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.

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.

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.

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.

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.

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.

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.

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.

Relationship between intestinal fatty acid-binding protein expression and necrotizing enterocolitis in neonatal rat model / 中华围产医学杂志

Objective To analyze the role of intestinal fatty acid-binding protein (I-FABP) expression in a neonatal rat model of necrotizing enterocolitis (NEC).Methods A total of 24 newborn rats were randomly divided into two groups:control group (n=6) and NEC group (n=18).Rats in the NEC group were fed with formula and experienced hypoxia,reoxygenation,cold stress and sequentially Lipopolysaccharide (10 mg/kg) lavage for three consecutive days to establish NEC model,after which were respectively sacrificed on day 1,2 and 3 (six for each day).Those in the control group were all sacrificed on day 3.Ileocecal tissues were collected for morphological and histological analysis.I-FABP expression was detected using Western blot and immunohistochemistry (IHC).One-way analysis of variance,LSD-t test,Kruskal-Wallis H test,Mann-Whitney U test and Pearson's correlation analysis were used for statistical analysis.Results The NEC model (intestinal pathological score ≥ 2) was established successfully without causing death.Compared with the control group,the NEC group showed less body weight gain [M (P25-P75):1.00 (0.48-1.35) vs 1.74 (1.62-1.86),1.25 (0.75-1.40) vs 2.61 (2.53-2.99),1.35 (0.88-1.48) vs 3.60 (3.48-3.73);Z=-2.898,-2.903,-2.892;all P＜0.05] and higher intestinal pathological scores [(2 (2-3),3 (2-3),4 (3-4) vs 0 (0-1);all P＜0.05] on day 1,2 and 3.The intestinal pathological score on day 3 was significantly higher than that on day 2 and day 1 (both P＜0.05).Expression of I-FABP and the number of I-FABP positive enterocytes in the NEC model group were increased compared with those in the control group [Western blot:0.179 (0.179-0.186),0.231 (0.211-0.245),0.202 (0.192-0.225) vs 0.091 (0.086-0.093);IHC:59 (55-60),80 (83-86),80 (84-88) vs 44 (39-47);all P＜0.05].Moreover,the expression of I-FABP protein and the number of I-FABP positive enterocytes on day 2 and day 3 were significantly higher than those on day 1 (all P＜0.05).I-FABP expression was positively associated with intestinal pathological score (Western blot:r=0.932,95％CI:0.872-0.969;IHC:r=0.709,95％CI:0.484-0.872).Conclusions I-FABP is an efficient marker for NEC and correlates with the severity of intestinal injury.

Oxidative stress assessment in intestine of newborn rats submitted to hypoxia and reoxygenation with tadalafil

Abstract Purpose: To evaluate the functional and structural response of tadalafil effects in the intestinal mucosa, using an experimental model of hypoxia and reoxygenation injury in rats. Methods: The animals were divided into 4 groups: CTL, H/R, H/R+Td and M+Td. The newborn rats allocated in groups H/R, H/R+Td and M+Td were submitted twice a day, to a gas chamber with CO2 at 100% for 10 minutes and afterward reoxygenation with O2 at 98% for 10 minutes, in the three first days of life. Tadalafil dose was given to newborn of group H/R+Td and to the pregnant rat of group M+Td. Histological analysis was made with hematoxylin-eosin technique and oxidative stress through nitrite and nitrate levels and lipid peroxidation. Results: The histological analysis showed a reduction of mucosa alterations in the groups that received tadalafil. In the oxidative stress evaluation, occurred an increase of NO levels and less lipidic peroxidation in the ileum segments that received tadalafil. Conclusion: Tadalafil provides tissue protection when administered independently to both, pregnant or newborns.

Radiological findings associated with the death of newborns with necrotizing enterocolitis / Achados radiológicos associados ao óbito de recém-nascidos com enterocolite necrosante

Abstract Objective: The aim of this study was to identify radiological and clinical risk factors for death in newborns with necrotizing enterocolitis. Materials and Methods: This was a retrospective cohort study, based on radiological examinations and medical charts of 66 infants with necrotizing enterocolitis, as confirmed by a finding of intestinal pneumatosis (stage IIA, according to modified Bell's staging criteria). Radiological and clinical variables were evaluated. Results: Of the 66 infants evaluated, 14 (21.2%) presented pneumatosis in the large and small bowel; 7 (10.6%) presented air in the portal system; and 12 (18.2%) died. Bivariate analysis revealed that the following variables were associated with death: bowel perforation; pneumatosis in the large and small bowel; air in the portal system; earlier gestational age; longer time on mechanical ventilation before the identification of pneumatosis; and longer time on mechanical ventilation before discharge or death. In the multivariate regression, the following variables remained as predictors of death: pneumatosis in the large and small intestines (odds ratio [OR] = 12.4; 95% confidence interval [95% CI] = 1.2-127.4; p = 0.035), perforation (OR = 23.2; 95% CI = 2.2-246.7; p = 0.009), and air in the portal system (OR = 69.7; 95% CI = 4.3-[not calculated]; p = 0.003). Conclusion: The set of factors most strongly associated with death in infants with necrotizing enterocolitis comprised extensive pneumatosis, pneumoperitoneum, and air in the portal system. Our findings confirm the importance of radiological imaging in the diagnosis and monitoring of necrotizing enterocolitis.

Resumo Objetivo: Determinar fatores de risco radiológicos e clínicos para o desfecho de óbito em recém-nascidos com enterocolite necrosante. Materiais e Métodos: Estudo de coorte retrospectivo de exames radiológicos e prontuários de 66 recém-nascidos com enterocolite necrosante confirmada pela presença de pneumatose intestinal (estágio IIA, segundo os critérios modificados de Bell). Foram estudados achados radiológicos e variáveis clínicas. Resultados: Catorze casos (21,2%) apresentaram pneumatose nos intestinos grosso e delgado, 7 (10,6%) apresentaram ar no sistema porta e 12 (18,2%) faleceram. As análises bivariadas indicaram que as variáveis significativas para o óbito foram: perfuração intestinal, pneumatose localizada nos intestinos grosso e delgado, ar no sistema porta, menor idade gestacional, longos períodos de ventilação mecânica até a identificação da pneumatose e longos períodos de ventilação mecânica até a data de alta/óbito. Na regressão multivariada, mantiveram-se como preditores do óbito: pneumatose localizada nos intestinos grosso e delgado (odds ratio [OR] = 12,4; intervalo de confiança de 95% [IC 95%] = 1,2-127,4; p = 0,035), perfuração (OR = 23,2; IC 95% = 2,2-246,7; p = 0,009) e ar no sistema porta (OR = 69,7; IC 95% = 4,3-não calculado; p = 0,003). Conclusão: Pneumatose extensa, pneumoperitônio e ar no sistema porta compuseram o melhor conjunto de fatores associados ao óbito. Esses achados corroboram a importância da radiografia simples de abdome no diagnóstico e acompanhamento da enterocolite necrosante.

Effect of red blood cell transfusion on the oxygenation of mesenteric tissue in premature infants / 中华儿科杂志

Objective@#To investigate the effect of red blood cell transfusion on the oxygenation of mesenteric tissue in premature infants.@*Methods@#In this prospective cohort study, preterm infants with gestational age <37 weeks who were treated with red blood cell transfusions were enrolled from June 2017 to March 2018 in Department of Neonatology, Children's Hospital of Fudan University. The infants were categorized into feeding intolerance group and feeding tolerance group according to the feeding intolerance standard. Near-infrared spectroscopy was applied to continuously monitor intestinal oxygen saturation from 2 h before red blood cell transfusion to 48 h after red blood cell transfusion. Intergroup differences of basic conditions were analyzed with t test, Mann-Whitney U test and χ2 test. Mixed linear model was used to compare intragroup and intergroup differences in intestinal oxygen saturation over time.@*Results@#A total of 73 cases with gestational age <37 weeks were enrolled, of whom 41 were males and 32 were females, with mean gestational age of (30±4)weeks and mean birth weight of (1 543±688)g; there were 33 cases in feeding intolerance group and 42 cases in feeding tolerance group. The average intestinal oxygen saturations at 2 h before blood transfusion, during blood transfusion, 2, 6, 12, 24, and 48 h after transfusion were 0.50±0.07, 0.52±0.07, 0.52±0.08, 0.51±0.08, 0.51±0.07, 0.51±0.08, and 0.51±0.07 respectively in feeding intolerance group and were 0.51±0.04, 0.55±0.04, 0.57±0.05, 0.57±0.04, 0.56±0.04, 0.56±0.04, and 0.56±0.05 respectively in feeding tolerance group. Compared with 2 h before transfusion, intestinal oxygen saturation were increased during transfusion in both group (feeding intolerance group t=4.992, P=0.000; feeding tolerance group t=9.615, P=0.000), however this effect lasted until 48 h after transfusion in feeding tolerance group (t=5.519, 12.409, 10.033, 9.133, 7.983, all P=0.000). Additionally, the increasement of intestinal oxygen saturation over time were lower in feeding intolerance group(F=8.876, P=0.000). Besides, the level of intestinal oxygen saturation was positively correlated with postmenstrual age (PMA)(F=4.863, P=0.031). In infants with PMA<30 weeks, particularly in feeding intolerance group, the level of intestinal oxygen saturation significantly decreased at 2 h after transfusion (t=23.063, P=0.002).@*Conclusions@#Feeding status and PMA may play a role in development of transfusion-associated necrotizing enterocolitis. Red blood cell transfusion may increase the risk for mesenteric ischemia and is more likely to cause necrotizing enterocolitis in preterm infants with PMA <30 weeks as well as feeding intolerance.@*Clinical Trail@#Children's Hospital of Fudan University, NCT02544100.

Laboratory-based characterization and traceability of an outbreak of necrotising enterocolitis / 中华预防医学杂志

Objective@#Laboratory-based characterization and traceability were performed on an outbreak of necrotising enterocolitis (NEC) happened in a maternal and child health care hospital in China.@*Methods@#Thirty-seven samples were collected from 3 NEC cases, that the clinical manifestations was bloody stools. Clostridium spp. isolation and identification were carried out on stool, breast milk, milk-based infant powder and environmental swab samples collected during NEC outbreak from October to November in 2016. Meanwhile, twenty-four swabs samples from ward environmental, staffs' hand as well as articles for neonates daily use were also collected and tested for Clostridium spp. after disinfection following outbreak. Pulsed-field gel electrophoresis (PFGE) analysis was performed on all Clostridium strains obtained.@*Results@#46% (17/37) samples were positive for a presumptive Clostridium spp. during the outbreak of NEC. One type of Clostridium spp. isolates was cultured from 10 samples including the hands of medical staffs, some medical equipments in the ward and milk-based infant powder ingested by the case, it was identified as C.butyricum. Another type of Clostridium spp. isolates was cultured from 2 samples including breast milk and inner wall of breast milk fresh-keeping bag, it was identified as C.sporogens. Both of these two types isolates were cultured from 5 samples including inner wall of breast milk box, inner wall of refrigerator, the handle of case's incubator and the case's stool. PFGE analysis showed that all 15 strains of C. butyricum and 7 strains of C.sporogens isolated from the samples mentioned above produced indistinguishable pulsotypes respectively. No NEC cases were found after disinfection following the outbreak and all samples collected after outbreak were negative for Clostridium spp.@*Conclusion@#The outbreak of NEC was highly related to C. butyricum contamination within the hospital.

A correlation study of necrotizing enterocolitis and encephalopathy of prematurity in premature infants with gestational age ＜ 32 weeks / 中国新生儿科杂志

Objective To study the correlation of necrotizing enterocolitis (NEC) and encephalopathy of prematurity (EOP) in premature infants with gestational age (GA) ＜ 32 weeks.Method From January 2009 to December 2014,clinical data of preterm infants (GA ＜ 32 weeks) admitted to department of neonatology of Children's Hospital of Fudan University and received brain magnetic resonance imaging (MRI) at corrected GA of full term or near full term were collected.NEC patients were assigned into the NEC group.At the same time,patients with similar GA and birth weight without NEC were assigned into the control group.The incidence and MRI characteristics of EOP were studied using Chi-square method.Result A total of312 preterm infants were included in our study,104 in the NEC group,and 208 in the control group.The incidence of EOP in the NEC group was higher than the control group (27.9％ vs.17.3％).The difference between the two groups were statistically significant (P =0.030).The incidence of non-cystic EOP in the NEC group was significantly higher than the control group (89.7％ vs.63.9％,P =0.017).Conclusion NEC and EOP may be correlated in preterm infants with GA ＜32 weeks.Most of EOP were non-cystic injury.