Necrotizing enterocolitis in premature infants at different gestation ages.

OBJECTIVE: Aim: To compare X-ray signs in different gestational and body weight groups of patients with NEC. PATIENTS AND METHODS: Materials and Methods: We conducted a retrospective study, enrolling 52 preterm newborns with symptoms of NEC regardless of onset time, who underwent treatment at Neonatal Intensive Care Units in Municipal Non-commercial enterprise "City Children Hospital №2", Odesa. The patients were split into 3 clinical groups: very preterm newborns (VPN), moderately preterm newborns (MPN), and moderately preterm newborns with intrauterine growth restriction (MPN+IUGR). RESULTS: Results: In the VPN group NEC was diagnosed at stage II (58,82±12,30) % and III (41,18±12,30) % by Bell MJ, р>0,05. In the group MPN+IUGR, NEC stage II (33,33±14,21) % and stage III (66,66 ±14,21) %, р>0,05, were equally observed. In the MPN group, NEC was diagnosed at stage I (41,67±10,28) % and II (58,33±10,28) %, р>0,05, without prevalence of any. Also only localized forms were observed. In VPN, we observed localized forms in most cases, while diffuse forms were diagnosed in (11,76±8,05) % cases, р<0,05. In the MPN+IUGR group, we found diffuse form of the NEC in half of the cases - (50,00±15,08) %. In the VPN and MPN+IUGR groups, NEC developed at 13,23±0,39 and 14,33±1,19 days, respectively. However, in MPN without IUGR, NEC developed at 17,75±0,55 days, significantly later than in the MPN+IUGR group, р<0,05. CONCLUSION: Conclusions: We have described distinct features of NEC in MPN with IUGR. Compared to MPN without IUGR, NEC had more severe course and earlier manifestation in such neonates.

Timing of Red Blood Cell Transfusions and Occurrence of Necrotizing Enterocolitis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Observational studies often report that anemia and red blood cell (RBC) transfusions are associated with a higher risk of necrotizing enterocolitis (NEC) among extremely low-birthweight (ELBW) infants. Objective: To evaluate whether there is a temporal association between 72-hour hazard periods of exposure to RBC transfusions and NEC among ELBW infants randomized to either higher or lower hemoglobin transfusion thresholds. Design, Setting, and Participants: This post hoc secondary analysis of 1690 ELBW infants who survived to postnatal day 10 enrolled in the Transfusion of Prematures (TOP) randomized multicenter trial between December 1, 2012, and April 12, 2017, was performed between June 2021 and July 2023. Exposures: First, the distribution of RBC transfusions and the occurrence of NEC up to postnatal day 60 were examined. Second, 72-hour posttransfusion periods were categorized as hazard periods and the pretransfusion periods of variable duration as control periods. Then, the risk of NEC in posttransfusion hazard periods was compared with that in pretransfusion control periods, stratifying the risk based on randomization group (higher or lower hemoglobin transfusion threshold group). Main Outcomes and Measures: The primary outcome was incidence of NEC stage 2 or 3. Secondary outcomes included the incidence rates of NEC within five 10-day intervals, taking into account the number of days at risk. Results: Of 1824 ELBW infants randomized during the TOP trial, 1690 were included in the present analysis (mean [SD] gestational age, 26.0 [1.5] weeks; 899 infants [53.2%] were female). After categorizing 4947 hazard periods and 5813 control periods, we identified 133 NEC cases. Fifty-nine of these cases (44.4%) occurred during hazard periods. Baseline and clinical characteristics of infants with NEC during hazard periods did not differ from those of infants with NEC during control periods. The risk of NEC was 11.9 per 1000 posttransfusion hazard periods and 12.7 per 1000 control periods (adjusted risk ratio, 0.95; 95% CI, 0.68-1.32; P = .74). This risk did not differ significantly between randomization groups, but the incidence rate of NEC per 1000 days peaked between postnatal days 20 and 29 in the lower hemoglobin transfusion threshold group. Conclusions and Relevance: The findings of this post hoc analysis suggest that, among ELBW infants with the hemoglobin ranges occurring in the TOP trial, exposure to RBC transfusions was not temporally associated with a higher risk of NEC during 72-hour posttransfusion hazard periods. Given that the incidence rate of NEC peaked between postnatal days 20 and 29 among infants with lower hemoglobin values, a more in-depth examination of this at-risk period using larger data sets is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01702805.

Effects of implementation of a care bundle on rates of necrotising enterocolitis and own mother's milk feeding in the East Midlands: protocol for a mixed methods impact and process evaluation study.

INTRODUCTION: Prevention of necrotising enterocolitis (NEC) is vital for improving neonatal outcomes. Feeding own mother's milk helps prevent NEC. Rates of own mother's milk feeding in the East Midlands are lower than the national average and the incidence of NEC is higher. The East Midlands Neonatal Operational Delivery Network (EMNODN) has created a care bundle to improve these in babies born at <32 weeks' gestation, the group at the highest risk of NEC. The bundle was introduced in September 2022 and embedded by December 2022. We will evaluate its effectiveness and conduct a process evaluation to understand barriers and facilitators to implementation. METHODS AND ANALYSIS: We will conduct a retrospective cohort study (workstream 1) using data from the National Neonatal Research Database (NNRD). We will identify infants receiving any own mother's milk on day 14 and at discharge, and cases of severe NEC. We will aggregate outcomes by birth month and use interrupted time series analysis to estimate an incidence rate ratio for changes after the care bundle was embedded, relative to pre-implementation. We will model data from all other NNRD units and assess whether there are any concurrent changes to exclude confounding due to other events.We will apply the RE-AIM framework (workstream 2), supplemented by the Consolidated Framework for Implementation Research and Framework for Implementation Fidelity, to conduct a mixed methods evaluation in EMNODN units. We will triangulate data from several sources, including questionnaires and semistructured interviews with parents and healthcare professionals, and data from patient records. ETHICS AND DISSEMINATION: The study has approval from the South East Scotland Research Ethics Committee 01 and the Health Research Authority and Health and Care Research Wales (IRAS 323099). Results will be disseminated via scientific journals and conferences, to neonatal service commissioners and through public-facing infographics. TRIAL REGISTRATION NUMBER: NCT05934123.

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

INTRODUCTION: Necrotizing enterocolitis (NEC) is a life-threatening condition that afflicts neonates. Breastfeeding has demonstrated to play a protective role against it. By administering lipopolysaccharides (LPS) orally in newborn rats (NBR), we have developed an experimental model to induce NEC-like gut damage. Our aim was to assess the macroscopic and microscopic appearance of the gut, to evaluate the presence of NEC and study the role of breast milk (BM). MATERIALS AND METHODS: NBR were divided into 3 groups: Group A (control, n= 10) remained with the mother, group B (LPS, n= 25) was isolated after birth, gavage-fed with special rat formula and oral LPS, then submitted to stress (hypoxia after gavage) and group c (BM, n= 12) was breastfed once after birth, then isolated, and submitted to stress like group B. On day 4, NBR were sacrificed, and intestine was harvested 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 developed histologic signs of NEC (85%) and group C showed a statistically lower incidence of NEC (50%, p= 0.04), playing the BM a protective role against NEC (OR= 0.19; 95% CI: 0.40-0.904). CONCLUSION: Our model showed a significant incidence of NEC in NBR (73%) with the same protective role of BM as in newborn humans, achieving a reliable and reproducible experimental NEC model. This will allow us to investigate new potential therapeutic targets for a devastating disease that currently lacks treatment.

INTRODUCCION: La enterocolitis necrotizante (ECN) es una enfermedad potencialmente mortal que afecta a los neonatos, y frente a la que 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 un daño intestinal similar al que provoca la ECN con objeto de evaluar el aspecto macroscópico y microscópico del intestino, y de ese modo, analizar la presencia de ECN y estudiar el papel que desempeña la leche materna (LM). MATERIAL Y METODOS: Las RRN se dividieron en tres grupos: el grupo A (control, n= 10) permaneció con su madre; el grupo B (LPS, n= 25) fue aislado tras el nacimiento, alimentado por sonda con una fórmula especial 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 el nacimiento y posteriormente aislado y sometido a estrés al igual que el grupo B. El día 4 se sacrificó a las RRN y se recuperaron sus intestinos para su posterior evaluación. RESULTADOS: En el grupo de control, no se observó ECN ni macroscópica ni histológicamente, mientras que los dos grupos sometidos a estrés (B y C) presentaron una incidencia global de la ECN del 73%. La mayoría de los sujetos del grupo B desarrollaron signos histológicos de ECN (85%), y los del grupo C registraron una incidencia de la ECN estadísticamente menor (50%, p= 0,04), lo que significa que la LM desempeña una función protectora frente a la ECN (OR= 0,19; IC 95%: 0,40-0,904). CONCLUSION: Nuestro modelo reveló una incidencia significativa de la ECN en RRN (73%), desempeñando la LM la misma función protectora que en el caso de los humanos recién nacidos, lo que significa que este modelo experimental de ECN es fiable y reproducible. Gracias a dicho logro, podremos investigar nuevos y potenciales objetivos terapéuticos para una peligrosa enfermedad que, a día de hoy, carece de tratamiento.

Probiotic supplementation and risk of necrotizing enterocolitis and mortality among extremely preterm infants-the Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial: study protocol for a multicenter, double-blinded, placebo-controlled, and registry-based randomized controlled trial.

BACKGROUND: Extremely preterm infants, defined as those born before 28 weeks' gestational age, are a very vulnerable patient group at high risk for adverse outcomes, such as necrotizing enterocolitis and death. Necrotizing enterocolitis is an inflammatory gastrointestinal disease with high incidence in this cohort and has severe implications on morbidity and mortality. Previous randomized controlled trials have shown reduced incidence of necrotizing enterocolitis among older preterm infants following probiotic supplementation. However, these trials were underpowered for extremely preterm infants, rendering evidence for probiotic supplementation in this population insufficient to date. METHODS: The Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial is a multicenter, double-blinded, placebo-controlled and registry-based randomized controlled trial conducted among extremely preterm infants (n = 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. Enrolled infants will be allocated to receive either probiotic supplementation with ProPrems® (Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus) diluted in 3 mL breastmilk or placebo (0.5 g maltodextrin powder) diluted in 3 mL breastmilk per day until gestational week 34. The primary composite outcome is incidence of necrotizing enterocolitis and/or mortality. Secondary outcomes include incidence of late-onset sepsis, length of hospitalization, use of antibiotics, feeding tolerance, growth, and body composition at age of full-term and 3 months corrected age after hospital discharge. DISCUSSION: Current recommendations for probiotic supplementation in Sweden and Denmark do not include extremely preterm infants due to lack of evidence in this population. However, this young subgroup is notably the most at risk for experiencing adverse outcomes. This trial aims to investigate the effects of probiotic supplementation on necrotizing enterocolitis, death, and other relevant outcomes to provide sufficiently powered, high-quality evidence to inform probiotic supplementation guidelines in this population. The results could have implications for clinical practice both in Sweden and Denmark and worldwide. TRIAL REGISTRATION: ( Clinicaltrials.gov ): NCT05604846.

Risk factors of necrotizing enterocolitis in twin preterm infants.

PURPOSE: This study was aimed to investigate the risk factors of necrotizing enterocolitis (NEC) in twin preterm infants. METHODS: The clinical data of 67 pairs of twin preterm infants admitted to the neonatal department of our hospital from January 2010 to December 2021 were retrospectively collected. One of the twins had NEC (Bell II and above) and the other twin without NEC. They were divided into NEC group and control group according to whether NEC occurred or not. RESULTS: Univariate analysis showed that NEC was associated with congenital heart disease, small for gestational age, mild asphyxia at birth and feeding intolerance (P < 0.05). CONCLUSION: Occurrence of NEC was associated with congenital heart disease, small for gestational age, and asphyxia at birth. For twin preterm infants with congenital heart disease, small for gestational age, or asphyxia at birth, special attention should be paid to the occurrence of NEC to minimize and avoid the occurrence of NEC.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

The role of nutrition in analysis of risk factors and short-term outcomes for late-onset necrotizing enterocolitis among very preterm infants: a nationwide, multicenter study in China.

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times. METHOD: Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups. RESULTS: Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P < 0.05). After adjustment for the confounding factors, high proportion of breastfeeding were identified as protective factors and long fasting time before NEC were identified as risk factors for LO-NEC; early feeding were identified as protective factors and low gestational age, grade III ~ IV neonatal respiratory distress syndrome (NRDS), high accumulation of the MCT/LCT emulsion in the first week were identified as risk factors for LO-NEC occurring between 8 ~ 14d. Logistic regression analysis showed that LO-NEC was a risk factor for late-onset sepsis, parenteral nutrition-associated cholestasis, metabolic bone disease of prematurity, and extrauterine growth retardation. CONCLUSION: Actively preventing premature birth, standardizing the treatment of grade III ~ IV NRDS, and optimizing enteral and parenteral nutrition strategies may help reduce the risk of LO-NEC, especially those occurring between 8 ~ 14d, which may further ameliorate the short-term clinical outcome of VPIs. TRIAL REGISTRATION: ChiCTR1900023418 (26/05/2019).

The Incidence of Necrotizing Enterocolitis and Late-Onset Sepsis during the COVID-19 Pandemic in Sweden: A Population-Based Cohort Study.

INTRODUCTION: The effect of the pandemic restrictions in the NICUs is not well studied. Necrotizing enterocolitis (NEC) is characterized by intestinal inflammation and bacterial invasion. This study aimed to investigate whether the incidence of NEC has changed during the COVID-19 pandemic in Sweden and whether it was associated with a change in the frequency of extremely preterm births. METHODS: Data were retrieved from the Swedish Neonatal Quality Register (SNQ) for infants registered between January 2017 and December 2021 born below a gestational age of 35 weeks. The registry completeness is 98-99%. The diagnosis of NEC was the primary outcome. Generalized linear model analysis was used to calculate the risk ratio for NEC. RESULTS: Totally 13,239 infants were included. 235 (1.8%) infants developed NEC, out of which 91 required surgical treatment. 8,967 infants were born before COVID-19 pandemic and 4,272 during. Median gestational age at birth was 32.8 weeks in both periods. The incidence of NEC was significantly lower during COVID-19 pandemic compared to the prior period (1.43 vs. 1.94%, p 0.037), but not the incidence of surgical NEC. The crude risk ratio of developing NEC during COVID-19 pandemic was 0.74 (95% CI: 0.55-0.98). The incidence of late-onset sepsis with positive culture was also declined during COVID-19 (3.21 vs. 4.15%, p value 0.008). CONCLUSION: While we found significant reduction in the incidence of NEC and culture-positive late-onset sepsis during the COVID-19 pandemic, the number of extremely preterm births was unchanged.

Erythropoietin and retinopathy of prematurity: a retrospective cohort study in Japan, 2008-2018.

BACKGROUND: Erythropoietin has an angiogenic effect on the retina and might increase the risk of retinopathy of prematurity (ROP). METHODS: This retrospective cohort study included infants born at 22 to 27 weeks' gestation between 2008 and 2018 who were admitted to neonatal intensive care units (NICUs). We compared mortality and morbidities between infants who received erythropoietin and those who did not. RESULTS: Among 18,955 livebirth infants, this study included 16,031 infants, among which 14,373 infants received erythropoietin. The risk of ROP requiring treatment was significantly higher in the erythropoietin group than in the control group (33% vs. 26%; aOR 1.50 [95% CI 1.28-1.76]). On the other hand, the erythropoietin group had lower risks of death and necrotizing enterocolitis. CONCLUSIONS: This study with a large sample size found that erythropoietin use was associated with increased risk of ROP requiring treatment, while being associated with reductions in deaths and NEC.

Effect of oropharyngeal colostrum therapy on neonatal sepsis in preterm neonates: A systematic review and meta-analysis.

Various studies have shown that oropharyngeal colostrum application (OPCA) is beneficial to preterm neonates. We performed a systematic review and meta-analysis to assess whether OPCA reduces the incidence of culture-proven neonatal sepsis in preterm neonates. Randomized controlled trials comparing OPCA with placebo or standard care in preterm neonates were included. Medline, Embase, Web of Science, Cumulated Index to Nursing and Allied Health Literature, Scopus, and CENTRAL were searched for studies published up to June 15, 2023. We used the Cochrane Risk of Bias tool, version 2, for risk of bias assessment, the random-effects model (RevMan 5.4) for meta-analysis, and Gradepro software for assessing the certainty of evidence. Twenty-one studies involving 2393 participants were included in this meta-analysis. Four studies had a low risk of bias, whereas seven had a high risk. Oropharyngeal colostrum significantly reduced the incidence of culture-proven sepsis (18 studies, 1990 neonates, risk ratio [RR]: 0.78, 95% confidence interval [95% CI]: 0.65, 0.94), mortality (18 studies, 2117 neonates, RR: 0.73, 95% CI: 0.59, 0.90), necrotizing enterocolitis (NEC) (17 studies, 1692 neonates, RR: 0.59, 95% CI: 0.43, 0.82), feeding intolerance episodes (four studies, 445 neonates, RR: 0.59, 95% CI: 0.38, 0.92), and the time to full enteral feeding (19 studies, 2142 neonates, mean difference: -2 to 21 days, 95% CI: -3.44, -0.99 days). There was no reduction in intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, ventilator-associated pneumonia, neurodevelopmental abnormalities, hospital stay duration, time to full oral feeding, weight at discharge, pneumonia, and duration of antibiotic therapy. The certainty of the evidence was high for the outcomes of culture-positive sepsis and mortality, moderate for NEC, low for time to full enteral feeding, and very low for feeding intolerance. OPCA reduces culture-positive sepsis and mortality (high certainty), NEC (moderate certainty), and time to full enteral feeding (low certainty) in preterm neonates. However, scarcity of data from extremely premature infants limits the generalizability of these results to this population.

Identifying Risk Factors for Surgical Site Infection After Stoma Closure in Infants for Targeted Implementation of Surgical Site Infection Reduction Bundle.

Background: To determine risk factors for surgical site infection (SSI) in infants after stoma closure, to identify at-risk patients, plan timing of surgery, and implement SSI-reduction strategies. Patients and Methods: A single center retrospective comparison study of all children less than one year of age who underwent enterostomy closure (2018-2020) with SSI diagnosed through a prospective surveillance program, using criteria from Public Health England (PHE). Demographics and risk factors, types of SSI, systemic sepsis, mortality and length of stay were compared between SSI and non-SSI. Significant factors associated with SSI were analyzed in a multivariate binomial logistic regression model. Results: Eighty-nine stoma closures were performed, most commonly for necrotizing enterocolitis (NEC) and anorectal malformation. Fourteen had SSI (16%): 12 superficial and two deep; three developed systemic sepsis, but no 30-day mortality. Surgical site infection was associated with NEC (12/14 vs. 32/75; p = 0.003), younger age (median 76 vs. 89 days; p = 0.014), lower corrected gestation (cutoff: 39 weeks gestation; 11/14 vs. 27/75; p = 0.004) and lower weight (cutoff: 2.2 kg; 7/14 vs. 16/75; p = 0.032), compared with non-SSI. After correcting for age, gestation, and weight, logistic regression showed NEC was an independent predictor for SSI (odds ratio [OR], 12; 95% confidence interval [CI],1.2-125). The at-risk cohort (n = 56; 63%) had seven-fold increased risk of SSI and four-fold longer hospital stay, which may be the target for SSI-reduction strategies. Conclusions: Necrotizing enterocolitis-related stoma closure is at increased risk for SSI. Considerations for delaying stoma closure until achieving 39 weeks gestation or 2.2 kg in weight may further reduce SSI. Targeting SSI-reduction strategies using these criteria may improve resource-rationalization.

Factors influencing necrotizing enterocolitis in premature infants in China: a systematic review and meta-analysis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease with high morbidity and mortality among premature infants. However, studies with large samples on the factors of NEC in China have not been reported. This meta-analysis aims to systematically review the literature to explore the influencing factors of necrotizing enterocolitis in premature infants in China and provide a reference for the prevention of NEC. METHODS: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), Wanfang and VIP databases were systematically searched from inception to February 2023. We used Stata14.0 software to perform the systematic review and meta-analysis. We used fixed or random effects models with combined odds ratios (ORs) and 95% confidence intervals (CIs), and quality was evaluated using the Newcastle‒Ottawa Scale (NOS). RESULTS: The total sample was 8616 cases, including 2456 cases in the intervention group and 6160 cases in the control group. It was found that 16 risk factors and 3 protective factors were related to necrotizing enterocolitis in premature infants. Septicemia (OR = 3.91), blood transfusion (OR = 2.41), neonatal asphyxia (OR = 2.46), pneumonia (OR = 6.17), infection (OR = 5.99), congenital heart disease (OR = 4.80), intrahepatic cholestasis of pregnancy (ICP) (OR = 2.71), mechanical ventilation (OR = 1.44), gestational diabetes mellitus (GDM) (OR = 3.08), respiratory distress syndrome (RDS) (OR = 3.28), hypoalbuminemia (OR = 2.80), patent ductus arteriosus (PDA) (OR = 3.10), respiratory failure (OR = 7.51), severe anemia (OR = 2.86), history of antibiotic use (OR = 2.12), and meconium-stained amniotic fluid (MSAF) (OR = 3.14) were risk factors for NEC in preterm infants in China. Breastfeeding (OR = 0.31), oral probiotics (OR = 0.36), and prenatal use of glucocorticoids (OR = 0.38) were protective factors for NEC in preterm infants. CONCLUSIONS: Septicemia, blood transfusion, neonatal asphyxia, pneumonia, infection, congenital heart disease, ICP, GDM, RDS, hypoproteinemia, PDA, respiratory failure, severe anemia, history of antibiotic use and MSAF will increase the risk of NEC in premature infants, whereas breastfeeding, oral probiotics and prenatal use of glucocorticoids reduce the risk. Due to the quantity and quality of the included literature, the above findings need to be further validated by more high-quality studies.

Management of Hematochezia in Infants with Congenital Heart Disease Admitted to the Acute Care Cardiology Unit: A Multicenter Retrospective Pilot Study.

OBJECTIVE: To assess the evaluation and prevalence of benign hematochezia (BH) vs necrotizing enterocolitis (NEC) in infants with congenital heart disease (CHD) <6 months old admitted to the acute care cardiology unit. STUDY DESIGN: This was a multicenter retrospective review of patient characteristics and evaluation of all hematochezia events in patients with CHD <6 months admitted to acute care cardiology unit at 3 high-volume tertiary care centers from February 2019 to January 2021. NEC was defined by the Bell staging criteria. Patients with gastrointestinal disorders were excluded. RESULTS: In total, 180 hematochezia events occurred in 121 patients; 42 patients had more than 1 event. In total, 61% of affected patients had single-ventricle physiology (38% hypoplastic left heart syndrome). Median age and weight at hematochezia were 38 days (IQR 24, 79) and 3.7 kg (IQR 3.2, 4.4). In total, 77% of hematochezia events were BH, and 23% were NEC. There were no surgical interventions for NEC or deaths from NEC. Those with NEC were significantly younger (34 vs 56 days, P < .01) and smaller (3.7 vs 4 kg, P < .01). Single-ventricle physiology was significantly associated with NEC. Initial bloodwork and diagnostic imaging at each center were assessed. There was no significant difference in white blood cell count or C-reactive protein in those with NEC compared with BH. Blood culture results were all negative. CONCLUSIONS: The majority of infants with CHD with hematochezia have BH over NEC, although single-ventricle and surgical patients remain at greater risk. Infants <45 days are more vulnerable for developing NEC. Bloodwork was noncontributory in the identification of cardiac NEC. Expansion to a prospective study to develop a treatment algorithm is important to avoid overtreatment.

Time to Attain Full Enteral Feeds Among Preterm Fetal Growth Restricted Neonates With Absent/Reversed End-Diastolic Flow.

OBJECTIVES: To determine the difference in time to attainment of full enteral feeds between fetal growth restricted (FGR) preterm neonates with and without absent/reversed end-diastolic flow (AREDF). Secondary objectives were to compare the short-term outcomes including the incidence of necrotizing enterocolitis (NEC) and feed intolerance between the two groups and to determine the factors affecting the time to attainment of full enteral feeds (FEF) among preterm FGR neonates. METHODS: A prospective cohort study was conducted among consecutive preterm FGR neonates delivered at 28-36 weeks gestation admitted in level III NICU. An umbilical artery doppler ultrasound was performed antenatally for all participants to detect AREDF. FGR neonates with AREDF were taken as the study group and those without AREDF were taken as the comparison group. Time to attain FEF was defined as time taken to establish enteral feeds of 150 ml/kg/day and tolerating it for the next 3 consecutive days. Delayed attainment of FEF was taken as ≥10 days needed to attain FEF. RESULTS: The median (IQR) time to attainment of full feeds was longer among neonates with AREDF compared to those without AREDF [12 (8, 16.5) vs 8 (5, 10) days; P < 0.001]. Neonates with AREDF had more feed intolerance [RR, 95% CI = 1.51 (1.13 - 2.02); P = 0.004], higher mortality [RR, 95% CI = 2.5 (1.02 - 6.2); P = 0.036], prolonged time to regain birth weight [15 (11.5, 19) days, P = 0.035], longer NICU stay [10 (7, 15), P < 0.001] and longer hospital stay [33 (23, 49), P < 0.001]. Also, neonates with AREDF had more hypoglycemia [RR, 95% CI=2.15 (1.2-3.7); P = 0.004], hypoxic ischemic encephalopathy [RR, 95% CI 5.05 (1.13 - 22.4); P = 0.016], hypothyroidism [RR, 95% CI= 8.08 (1.02 - 63.4), P = 0.016], cholestasis (P = 0.007), prolonged parenteral nutrition requirement [10 (7, 15) days, P < 0.001] and oxygen requirement [4.5 (2, 8) days, P < 0.001]. Multivariable logistic regression showed, AREDF [aOR 95% CI 2.91 (1.49 - 5.68), P = 0.002], lower gestational age [aOR 95% CI 0.724 (0.604 - 0.867), P < 0.001] and thrombocytopenia at birth [aOR 95% CI 2.625 (1.342 - 5.136), P = 0.005] are significant predictors of delayed attainment of full feeds among preterm FGR neonates. CONCLUSION: Preterm FGR neonates with AREDF are slower to attain FEF, have more feed intolerance, higher mortality, need longer time to regain birth weight, prolonged NICU stay and hospital stay. AREDF, lower gestation, sepsis and thrombocytopenia at birth are significant predictors of delayed full feed attainment among preterm FGR neonates. It is essential to devise strategies to reduce morbidity and mortality among this group of preterm neonates.

Neurodevelopmental impairment following surgical necrotizing enterocolitis with gestational age ≥ 28 weeks: who is at risk?

PURPOSE: Surgical necrotizing enterocolitis (NEC) is a severe medical condition that, even after surgery, a portion of the survival infants may still have neurological sequelae. The objective of this study was to identify the risk factors associated with the development of permanent neurodevelopmental impairment (NDI) in neonates with surgical NEC. METHODS: Between January 2016 and June 2022, a retrospective data collection was conducted on 98 individuals who experienced surgical NEC with gestational age ≥ 28 weeks. Among these patients, 27 patients were diagnosed with NDI, while the remaining 71 patients did not have NDI. Based on this division, the patients were categorized into the NDI group and the Non-NDI group. Demographics, comorbidities, and admission lab results were analyzed using univariate and logistic regression analyses. RESULTS: Of the 98 neonates following surgical NEC, 27(27.6%) developed permanent neurodevelopmental impairment (NDI). Predictors of NDI were identified through the final multivariable logistic regression analysis, which revealed that gestational age ≤ 32 weeks (p = 0.032; odds ratio [OR], 5.673), assisted mechanical ventilation after NEC onset (p = 0.047; OR, 5.299), postoperative acute kidney injury (p = 0.040; OR, 5.106), CRP day 3 after NEC onset (p = 0.049; OR, 1.037), time from presentation to surgery (p = 0.003; OR, 1.047) were significant risk factors. CONCLUSIONS: Our study identified gestational age ≤ 32 weeks, assisted mechanical ventilation after NEC onset, postoperative acute kidney injury, CRP day 3 after NEC onset, and time from presentation to surgery as significant risk factors for NDI in neonates with surgical NEC. These factors would be helpful to refine treatment modalities for better disease outcomes. We also determined the cut-off values of CRP day 3 after NEC onset and time from presentation to surgery, allowing for the individualized evaluation of NDI risk and the implementation of earlier targeted laparotomy.

Neonatal Diet Type and Associations With Adverse Feeding Outcomes in Neonates With Critical Congenital Heart Defects.

BACKGROUND: Neonates with critical congenital heart defects (CCHD neonates) experience high rates of feeding intolerance, necrotizing enterocolitis (NEC), and malnutrition. The benefits of human milk and direct chest/breastfeeding are well known, but research is limited in CCHD neonates. Therefore, the purpose of this study is to examine the impact of neonatal diet and feeding modality on the incidence of feeding intolerance, NEC, and malnutrition among a cohort of CCHD neonates. METHODS: A single-center retrospective study was conducted using electronic health record data of CCHD neonates admitted to a cardiac intensive care unit between April 2016 and April 2020. Regression models were fit to analyze associations between neonatal diet, feed modality, and adverse feeding outcomes. RESULTS: Seventy-four CCHD neonates were included. Increased days of direct chest/breastfeeding were associated with fewer signs of gastrointestinal distress ( P = .047) and bloody stools ( P = .021). Enteral feeding days of "all human milk" were associated with higher growth trajectory ( P < .001). CONCLUSIONS: Human milk and direct chest/breastfeeding may be protective against some adverse feeding outcomes for CCHD neonates. Larger, multicenter cohort studies are needed to continue investigating the effects of neonatal diet type and feeding modality on the development of adverse feeding outcomes in this unique population.

Maternal body mass index and necrotizing enterocolitis: A case-control study.

INTRODUCTION: Our aim was to determine if maternal body mass index (BMI) is associated with necrotizing enterocolitis (NEC) in a large urban delivery center. METHODS: This single center retrospective case-control study included 291 infants under gestational age of 33 weeks admitted to the neonatal intensive care unit (NICU) during a 10-year period. Cases of stage 2 and 3 NEC were matched at a ratio of 2 controls (n = 194) to 1 case (n = 97). Maternal BMI was categorized as normal (≤24.9), overweight (25-29.9) and obese (≥30). Chi-square and stepwise logistic regression were used for analysis. A power analysis was performed to determine if sample size was sufficient to detect an association. RESULTS: Stepwise logistic regression demonstrated no association between NEC and maternal obesity. Maternal hypertension, pre-eclampsia, premature rupture of membranes, maternal exposure to antibiotics, placental abruption and gestational diabetes were not associated with NEC. Power analysis showed the sample size was sufficient to detect an association of NEC with maternal BMI in three groups analyzed. In this case-control study, there was an association between NEC and maternal overweight but not obesity at delivery. DISCUSSION: Our results did not show a significant association of NEC with maternal obesity. The percent of overweight and obese mothers prior to pregnancy and at delivery was significantly higher in our population than the national average and may be responsible for the limited ability to reveal any association between maternal obesity and NEC.

Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China.

BACKGROUND: Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. METHODS: VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. RESULTS: Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (ß = 0.6, 95%CI:0.1, 1.0; P = 0.01). CONCLUSIONS: The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04283799).

[Analysis of clinical characteristics and risk factors of postoperative complications in infants with early-onset necrotizing enterocolitis after enterostomy].

Objective: To investigate the clinical characteristics of children with early-onset necrotizing enterocolitis (NEC) undergoing enterostomy and analyze the risk factors for postoperative complications. Methods: Retrospective analysis was conducted on the clinical data (perinatal conditions, clinical characteristics, clinical outcomes, etc.) of NEC patients who underwent enterostomy at Beijing Children's Hospital from May 2016 to May 2023. The patients were divided into two groups based on the age of onset: an early-onset enterostomy group (<14 days) and a late-onset enterostomy group (≥14 days). Furthermore, the children with NEC were categorized into complication group and non-complication group based on whether there were complications after enterostomy. The differences in clinical data between these groups were analyzed, and the clinical characteristics of children with early-onset NEC and enterostomy were summarized. Multivariate logistic regression model was employed to analyze the risk factors for postoperative complications in NEC children with enterostomy. Results: A total of 68 cases were enrolled, including 43 cases in the early-onset enterostomy group [26 males and 17 females, aged (6.5±3.0) days] and 25 cases in the late-onset enterostomy group [15 males and 10 females, aged (21.0±3.0) days]. There were 28 cases (17 males and 11 females), age [M (Q1, Q3)] 9 (5, 14) days in the complication group and 33 cases (22 males and 11 females), aged of 14 (6, 21) days in the non-complication group. Compared to the late-onset enterostomy group, the early-onset enterostomy group had significantly higher rates of intraventricular hemorrhage [30.2% (13/43) vs 8.0% (2/25)], hemodynamically significant patent ductus arteriosus [37.2% (16/43) vs 12.0% (3/25)], mechanical ventilation≥72 hours after birth [39.5% (17/43) vs 16.0% (4/25)], stage Ⅲ NEC [(69.8% (30/43) vs 40.0% (10/25)], extensive NEC [27.9% (12/43) vs 8.0% (2/25)], and short-term postoperative complications [56.8% (21/37) vs 29.2% (7/24)] (all P<0.05).Multivariate logistic regression model analysis revealed that residual length of proximal small intestine was a protective factor for postoperative complications after enterostomy in NEC infants (OR=0.764, 95%CI: 0.648-0.901, P=0.001), but stage Ⅲ NEC was a risk factor (OR=1.042, 95%CI: 1.004-5.585, P=0.017). Conclusions: The incidence of postoperative complications is high, and the prognosis is poor in children with early-onset NEC enterostomy. The residual length of proximal enterostomy is a protective factor for postoperative complications of NEC enterostomy, but stage Ⅲ NEC is a risk factor.