Enhancing Nursing Care for Children with Acute Gastroenteritis: Integrating Pediatric Early Warning Scores with the Situation-Background-Assessment-Recommendation System.

Background: Acute gastroenteritis is a frequently encountered diarrheal illness in children, often self-limiting but occasionally linked to substantial mortality and morbidity, demanding effective approaches for assessment and intervention. While the utilization of the Pediatric Early Warning Score (PEWS) and the Situation-Background-Assessment-Recommendation system (SBAR) in pediatric patient management is recognized as effective, research in this area remains limited. Objective: Our study aimed to investigate the potential impact of PEWS and SBAR systems on the outcomes of pediatric patients with acute gastroenteritis. Methods: We conducted a randomized controlled trial at our hospital, enrolling 124 children aged 3 to 12 years diagnosed with acute gastroenteritis. These participants were randomly assigned to either a control group (62 cases) or an intervention group (62 cases). Different outcomes were assessed, including the frequency and duration of diarrhea and vomiting, the Modified Vesikari Scale (MVS), the Clinical Dehydration Scale (CDS), and follow-up physician visits. We utilized a two-group independent sample t test to compare outcomes between the two groups. Results: Our study resulted in statistically significant findings favoring the intervention group regarding the frequency and duration of diarrhea and vomiting, the MVS, the CDS, and the need for repeat healthcare visits. Conclusions: The integration of PEWS with SBAR appears to offer improved outcomes for children afflicted with acute gastroenteritis.

Natural extracts, honey, and propolis as human norovirus inhibitors.

Norovirus is the most important cause of acute gastroenteritis, yet there are still no antivirals, vaccines, or treatments available. Several studies have shown that norovirus-specific monoclonal antibodies, Nanobodies, and natural extracts might function as inhibitors. Therefore, the objective of this study was to determine the antiviral potential of additional natural extracts, honeys, and propolis samples. Norovirus GII.4 and GII.10 virus-like particles (VLPs) were treated with different natural samples and analyzed for their ability to block VLP binding to histo-blood group antigens (HBGAs), which are important norovirus co-factors. Of the 21 natural samples screened, date syrup and one propolis sample showed promising blocking potential. Dynamic light scattering indicated that VLPs treated with the date syrup and propolis caused particle aggregation, which was confirmed using electron microscopy. Several honey samples also showed weaker HBGA blocking potential. Taken together, our results found that natural samples might function as norovirus inhibitors.

Qingke ß-glucan synergizes with a ß-glucan-utilizing Lactobacillus strain to relieve capsaicin-induced gastrointestinal injury in mice.

Capsaicin (CAP) is the main pungent component in capsicum fruits. Eating too much CAP leads to gastrointestinal injury. Previously, Qingke ß-glucan combined with ß-glucan-utilizing Lactobacillus plantarum S58 (LP.S58) ameliorated high fat-diet-induced obesity, but their effects on CAP-induced gastrointestinal injury have not been investigated. Our results showed that Qingke ß-glucan reduced the CAP-induced gastrointestinal injury in Kunming mice. The serum levels of inflammatory cytokines and gastrointestinal hormones, and the localized inflammation and the expression of EGF, EGFR, VEGF, and ZO-1 in the gastrointestinal tissues in CAP-treated mice were partly restored by Qingke ß-glucan. The CAP-induced increase in the abundances of proinflammatory intestinal bacteria was also reduced by Qingke ß-glucan. More importantly, we found that these beneficial effects of Qingke ß-glucan were markedly enhanced by ß-glucan-utilizing LP.S58 supplementation. Our study indicated that Qingke ß-glucan coupled with ß-glucan-utilizing LP.S58 relieved CAP-induced gastrointestinal injury.

An expert consensus-based guideline for the integrative anthroposophic treatment of acute gastroenteritis in children.

OBJECTIVES: Acute gastroenteritis is one of the major causes of hospital admission in childhood. The primary objective of the treatment is rehydration, but conventional drug therapies are limited. Therefore, several pediatricians supplement conventional treatment with complementary and alternative therapies. In the two German departments for pediatric integrative medicine, children suffering from an acute gastroenteritis are treated with supportive therapy based on anthroposophic medicine. However, up to now scientifically validated guidelines for these therapies are lacking. DESIGN: We consulted an expert pool of 50 physicians with expertise in anthroposophic medicine as well as pediatrics and invited them to participate in an online-based Delphi process. Results were analyzed by means of qualitative content analysis with two independent raters using MAXQDA. Using four rounds of questioning, a consensus-based guideline was developed. RESULTS: A strong consensus (>90%) or consensus (>75-90%) was achieved for 14 of 16 subsections. The guideline describes disease characteristics, the most useful diagnostics, drug as well as non-drug treatment recommendations and advises for a good physician-patient interaction. CONCLUSION: The guideline will help clinicians, as well as family doctors, in their daily routine and make anthroposophic medicine more tangible for parents and health insurance companies.

The pros, cons, and many unknowns of probiotics.

Consumption of over-the-counter probiotics for promotion of health and well-being has increased worldwide in recent years. However, although probiotic use has been greatly popularized among the general public, there are conflicting clinical results for many probiotic strains and formulations. Emerging insights from microbiome research enable an assessment of gut colonization by probiotics, strain-level activity, interactions with the indigenous microbiome, safety and impacts on the host, and allow the association of probiotics with physiological effects and potentially useful medical indications. In this Perspective, we highlight key advances, challenges and limitations in striving toward an unbiased interpretation of the large amount of data regarding over-the-counter probiotics, and propose avenues to improve the quality of evidence, transparency, public awareness and regulation of their use.

A model for rapid, active surveillance for medically-attended acute gastroenteritis within an integrated health care delivery system.

BACKGROUND: This study presents a novel methodology for estimating all-age, population-based incidence rates of norovirus and other pathogens that contribute to acute gastroenteritis in the United States using an integrated healthcare delivery system as a surveillance platform. METHODS: All cases of medically attended acute gastroenteritis within the delivery system were identified from April 1, 2014 through September 30, 2016. A sample of these eligible patients were selected to participate in two phone-based surveys and to self-collect a stool sample for laboratory testing. To ascertain household transmission patterns, information on household members with acute gastroenteritis was gathered from participants, and symptomatic household members were contacted to participate in a survey and provide stool sample as well. RESULTS: 54% of individuals who met enrollment criteria agreed to participate, and 76% of those individuals returned a stool sample. Among household members, 85% of eligible individuals agreed to participate, and 68% of those returned a stool sample. Participant demographics were similar to those of the eligible population, although minority racial/ethnic groups were somewhat underrepresented in the final sample. CONCLUSIONS: This study demonstrates the feasibility of conducting acute infectious disease research within an integrated health care delivery system. The surveillance, sampling, recruitment, and data collection methods described here are broadly applicable to conduct baseline and epidemiological assessments, as well as for other research requiring representative samples of stool specimens.

[Management of Acute Gastroenteritis in Children: A Systematic Review of Anthroposophic Therapies].

BACKGROUND: Acute gastroenteritis in children accounts for about 10% of hospital admissions and is still one of the major causes of death worldwide. As many children are treated with complementary and alternative medicine (CAM) and anthroposophic medicine, respectively, especially in Europe, the aim of this review was to descriptively present published anthroposophic therapies applied for the treatment of acute gastroenteritis in childhood. METHODS: A complex search strategy recording a broad spectrum of CAM therapies was developed to identify anthroposophic therapy options for the treatment of gastroenteritis in children. The search was conducted in 4 general scientific as well as 3 CAM-specific databases. RESULTS: In total, 3,086 articles were identified and screened for anthroposophic related content. The majority of hits deal with nutritional/dietary therapies. Articles considering anthroposophic approaches constitute only 3.1% (7/227) of all CAM-related articles. Among these articles 2 observational studies, 3 experience reports and 2 reviews were identified. In the experience reports, a variety of anthroposophic remedies was recommended but mostly unsupported by scientific evidence. However, observational studies for the anthroposophic medications, Bolus alba comp. and Gentiana comp., were detected. Additionally, studies investigating the efficacy and safety of Chamomilla, Ipecacuanha, Podophyllum or Tormentilla preparations in homeopathy and phytomedicine, respectively, were presented. CONCLUSIONS: Most CAM-associated therapies for gastroenteritis in childhood comprise dietary recommendations. Studies concerning anthroposophic approaches and medications, respectively, are deficient. The results of this study underline that effort is needed to evaluate anthroposophic therapies in a clinical setting.

The Use of a Triage-Based Protocol for Oral Rehydration in a Pediatric Emergency Department.

BACKGROUND: Guidelines recommend oral rehydration therapy (ORT) and avoidance of laboratory tests and intravenous fluids for mild to moderate dehydration in children with gastroenteritis; oral ondansetron has been shown to be an effective adjunct. OBJECTIVES: The aim of this study was to determine if a triage-based, nurse-initiated protocol for early provision of ondansetron and ORT could safely improve the care of pediatric emergency department (ED) patients with symptoms of gastroenteritis. METHODS: This study evaluated a protocol prompting triage nurses to assess dehydration in gastroenteritis patients and initiate ondansetron and ORT if indicated. Otherwise well patients aged 6 months to 5 years with symptoms of gastroenteritis were eligible. Prospective postintervention data were compared with retrospective, preintervention control subjects. RESULTS: One hundred twenty-eight (81 postintervention and 47 preintervention) patients were analyzed; average age was 2.1 years. Ondansetron use increased from 36% to 75% (P < 0.001). Time to ondansetron decreased from 60 minutes to 30 minutes (P = 0.004). Documented ORT increased from 51% to 100% (P < 0.001). Blood testing decreased from 37% to 21% (P = 0.007); intravenous fluid decreased from 23% to 9% (P = 0.03). Fifty-two percent of postintervention patients were discharged with prescriptions for ondansetron. There were no significant changes in ED length of stay, admissions, or unscheduled return to care. CONCLUSIONS: A triage nurse-initiated protocol for early use of oral ondansetron and ORT in children with evidence of gastroenteritis is associated with increased and earlier use of ondansetron and ORT and decreased use of IV fluids and blood testing without lengthening ED stays or increasing rates of admission or unscheduled return to care.

Clinical Pathway Produces Sustained Improvement in Acute Gastroenteritis Care.

BACKGROUND AND OBJECTIVES: Despite widespread use of the rotavirus vaccine in the last decade, dehydrating illnesses impact almost 2 billion children worldwide annually. Evidence supports oral rehydration therapy as a first-line treatment of mild to moderate dehydration. Ondansetron has proven to be a safe and effective adjunct in children with vomiting. We implemented a clinical pathway in our pediatric emergency department (ED) in January 2005 to improve care for this common condition. Our objective in this study was to determine the long-term impact of the pathway for acute gastroenteritis (AGE) on the proportion of patients receiving intravenous (IV) fluids and ED length of stay (LOS) for discharged patients. METHODS: Cases were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. We used statistical process control to analyze process and outcome measures for 2 years before and 10 years after pathway implementation. RESULTS: We included 30 519 patients. We found special cause variation with a downward shift in patients receiving IV fluids after initiation of the pathway and later with addition of ondansetron to the pathway from 48% to 26%. Mean ED LOS for discharged patients with AGE decreased from 247 to 172 minutes. These improvements were sustained over time. CONCLUSIONS: Implementation of a clinical pathway emphasizing oral rehydration therapy and ondansetron for children with AGE led to decreased IV fluid use and LOS in a pediatric ED. Improvements were sustained over a 10-year period. Our results suggest that quality-improvement interventions for AGE can have long-term impacts on care delivery.

Therapeutic interventions for gut dysbiosis and related disorders in the elderly: antibiotics, probiotics or faecal microbiota transplantation?

Ageing and physiological functions of the human body are inversely proportional to each other. The gut microbiota and host immune system co-evolve from infants to the elderly. Ageing is accompanied by a decline in gut microbial diversity, immunity and metabolism, which increases susceptibility to infections. Any compositional change in the gut is directly linked to gastrointestinal disorders, obesity and metabolic diseases. Increase in opportunistic pathogen invasion in the gut like Clostridium difficile leading to C. difficile infection is more common in the elderly population. Frequent hospitalisation and high prevalence of nosocomial infections with the ageing is also well documented. Long-term utilisation of broad-spectrum antibiotic therapy is being followed in order to control these infections. Nosocomial infections and antibiotic therapy in combination or alone is leading to gastroenteritis followed by Clostridium associated diarrhoea or antibiotic associated diarrhoea. Above all, use of broad-spectrum antibiotics is highly debated all over the world due to growing antimicrobial resistance. The use of narrow spectrum antibiotics could be helpful to some extent. Dietary supplementation of probiotics with prebiotics (synbiotics) or without prebiotics has improved gut commensal diversity and regulated the immune system. The recent emergence of faecal microbiota transplantation has played an important role in treating recurrent Clostridium associated diarrhoea. This review focuses on various therapeutic interventions for gut dysbiosis and gastrointestinal diseases in the elderly. The possible mechanism for antimicrobial resistance and mechanism of action of probiotics are also discussed in detail.

A review of dose-responses of probiotics in human studies.

The probiotic definition requires the administration of an 'adequate amount' in order to obtain a health benefit. What that amount should be is not indicated. Here, an overview is given of studies that investigated the dose-response relation of probiotics in human interventions. Studies were divided in; meta-analyses, meta-analyses on specific probiotic strains, and studies testing two or more doses of a probiotic (combination) in the same study. Meta-analyses on the effect of probiotics on antibiotic associated diarrhoea (AAD) suggest a dose-response effect; for Clostridium difficile-associated diarrhoea on the other hand no dose-response was observed. For other end-points; such as necrotising enterocolitis, prevention of atopic dermatitis and slow intestinal transit, no dose-response relation was identified in meta-analyses. For prophylaxis in colorectal cancer and relief of irritable bowel syndrome, no dose-response relation was determined. However, for blood pressure, a meta-analysis observed that higher doses (greater than 1011 cfu) were more effective than lower doses. Meta-analyses of specific strains suggest a break-point for effectiveness of Lactobacillus rhamnosus GG in the treatment of acute gastroenteritis in children; no dose-response was observed for two other probiotics assessed. Studies comparing two or more doses indicate that faecal recovery and risk reduction of AAD follow a positive dose-response relationship. Other end-points such as immune markers, general health, and bowel function did not exhibit clear dose-response relations. For AAD, the findings are very compelling; both meta-analyses and dedicated dose-response studies observe a positive correlation between dose and AAD risk. These findings do not allow for extrapolation, but suggest that studying higher doses for this end-point would be worthwhile. The lack of a clear dose-response for other end-points, does not mean it does not exist; present data does just not allow drawing any conclusions.

Microbiota y enfermedades gastrointestinales / Microbiota and gastrointestinal diseases

La colonización bacteriana se establece inmediatamente después del nacimiento, por contacto directo con la microbiota materna, y puede modificarse durante la lactancia. Están apareciendo datos indicativos de que modificaciones cuantitativas y cualitativas de la microbiota intestinal son capaces de estimular cambios en la activación del sistema inmune que pueden conducir a la aparición de enfermedades gastrointestinales o extraintestinales. El equilibrio entre la microbiota patógena y beneficiosa durante la niñez y la adolescencia es importante para la salud gastrointestinal, incluyendo la protección frente a patógenos, la inhibición de patógenos, el procesamiento de nutrientes (síntesis de vitamina K), el estímulo de la angiogénesis y la regulación del almacenamiento de la grasa corporal. También los probióticos pueden modular la microbiota intestinal para favorecer la salud del huésped. Este artículo es una revisión sobre la acción moduladora de la microbiota intestinal en la prevención y el tratamiento coadyuvante de las enfermedades gastrointestinales pediátricas

The bacterial colonisation is established immediately after birth, through direct contact with maternal microbiota, and may be influenced during lactation. There is emerging evidence indicating that quantitative and qualitative changes on gut microbiota contribute to alterations in the mucosal activation of the immune system, leading to intra- or extra-intestinal diseases. A balance between pathogenic and beneficial microbiota throughout childhood and adolescence is important to gastrointestinal health, including protection against pathogens, inhibition of pathogens, nutrient processing (synthesis of vitamin K), stimulation of angiogenesis, and regulation of host fat storage. Probiotics can promote an intentional modulation of intestinal microbiota favouring the health of the host. A review is presented on the modulation of intestinal microbiota on prevention, and adjuvant treatment of some paediatric gastrointestinal diseases

[Fecal transplantation the future therapy?]. / Transplantacja stolca terapia przyszlosci?

Intestinal bacteria play an important role in human physiology, taking part in the metabolism, absorption of nutrients and regulation of the immune system. In many illnesses the bacterial imbalance in the digestive tract occurs, and fecal transplantation is one method that allows you to restore the balance. The essence of the described method is to replace the pathogenesis, abnormal bacterial flora with the flora occurring in normal healthy individuals. So far, the main use of the method described in the article is resistant to antibiotics Clostridium difficile infection, which gives you a chance to avoid total colectomy. The article presents an accurate description of the same procedure to prepare the material, the selection of donor, recipient preparation and diseases, such as inflammatory bowel diseases, irritable bowel syndrome, diabetes and obesity, in which this method of treatment is currently practised.

Effects of dietary supplementation of lipid-encapsulated zinc oxide on colibacillosis, growth and intestinal morphology in weaned piglets challenged with enterotoxigenic Escherichia coli.

This study was aimed to evaluate the effect of dietary supplementation of lipid-encapsulated (coated) zinc oxide ZnO on post-weaning diarrhea (colibacillosis) in weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC). Thirty-two 35-day-old weaned piglets were orally challenged with 3 × 10(10) colony forming units of ETEC K88 while eight piglets received no challenge (control). Each eight challenged piglets received a diet containing 100 ppm ZnO (low ZnO), 2500 ppm ZnO (high ZnO) or 100 ppm of lipid (10%)-coated ZnO (coated ZnO) for 7 days; control pigs received the low ZnO diet. Daily gain, goblet cell density in the villi of the duodenum, jejunum and ileum, and villus height in the jejunum and ileum, which decreased due to the challenge, were equally greater in the coated ZnO and high ZnO groups versus low ZnO group. Fecal consistency score, serum interleukin-8 concentration, subjective score of fecal E. coli shedding, and digesta pH in the stomach, jejunum and ileum, which increased due to the challenge, were equally low in the coated ZnO and high ZnO groups versus low ZnO. Results suggest that a low level of coated ZnO might well substitute for a pharmacological level of native ZnO in dietary supplementation to alleviate colibacillosis of weaned piglets.

Proximal collagenous gastroenteritides: clinical management. A systematic review.

AIM: While collagenous colitis represents the most common form of the collagenous gastroenteritides, the collagenous entities affecting the proximal part of the gastrointestinal tract are much less recognized and possibly overlooked. The aim was to summarize the latest information through a systematic review of collagenous gastritis, collagenous sprue, and a combination thereof. METHOD: The search yielded 117 studies which were suitable for inclusion in the systematic review. Excluding repeated cases, 89 case reports and 28 case series were reported, whereas no prospective studies with or without control groups were identified. Further, no randomized, controlled trials were identified. The total number of patients with proximal collagenous gastroenteritides reported was 330. RESULTS: An overview of clinical presentations, prognosis, pathophysiology and histopathology, as well as management of these disorders is presented. The prognosis of both collagenous gastritis and sprue seems not to be as dismal as considered previously. Data point to involvement of immune or autoimmune mechanisms potentially driven by luminal antigens initiating the fibroinflammatory condition. CONCLUSIONS: To reach the diagnosis it is recommended that biopsies are obtained during gastroduodenoscopies. Therapies with anti-secretory strategies, glucocorticoids, and in some cases iron supplementation are suggested, although rational treatment options from randomized, controlled trials do not exist for these rare or even overlooked disorders.

Faecal transplantation for the treatment of Clostridium difficile infection: a review.

Clostridium difficile infection (CDI) remains a major healthcare burden despite recent global falls in its prevalence. The risk of recurrence is high when using antibiotics such as vancomycin, particularly in already recurrent disease. In light of this, new therapy options are being perused, including novel antibiotics such as fidaxomicin, probiotics, intravenous immunoglobulin and faecal transplantation. Faecal transplantation, referred to here as human probiotic infusion (HPI), is attracting an increasing amount of interest from physicians and patients. Its use has been documented in ca. 500 cases for the treatment of CDI, with overall efficacy rates reported to be ca. 91%. The first randomised controlled trial (RCT) demonstrated that HPI was superior to a 14-day course of vancomycin (89% vs. 31%; P<0.001) and reported no deaths or serious adverse events. Safety and patient acceptability are often cited as limitations to the widespread use of this technique. However, data suggest that the short-term safety profile is encouraging, and concerns over patient acceptability are not warranted in the majority of cases. It seems appropriate to treat an infection which is caused by a major disturbance in the gut microbiota with a treatment that reverses this disturbance, rather than antibiotics that may exacerbate the problem. However, to fully understand the role of HPI in the management of CDI, further RCTs are needed with comparator antibiotics such as fidaxomicin and to establish the most efficacious HPI protocol for administration and preparation.

Effect of a synbiotic on infantile acute gastroenteritis.

Acute gastroenteritis is still a common disease worldwide. Synbiotics are being used to alleviate the effects of acute gastroenteritis-related diarrhoea. The objective of this study was to determine the efficacy of a synbiotic in reducing the duration of diarrhoea in children with acute gastroenteritis. The study has been carried out on data gathered from children with acute gastroenteritis between the age of three months and 14 years seen in paediatric polyclinics between August 2009 and April 2010. While synbiotic group patients got a sachet containing Bifidobacterium lactis 2211 with a minimum of 5×106 cfu active bacteria and 900 mg chicory inulin twice daily for five days together with an oral rehydration solution, the control group only received an oral rehydration solution. Therapy with synbiotic plus an oral rehydration solution shortened the duration of acute diarrhoea in children by approximately one day compared to oral rehydration solution only.

Protective effects of Lactobacillus rhamnosus GG against human rotavirus-induced diarrhoea in a neonatal mouse model.

Group A human rotaviruses (RV) are a leading cause of severe dehydration and gastroenteritis in infants and young children. A large body of evidence suggests that Lactobacillus rhamnosus GG (LGG) has an effect on the incidence and severity of acute RV-induced diarrhoea; however, the timing and dosage of LGG treatment remains controversial. In the present study, a neonatal mouse model with human RV-induced diarrhoea was set up and the pathophysiological characteristics of the animals were examined. Our results indicated that RV-infected mice developed diarrhoea, accompanied by increased secretion of intestinal mucosa sIgA and serum interferon (IFN)-γ, tumour necrosis factor (TNF)-α, as well as decreased serum IgA. In addition, epithelium vacuolation was noticed in the jejunum microvillus of RV-infected mice. After intragastric administration of low (2 × 10(5) CFU), middle (2 × 10(7) CFU) or high (2 × 10(9) CFU) levels of LGG for four consecutive days before or after RV infection respectively, the RV-infected mice showed a shortened duration of diarrhoea and decreased epithelium vacuolation in the jejunum. Administration of a high dose of LGG before the RV infection was found to have better protective effects against RV infection than other regimens. This study demonstrates that the protective effects of LGG against RV-induced diarrhoea are highly correlated with the timing and dosage of LGG administration in neonatal mice.

Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates.

Preterm neonates are susceptible to gastrointestinal disorders such as necrotizing enterocolitis (NEC). Maternal milk and colostrum protects against NEC via growth promoting, immunomodulatory, and antimicrobial factors. The fetal enteral diet amniotic fluid (AF), contains similar components, and we hypothesized that postnatal AF administration reduces inflammatory responses and NEC in preterm neonates. Preterm pigs (92% gestation) were delivered by caesarean section and fed parental nutrition (2 days) followed by enteral (2 days) porcine colostrum (COLOS, n = 7), infant formula (FORM, n = 13), or AF supplied before and after introduction of formula (AF, n = 10) in experiment 1, and supplied only during the enteral feeding period in experiment 2 (FORM, n = 16; AF, n = 14). The NEC score was reduced in both AF and COLOS pigs, relative to FORM, when AF was provided prior to full enteral feeding (9.9 and 7.7 compared with 17.3, P < 0.05). There was no effect of AF when provided only during enteral feeding. AF pigs showed decreased bacterial abundance in colon and intestinal inflammation-related genes (e.g., TNF-α, IL-1α, IL-6, NOS) were downregulated, relative to FORM pigs with NEC. Anti-inflammatory properties of AF were supported by delayed maturation and decreased TNF-α production in murine dendritic cells, as well as increased proliferation and migration, and downregulation of IL-6 expression in intestinal cells (IEC-6, IPEC-J2). Like colostrum, AF may reduce NEC development in preterm neonates by suppressing the proinflammatory responses to enteral formula feeding and gut colonization when provided before the onset of NEC.