result, a change in blood flow in the mesenteral vascular system. This disease more often affects the intestinal wall of premature babies. In typical cases, mucosal necrosis develops in the terminal iliac and right parts of the colon, and when the process progresses, it can spread to the entire thickness of the intestinal wall, causing its perforation, so peritonitis is a frequent complication of NEC. But in addition, distant complications of NEC are distinguished, which include the development of intestinal obstruction in view of a decrease in the contractility of the intestinal wall section due to its fibrosis and, as a result, narrowing of the lumen.We report the clinical case of surgical treatment of the twisting of stenosed portion of the ileum in a child who underwent NEC in the early neonatal period. A mother sought assistance with a child of 3 months at the Reginal Children’s Hospital (born at 28 weeks of gestation). After birth, there was a violation of the absorption of enteral nutrition (periodic posseting, bloating), blood in the stool was determined. On the 14th day of life a pediatric surgeon examined the baby: necrotizing enterocolitis II A. After stabilizing the condition (2 months), the child was transferred from the perinatal center to a pediatric hospital with a diagnosis of bronchopulmonary dysplasia, a new form, a severe course, and a period of exacerbation. At the age of 2.5 months, he was discharged in a satisfactory condition to the outpatient stage. On the 15th day from the moment of discharge (3 months of life), the mother noted the expressed anxiety of the baby, bloating, stool retention. On the 16th day from the moment of discharge during feeding, the child began to suck sluggishly, did not absorb the age norm. He was examined by a pediatrician, the consultation of a pediatric surgeon was recommended. Due to the severity of the condition, the baby was hospitalized.In the initial examination, no data for intestinal obstruction were detected. The patient received parenteral nutrition, antibacterial therapy. Ultrasound and radiography of abdominal organs were performed daily. On the third day of observation, deterioration is noted (abdomen bloated mainly in the upper parts, soft upon with palpation, the baby was anxious, peristalsis was reduced), with ultrasound: between the loops of the enlarged intestine, an echogenic band of up to 18 mm (adhesion?) was determined, there was the liquid component between the loops. A laparotomy was performed, during the revision there was a displacement of the large intestine into the left parts of the abdominal cavity. Ten cm from the ileocecal angle, a section of the ileum with a length of up to 15 cm was found, which was like a “double trunk” wrapped at the base around its axis around a cord-like adhesive stretching to the posterior abdominal wall. Visually, the loop was dark bard in color, its walls were swollen, infiltrated, and their cartilaginous density was determined upon palpation in the contact area of the walls of the intestine. The resection of this loop was performed, end-to-end anastomosis was formed according to the method of J. Louw. After the operation, the baby received treatment in the intensive care unit, enteral feeding on day 5, on day 9, after expanding the volume of feeding, he was transferred to the department of pediatric surgery. Discharged in satisfactory condition on the 12th day after surgery.

Effectiveness of a neonatal intensive care unit-specific antimicrobial stewardship program: A ten-year review.

To evaluate the change in consumption of specific antibiotics in a neonatal intensive care unit after the implementation of an antimicrobial stewardship program (ASP). Retrospective cohort study between January 1, 2010, and December 31,2019. The neonatal intensive care unit at British ColumbiaWomen's Hospital (Vancouver Canada), a tertiary-care center. Admitted neonates prescribed antibiotics. We implemented an ASP with an early implementation phase starting in January 2014 (period 2) and a later phase starting in January 2017 (period 3). Patient demographics were collected, including birth weight, gestational age, history of necrotizing enterocolitis (NEC), and surgical operations from existing databases. Interrupted time-series analysis was used, and comparison of antibiotic days of therapy (DOT) averages were conducted across the preimplementation period (period 1), period 2, and period 3 regarding total patients and subgroups. We identified 4,512 infants. There was a significant decrease in DOT from 472 (95% confidence interval [CI], 431-517) in period 1 to 405 (95% CI, 367-446) in period 2 to 313 (95% CI, 280-350) in period 3. We detected a significant decrease in the use of ampicillin, aminoglycosides, cloxacillin, and linezolid but not in vancomycin or cefotaxime. Subgroup analyses of infants <1,500 g and those without NEC or surgery showed decreases in the use of cloxacillin, aminoglycosides, and linezolid. The implementation of an ASP was associated with a significant decrease in the overall DOT and use of certain antibiotics. This study presents important targets for ongoing ASP work.

Early Empirical Antibiotics and Adverse Clinical Outcomes in Infants Born Very Preterm: A Population-Based Cohort.

The objective of this study was to evaluate the association between empirical antibiotic therapy in the first postnatal week in uninfected infants born very preterm and the risk of adverse outcomes until discharge. Population-based, nationwide registry study in Norway including all live-born infants with a gestational age <32weeks surviving first postnatal week without sepsis, intestinal perforation, or necrotizing enterocolitis (NEC) between 2009 and 2018. Primary outcomes were severe NEC, death after the first postnatal week, and/or a composite outcome of severe morbidity (severe NEC, severe bronchopulmonary dysplasia [BPD], severe retinopathy of prematurity, late-onset sepsis, or cystic periventricular leukomalacia). The association between empirical antibiotics and adverse outcomes was assessed using multivariable logistic regression models, adjusting for known confounders. Of 5296 live-born infants born very preterm, 4932 (93%) were included. Antibiotics were started in first postnatal week in 3790 of 4932 (77%) infants and were associated with higher aOR of death (aOR 9.33; 95% CI: 1.10-79.5, P=.041), severe morbidity (aOR 1.88; 95% CI: 1.16-3.05, P=.01), and severe BPD (aOR 2.17; 95% CI: 1.18-3.98; P=.012), compared with those not exposed. Antibiotics ≥ 5days were associated with higher odds of severe NEC (aOR 2.27; 95% CI: 1.02-5.06; P=.045). Each additional day of antibiotics was associated with 14% higher aOR of death or severe morbidity and severe BPD. Early and prolonged antibiotic exposure within the first postnatal week was associated with severe NEC, severe BPD, and death after the first postnatal week.

Nucleated red blood cells as a potential biomarker for predicting spontaneous intestinal perforation in premature infants

Background: The specific etiology of spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) remains elusive. Both can present acutely without antecedent signs and can be difficult to differentiate. Neonatal nucleated red blood cell (NRBC) counts are part of the routine admission and serial CBCs drawn on premature neonates. Elevated NRBC counts could represent relative intrauterine hypoxemia, a possible risk factor for the development of SIP or NEC. Methods: We compared premature neonates with SIP to premature neonates with NEC and controls, matched gestational age (GA) and birth weight (BW). Kruskal-Wallis, Chi-Square, or Fisher's exact tests and univariate and multivariate nominal logistic regression models were used to estimate the association of baseline NRBC. Median times to SIP and NEC were calculated using the Kaplan-Meier method. All analyses were performed with SAS 9.4. Results: Male sex (72.5%), lower GA [Median (Q1, Q3): 25.1 (23.8, 28)], and lower BW [Median (Q1, Q3): 690 g (585, 1072)] had the highest incidence of SIP compared to NEC or controls. Increased baseline NRBC was associated with lower odds of developing NEC compared to controls [Median (Q1, Q3): 9 (5, 29) vs 19 (10, 51); OR (CI) 0.70 (0.55, 0.89), p-value = 0.0033]. Increased baseline NRBC was associated with higher odds of developing SIP compared to NEC [Median (Q1, Q3): 9 (5, 29) vs 19 (10, 51); OR (CI) 1.61 (1.18, 2.20) p-value = 0.0027]. There were no significant differences between intrauterine growth restriction (IUGR), maternal hypertension, chorioamnionitis, multiple births, or depressed APGAR scores in all three groups. NRBC for SIP neonates remained significantly higher at the day of life (DOL) 1-3 compared to other groups [Median (Q1, Q3): 23 (6, 93), p-value = 0.0020]. The percentage of patients with NRBC &gt;4, remained elevated for patients with SIP as late as week three (p = 0.0023). Conclusion: ELBW, male sex, and elevated baseline NRBC were significantly associated with the risk of developing SIP compared to NEC or controls. NRBC remained significantly elevated on DOL 1-3, compared to NEC or controls. Between the groups, there were no significant differences in perinatal stressors.