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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.

Necrotizing Enterocolitis (NEC) is one of the leading causes of gastrointestinal emergency in preterm infants. Although NEC was formally described in the 1960's, there is still difficulty in diagnosis and ultimately treatment for NEC due in part to the multifactorial nature of the disease. Artificial intelligence (AI) and machine learning (ML) techniques have been applied by healthcare researchers over the past 30 years to better understand various diseases. Specifically, NEC researchers have used AI and ML to predict NEC diagnosis, NEC prognosis, discover biomarkers, and evaluate treatment strategies. In this review, we discuss AI and ML techniques, the current literature that has applied AI and ML to NEC, and some of the limitations in the field.

Purpose Necrotizing enterocolitis (NEC) totalis is a devastating disease of the newborn intestine. A precise clinical definition of the extent of gastrointestinal involvement is lacking in the existing literature, and the clinical outcomes are typically viewed as grim. Methods Herein, we present a series of clinical case examples of patients with varying degrees of NEC totalis and other co-morbid conditions, with possible anticipated outcomes based on current data. Results We define the key ethical issues and provide a framework and discussion of the ethical issues involved in the care of patients with NEC totalis and recommendations of how to approach discussions with the family of these patients We discuss the ethical considerations for both the providers caring for these patients, and the patient's family members. Conclusion The management of patients with NEC totalis is complex and ethically challenging. Level of evidence V

Background: The pathophysiology of necrotizing enterocolitis (NEC) is not clear, but increasing information suggests that the risk and severity of NEC may be influenced by abnormalities in the enteric nervous system (ENS). Objective: The purpose of this review was to scope and examine the research related to ENS-associated abnormalities that have either been identified in NEC or have been noted in other inflammatory bowel disorders (IBDs) with histopathological abnormalities similar to NEC. The aim was to summarize the research findings, identify research gaps in existing literature, and disseminate them to key knowledge end-users to collaborate and address the same in future studies. Methods: Articles that met the objectives of the study were identified through an extensive literature search in the databases PubMed, EMBASE, and Scopus. Results: The sources identified through the literature search revealed that: (1) ENS may be involved in NEC development and post-NEC complications, (2) NEC development is associated with changes in the ENS, and (3) NEC-associated changes could be modulated by the ENS. Conclusions: The findings from this review identify the enteric nervous as a target in the development and progression of NEC. Thus, factors that can protect the ENS can potentially prevent and treat NEC and post-NEC complications. This review serves to summarize the existing literature and highlights a need for further research on the involvement of ENS in NEC.

In order to develop prognostic criteria for the development of necrotizing enterocolitis, the authors studied clinical and biochemical data of 108 premature infants born and nursed in the departments of the Republican Perinatal Center. The prognostic scale is based on the modification of the probabilistic Bayes method – the method of normalized intensive indicators with the calculation of prognostic, weight indices, normalized intensive and integrated indicators. Individual forecast of the development of necrotizing enterocolitis allows the development of treatment, prevention and rehabilitation measures.

Background There are limited data regarding the risk factors for hyperglycemia in extremely low birth weight infants (ELBWIs). The aim of this observational study was to investigate the incidence of hyperglycemia among ELBWIs during the first 14 days of life and identify independent risk factors for hyperglycemia development. Methods We retrospectively evaluated 55 ELBWIs (32 male infants) between January 2015 and March 2020. Hyperglycemia was diagnosed when the glucose level was ≥180 mg/dL. Demographic and clinical data were extracted from the patients’ medical records. The risk factors associated with the onset of hyperglycemia were identified by Cox proportional hazards regression analysis with variables that had previously been identified as risk factors for hyperglycemia. Results Hyperglycemia developed in 23 patients (41.8%) within the first 14 days of life. Gestational age, chorioamnionitis, postnatal intravenous glucocorticoids, and probiotic type were included in the analysis. The results indicated that hyperglycemia was significantly associated with gestational age (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.48–0.87; P = 0.004). Further, Bifidobacterium breve (B. breve M-16V) use was related to hyperglycemia in ELBWIs (HR, 2.95; 95% CI, 1.10–7.87; P = 0.031). Conclusion Hyperglycemia was strongly associated with lower gestational age and B. breve M-16V use in our study population. Although probiotic supplementation may be beneficial for preterm infants to reduce the incidence of necrotizing enterocolitis, the dextrin used as an excipient in B. breve M-16V may lead to an undesirable carbohydrate load in ELBWIs.

BackgroundCritical decision making in surgical necrotizing enterocolitis (NEC) is highly complex and hard to capture in decision rules due to case-specificity and high mortality risk. In this choice experiment, we aimed to identify the implicit weight of decision factors towards future decision support, and to assess potential differences between specialties or centers.MethodsThirty-five hypothetical surgical NEC scenarios with different factor levels were evaluated by neonatal care experts of all Dutch neonatal care centers in an online environment, where a recommendation for surgery or comfort care was requested. We conducted choice analysis by constructing a binary logistic regression model according to behavioral artificial intelligence technology (BAIT).ResultsOut of 109 invited neonatal care experts, 62 (57%) participated, including 45 neonatologists, 16 pediatric surgeons and one neonatology physician assistant. Cerebral ultrasound (Relative importance = 20%, OR = 4.06, 95% CI = 3.39–4.86) was the most important factor in the decision surgery versus comfort care in surgical NEC, nationwide and for all specialties and centers. Pediatric surgeons more often recommended surgery compared to neonatologists (62% vs. 57%, p = 0.03). For all centers, cerebral ultrasound, congenital comorbidity, hemodynamics and parental preferences were significant decision factors (p Sex (p = 0.14), growth since birth (p = 0.25), and estimated parental capacities (p = 0.06) had no significance in nationwide nor subgroup analyses.ConclusionWe demonstrated how BAIT can analyze the implicit weight of factors in the complex and critical decision for surgery or comfort care for (surgical) NEC. The findings reflect Dutch expertise, but the technique can be expanded internationally. After validation, our choice model/BAIT may function as decision aid.

Background: Synbiotics are a mixture comprising of live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. There is an increasing number of studies investigating their role in different diseases and disorders. Aim: The purpose of this article is to provide recommendations for the use of synbiotics in the management of pediatric gastrointestinal disorders. The recommendations are developed by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications. Methods: From existing literature databases, we searched and appraised all systematic reviews and/or meta-analyses, and subsequently published randomized controlled trials (RCTs) that compared the use of synbiotics, in all delivery vehicles and formulations, at any dose, compared to no synbiotics. Synbiotics which are part of infant formula were not assessed. The recommendations were formulated only if at least 2 RCTs that used a well-defined synbiotic were available. Results: Based on the currently available evidence, no recommendation can be formulated in favor or against the use of evaluated synbiotic combination in the treatment of acute gastroenteritis, prevention of necrotizing enterocolitis, Helicobacter pylori infection, inflammatory bowel disease, functional gastrointestinal disorders, and allergy in infants and children. Conclusions: There is a need for more, well- designed RCTs on the role of synbiotics in gastrointestinal disorders with the same outcome measures to enable the inter-studies comparisons.

BackgroundWhile necrotizing enterocolitis (NEC) is a prevalent condition in preterm neonates admitted to neonatal intensive care unit (NICU), intussusception is exceedingly uncommon and often overlooked. This is due to the fact that they share many clinical characteristics. The initial misdiagnosis of intussusception in preterm neonates (IPN) especially has led to a delay in their management, which increases the risk of developing compromised bowel. Additionally, it is difficult to reach a diagnosis as neonatal intussusception does not have any classical radiological signs even when contrast enema is used. This systematic review is based on the published literature including case reports and case series to review the clinical features of IPN and how to differentiate it from NEC in order to shed the light on this rare disease and how having a high index of suspicion would help practitioners to make an early and accurate diagnosisMethodsA systematic literature search to report all cases of relevant articles that reported IPN till date. All cases that were born before 37 weeks gestational age, presented within the neonatal period and having well established documentation were included in the study. Any case that did not have these criteria was excluded from our study.ResultsOnly 52 cases met these criteria during the period from 1963 till date. An average of 10 days had elapsed before the cases were confirmed to have IPN either clinically or intraoperatively. The most frequent manifestations were abdominal distension and bilious gastric residuals, occurring in 85% and 77% of the cases respectively, followed by bloody stools in 43% of cases. However, this triad was present only in approximately one-third of the cases. Only 13 cases were diagnosed as having intussusception preoperatively. About two thirds of the intussusception were located in the ileum. Pathological lead point was present in 7 cases only; 4 of them were due to Meckel’s diverticulum. Nine cases only out of the 52 cases with IPN died.ConclusionIt is crucial to detect the clues for diagnosis of intussusception because in contrast to NEC, it is unresponsive to conservative management, affects the viability of the bowel and surgery is essential.

Background Postnatal infection with cytomegalovirus (CMV) in very-preterm and very-low-birth-weight infants, transmitted through breast milk (BM), is potentially associated with adverse outcomes. This study aimed to investigate the incidence and clinical significance of postnatal CMV infection in a tertiary neonatal intensive care unit. Methods Infants of CMV-seropositive mothers born in a neonatal intensive care unit in Melbourne, Australia, were observed for 14 weeks from birth in a prospective cohort study. Maternal BM and infant urine were tested weekly for CMV by culture and polymerase chain reaction, respectively. Clinical and laboratory data were collected and analyzed in relation to the infants' CMV infection status. Results Data from 65 infants of 56 CMV-seropositive mothers were available for analysis. Of these mothers, 88% (49/56) shed CMV in their BM. Of the 58 infants exposed to CMV-positive BM, 27 (47%) became urine polymerase chain reaction CMV-positive. There was no significant difference in gestational age, birth weight, incidence of bronchopulmonary dysplasia, or necrotizing enterocolitis between the CMV-positive and CMV-negative groups. However, CMV-positive infants had a longer length of hospital stay and more episodes of prolonged neutropenia. Of the CMV-positive infants, 30% (8/27) remained asymptomatic, 48% (13/27) had symptoms categorized as mild and 22% (6/27) as severe. Conclusions About half of preterm and very-low-birth-weight infants exposed to CMV-positive BM become infected, and a fifth develop significant clinical symptoms. Future studies should address the maternal and neonatal factors that determine the risk of mother-to-infant CMV transmission, as well as those leading to clinical deterioration and long-term sequelae.

To evaluate the effect of bilirubin levels in the first week of life on the frequency of oxidative-stress related morbidity. We included all preterm infants with a gestational age less than 32 weeks. The mean total serum bilirubin of the first week of life was measured and compared between infants with and without oxidative stress related morbidity. A total of 116 preterm infants were included. Univariate analysis showed that mean ± SD TSB levels were statistically significantly lower in infants with chronic lung disease (95 ± 31.4micromole/l vs 119 ± 31micromole/l, p = 0.019), necrotizing enterocolitis (94.4 ± 29micromole/l vs 118 ± 31micromole/l p = 0.044) and patent ductus arteriosus (104 ± 33micromole/l vs 120 ± 30micromole/l p = 0.018). However, when adjusted for gestational age, there were no longer statistically significant differences observed. Elevated bilirubin levels in the first week of life are not protective against the oxidative stress related morbidity in very preterm infants.

BACKGROUND: Early empiric antibiotic exposure appears to negatively influence feeding tolerance in preterm infants. However, the effect of prolonged antibiotic treatment is unknown. The objective of this study was to investigate whether prolonged antibiotics impact the time to full enteral feed in infants less than 29 weeks of gestational age with negative blood cultures. METHODS: Retrospective data for infants less than 29 weeks gestation age were retrieved from the PEARL-Peristat perinatal registry in Qatar. Exclusion criteria were major congenital anomalies, conditions requiring surgery in the first 10 days of life, positive blood cultures in the first 48 hours of life, and death within the first week of life. Antibiotic courses were categorized as prolonged if continued more than 48 hours. The primary outcome was the duration of total parenteral nutrition. RESULTS: Of 199 study infants, 185 (92.9%) underwent antibiotic treatment for > 48 hours despite negative blood cultures. The median duration of parenteral nutrition was not significantly different between the prolonged and short antibiotic groups (25 and 22 days, respectively; p = 0.139). Infants with prolonged antibiotic courses experienced non-significantly higher levels of necrotizing enterocolitis (7.1% and 18.4%, respectively), bronchopulmonary dysplasia (28.6% and 45.4%, respectively), and retinopathy of prematurity (14.3% and 38.4%, respectively). There were no differences in the late-onset sepsis rate (78.6% and 82.1%, respectively) and the in-hospital death rate (7.1% and 7.6%, respectively). CONCLUSIONS: Prolonged antibiotic treatment in infants less than 29 weeks gestation with negative blood cultures has no significant impact on the time to full enteral feed.

Necrotizing enterocolitis (NEC), one of the most severe emergencies in neonates, is a multifactorial disease with diverse risk factors. To compare between the clinical and laboratory characteristics of premature infants diagnosed with early-onset NEC (EO-NEC) and those with late-onset NEC (LO-NEC). Enrolled infants were identified from prospective local data collected for the Israel National very low birth weight (VLBW

Purpose Incisional hernia (IH) is a complication following abdominal surgery extensively studied in adults but less so in infants. This study aimed to identify the incidence, high risk diseases and risk factors of IH following abdominal surgery in infants. Methods Infants undergoing abdominal surgery before the age of three years in our tertiary centre between 1998 and 2018 were included. Patient demographics, peri‑operative details and the course during follow up were retrospectively extracted from patient records. Multivariate logistic regression was performed to identify risk factors. Results The incidence of incisional hernia was 5.2% (107/2055). Necrotizing enterocolitis (12%), gastroschisis (19%), and omphalocele (17%) had the highest incidences of IH. Wound infection (OR: 5.3, 95%-CI:2.9–9.5), preterm birth (OR: 4.2, 95%-CI:2.6–6.7) and history of stoma (OR 1.7, 95%-CI:1.1–2.8) were significant risk factors for IH. Whilst age at surgery, surgical approach and total number of operations did not significantly influence IH development. The IH resolved in 15% (16/107) without surgery. Conclusion One in twenty infants experiences IH following abdominal surgery, which is higher than previously described. Understanding the incidence of IH and associated risk factors will allow physicians to identify infants that may be at increased risk for IH and to possibly act pre-emptively.

Background Early-stage symptomology of necrotizing enterocolitis (NEC) is similar in presentation to non-NEC sepsis, though the treatment plans differ based on antibiotic administration and withholding of feeds. Improved diagnostics for NEC differentiation would allow clinicians to more rapidly set individual patients on a targeted treatment path. Extracellular vesicle-derived miRNAs, have previously demonstrated efficacy as disease biomarkers. To determine if these miRNAs are differentially-expressed in NEC infants, we performed transcriptomic analysis of urine-derived extracellular vesicle-derived miRNAs. Methods Urine was non-invasively obtained from infants in one of four groups (n ≥ 8) (Medical NEC, Surgical NEC, non-NEC sepsis, and healthy age-matched controls). EV-derived miRNAs were isolated and transcriptomic analysis was performed. Results Multiple miRNAs, including miR-376a, miR-518a-3p and miR-604, were significantly altered when comparing NEC to non-NEC sepsis and healthy controls, and could potentially be used as specific NEC biomarkers. Additionally, Ingenuity Pathway Analysis demonstrated that miRs differentially-expressed in NEC were associated with inflammatory disease and intestinal disease. Signal transduction molecules associated with NEC including TP53 and RPS15, which were also reduced transcriptionally in a rat model of NEC. Conclusion These data indicate that there is a pool of potential urine EV-derived miRNAs that may be validated as NEC biomarkers in the differentiation of NEC from non-NEC sepsis and from age-matched controls. Additionally, signal transduction molecules associated with miRNAs differentially-expressed in human NEC are altered in a murine model of NEC, suggesting potential crossover between murine models of the disease and actual human presentation. Level of Evidence Level III Study of Diagnostic Test.

BackgroundIncreasing evidence recognizes the harm of excess oxygen to lungs, eyes, and brain of preterm infants, but not yet to the intestine. We assessed changes in splanchnic oxygenation during reoxygenation with 21% compared to 100% O-2 in a newborn piglet model of perinatal asphyxia.MethodsWe randomized 25 piglets to control or intervention. Intervention groups underwent global hypoxia until acidosis and hypotension occurred. Piglets were reoxygenated for 30 min with 21% or 100% O-2 and observed for 9 h. We continuously measured regional splanchnic oxygen saturation (r(s)SO(2)) using near-infrared spectroscopy (NIRS). We calculated mean r(s)SO(2) and r(s)CoVar (as SD/mean). We measured PaO2 and SaO(2), sampled from the right carotid artery. ResultsReoxygenation after global hypoxia restored r(s)SO(2). Reoxygenation with 100% O-2 increased r(s)SO(2) to values significantly higher than baseline. In intervention groups, r(s)CoVar decreased during observation compared to baseline. We found a correlation between r(s)SO(2) and PaO2 (r = 0.420, P < 0.001) and between r(s)SO(2) and SaO(2) (r = 0.648, P < 0.001) in pooled data from the entire experiment.ConclusionReoxygenation after global hypoxia improves splanchnic oxygenation, but is associated with reduced variability of r(s)SO(2). Reoxygenation with 100% O-2 exposes the intestine to hyperoxia. Splanchnic NIRS is able to detect intestinal hypoxia and hyperoxia.ImpactSplanchnic oxygenation improves during reoxygenation after global hypoxia, though reoxygenation with 100% O2 exposes the intestine to hyperoxia. Decreased variability of splanchnic oxygenation several hours after hypoxia and reoxygenation seems to be independent of the resuscitation strategy, and may indicate intestinal injury. Splanchnic NIRS monitoring was able to detect intestinal hypoxia and exposure to hyperoxia, as evidenced by a strong correlation between splanchnic oxygenation and arterial oxygen content.

Objective To examine associations of maternal primary language with neonatal intensive care unit (NICU) outcomes (mother's milk at discharge, necrotizing enterocolitis [NEC], late-onset sepsis, weight gain) DESIGN: We performed a retrospective cohort study of mother-infant dyads ( Results Among 1402 mothers, 85% spoke English, 7% spoke Spanish, and 7% spoke another language. Compared to English, infants with Spanish-speaking mothers had slower growth (-0.34 z-score units [-0.58, -0.10]). Infants with other non-English-speaking mothers had increased mother's milk at discharge (aOR 1.48 [1.18, 1.85]), NEC (aOR 1.43 [1.05, 1.95]), late-onset sepsis (aOR 2.84) [1.67, 4.83] and slower growth (-0.17 z-score units [-0.29, -0.05]). Conclusions After adjustments, preterm infants with non-English-speaking mothers had worse outcomes than infants with English-speaking mothers.

Congenital complete heart block (CCHB) is a very rare condition, with high risk of mortality. Prematurity is associated with immaturity of the cardiovascular system. Morbidity related to CCHB and prematurity has never been described. We describe a tertiary perinatal center experience over a 15-year period on CCHB management and complications in preterm infants. This is a single-center observational cohort study. All neonates admitted to neonatal intensive care unit with a diagnosis of isolated CCHB between January 2006 and January 2021 were identified. All preterm neonates (

BACKGROUND Necrotizing enterocolitis (NEC) is the leading cause of death due to gastrointestinal disease in preterm neonates; yet, clinicians lack reliable and noninvasive predictive tools. PURPOSE We aimed to test that diminished high-frequency heart rate variability (HF-HRV) and elevated levels of proinflammatory cytokines would have utility in NEC prediction. METHODS In this multisite prospective study, we enrolled 250 preterm (26-34 weeks' postmenstrual age [PMA]) neonates with physiological stability at 72 hours of life. HRV was measured noninvasively using electrocardiograhic data from standardized cardiorespiratory monitors at postnatal week 1 of life and weekly thereafter until 35 weeks' PMA or discharge; blood was collected for cytokines at postnatal weeks 1 and 3. NEC was diagnosed via Modified Bell's Staging Criteria. RESULTS HF-HRV was decreased at weeks 1 and 2 in neonates (47% females) who developed feeding intolerance or stage 2+ NEC. In addition, these neonates displayed elevated levels of IL-8 at week 1 and increased levels of IL-1β, IL-6, TNF-α, and IL-8 at week 3 of life. Low HF-HRV was associated with elevated IL-6 or IL-8 levels at weeks 1 and 3 of life. Logistic regression indicated that only HF-HRV was a significant predictor of feeding intolerance or NEC development. IMPLICATIONS FOR PRACTICE AND RESEARCH HRV is a promising noninvasive modality for NEC risk detection. The association of low HF-HRV with elevated proinflammatory cytokines provides evidence for a putative role of the vagal cholinergic pathway in NEC pathogenesis. Future studies should focus on application of these techniques to test clinical therapeutics.Video Abstract available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?autoPlay=false&videoId=54.

Background Very low birth-weight (VLBW) infants are disproportionately affected by inflammatory morbidities including necrotizing enterocolitis. Despite the influence of social and demographic factors on infant health outcomes, their relationship with intestinal inflammation is unknown. Purpose To explore the influence of maternal race, maternal socioeconomic status, and infant sex on intestinal inflammation in VLBW infants. Methods This was a secondary analysis of existing data from a randomized controlled trial of 143 infants 32 weeks' gestation or less and weighing 1250 g or less. In the previous study, fecal calprotectin and S100A12 values were collected at weeks 3 and 6. The infant sample was determined on the basis of the availability of these results, which served as intestinal inflammation biomarkers for the present study. General linear mixed models assessed the relationship between biomarkers and social and demographic factors. Gestational age, antibiotic exposure, mother's own milk feeding, acuity, and week of sample collection were used as control variables. Findings/results The sample included 124 infants. Fifty-two infants (42%) were African American, 86 (69%) had Medicaid coverage, and 65 (53%) were male. Fecal calprotectin levels were higher in African American infants (P = .02) and infants with private insurance coverage (P = .009); no difference was found between sexes. There was no association between S100A12 levels and infant sex, maternal race, or socioeconomic status. Implications for practice and research Consideration of social and demographic factors may be important when caring for VLBW infants. Further exploration of factors contributing to associations between social or demographic factors and intestinal inflammation is needed.

Purpose Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are devastating diseases in preterm neonates, often requiring surgical treatment. Previous studies evaluated outcomes in peritoneal drain placement versus laparotomy, but the accuracy of the presumptive diagnosis remains unknown without bowel visualization. Predictive analytics provide the opportunity to determine the etiology of perforation and guide surgical decision making. The purpose of this investigation was to build and evaluate machine learning models to differentiate NEC and SIP. Methods Neonates who underwent drain placement or laparotomy NEC or SIP were identified and grouped definitively via bowel visualization. Patient characteristics were analyzed using machine learning methodologies, which were optimized through areas under the receiver operating characteristic curve (AUROC). The model was further evaluated using a validation cohort. Results 40 patients were identified. A random forest model achieved 98% AUROC while a ridge logistic regression model reached 92% AUROC in differentiating diseases. When applying the trained random forest model to the validation cohort, outcomes were correctly predicted. Conclusions This study supports the feasibility of using a novel machine learning model to differentiate between NEC and SIP prior to any intended surgical interventions. Level of Evidence level II Type of Study Clinical Research Paper

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious, often fatal, disease of neonates. Minimal data exists regarding the optimal method for reintroducing feeds after successful treatment. This study aims to compare outcomes in patients reintroduced to bolus or continuous feeds after treatment for medical NEC. METHODS: A retrospective review of infants treated for medical NEC in the neonatal intensive care unit (NICU) from 2011-2018 was performed. Demographics, information about initial feeds, clinical diagnosis data, and information about reintroduction of feeds were recorded. Patients with significant congenital heart disease or those who required procedures for treatment were excluded. RESULTS: Sixty-one patients were analyzed; 45 were reintroduced to bolus feeds and 16 to continuous feeds. There were no differences between the two groups. Bolus-fed patients reached goal feeds quicker (p = 0.007), required fewer days of parenteral nutrition (p = 0.002), had shorter hospital stays (p = 0.013) and were discharged faster from diagnosis to discharge (p = 0.002). Differences were confirmed with multivariate regression. CONCLUSION: Infants given bolus feeds reached goal feeds faster, required less time on PN, and were discharged quicker than those fed continuously. This suggests that, compared to continuous feeding, bolus feeding is associated with superior clinical outcomes among patients treated for medical NEC.

Infants with congenital heart disease (CHD) are at an increased risk of developing necrotising enterocolitis (NEC), a serious inflammatory intestinal condition classically associated with prematurity. CHD not only increases the risk of NEC in preterm infants but is one of the most commonly implicated risk factors in term infants. Existing knowledge on the topic is limited largely to retrospective studies. This review acts to consolidate existing knowledge on the topic in terms of disease incidence, pathophysiology, risk factors, outcomes and the complex relationship between NEC and enteral feeds. Potential preventative strategies, novel biomarkers for NEC in this population, and the role of the intestinal microbiome are all explored. Numerous challenges exist in the study of this complex multifactorial disease which arise from the heterogeneity of the affected population and its relative scarcity. Nevertheless, its high related morbidity and mortality warrant renewed interest in identifying those infants most at risk and implementing strategies to reduce the incidence of NEC in infants with CHD.

BACKGROUND Necrotizing enterocolitis (NEC) and postnatal growth restriction are significant clinical dilemmas that contribute to short- and long-term morbidities for the most premature infants. PURPOSE After a rise in NEC rates in a regional neonatal intensive care unit (NICU), improvement practices were implemented by an interdisciplinary quality improvement (QI) work group whose focus was initially on nutrition and growth. QI work was refocused to address both NEC and growth concurrently. METHODS Through various QI initiatives and with evolving understanding of NEC and nutrition, the work group identified and implemented multiple practices changes over 2-decade time span. A standardized tool was used to review each case of NEC and outcomes were continually tracked to guide QI initiatives. LOCAL FINDINGS Focused QI work contributed to a significant reduction in NEC rates from 16.2% in 2007 to 0% in 2018 for inborn infants. Exclusive human milk diet was a critical part of the success. Postnatal growth outcomes initially declined after initial NEC improvement work. Improvement work that focused jointly on NEC and nutrition resulted in improved growth outcomes without impacting NEC. IMPLICATIONS FOR PRACTICE Use of historical perspective along with evolving scientific understanding can guide local improvement initiatives. Work must continue to optimize lactation during NICU hospitalization. More research is needed to determine impact of care practices on gastrointestinal inflammation including medication osmolality, probiotics, and noninvasive respiratory support.

As the major source of energy for colonic mucosal cells and as an important regulator of gene expression, inflammation, differentiation, and apoptosis in host cells, microbiota-derived butyrate can enhance the intestinal mucosal immune barrier, modulate systemic immune response, and prevent infections. Maintaining a certain level of butyrate production in the gut can help balance intestinal microbiota, regulate host immune response, and promote the development and maintenance of the intestinal mucosal barrier. Butyrate-producing bacteria act as probiotics and play important roles in a variety of normal biological functions. Bacteriotherapeutic supplementation by using fecal microbiota transplantation to restore butyrate-producing commensal bacteria in the gut has been very successful in the treatment of recurrent and refractory Clostridium difficile (C. difficile) infection or C. difficile-negative nosocomial diarrhea. Administration of probiotics that include butyrate-producing bacteria may have a role in the treatment of inflammatory bowel diseases and in the prevention of necrotizing enterocolitis and late-onset sepsis in premature infants. Furthermore, modulating gut microbiota with dietary approaches may improve intestinal dysbiosis commonly seen in patients with obesity-associated metabolic disorders. Supplementation with a butyrate-producing bacterial stain might be used to increase energy expenditure, improve insulin sensitivity, and to help control obesity and metabolic syndrome.

The study was aimed at describing potential indirect effects of pandemic-related measures on very-low-birthweight infants in four Italian NICUs. No overall change in late-onset sepsis (LOS) and necrotizing enterocolitis was documented. However, in the NICU where baseline LOS rate was high, a significant reduction in LOS incidence was recorded. Conclusion: COVID-19-related implementation of NICU hygiene policies is likely to reduce the occurrence of LOS in high-risk settings. What is Known: • COVID-19 pandemic has disrupted routine care in Neonatal Intensive Care Units (NICUs), mostly by tightening infection control measures and restricting parental presence in the NICU. • Beyond the described psychological impact of COVID-19 related measures on healthcare workers and NICU families, their consequences in terms of preterm infants’ clinical outcomes have not been described in detail yet. What is New: • Strengthened infection-control measures do not seem to have an overall influence on the incidence of necrotising enterocolitis and late-onset sepsis in very-low-birth-weight infants. • However, the implementation of these measures appears to reduce the occurrence of late-onset sepsis in settings where the baseline incidence of the disease is high.

Background Thrombocytopenia is a common perioperative clinical problem and preoperative platelet transfusion prior to surgery is standard practice. Recent platelet trials and literature reviews have found no association between platelet count and bleeding incidence except when platelet count is extremely low. Our aim was to evaluate the bleeding risk and the overall platelet transfusion management among pediatric patients with severe thrombocytopenia based on whether they were preoperatively transfused versus transfused at time of incision. Methods This is a retrospective analysis of pediatric patients with a platelet count ≤50 × 109/L in the 12 h prior to surgery at a single tertiary pediatric hospital from 2011 to 2016. Eligible patients were ≤21 years old. Patients with necrotizing enterocolitis and neonates were excluded. The primary outcome was postoperative bleeding complications. Additional outcomes were preoperative platelet change and weight adjusted transfusion volumes. Results A total of 37 patients were included in this analysis of which 29 (78%) received preoperative platelet transfusions within 12 h prior to surgery. No postoperative bleeding complications occurred 30 days after operation, regardless of preoperative transfusion status. There was no significant difference in platelet change by preoperative transfusion status and preoperative transfusion volume was a poor predictor of change in preoperative platelet count (crude: r2=0.19, age/gender adjusted: r2=0.48). Conclusion Patients transfused at time of surgical procedure did not have an increased risk of bleeding over those preoperatively transfused. This finding is in agreement with previous studies in adult populations, supporting the safety of deferring platelet transfusions until the time of incision for thrombocytopenic pediatric surgical patients. Level of evidence: III

Background: Adhesions following abdominal surgery can cause small bowel obstruction (SBO) necessitating surgery. Whilst some studies have addressed SBO in children, the incidence of SBO, the diseases that are of increased risk as well as risk factors in young children remain unclear. Therefore, this study aims to determine; (1) the general incidence of SBO in young children, (2) which diseases entail highest incidence of SBO and (3) risk factors for SBO in young children. Study design: Young children (≤ 3 years of age) who underwent abdominal surgery in our tertiary referral centre between 1998–2018 were retrospectively included. Both general incidence and incidence per disease of SBO were determined. Independent risk factors for SBO were identified using cox-regression. Results: The incidence of SBO was 5% (N = 88/1931) in our cohort. Five of the SBOs developed following laparoscopic treatment. Patients treated for gastroschisis (17%,N = 9/53), necrotizing enterocolitis (8%,N = 15/188) and intestinal atresia (7%,N = 13/177) were at high risk of experiencing SBO. Diaphragmatic hernia (28%,N = 7/25) and meconium ileus (28%,N = 7/25) also showed high SBO proportions. Having a history of stoma (HR:3.2, 95%-CI:2.0–5.2), undergoing emergency surgery (HR:2.2, 95%-CI:1.3–3.7) and postoperative infections (HR:1.9, 95%-CI:1.2–3.1) were general risk factors for the development of SBO. Conclusion: The incidence of SBO in young children seems higher than what has previously been reported in older children, which is why they should be studied separately. The incidence of SBO differs between diseases. Having a history of a stoma, emergency surgery and postoperative infections were independent risk factors for SBO development. Although less at risk, SBOs do develop after laparoscopies, which is why they should be included in more long-term follow-up studies. Level of evidence: II

Background Necrotizing enterocolitis (NEC) is a major challenge for premature infants in neonatal intensive care units and efforts toward the search for indicators that could be used to predict the development of the disease have given limited results until now. Methods In this study, stools from 132 very low birth weight infants were collected daily in the context of a multi-center prospective study aimed at investigating the potential of fecal biomarkers for NEC prediction. Eight infants (~6%) received a stage 3 NEC diagnosis. Their stools collected up to 10 days before diagnosis were included and matched with 14 non-NEC controls and tested by ELISA for the quantitation of eight biomarkers. Results Biomarkers were evaluated in all available stool samples leading to the identification of lipocalin-2 and calprotectin as the two most reliable predicting markers over the 10-day period prior to NEC development. Pooling the data for each infant confirmed the significance of lipocalin-2 and calprotectin, individually and in combination 1 week in advance of the NEC clinical diagnosis. Conclusions The lipocalin-2 and calprotectin tandem represents a significant biomarker signature for predicting NEC development. Although not yet fulfilling the “perfect biomarker” criteria, it represents a first step toward it. Impact Stool biomarkers can be used to predict NEC development in very low birth weight infants more than a week before the diagnosis. LCN2 was identified as a new robust biomarker for predicting NEC development, which used in conjunction with CALPRO, allows the identification of more than half of the cases that will develop NEC in very low birth weight infants. Combining more stool markers with the LCN2/CALPRO tandem such as PGE2 can further improve the algorithm for the prediction of NEC development.

Background Preterm infants frequently experience intermittent hypoxia (IH) episodes, rendering them susceptible to oxidative stress and gut dysbiosis. We tested the hypothesis that early supplementation with antioxidants and/or fish oil promotes gut biodiversity and mitigates IH-induced gut injury. Methods Newborn rats were exposed to neonatal IH from birth (P0) to P14 during which they received daily oral supplementation with: (1) coenzyme Q10 (CoQ10) in olive oil, (2) fish oil, (3) glutathione nanoparticles (nGSH), (4) CoQ10 + fish oil, or (5) olive oil (placebo control). Pups were placed in room air (RA) from P14 to P21 with no further treatment. RA controls were similarly treated. Stool samples were assessed for microbiota and terminal ileum for histopathology and morphometry, total antioxidant capacity, lipid peroxidation, and biomarkers of gut injury. Results Neonatal IH induced histopathologic changes consistent with necrotizing enterocolitis, which were associated with increased lipid peroxidation, toll-like receptor, transforming growth factor, and nuclear factor kappa B. Combination of CoQ10 + fish oil and nGSH were most effective for preserving gut integrity, reducing biomarkers of gut injury, and increasing commensal organisms. Conclusions Combination of antioxidants and fish oil may confer synergistic benefits to mitigate IH-induced injury in the terminal ileum. Impact Antioxidant and fish oil (PUFA) co-treatment was most beneficial for reducing neonatal IH-induced gut injury. The synergistic effects of antioxidant and fish oil is likely due to prevention of IH-induced ROS attack on lipids, thus preserving and augmenting its therapeutic benefits. Combination treatment was also effective for increasing the abundance of the non-pathogenic Firmicutes phylum, which is associated with a healthy gastrointestinal system of the newborn. Extremely low gestational age neonates who are at high risk for frequent, repetitive neonatal IH and oxidative stress-induced diseases may benefit from this combination therapy.

BACKGROUND Congenital heart diseases (CHD) are the most common birth defects. Necrotizing enterocolitis (NEC) is an important cause of morbidity and mortality in premature infants, and probiotics can be used to protect NEC. CASE REPORT We present a term infant with aortic coarctation who developed sepsis with Lactobacillus rhamnosus GG after probiotic use, successfully treated with ampicillin. The baby unfortunately died of acute cardiac arrest on the 90th day of life. CONCLUSION Probiotic-associated sepsis may develop in infants with various risk factors such as central catheterization, long-term mechanical ventilation and in those at risk for NEC.

OBJECTIVE Infants requiring intestinal resection because of necrotizing enterocolitis (NEC) or small bowel atresia (SBA) may benefit from mucous fistula refeeding (MFR) of enterostomy output to improve nutrition and bowel adaptation before reanastomosis. Previous series demonstrated improved outcomes with MFR but did not account for varied patient characteristics as potential sources of bias. We performed a cohort analysis using multivariable adjusted models to compare outcomes of patients with and without MFR. METHODS Retrospective chart review was performed for patients with NEC or SBA and small bowel resection with enterostomy and MF. Demographic and outcome data was compared between MFR and non-MFR groups using adjusted multivariable analysis for potential confounding variables. RESULTS MFR was performed in 65 of 101 patients (64%), including 45 of 75 patients with NEC and 20 of 26 patients with SBA. Reasons for not receiving MFR included bowel stricture, technical limitation, or not otherwise specified. NEC patients receiving MFR had 14 fewer days to achieve full enteral feeds after intestinal reconnection, 22 fewer days of parenteral nutrition, lower peak direct bilirubin by 2.4 mg/dL, and 77% less odds of ursodiol use (all P

Necrotizing enterocolitis is one of the most frequent and severe gastrointestinal diseases that affect preterm newborns in Neonatal Intensive Care Units. It was firstly described in 1960s, but this clinical entity was not widely recognized until the advent of modern neonatal intensive care. The disease is characterized by submucosal edema, infiltration of intestinal wall by immune cells, specifically neutrophils and, in severe forms, wall necrosis that leads to intestinal perforation. Its incidence is inversely associated to birth weight and gestational age. Necrotizing enterocolitis has been responsible for high rates of morbidity and mortality (15-30%), despite improvements made in neonatal care in the last decades. The challenge is to optimize strategies for early diagnosis, define the best medical and surgical treatments and standardize preventive measures. Several biomarkers have been proposed for the early prediction of necrotizing enterocolitis onset in preterm newborns and can be useful not only for diagnostic purposes but also for prediction of disease progression and severity. The purpose of this paper is to illustrate the most recent evidence regarding the diagnosis and prevention of necrotizing enterocolitis. This manuscript contributes to clinical decision-making in preterm neonates at high risk of developing necrotizing enterocolitis.

BackgroundOropharyngeal administration of colostrum (OAC) may provide immunoprotective and anti-inflammatory effects that potentially reduce the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis and improve short-term outcomes. Our objective was to evaluate the role of OAC in the early prevention of NEC and late-onset sepsis in preterm infants with gestational age (GA) ≤ 32 weeks.MethodsA pilot, single-center, 1:1 parallel randomized controlled trial was conducted in a 40-bed tertiary neonatal intensive care unit (NICU) in China from 1 January 2019 to 30 September 2020. Preterm infants were randomly divided into two groups with GA ≤ 32 weeks. The OAC group included preterm infants who received 0.4 ml of maternal colostrum via the oropharyngeal route every 3 h for 10 days beginning within the first 48 h after birth, and the control group included preterm infants who received normal saline instead. Data from the two groups were collected and compared.ResultsA total of 127 infants in the OAC group and 125 infants in the control group were enrolled. The incidence of NEC (Bell stage 2 or 3) and late-onset sepsis were lower in the OAC group [2.36% vs. 10.40%, relative risk (RR) 0.23 (95% confidence interval (CI) 0.07, 0.78), adjusted RR 0.23 (95% CI 0.06, 0.84); 4.72% vs. 13.60%, RR 0.35 (95% CI 0.14, 0.85), adjusted RR 0.36 (95% CI 0.14, 0.95)]. In addition, the incidence of proven sepsis and intraventricular hemorrhage (IVH) (stage 3 or 4) were lower in the OAC group [2.36% vs. 8.80%, RR 0.27 (95% CI 0.08, 0.94); 1.57% vs. 7.20%, RR 0.22 (95% CI 0.05, 0.99)], and the time to achieve full enteral feeding was shorter (23.13 ± 9.45 days vs. 28.50 ± 14.80 days). No adverse reactions were observed in either group.ConclusionsOropharyngeal administration of colostrum is a safe and simple NICU procedure that may yield a potential effect in decreasing the incidences of NEC, late-onset sepsis, and severe IVH and shorten the time to achieve full enteral feeding in preterm infants with GA ≤ 32 weeks.Trial registrationChinese Clinical Trial Registry,ChiCTR1900023697, Registered 8 June 2019, retrospectively registered.

Intestinal malrotation is life-threatening and often presents during infancy with bilious vomiting. The prevalence and presentation among extremely premature infants are unknown. We retrospectively reviewed all infants born at less than 28 weeks’ gestation diagnosed with symptomatic intestinal malrotation in a tertiary neonatal intensive care unit over a 10-year period (2010–2020). Seven of 514 (1.4%) extremely premature infants developed symptomatic intestinal malrotation during this period. All were non-syndromic. In comparison, the prevalence of symptomatic intestinal malrotation in 7382 infants ≥ 28 weeks’ gestation admitted during the same period was 0.2%. Intestinal malrotation was confirmed at laparotomy in all extremely premature infants and six of seven had midgut volvulus. All but one presented with marked abdominal distension; none had bilious vomiting and only three had bilious gastric aspirates. A subacute onset with non-specific features such as recurrent apnoea and bradycardia, feed intolerance, and intermittent abdominal distension was common. All infants underwent a Ladd procedure. Two required extensive bowel resection resulting in short gut syndrome and three underwent further surgery for adhesive small bowel obstruction. One patient died at 10 months of age from respiratory failure but the others were well 1–3 years later. Symptomatic intestinal malrotation in extremely premature infants has a relatively high prevalence. It may present with marked abdominal distension without bilious vomiting, demanding a high index of suspicion. An atypical presentation, potential alternative abdominal pathologies, coexisting comorbidities, and concerns about survival in these fragile babies may deter the surgeon despite the opportunity of a good outcome.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal illness that affects high-risk populations such as those with congenital heart disease (CHD). A diagnosis of NEC, before and after cardiac surgery, can have serious and irreversible consequences. Here, we review perioperative management strategies that could potentially reduce the incidence of NEC in CHD. The literature is rich in investigative work regarding NEC in preterm infants; however, these data are extrapolated to infants with CHD. The pathogenesis of NEC in CHD is thought to be multifactorial, with splanchnic hypoperfusion being a major contributor. The data suggest that early enteral feeding with human milk, the use of probiotics, thoughtful use of red blood cell transfusions, and near-infrared spectroscopy may be useful tools in the prevention of NEC. NEC is an illness with the potential for high morbidity and mortality, particularly in CHD. Therefore, prevention of NEC should be the clinician’s focus when caring for these infants. Well-designed studies and evidence-based guidelines to standardize care in these infants are much needed to improve the outcome of NEC.

To assess whether early total enteral nutrition (80 mL/kg/d) started on day 1 of life in hemodynamically stable preterm very-low-birth-weight (VLBW) neonates with the rapid advancement of feeds (20 mL/kg/d) help in the earlier achievement of full feeds (180 mL/kg/d). Early total enteral nutrition (intervention) group feeding was started with 80 mL/kg/d on the first day in all hemodynamically stable neonates admitted with birth weight of 1000–1499 grams, born at 29–33 wk of gestation as determined by first-trimester ultrasonography (USG) or expanded New Ballard Score (NBS) and was advanced by 20 mL/kg/d until maximum feeds of 180 mL/kg/d were achieved; while in control group feeding was started with 30 mL/kg/d on the first day and was advanced by 20 mL/kg/d until maximum feeds were achieved. Primary outcome measure was time taken to achieve full feeds; secondary outcomes were duration of hospital stay, necrotizing enterocolitis (NEC), time to regain birth weight, duration of antibiotics, and death. Sixty VLBW neonates (1000–1499 g) with comparable baseline demographics were randomized within 24 h of admission to two groups. Early total enteral nutrition intervention group (group I, n = 31) achieved the target of full enteral nutrition at median 6 d; IQR: 0 to 7.8 d, a significantly shorter time compared to the controls (n = 29) (median 10 d; IQR: 9 to 11.0 d; p = < 0.05). Early total enteral nutrition started from the first day of life results in significantly less time to achieve full feeds in hemodynamically stable preterm and VLBW infants.

The objective of this study was to determine the risk factors and outcomes of white matter brain injury (WMBI) on magnetic resonance imaging (MRI) at term-equivalent age in infants with surgical necrotizing enterocolitis (NEC).This retrospective study compared clinical/pathological information between infants with and those without WMBI.Out of 69 infants with surgical NEC, 17 (24.6%) had mild WMBI, 13 (18.8%) had moderate WMBI, and six (8.7%) had severe WMBI on the brain MRI. Several clinical factors (gestational age, more red blood cell (RBC) transfusions before NEC onset, pneumoperitoneum, earlier NEC onset age, postoperative ileus, acute kidney injury (AKI) by serum creatinine, postnatal steroids, hospital stay) and histopathological findings (necrosis, hemorrhage) had univariate associations with WMBI. Associations with RBC transfusion (odds ratio (OR) 23.6 [95% confidence interval (CI): 4.73-117.97]; p = 0.0001), age at NEC onset (OR 0.30 [95%CI: 0.11-0.84]; p = 0.021), necrosis (OR 0.10 [95%CI: 0.01-0.90]; p = 0.040), and bowel hemorrhage (OR 7.79 [95%CI: 2.19-27.72]; p = 0.002) persisted in multivariable association with grade 3-4 WMBI. The infants with WMBI had lower mean motor, cognitive, language scores, and higher ophthalmic morbidity at 2 years of age.The WMBI was most likely associated with earlier NEC onset, higher RBC transfusions, and less necrosis and greater hemorrhage lesions on intestinal pathology in preterm infants with surgical NEC.In preterm infants with surgical NEC, brain MRI showed injury in the white matter in 52%, gray matter in 10%, and cerebellar region in 30%. Preterm infants with severe WMBI (grade 3-4) had less necrosis and greater hemorrhagic lesions on histopathology of the bowel. Preterm infants with WMBI were more likely to have a more severe postoperative course, AKI, and longer length of hospitalization. Neuroprotective strategies to prevent brain injury in preterm infants with surgical NEC are needed with the goal of improving the neurodevelopmental outcomes.

Objective This study aimed to assess whether bedside ultrasound (BUS) as the first imaging modality allows an earlier diagnosis of necrotizing enterocolitis (NEC) compared with abdominal radiography. Study Design A before-after controlled study in preterm infants with suspected NEC. The intervention group (October 2019-October 2021) received BUS as the first imaging modality and was managed accordingly to BUS findings. The control group (October 2015-September 2019) received radiography as the first imaging modality. The main outcome was NEC confirmation at the time of initial imaging. Secondary outcomes included time to diagnosis, laboratory data, and treatment requirements. Results Thirty-five episodes of suspected NEC with 14 (40%) confirmed NEC cases and 49 episodes of suspected NEC with 22 (44.9%) confirmed NEC cases were included in the intervention and control groups, respectively. In the intervention group, 11 of 14 (78.6%) NEC cases were confirmed at initial evaluation compared with 5 of 22 (22.7%) in the control group ( p = 0.001). Infants in the intervention group developed thrombocytopenia and coagulopathy less frequently, were exposed to less radiation, and required less days of parenteral nutrition compared with the control group ( p < 0.05). Conclusion The use of BUS as the first imaging modality allowed an earlier diagnosis and timely treatment of NEC compared with abdominal radiography. Key Points This is the first study that has assessed the role of BUS as the first imaging modality in NEC. BUS improves early diagnosis of NEC compared with abdominal radiography. BUS shortens time to NEC confirmation and treatment initiation which may reduce clinical severity of the NEC episode.

Intraamniotic infection is associated with an increased risk of multiple adverse outcomes in offspring, especially neonatal necrotizing enterocolitis (NEC), which is one of the serious gastrointestinal diseases in neonates. However, the underlying mechanism remains undefined. We hypothesize that bacterial endotoxin-induced maternal inflammation causes intestinal injury in offspring, thereby affecting the composition of the intestinal microbiome.Pregnant Sprague Dawley rats were received intraperitoneal injections with 700 μg/kg lipopolysaccharide (LPS, which was the same as bacterial endotoxin) or saline at 15 days of gestation. Pups were allowed to deliver naturally and euthanized at days 0, 3 and 7 after birth. Intestinal tissue and feces samples from offspring were collected to evaluate the effects of maternal inflammation on intestinal flora colonization and intestinal mucosal development.Significant intestinal injury of the offspring induced by prenatal LPS exposure was observed on day 0 and 3 after birth. In addition, prenatal LPS exposure also induced significant changes in the intestinal microbiome of the offspring with a significant increase inThus, our findings suggest that LPS-induced maternal inflammation induces intestinal injury in offspring and subsequently leads to NEC-like changes in the composition of the intestinal microbiome.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants, with significant mortality and long-term morbidity among survivors. Multiple NEC definitions exist, but no formal head-to-head evaluation has been performed. We hypothesized that contemporary definitions would perform better in evaluation metrics than Bell’s and range features would be more frequently identified as important than yes/no features. Two hundred and nineteen patients from the University of Iowa hospital with NEC, intestinal perforation, or NEC concern were identified from a 10-year retrospective cohort. NEC presence was confirmed by a blinded investigator. Evaluation metrics were calculated using statistics and six supervised machine learning classifiers for current NEC definitions. Feature importance evaluation was performed on each decision tree classifier. Newer definitions outperformed Bell’s staging using both standard statistics and most machine learning classifiers. The decision tree classifier had the highest overall machine learning scores, which resulted in Non-Bell definitions having high sensitivity (0.826, INC) and specificity (0.969, ST), while Modified Bell (IIA+) had reasonable sensitivity (0.783), but poor specificity (0.531). Feature importance evaluation identified nine criteria as important for diagnosis. This preliminary study suggests that Non-Bell NEC definitions may be better at diagnosing NEC and calls for further examination of definitions and important criteria.

Despite lack of evidence, the practice of routine prefeed gastric residue aspiration before the next feed is common. Recent studies suggest that this practice might be even harmful. Therefore, we aimed to evaluate the effect of avoiding routine prefeed gastric residue aspiration as compared to routine aspiration, on various clinical outcomes in preterm infants. We searched five different electronic databases (MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane Library) until March 8, 2021. Only randomized controlled trials comparing the practice of routine prefeed gastric aspiration with no routine aspiration in preterm infants were considered eligible. The random-effects meta-analysis was done using RevMan 5.3 software. Of the 894 unique records identified by our search, we included 6 studies (451 participants) in the review. There was no significant difference in the incidence of necrotizing enterocolitis (RR 0.80; 95% CI 0.31 to 2.08; 421 participants in 5 trials). Avoiding routine prefeed aspiration was associated with achieving full enteral feeds earlier (MD - 3.19 days, 95% CI - 4.22 to - 2.16), shorter duration of hospitalization (MD - 5.32 days; 95% CI - 10.25 to - 0.38), and lower incidence of late-onset sepsis (RR 0.77; 95% CI 0.60 to 0.99). Time to regain birth weight, days of total parenteral nutrition or central venous line usage, culture-positive sepsis, and all-cause mortality did not differ between the two groups.Conclusion: In the absence of other signs of feed intolerance, routine prefeed gastric residue aspiration should be avoided in preterm infants.Prospero registration number: CRD42020197657 What is Known: • Though, routine prefeed aspiration before next feed is a common practice in preterm gavage-fed infants. • Recent study suggests that the omission of routine gastric residual evaluation led to improved weight gain and earlier hospital discharge. What is New: • Low- to moderate-quality evidence suggest that avoiding routine prefeed gastric residue monitoring helps in the reduction of late-onset sepsis, achieving full enteral feeds earlier, and earlier discharge from the hospital. • Abandoning the practice of routine prefeed aspiration in absence of other signs of feed intolerance in preterm low birthweight neonates is safe.

Objective The study aimed to analyze the risk factors and clinical features of metabolic bone disease of prematurity (MBDP) in premature infants compared with infants of similar gestational age and birth weight without MBDP. Study Design This retrospective case–control study was performed by comparing 81 cases of MBDP with 63 controls to identify potential risk factors. Premature infants with a gestational age ≤33 weeks and birth weight Results Bone fractures and invasive ventilator dependence were the most common clinical features of MBDP. Duration of invasive ventilation and total mechanical ventilation days, necrotizing enterocolitis, corticosteroid use, anticonvulsive drug use, duration of dexamethasone and caffeine use, total parenteral nutrition, and length of hospitalization were significantly higher in neonates with MBDP (p Conclusion Our results show that anticonvulsive drug use is a significant risk factor for the development of MBDP. If long-term use is not required, anticonvulsive drugs should be stopped as soon as possible. Further studies involving patients with MBDP are required to determine the risk factors and clinical features. Key Points

Background Necrotizing enterocolitis (NEC) is a serious infection of the bowel wall induced by multiple pathological factors, which include inflammation and tissue invasion with bacteria known to cause severe infections. NEC is now understood to be several disease processes under one umbrella. The most common form occurs in premature infants and can exert significant impacts to preterm morbidity and mortality. Purpose This narrative review describes current knowledge of the clinical presentation and pathophysiology of NEC in premature infants. Methods/search strategy A review of literature was conducted using key words in PubMed and CINAHL with preference for years 2015 to 2020. Findings/results Several converging and interrelated factors including characteristics of the premature intestinal mucosa, gut ischemia, dysregulation of the microbiome, enteral feeding, and genetics create an environment where NEC is more likely to occur. Implications for practice To recognize and diagnose NEC in preterm infants, an understanding of underlying factors that create an optimal environment for disease acquisition in premature infants is essential. Implications for research Prevention of NEC remains the most important strategy for decreasing morbidity and mortality. Multiple areas of potential study exist for NEC pathophysiology including those that consider how the factors discussed in this review are interrelated and how each particular pathway can be optimized to prevent the onset of NEC.

Necrotizing enterocolitis (NEC) is a disease with high morbidity and mortality that occurs mainly in premature born infants. The pathophysiologic mechanisms indicate that gastrointestinal dysbiosis is a major risk factor. We searched for relevant articles published in PubMed and Google Scholar in the English language up to October 2020. Articles were extracted using subject headings and keywords of interest to the topic. Interesting references in included articles were also considered. Network meta-analysis suggests the preventive efficacy of Bifidobacterium and Lactobacillus spp., but even more for mixtures of Bifidobacterium, Streptococcus, and Bifidobacterium, and Streptococcus spp. However, studies comparing face-to-face different strains are lacking. Moreover, differences in inclusion criteria, dosage strains, and primary outcomes in most trials are major obstacles to providing evidence-based conclusions. Although adverse effects have not been reported in clinical trials, case series of adverse outcomes, mainly septicemia, have been published. Consequently, systematic administration of probiotic bacteria to prevent NEC is still debated in literature. The risk-benefit ratio depends on the incidence of NEC in a neonatal intensive care unit, and evidence has shown that preventive measures excluding probiotic administration can result in a decrease in NEC.

Contrast-enhanced ultrasound (CEUS) has emerged as a valuable modality for bowel imaging in adults and children. CEUS enables visualization of the perfusion of the bowel wall and of the associated mesentery in healthy and disease states. In addition, CEUS images can be used to make quantitative measurements of contrast kinetics, allowing for objective assessment of bowel wall enhancement. Bowel CEUS is commonly applied to evaluate inflammatory bowel disease and to monitor treatment response. It has also been applied to evaluate necrotizing enterocolitis, intussusception, appendicitis and epiploic appendagitis, although experience with these applications is more limited. In this review article, we present the current experience using CEUS to evaluate the pediatric bowel with emphasis on inflammatory bowel disease, extrapolating the established experience from adult studies. We also discuss emerging applications of CEUS as an adjunct or problem-solving tool for evaluating bowel perfusion. Electronic supplementary material The online version of this article (10.1007/s00247-020-04868-x) contains supplementary material, which is available to authorized users.

Background Spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) are complications of extremely low birth weight (ELBW, ≤ 1000 g) infants. ELBW infants at Texas Children's Hospital receive an exclusive human milk-based diet, which has been associated with a reduction of NEC. Objectives 1) Assess incidence of SIP and NEC (Stage II or greater) in ELBW infants receiving 100% human milk-based diet, 2) Describe mortality rates of ELBW infants with SIP and NEC. Methods Prospective single-center observational cohort study of ELBW infants born between 2010 and 2014 with SIP or NEC (exclusion: congenital anomalies and death within 48 h). Results Of 379 ELBW infants, 345 were eligible. Of these, 28 (8.1%) had SIP and 8 (2.3%) had NEC (medical n = 1, surgical n = 7). SIP infant mortality was 32% (n = 9) compared to 63% (n = 5) for NEC patients. Of SIP infants with PD (n = 25), 52% required subsequent exploratory laparotomy (LAP). Of NEC infants with peritoneal drainage (PD) (n = 2), both required subsequent LAP. Conclusion Using an exclusive human milk-based diet, the incidence of SIP exceeds NEC in ELBW infants at our institution. This shows a changing trend in the incidence of these two diagnoses in the era of human milk, as NEC had previously been more prevalent in ELBW infants. More than half of infants who initially received PD later required LAP. There were no differences in survival outcomes in both SIP and NEC groups based on surgical management.

Necrotizing enterocolitis (NEC) treatment remains unchanged for years. Data suggest that mild controlled hypothermia could potentially improve NEC outcomes. Our units presented unfavourable outcomes on NEC. The aim was to assess our experience with low technology, mild controlled hypothermia on NEC outcomes, and improve preterm infants' healthcare. This was a single-center quality improvement study with retrospective cohort design at the neonatal intensive care unit in the university hospital. Forty-three preterm infants with NEC (Modified Bell's Stage II/III) were included: 19 in the control group (2015-2018) and 24 in the hypothermia group (2018-2020). The control group received standard treatment (fasting, abdominal decompression, and broad-spectrum antibiotics). The hypothermia group underwent cooling to 35.5 °C for 48 h after NEC diagnosis, along with conventional treatment. The primary outcomes are intestinal perforation, need for surgery, duration of parenteral nutrition, death, and extensive resection of the small intestine. There was no statistical difference in the NEC score. The hypothermia group required less surgery (aRR 0.40; 95% CI 0.19-0.85), presented less bowel perforation (aRR 0.39; 95% CI 0.18; 0.83), had a shorter duration of parenteral nutrition (aHR 5.28; 95% CI 1.88-14.89), did not need extensive intestinal resection, (0 vs 15.7%), and did not experience any deaths (0 vs 31.6%).Conclusions: In our experience, low technology, mild controlled hypothermia was feasible, not related to adverse effects, and effective treatment for NEC Modified Bell's Stage II/III. It avoided surgery, bowel perforation, and extensive intestinal resection; reduced mortality; and shortened parenteral nutrition duration. What is Known: • New approaches have been proposed to avoid enterocolitis incidence; however, the treatment of enterocolitis stage 2 has been the same for decades, and unfavourable outcomes remain despite conventional management. • Studies suggest that hypothermia can be an alternative to enterocolitis treatment. What is New: • Mild controlled hypothermia can be an additional practice to treat enterocolitis stage 2, is feasible, and is not related to adverse effects to preterm infants. • It can decrease surgery needs, duration of parenteral nutrition, and death and avoids extensive intestinal resection in preterm infants.

Probiotics have been shown to reduce the risk of all-cause mortality, necrotizing enterocolitis (NEC ≥ stage II), late onset sepsis (LOS), and feeding intolerance in preterm infants. Considering the substantial health burden imposed by these conditions, the importance of probiotics in preterm infants cannot be overemphasized. Based on the data from experimental studies, and systematic reviews of randomized controlled trials (RCTs) and non-RCTs, the uptake of this intervention in neonatal medicine has been increasing over the last few years. However, many are still hesitating to adopt this intervention for various reasons, including concerns about probiotic sepsis, product quality, and lack of clarity on optimal strain/s or their combinations. Some question the validity of meta-analyses of studies involving different probiotic strains or their combinations because probiotics effects are considered to be strain-specific. Some of the early concerns about probiotics in preterm infants have been shown to be unjustified. However, the resistance to probiotics continues in many neonatal units around the world. The future of probiotics for preterm infants depends on continued efforts to develop high-quality probiotic products using stringent quality control, improving access to such products, and robust head-to-head comparisons to know the optimal strains or their combinations. Monitoring for adverse effects such as probiotic sepsis and development of antibiotic resistance is crucial. The authors review the current status of probiotics in preterm infants and discuss the scope for further research in this field.

Objectives The aim of this study was to investigate the trends of the incidence of and mortality from necrotizing enterocolitis (NEC) in South Korea. Methods Claim data were extracted with diagnosis code, including all stage of NEC. Kaplan-Meier curves for cumulative mortality rates are presented by birth weight (Bwt) and gestational age (GA). Result The total number of NEC cases was 5840. The ratio of males to females was 1.2:1. There were 11.9 cases per 10,000 births. There were approximately 10 cases per 1000 preterm births and 50 per 1000 very preterm births. The mortality of patients born under 37 weeks decreased from 38.7% in 2007 to 20.9% in 2017. Male sex, lower GA, and lower Bwt were risk factors for mortality. Conclusions NEC incidence and mortality have been decreasing over time in South Korea. Male sex, lower GA, and Bwt were risk factors for mortality.