Effectiveness of two probiotics in preventing necrotising enterocolitis in a cohort of very-low-birth-weight premature new-borns

According to previous research, the incidence of necrotising enterocolitis (NEC) decreases after supplementation with probiotics. However, few studies have considered the equivalence or otherwise of different strains of probiotics in this respect. Accordingly, this prospective observational study was conducted in a cohort of 245 very-low-birth-weight (VLBW) new-borns to assess the prevalence of NEC after supplementation with the probiotic Inforan® (Berna Biotech, Madrid, Spain) 250 mg capsules containing 109 cfu of Lactobacillus acidophilus (ATCC 4356) and 109 cfu of Bifidobacterium bifidum (ATCC 15696); or with Bivos® (Ferring, Madrid, Spain) containing Lacticaseibacillus (formerly Lactobacillus) rhamnnosus (LGG) (ATCC 53103) (109 cfu); or with no probiotic supplementation. Statistical analysis was performed using multivariant regression for the duration of parenteral nutrition, length of neonatal intensive care unit stay, use of oxygen therapy and presence of chorioamnionitis. Of the VLBW new-borns in the study group, 65 received Infloran, 108 received Bivos and 72 received no probiotic. A significant association was observed between a reduced presence of NEC Stage ≥2 and probiotic supplementation. The odds risk (OR) obtained was 0.174 (95% confidence interval (CI): 0.032-0.936) for Infloran and 0.196 (95%CI: 0.053-0.732) for Bivos. Therefore, both probiotics are associated with a lower prevalence of NEC in VLBW new-borns, with no significant differences.

Human Breastmilk Feeding in Necrotising Enterocolitis Patients With Surgical Treatment A Retrospective Chart Review Study

Background One of the surgical treatments for necrotising enterocolitis (NEC) is to resect the necrotic bowel and defunction the gut by stoma, which can come with severe complications impacting infant growth. Human breastmilk feeding has been proved to prevent NEC, world-widely. This study is to identify whether human breastmilk could reduce the incidence of stoma related complications in NEC patients after primary surgery.MethodsA retrospective chart review was done on patients who had intestine resection and stoma for NEC in the period from 2015-1-1 to 2021-4-30 at Anhui Provincial Children’s Hospital (APCH). Demographics, feeding methods (human milk feeding versus formula milk feeding) and stoma related complications were collected, and the factors, potentially associated with stoma related complications, were analysed. ResultsA total of 58 patients, including 35 males and 23 females, had stoma for NEC. The mean gestational age was 34 weeks (28 to 40). The mean body weight at surgery was 2.83kg (1.03 to 4.80). Before surgery, 38 patients had perforation. Additionally, 46 patients had ileostomy; 12 had colostomy. After primary operation, 40 of them were fed with human breastmilk while 18 of them were fed with formula milk. 26 of 58 patients had stoma related complications, including fluid/electronic imbalance, stoma prolapse, and stoma stenosis. Feeding methods and gestational age were found significantly related to stoma related complications via a binary logistical multivariable analysis.ConclusionsIn this study, the most frequent stoma related complication was fluid/electronic imbalance. Younger gestational age was identified as a risk factor associated with stoma related complications; human breastmilk feeding can benefit patients against these complications.

Lactoferrin impact on gut microbiota in preterm infants with late-onset sepsis or necrotising enterocolitis: the MAGPIE mechanisms of action study

Background Preterm infants have high rates of morbidity, especially from late-onset sepsis and necrotising enterocolitis. Lactoferrin is an anti-infective milk protein that may act through effects on gut bacteria, metabolites and epithelial cell function. The impact of supplemental lactoferrin in reducing late-onset sepsis was explored in the Enteral LactoFerrin In Neonates (ELFIN) trial. Objectives The Mechanisms Affecting the Gut of Preterm Infants in Enteral feeding (MAGPIE) study was nested within the ELFIN trial and aimed to determine the impact of lactoferrin on gut microbiota and bacterial function, and changes preceding disease onset. We aimed to explore impacts on the stool bacteria and faecal/urinary metabolome using gas and liquid chromatography–mass spectrometry, and explore immunohistological pathways in resected tissue. Methods Preterm infants from 12 NHS hospitals were enrolled in the study, and daily stool and urine samples were collected. Local sample collection data were combined with ELFIN trial data from the National Perinatal Epidemiology Unit, Oxford. The longitudinal impact of lactoferrin in healthy infants was determined, and samples that were collected before disease onset were matched with samples from healthy control infants. Established, quality-controlled 16S ribonucleic acid, gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry analyses were conducted. Validated databases and standardised workflows were used to identify bacteria and metabolites. Tissue samples from infants undergoing surgery and matched controls were analysed. Results We recruited 479 preterm infants (mean gestation of 28.4 ± 2.3 weeks) and collected > 33,000 usable samples from 467 infants. 16S ribonucleic acid bacterial analysis was conducted on samples from 201 infants, of whom 20 had necrotising enterocolitis and 51 had late-onset sepsis, along with samples from healthy matched controls to explore longitudinal changes. The greatest change in relative bacterial abundance over time was observed in Staphylococcus, which decreased from 42% at aged 7–9 days to only 2% at aged 30–60 days (p < 0.001). Small but significant differences in community composition were observed between samples in each ELFIN trial group (R 2 = 0.005; p = 0.04). Staphylococcus (p < 0.01), Haemophilus (p < 0.01) and Lactobacillus (p = 0.01) showed greater mean relative abundance in the placebo group than in the lactoferrin group. Gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry analyses showed that lactoferrin had limited impact on the metabolome. Liquid chromatography–mass spectrometry showed significant metabolite differences between necrotising enterocolitis or late-onset sepsis infants and healthy controls. The resected gut tissue analysis revealed 82 differentially expressed genes between healthy and necrotic tissue. Limitations Although we recruited a large number of infants, collecting daily samples from every infant is challenging, especially in the few days immediately preceding disease onset. Conclusion We conducted a large mechanistic study across multiple hospital sites and showed that, although lactoferrin significantly decreased the level of Staphylococcus and other key pathogens, the impact was smaller than those of other clinical variables. Immunohistochemistry identified multiple inflammatory pathways leading to necrotising enterocolitis and showed that the use of NHS pathology archive tissue is feasible in the context of a randomised controlled trial. Future work We observed significant changes in the stool and urinary metabolome in cases preceding late-onset sepsis or necrotising enterocolitis, which provide metabolic targets for a future mechanistic and biomarker study. Trial registration Current Controlled Trials ISRCTN12554594. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 14. See the NIHR Journals Library website for further project information.