Enterocolitis necrotizante experimental con lipopolisacárido oral y función protectora de la lechematerna / Experimental necrotizing enterocolitis using oral lipopolysaccharide and protective role of breastmilk

Introducción: La enterocolitis necrotizante (ECN) es una enfermedad potencialmente mortal que afecta a los neonatos, y frente a laque la leche materna ha demostrado tener un papel protector. Administrando lipopolisacáridos (LPS) por vía oral en ratas recién nacidas(RRN), hemos desarrollado un modelo experimental para inducir undaño intestinal similar al que provoca la ECN con objeto de evaluarel aspecto macroscópico y microscópico del intestino, y de ese modo,analizar la presencia de ECN y estudiar el papel que desempeña laleche materna (LM). Material y métodos: Las RRN se dividieron en tres grupos: el grupoA (control, n= 10) permaneció con su madre; el grupo B (LPS, n=25)fue aislado tras el nacimiento, alimentado por sonda con una fórmulaespecial para ratas y LPS oral, y sometido a estrés (hipoxia tras sonda);y el grupo C (LM, n= 12) fue alimentado con leche materna tras elnacimiento y posteriormente aislado y sometido a estrés al igual que elgrupo B. El día 4 se sacrificó a las RRN y se recuperaron sus intestinospara su posterior evaluación. Resultados: En el grupo de control, no se observó ECN ni macroscópica ni histológicamente, mientras que los dos grupos sometidos aestrés (B y C) presentaron una incidencia global de la ECN del 73%.La mayoría de los sujetos del grupo B desarrollaron signos histológi-cos de ECN (85%), y los del grupo C registraron una incidencia de laECN estadísticamente menor (50%, p= 0,04), lo que significa que laLM desempeña una función protectora frente a la ECN (OR= 0,19; IC95%: 0,40-0,904). Conclusión: Nuestro modelo reveló una incidencia significativa dela ECN en RRN (73%), desempeñando la LM la misma función protectora que en el caso de los humanos recién nacidos, lo que significa que estemodelo experimental de ECN es fiable y reproducible. Gracias a dichologro, podremos investigar nuevos y potenciales objetivos terapéuticospara una peligrosa enfermedad que, a día de hoy, carece de tratamiento.(AU)

Introduction: Necrotizing enterocolitis (NEC) is a life-threateningcondition that afflicts neonates. Breastfeeding has demonstrated to playa protective role against it. By administering lipopolysaccharides (LPS)orally in newborn rats (NBR), we have developed an experimental modelto induce NEC-like gut damage. Our aim was to assess the macroscopicand microscopic appearance of the gut, to evaluate the presence of NECand study the role of breast milk (BM). Material and methods: NBR were divided into 3 groups: GroupA (control, n= 10) remained with the mother, group B (LPS, n= 25)was isolated after birth, gavage-fed with special rat formula and oralLPS, then submitted to stress (hypoxia after gavage) and group c (BM,n= 12) was breastfed once after birth, then isolated, and submitted tostress like group B. On day 4, NBR were sacrificed, and intestine washarvested and assessed. Results: In the control group NEC was not present either macroscopically or histologically. Both groups submitted to stress (B and C)presented a global incidence of NEC of 73%. Most of group B developedhistologic signs of NEC (85%) and group C showed a statistically lowerincidence of NEC (50%, p= 0.04), playing the BM a protective roleagainst NEC (OR= 0.19; 95% CI: 0.40- 0.904)Conclusion: Our model showed a significant incidence of NEC inNBR (73%) with the same protective role of BM as in newborn humans,achieving a reliable and reproducible experimental NEC model. This willallow us to investigate new potential therapeutic targets for a devastatingdisease that currently lacks treatment.(AU)

Impact of the Koala Project on clinical outcomes of preterm infants in two maternity hospitals / Impacto do Projeto Coala nos resultados clínicos de pacientes prematuros em duas maternidades

ABSTRACT Objective: To describe the impact of the Koala project (Actively Controlling Target Oxygen) on clinical outcomes in patients born with less than 36 weeks of gestation, in two maternity hospitals, comparing before and after the strategy implementation. Methods: This is an intervention study with 100 preterm infants with gestational age ≤36 weeks, who used oxygen in two maternity hospitals between January 2020 and August 2021. One of the hospitals was a private institution and the other was philanthropic. The goal for the target oxygen saturation with this project was 91-95%. Comparisons between the two stages (before and after the implementation of the project) were made evaluating the outcomes of retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, and deaths. The continuous variables were described using mean, median, standard deviation and interquartile interval. The significance level adopted was 5% and the software used was R Core Team 2021 (version 4.1.0). Results: After oxygen control use according to the Koala protocol, there was a significant reduction in the cases of retinopathy of prematurity (p<0.001) and bronchopulmonary dysplasia (p<0.001). There were no deaths in the second stage, and there was a non-significant increase in the absolute number of necrotizing enterocolitis cases. Conclusions: The Koala project seems to be an effective and feasible strategy to reduce adverse situations in the management of premature children, but research with a greater sample is needed.

RESUMO Objetivo: Descrever o impacto do projeto Coala (Controle Ativo de Oxigênio Alvo) nos desfechos clínicos em pacientes nascidos com menos de 36 semanas de gestação, em duas maternidades, comparando antes e depois da implementação da estratégia. Métodos: Trata-se de um estudo de intervenção com cem prematuros vivos, com idade gestacional ≤36 semanas, que utilizaram oxigênio em duas maternidades entre janeiro de 2020 e agosto de 2021. A meta para a saturação de oxigênio alvo com este projeto foi de 91-95%. Comparações entre as duas etapas (antes e depois da implantação do projeto) foram feitas avaliando os desfechos de retinopatia da prematuridade, displasia broncopulmonar, enterocolite necrosante e óbitos. As variáveis contínuas foram descritas por meio de média, mediana, desvio padrão e intervalo interquartil. O nível de significância adotado foi de 5% e o software empregado foi o R Core Team 2021 (versão 4.1.0). Resultados: Observou-se que, após o uso de controle de oxigênio segundo o protocolo Coala, houve redução significativa nos casos de retinopatia da prematuridade (p<0,001) e displasia broncopulmonar (p<0,001). Não houve óbitos na segunda etapa e houve aumento não significativo no número absoluto de casos de enterocolite necrosante. Conclusões: O projeto Coala parece ser uma estratégia eficaz e viável para reduzir situações adversas no manejo de crianças prematuras, mas pesquisas com amostras maiores são necessárias.

Progress in therapeutic potential of human breast milk-derived exosomes in neonate necrotizing enterocolitis / 中华围产医学杂志

Neonatal necrotizing enterocolitis (NEC) is one of the leading causes of neonatal death and no effective therapeutic drugs are currently available. Breastfeeding is a safe and effective preventive measure for NEC. Human breast milk-derived exosomes (HM-exos), which are membranous vesicles in breast milk, play an important role in maintaining the integrity of the intestinal barrier and promoting the repair of intestinal epithelial cells (IECs) damage through protecting IECs from oxidative stress, improving the proliferation and migration of IECs, maintaining the tight connection between IECs, inhibiting inflammatory response and regulating immune response.

Clinical and epidemiological characterization of newborns with necrotizing enterocolitis / Caracterização clínica e epidemiológica de recém-nascidos com enterocolite necrosante

INTRODUCTION: Necrotizing enterocolitis (NEC) is a severe inflammatory disorder that can affect the whole gastrointestinal system, particularly the ileum, and is a major cause of morbidity in premature infants. OBJECTIVE: To describe the clinical and epidemiological profile of newborns with NEC, seeking to identify the causes, evolution and severity of the disease. METHODS: The study selected 94 patients who developed NEC (cases) and 60 patients who did not develop the disease during hospitalization (controls) and presented similar clinical signs of the case group. The variables analyzed divided into maternal and neonatal. The frequency tests were applied using the Statistical Package for the Social Sciences (SPSS) version 21.0 and comparative analysis using the GraphPad Prism® 5.0 software. RESULTS: There was a higher number of prenatal consultations in cases with NEC. Newborns with NEC had shorter hospital stay, longer parenteral nutrition and antibiotics use and a predominant use of infant formula. The Bell criteria modified by Walsh and Kleigman was negatively correlated to maternal age and positively correlated to gestational age, birth weight and time of parenteral nutrition. CONCLUSION: Although being a disease of the newborn, the present study indicated that maternal characteristics may be related to its onset of NEC. Therefore, the greater number of prenatal consultations and neonatal factors such as length of stay, prolonged use of parenteral nutrition and antibiotic therapy, and formula use may influence the development of the disease.

INTRODUÇÃO: A Enterocolite Necrosante (ECN) é um grave distúrbio inflamatório que pode afetar todo o sistema gastrointestinal, em particular o íleo, é uma causa de morbiletalidade em prematuros. OBJETIVO: Delinear o perfil clínico-epidemiológico de recém-nascidos com ECN, buscando identificar as causas, modo de evolução e gravidade da doença. MÉTODOS: Foram selecionados 94 pacientes que desenvolveram ECN (casos) e 60 pacientes que não desenvolveram a doença no período de internação (controles) e apresentavam sinais clínicos semelhantes do grupo caso. As variáveis analisadas foram classificadas em maternas e neonatais. Foram realizados testes de frequência usando o programa Statistical Package for the Social Sciences (SPSS) versão 21.0 e análise comparativa usando o teste programa GraphPad Prism® 5.0. RESULTADOS: Nos casos com ECN houve maior número de consultas pré-natal. Os recém-nascidos com ECN apresentaram menor tempo de internação, maior tempo de nutrição parenteral e uso de antibióticos tiveram predomínio no uso de fórmula infantil. A classificação modificada de Bell por Walsh and Kleigman apresentou correlação negativa com idade materna e positiva com idade gestacional, peso ao nascer e o tempo de nutrição parenteral. CONCLUSÃO: Apesar de ser uma doença do recém-nascido, esse estudo sugere que características maternas podem ter relação com o aparecimento da ECN. O número maior de consultas pré-natal e os fatores neonatais como o tempo de internação, uso prolongado de nutrição parenteral, antibioticoterapia e uso de fórmulas pode influenciar o desenvolvimento da doença.

Is -94ins/delattg polymorphism in the nuclear factor kappa-b1 gene (nfkb1) associated with necrotizing enterocolitis? / Polimorfismo -94ins/delattg no gene do fator nuclear kappa-b1 (nfkb1) está associado à enterocolite necrosante?

ABSTRACT BACKGROUND: Abnormalities in the different stages of the intestinal maturation process cause metabolic and molecular changes. Among the genetic alterations associated with necrotizing enterocolitis, the -94ins/delATTG polymorphism in NFKB1 gene leads to unregulated activation of the NFKB protein due to an increase in the inherent pro-inflammatory state of the premature intestine. AIMS:To determine the prevalence of the -94ins/delATTG polymorphism in NFKB1 gene in neonates with and without necrotizing enterocolitis. METHODS:This is a case-control study, in which 25 neonates were evaluated as the case group and 50 neonates as the control group, of both genders. DNA was extracted from peripheral blood leukocytes, and the site encompassing the polymorphism was amplified by molecular techniques (polymerase chain reaction/polymorphism in restriction fragment length). RESULTS:Necrotizing enterocolitis was diagnosed in 25 (33%) neonates and, of these, 3 (12%) died. Male gender was more prevalent in both groups (p=0.1613): cases (52%) and controls (62%). Moderate and extreme preterm newborns were predominant in both groups: cases (80%) and controls (88%) (p=0.3036). Low birth weight and extremely low birth weight newborns were the most prevalent in cases (78%), and very low birth weight and extremely low birth weight were the most prevalent in controls (81%) (p=0.1073). Clinical treatment was successful in 72%, and hospital discharge was achieved in 88% of newborns with NEC. The -94ins/delATTG polymorphism in NFKB1 gene was not identified in all the 150 alleles analyzed (100%). CONCLUSIONS:The absence of the -94ins/delATTG polymorphism in NFKB1 gene in newborns with and without necrotizing enterocolitis does not rule out the possibility of alterations in this and/or in other genes in newborns with this condition, which reinforces the need for further research.

RESUMO RACIONAL:Anormalidades nas diferentes fases do processo de maturação intestinal causam alterações metabólicas e moleculares. Dentre as alterações genéticas associadas à enterocolite necrotizante, o polimorfismo -94ins/delATTG no gene NFKB1 leva à ativação desregulada da proteína NFKB devido ao aumento do estado pró-inflamatório inerente ao intestino prematuro. OBJETIVOS:Determinar a prevalência do polimorfismo -94ins/delATTG no gene NFKB1 em neonatos com e sem enterocolite necrotizante. MÉTODOS: Trata-se de um estudo caso-controle, no qual foram avaliados 25 neonatos como grupo caso e 50 neonatos como grupo controle, de ambos os sexos. O DNA foi extraído de leucócitos do sangue periférico e o sítio que engloba o polimorfismo foi amplificado por técnicas moleculares (reação em cadeia da polimerase/polimorfismo no comprimento do fragmento de restrição). RESULTADOS: Enterocolite necrosante foi diagnosticada em 25 (33%) neonatos e, destes, 3 (12%) foram a óbito. O gênero masculino foi mais prevalente em ambos os grupos (p=0,1613): casos (52%) e controles (62%). Os prematuros moderados e extremos foram predominantes em ambos os grupos: casos (80%) e controles (88%) (p=0,3036). Recém-nascidos de baixo peso e extremo baixo peso foram os mais prevalentes nos casos (78%) e de muito baixo peso e extremo baixo peso foram os mais prevalentes nos controles (81%) (p=0,1073). O tratamento clínico foi bem-sucedido em 72% e a alta hospitalar foi obtida em 88% dos recém-nascidos com enterocolite necrotizante. O polimorfismo -94ins/delATTG no gene NFKB1 não foi identificado em todos os 150 alelos analisados (100%). CONCLUSÕES: A ausência do polimorfismo -94ins/delATTG no gene NFKB1 em recém-nascidos com e sem enterocolite necrosante não afasta a possibilidade de alterações neste e/ou em outros genes em recém-nascidos com esta condição, o que reforça a necessidade de novas pesquisas.

In-hospital outcomes in preterm and small-for-gestational-age newborns: a cohort study

ABSTRACT Objective To compare in-hospital outcomes between small-for-gestational-age and appropriate-for-gestational-age preterm neonates who needed intensive care. Methods A retrospective cohort study with preterm newborns, from January to December 2017. The results are presented as median, frequency, and odds ratio. Numerical variables were compared using the Wilcoxon test. Categorical variables were compared using the χ2 test. We considered p<0.05 as significant. Results Out of 129 preterm newborns included, 20.9% were small-for-gestational-age. Median gestational age was 31 2/7 weeks, birthweight was 1,450g, and length of hospital stay was 39 days. Preterm small-for-gestational-age newborns presented a higher chance of peri-intraventricular hemorrhage (odds ratio of 3.23; p=0.02), retinopathy of prematurity (odds ratio of 2.78 p=0.02), patent ductus arteriosus (odds ratio of 2.50; p=0.04) and a lower chance of presumptive early-onset sepsis (odds ratio of 0.37; p=0.03). Conclusion Preterm small-for-gestational-age neonates were associated with peri-intraventricular hemorrhage, retinopathy of prematurity and patent ductus arteriosus. This emphasizes the need of special care for these neonates.

Progress in fecal microbiota transplantation in neonatal necrotizing enterocolitis / 中华围产医学杂志

Neonatal necrotizing enterocolitis (NEC) is one of the leading causes of morbidity and mortality in newborns, especially in premature infants. The pathogenesis of NEC is closely related to intestinal microbiota disorders. In recent years, fecal microbiota transplantation (FMT) has been widely used in the treatment of gastrointestinal diseases and extra-gastrointestinal diseases in adults and children. A large number of studies have also been conducted in NEC animal models. This article reviews the possible mechanism of FMT in the treatment of NEC and the progress in this respect.

Target inhibition of Toll-like receptor 4 signaling pathway and necrotizing enterocolitis / 中华围产医学杂志

The pathogenesis of neonatal necrotizing enterocolitis (NEC) is still unclear. Toll-like receptor 4 (TLR4) signaling pathway, mediated by TLR4 in the intestinal epithelial cells, is considered to play an important role in activating inflammatory storm in NEC. This paper elaborates the association between NEC and the inhibition of TLR4 signal pathway and its upstream and downstream signal targets, critical pattern recognition receptors, and negative regulation of TLR4 by certain receptors to gain more insight into possible target interventions for NEC.

Oropharyngeal administration of colostrum for preventing necrotizing enterocolitis and late-onset sepsis in preterm infants with gestational age ≤ 32 weeks: a pilot single-center randomized controlled trial.

BACKGROUND: Oropharyngeal 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. METHODS: A 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. RESULTS: A 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. CONCLUSIONS: Oropharyngeal 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 REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900023697 , Registered 8 June 2019, retrospectively registered.

Nutritional management in newborn babies receiving therapeutic hypothermia: two retrospective observational studies using propensity score matching.

BACKGROUND: Therapeutic hypothermia is standard of care for babies with moderate to severe hypoxic-ischaemic encephalopathy. There is limited evidence to inform provision of nutrition during hypothermia. OBJECTIVES: To assess the association during therapeutic hypothermia between (1) enteral feeding and outcomes, such as necrotising enterocolitis and (2) parenteral nutrition and outcomes, such as late-onset bloodstream infection. DESIGN: A retrospective cohort study using data held in the National Neonatal Research Database and applying propensity score methodology to form matched groups for analysis. SETTING: NHS neonatal units in England, Wales and Scotland. PARTICIPANTS: Babies born at ≥ 36 gestational weeks between 1 January 2010 and 31 December 2017 who received therapeutic hypothermia for 72 hours or who died during treatment. INTERVENTIONS: Enteral feeding analysis - babies who were enterally fed during therapeutic hypothermia (intervention) compared with babies who received no enteral feeds during therapeutic hypothermia (control). Parenteral nutrition analysis - babies who received parenteral nutrition during therapeutic hypothermia (intervention) compared with babies who received no parenteral nutrition during therapeutic hypothermia (control). OUTCOME MEASURES: Primary outcomes were severe and pragmatically defined necrotising enterocolitis (enteral feeding analysis) and late-onset bloodstream infection (parenteral nutrition analysis). Secondary outcomes were survival at neonatal discharge, length of neonatal stay, breastfeeding at discharge, onset of breastfeeding, time to first maternal breast milk, hypoglycaemia, number of days with a central line in situ, duration of parenteral nutrition, time to full enteral feeds and growth. RESULTS: A total of 6030 babies received therapeutic hypothermia. Thirty-one per cent of babies received enteral feeds and 25% received parenteral nutrition. Seven babies (0.1%) were diagnosed with severe necrotising enterocolitis, and further comparative analyses were not conducted on this outcome. A total of 3236 babies were included in the matched enteral feeding analysis. Pragmatically defined necrotising enterocolitis was rare in both groups (0.5% vs. 1.1%) and was lower in babies who were fed during hypothermia (rate difference -0.5%, 95% confidence interval -1.0% to -0.1%; p = 0.03). Higher survival to discharge (96.0% vs. 90.8%, rate difference 5.2%, 95% confidence interval 3.9% to 6.6%; p < 0.001) and higher breastfeeding at discharge (54.6% vs. 46.7%, rate difference 8.0%, 95% confidence interval 5.1% to 10.8%; p < 0.001) rates were observed in enterally fed babies who also had a shorter neonatal stay (mean difference -2.2 days, 95% confidence interval -3.0 to -1.2 days). A total of 2480 babies were included in the matched parenteral nutrition analysis. Higher levels of late-onset bloodstream infection were seen in babies who received parenteral nutrition (0.3% vs. 0.9%, rate difference 0.6%, 95% confidence interval 0.1% to 1.2%; p = 0.03). Survival was lower in babies who did not receive parenteral nutrition (90.0% vs. 93.1%, rate difference 3.1%, 95% confidence interval 1.5% to 4.7%; p < 0.001). LIMITATIONS: Propensity score methodology can address imbalances in observed confounders only. Residual confounding by unmeasured or poorly recorded variables cannot be ruled out. We did not analyse by type or volume of enteral or parenteral nutrition. CONCLUSIONS: Necrotising enterocolitis is rare in babies receiving therapeutic hypothermia, and the introduction of enteral feeding is associated with a lower risk of pragmatically defined necrotising enterocolitis and other beneficial outcomes, including rates of higher survival and breastfeeding at discharge. Receipt of parenteral nutrition during therapeutic hypothermia is associated with a higher rate of late-onset infection but lower mortality. These results support introduction of enteral feeding during therapeutic hypothermia. FUTURE WORK: Randomised trials to assess parenteral nutrition during therapeutic hypothermia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN474042962. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 36. See the NIHR Journals Library website for further project information.

Every year, approximately 1200 babies in the UK suffer a lack of oxygen to the brain around birth. This is called hypoxic­ischaemic encephalopathy and can lead to brain injury or death. To treat hypoxic­ischaemic encephalopathy, babies receive cooling treatment in which their body temperature is lowered. Doctors do not know the best way to give nutrition to babies receiving cooling treatment. Babies can either be fed milk into their stomach (enteral nutrition) or be given nutrients through their veins (parenteral nutrition). We compared babies who were fed milk while they were being cooled with babies from whom milk was withheld while they were being cooled to see if there was a difference in the frequency of necrotising enterocolitis, a severe gut disease. In addition, we compared babies who received parenteral nutrition while they were being cooled with babies who did not to see if there was a difference in infections. Finally, we looked at other outcomes, including survival and breastfeeding. We used the National Neonatal Research Database, which holds de-identified (i.e. no baby can be identified) information on all babies who have received NHS neonatal care. We used a statistical approach to match babies in each group (i.e. fed babies and not fed babies) as closely as possible so that any difference in outcomes was because of different nutrition and not because of other differences. We included > 6000 babies with hypoxic­ischaemic encephalopathy. Approximately one in three babies received milk feeds and one in four babies received parenteral nutrition during cooling. Necrotising enterocolitis was very rare. More babies who were fed milk during cooling had good outcomes (e.g. being breastfed at discharge) and fewer had necrotising enterocolitis. Most of these babies received only a small amount of milk in the first 3 days. More babies given parenteral nutrition had infections, but also more survived. This suggests that it is probably safe and may be beneficial to feed babies milk during cooling. More research should look at milk feeding and parenteral nutrition during cooling.

Probiotics in the Prevention and Treatment of Necrotizing Enterocolitis.

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.

Differentiation of food protein-induced enterocolitis syndrome and necrotizing enterocolitis in neonates by abdominal sonography

Abstract Objectives: To summarize and differentiate abdominal ultrasound findings of necrotizing enterocolitis and food protein-induced enterocolitis syndrome. Methods: From January 2017 to December 2018, the abdominal ultrasound results of 304 cases diagnosed necrotizing enterocolitis or food protein-induced enterocolitis syndrome were retrospectively analyzed. The presence of pneumatosis intestinalis, portal venous gas, bowel wall thickening, intestinal motility, focal fluid collections and hypoechoic change of gallbladder wall were calculated, and the results were compared and analyzed. Results: Pneumatosis intestinalis, portal venous gas, bowel wall thickening, intestinal motility weakened/absent, focal fluid collections and hypoechoic change of gallbladder wall can be found in both necrotizing enterocolitis and food protein-induced enterocolitis syndrome infants. However, in infants with necrotizing enterocolitis, intestinal motility was weakened/absent in whole abdomen, and in food protein-induced enterocolitis syndrome, it only involved isolated segment of bowel. The positive rates of above signs in necrotizing enterocolitis infants were significantly higher than those in food protein-induced enterocolitis syndrome (p < 0.01). Moreover, it was observed that the rate of weakened intestinal motility besides the lesion segment of bowel in necrotizing enterocolitis infants was 100%, and in food protein-induced enterocolitis syndrome infants, it was 0%, which is supposed to be a main sign for identification. Conclusion: In the early stage, abdominal ultrasound can be used to differentiate necrotizing enterocolitis and food protein-induced enterocolitis syndrome.

Differentiation of food protein-induced enterocolitis syndrome and necrotizing enterocolitis in neonates by abdominal sonography.

OBJECTIVES: To summarize and differentiate abdominal ultrasound findings of necrotizing enterocolitis and food protein-induced enterocolitis syndrome. METHODS: From January 2017 to December 2018, the abdominal ultrasound results of 304 cases diagnosed necrotizing enterocolitis or food protein-induced enterocolitis syndrome were retrospectively analyzed. The presence of pneumatosis intestinalis, portal venous gas, bowel wall thickening, intestinal motility, focal fluid collections and hypoechoic change of gallbladder wall were calculated, and the results were compared and analyzed. RESULTS: Pneumatosis intestinalis, portal venous gas, bowel wall thickening, intestinal motility weakened/absent, focal fluid collections and hypoechoic change of gallbladder wall can be found in both necrotizing enterocolitis and food protein-induced enterocolitis syndrome infants. However, in infants with necrotizing enterocolitis, intestinal motility was weakened/absent in whole abdomen, and in food protein-induced enterocolitis syndrome, it only involved isolated segment of bowel. The positive rates of above signs in necrotizing enterocolitis infants were significantly higher than those in food protein-induced enterocolitis syndrome (p<0.01). Moreover, it was observed that the rate of weakened intestinal motility besides the lesion segment of bowel in necrotizing enterocolitis infants was 100%, and in food protein-induced enterocolitis syndrome infants, it was 0%, which is supposed to be a main sign for identification. CONCLUSION: In the early stage, abdominal ultrasound can be used to differentiate necrotizing enterocolitis and food protein-induced enterocolitis syndrome.

Interleukin 8 may predict surgical necrotizing enterocolitis in infants born less than 1500 g.

Necrotizing enterocolitis (NEC) often leads to gastrointestinal emergency resulting high mortality in very low birth weight infants (VLBWIs) requiring surgery. To date, few studies have explored the role of serum cytokines in the development of feeding intolerance (FI) or NEC outcomes in VLBWIs. Infants born weighing <1500 g or of 32 weeks of gestational age were prospectively enrolled from May 2018 to Dec 2019. We measured several cytokines routinely within 72 h of life, even before NEC-like symptoms developed. NEC or FI group comprised 17 (27.4%) infants, and 6 (9.7%) infants had surgical NEC. The gestational age and birth weight were significantly lower in the NEC or FI group with more prematurity-related complications. The surgical NEC group also demonstrated significantly lower gestational age and birth weight along with more infants experiencing refractory hypotension within a 1 week of life, pulmonary hypertension, and patent ductus arteriosus. IL-10 levels were significantly higher in the NEC or FI group, whereas IL-8 levels were significantly higher in the infants with surgical NEC. Our findings indicated to IL-8 can predict surgical NEC while increased IL-10 can predict NEC development in VLBWIs.

Routine blood test, C-reactive protein and blood culture for predicting necrotizing enterocolitis in preterm infants with late-onset sepsis / 中华围产医学杂志

Objective:To explore the value of blood routine indexes, C-reactive protein(CRP), and blood culture in predicting the occurrence of neonatal necrotizing enterocolitis (NEC) secondary to late-onset sepsis (LOS) in preterm infants.Methods:This study retrospectively enrolled 80 premature infants with LOS admitted to the First Hospital Affiliated to Army Medical University from January 1, 2015 to January 1, 2020. Based on whether complicated by NEC or not, all the subjects were assigned into the NEC group ( n=11) and non-NEC group ( n=69). Laboratory data for perinatal conditions, complete blood cell count, CRP, and blood culture in the early stage of LOS were recorded, and the decreased value of the hemoglobin concentration before and at early stage of LOS was calculated. Mann-Whitney U test, Chi-square test or Fisher exact probability method was used to compare the differences in perinatal conditions, blood routine, CRP and blood culture results between different groups. Binomial stepwise logistic regression analysis and the receiver operating characteristic (ROC) curve were used to evaluate the risk factors and their predictive value for NEC secondary to LOS, respectively. Results:(1) There was no significant difference in gestational age, birth weight or other perinatal factors between the NEC group and non-NEC group (all P>0.05). (2) Mean platelet volume (MPV), CRP, and the hemoglobin decreased value in NEC group were greater than those in non-NEC group [11.7 fl (10.9-12.6 fl) vs 10.7 fl (10.3-11.6 fl), Z=－2.773; 33.3 mg/L (21.3-92.9 mg/L) vs 13.5 mg/L (4.7-27.3 mg/L), Z=－2.662; 25.0 g/L (18.0 -36.0 g/L) vs 13.0 g/L (1.0-19.0 g/L), Z=－3.803; all P<0.01]. (3) Binomial stepwise logistic regression analysis suggested that higher MPV at early stage of LOS ( OR=3.213, 95% CI: 1.104-9.354, P=0.032) and the decreased hemoglobin ( OR=1.153, 95% CI: 1.057-1.257, P=0.001) were independent risk factors for NEC secondary to LOS in preterm infants. (4) The cut-off values of MPV combined with the decreased value of hemoglobin for predicting NEC in premature infants with LOS were 11.2 fl and 14.0 g/L, respectively, with a sensitivity of 1.00 and specificity of 0.71. Conclusions:MPV combined with the decreased value of hemoglobin may help to predict NEC in the early stage of LOS for preterm infants.

Complications and nutritional status following different timings of post-enterostomy stoma reversal in necrotizing enterocolitis / 中国新生儿科杂志

Objective:To study the incidences of postoperative complications and nutritional status following different timings of stoma reversal in necrotizing enterocolitis (NEC).Method:From January 2017 to December 2019, NEC patients receiving enterostomy surgery and later stoma reversal in our hospital were retrospectively analyzed. They were assigned into three groups according to the timing of stoma reversal: early group (reversal within 8 weeks of stoma formation), middle group (reversal at 8~12 weeks from stoma formation) and late group (reversal after 12 weeks from stoma formation). Weight-for-age-Z-score (WAZ) was used to evaluate nutritional status.Result:A total of 56 infants were enrolled, including 6 cases in the early group, 11 cases in the middle group, and 39 cases in the late group. The gestational age and birth weight were (33.4±3.4) weeks and (1 894±640) g, respectively. The median age of stoma formation and the interval between stoma formation and reversal were 16.5 (8.0, 28.2) days and 94.0 (76.5, 126.5) days. No significant differences existed on gestational age, birth weight, age of stoma formation and complications of stoma reversal among the three groups ( P>0.05). The incidence of growth retardation (WAZ<-2) was 14.3% at stoma formation, and significantly increased to 62.5% at stoma reversal ( P<0.05). The WAZ at stoma reversal in early, middle and late groups were (-3.2±1.9), (-3.0±1.6) and (-2.3±1.5), without significant differences( P>0.05). The WAZ gradually increased to (-0.7±1.2), (-0.1±2.0) and (-0.1±0.8) at 42~48 weeks after reversal, respectively. Conclusion:The timing of stoma reversal may not influence the complications of reversal. Growth retardation are common in NEC infants with stoma formation and stoma reversal may improve the nutritional status of the infants. Early reversal of stoma is suggested to improve the nutritional status of patients with poor weight gain after stoma formation.

Risk factors of necrotizing enterocolitis after surgery for intestinal atresia / 中国新生儿科杂志

Objective:To study the risk factors of necrotizing enterocolitis (NEC) after surgery for intestinal atresia.Method:From August 2013 to June 2020, children with intestinal atresia receiving surgery in our hospital were retrospectively reviewed. The patients were assigned into NEC group and non-NEC group according to the occurrence of postoperative NEC. Demographic data and clinical characteristics were summarized and the risk factors for postoperative NEC were analyzed using Logistic regression analysis method.Result:A total of 96 infants were enrolled and NEC occurred in 13 patients (13.5%) after surgery for intestinal atresia. Compared with the non-NEC group, the NEC group were diagnosed of intestinal atresia [4.0(1.5,6.0)d vs. 1.4(0,2.0)d, P<0.001] and received surgery [4.8(2.0,7.0)d vs. 3.1(1.0,4.0)d, P=0.034] at later ages. The incidences of complex intestinal atresia [76.9%(10/13) vs. 44.6%(37/83), P=0.030] and blood transfusion [46.2%(6/13) vs. 13.3%(11/83), P=0.007] in the NEC group were higher than the non-NEC group. Logistic regression analysis showed that the age of initial diagnosis of intestinal atresia ( OR=3.346, 95% CI 1.493~7.500, P=0.003), complex intestinal atresia ( OR=9.052, 95% CI 1.119~73.209, P=0.039) and blood transfusion ( OR=6.835, 95% CI 1.399~33.380, P=0.018) were independent risk factors for postoperative NEC. Conclusion:Patients with delayed diagnosis of intestinal atresia, complex intestinal atresia and blood transfusion within 48 hours after surgery should be monitored for the occurrence of postoperative NEC.

Histological analysis of the intestinal wall of newborn rats submitted to hypoxia and reoxygenation to evaluate the protective effect of N-Acetylcysteine

Abstract Purpose To evaluate the effect of N-Acetylcysteine (NAC) in newborn rats submitted to hypoxia and reoxygenation (H/R) conditions in an experimental model of necrotizing enterocolitis. Methods Eight pregnant rats and their 70 cubs were used (5 groups) and exposed to H/R conditions and received NAC at different times. The animals in the H/R groups were placed in a gas chamber (100% CO2) for 10 minutes and then reoxygenated for 10 minutes (100% O2), twice a day for the first three days of life, with a six-hour span between events. On the third day of life, the animals were anesthetized, laparotomized and the intestines were resected. Results The H/R and NAC groups showed changes in the intestinal wall in relation to the number, height and width of the villi when compared to the control group (p<0.0001), but with better preservation of structures in the NAC group. There were no differences between groups regarding the number (%) of mitoses. Conclusion The administration of NAC decreased the lesions in the intestinal wall of rats submitted to H/R, therefore suggesting that this drug can be used to prevent the development of necrotizing enterocolitis in newborns.

Non-targeted metabolomics of intestinal contents of neonatal rats with necrotizing enterocolitis / 中国新生儿科杂志

Objective To study the change and characterization of metabolic profile of intestinal contents of the neonatal rats with necrotizing enterocolitis (NEC) using metabolomics approach,in order to figure out potential biomarkers of NEC.Method Twenty rats with three-postnatal day-old fed with special formula were assigned to control group (n =8) and NEC group (n =12) randomly.Experimental NEC of rats in NEC group were induced by exposing to cold stimulation at 4 degrees Celsius for 10 minutes and to hypoxia at 95％ nitrogen for 10 minutes,three times a day for three consecutive days.All the rats were sacrificed after model preparation.Segments of the ileum of all the rats were collected for hematoxylin-eosin staining and subsequent pathological damage evaluation.The intestinal contents of the ileum and colon were collected by perfusion,followed by lyophilization and analyzed by UHPLC-QE-MS in order to conduct the non-target metabolomic determination.The information of the metabolites determined was calculated by multivariable analysis using SIMCA software.Result The pathological damage scores of NEC group were higher than those of the control group [(3.13 ± 0.83) vs.(0.25 ± 0.46),P ＜ 0.001].The results of orthogonal partial least squares discriminant analysis (OPLS-DA) model showed that in the ESI + mode,R2(x) =0.604,R2(y) =0.583,Q2 =0.960,while in the ESI-mode,the OPLS-DA model R2(x) =0.828,R2(y) =0.999,and Q2 =0.713,indicating that there is a significant difference in the intestinal content metabolic profile between the control group and the NEC group.Forty-eight differential metabolites related to NEC were identified.In ESI-mode,there were 22 differential metabolites,including L-isoisoleucine (+ 221％) and D-phenylalanine (+ 230％),L-histidine (+ 284％),xanthine (+ 207％),glutamyl leucine (+ 246％),allose (-70％),myristic acid (-57％) and pentadecanoic acid (-35％).What is more,in the ESI + mode,26 other differential metabolites were identified,including ornithine (+ 268％),D-leucine (+ 176％),L-iso Leucine (+ 213％),acetylcholine (+ 195％),nicotinamide adenine dinucleotide (+ 199％),citrulline (+ 158％),cytosine (-58％),xanthoic acid (-64％).These metabolites were reflected to 33 different metabolic pathways in KEGG databases.The pathway enrichment analysis and pathway topology analysis with MetaboAnalyst indicated that the arginine and proline metabolic pathways,histidine metabolic pathways,and glutathione metabolic pathways were the top altered pathways in the condition of NEC.Conclusion The metabolic profile of intestinal contents in NEC rats was significantly different from that in normal rats,which was characterized by amino acid accumulation,mainly involving the metabolic pathways of arginine,proline,histidine and glutathione.The detection of intestinal contents metabolic profile,especially amino acid metabolize group may be of great significance for the diagnosis of NEC,and improving intestinal microenvironment may be the key strategy for the prevention and treatment of NEC.

Enterocolitis necrotizante del adulto, ¿una presentación atípica de la isquemia mesentérica? / Adult necrotizing enterocolitis, an atypical presentation of mesenteric ischemia?

La enterocolitis necrosante en adultos (ECNA) es una enfermedad de etiología incierta, muy infrecuente, con apenas casos descritos en la literatura y con elevada mortalidad. Existe una fuerte correlación entre eventos vasculares e infecciosos implicados en la patogenia de necrosis intestinal masiva en esta entidad.

Necrotizing enterocolitis in adults (ECNA) is a disease of uncertain etiology, very rare, with very few cases described in the literature and with high mortality. There is a strong correlation between vascular and infectious events involved in the pathogenesis of massive intestinal necrosis in this entity.