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Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are devastating diseases in preterm neonates, often requiring surgical treatment. Previous studies evaluated outcomes in peritoneal drain placement versus laparotomy, but the accuracy of the presumptive diagnosis remains unknown without bowel visualization. Predictive analytics provide the opportunity to determine the etiology of perforation and guide surgical decision making. The purpose of this investigation was to build and evaluate machine learning models to differentiate NEC and SIP. Neonates who underwent drain placement or laparotomy NEC or SIP were identified and grouped definitively via bowel visualization. Patient characteristics were analyzed using machine learning methodologies, which were optimized through areas under the receiver operating characteristic curve (AUROC). The model was further evaluated using a validation cohort. 40 patients were identified. A random forest model achieved 98% AUROC while a ridge logistic regression model reached 92% AUROC in differentiating diseases. When applying the trained random forest model to the validation cohort, outcomes were correctly predicted. This study supports the feasibility of using a novel machine learning model to differentiate between NEC and SIP prior to any intended surgical interventions. level II Clinical Research Paper [ABSTRACT FROM AUTHOR]

Objective: To compare mothers' own milk (MOM) consumption by infants born extremely preterm before and after implementation of a donor human milk (DHM) program and determine healthcare provider's knowledge and practices regarding DHM.Study Design: One hundred fifty-seven infants born at <30 weeks of gestation were enrolled during 3 time-periods. Group 1: before DHM program implementation, Group 2: the year following implementation, and Group 3: the second year after implementation. The proportion of feeds consisting of MOM for 6 weeks following birth was analyzed using a generalized linear mixed model. The study's second phase surveyed healthcare providers regarding knowledge and practices concerning DHM.Results: Group 1 consumed feeds with a greater proportion of MOM than Group 3 during weeks 1 (P < .001) and 3 (P = .007) and more than both Group 2 (P = .033) and 3 (P = .021) in week 4. During the first 14 days, Group 1 consumed feeds with 23.6% more MOM than Group 3 (P = .002) and had a greater odds of consuming feeds with > 90% MOM (P < .001) than Group 3. During days 1-28, Group 1 consumed feeds with 22% more MOM than Group 3 (P = .003) and had greater odds of consuming feeds with >90% MOM than Group 2 (P = .020) and 3 (P = .004). Knowledge regarding DHM was inconsistent among providers and they were unlikely to communicate potential risks and benefits of DHM to mothers.Conclusions: Following implementation of a DHM program, MOM consumption decreased over 2 years. Strategies focused on lactation success are necessary to increase MOM consumption. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is a disease of preterm infants and associated with significant mortality and morbidity. Although the pathogenesis of NEC is not clear, microbial dysbiosis, with a bloom of the phylum Proteobacteria, has been reported. Antibiotics and the use of H2 blockers, which affect the gut microbiome, are associated with increased incidence of NEC. In association with dysbiosis, inflammatory processes are upregulated with increased Toll-like receptor signaling, leading to translocation of nuclear factor kappa-β, a transcription factor that induces transcription of various pro-inflammatory cytokines and chemokines. Microbial metabolites, short chain fatty acids including acetate and butyrate, may modulate immunity, inflammation, intestinal integrity and regulate transcription by epigenetic mechanisms. Evaluation of microbiome and metabolome may provide biomarkers for early diagnosis of NEC and microbial therapeutic approaches to correct microbial dysbiosis. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis is an important disease in infants born premature. However, other disease entities present with similar signs and symptoms. This series reviews 5 atypical cases initially diagnosed as necrotizing enterocolitis that may be more consistent with food protein-induced enterocolitis. Food protein-induced enterocolitis may be underdiagnosed in this population. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of necrotizing enterocolitis (NEC) remains poorly understood.Objective: We assessed the relation between feeding strategies, intestinal microbiota composition, and the development of NEC.Design: We performed a prospective nationwide population-based study, EPIPAGE 2 (Etude Epidémiologique sur les Petits Ages Gestationnels), including preterm infants born at <32 wk of gestation in France in 2011. From individual characteristics observed during the first week of life, we calculated a propensity score for the risk of NEC (Bell's stage 2 or 3) after day 7 of life. We analyzed the relation between neonatal intensive care unit (NICU) strategies concerning the rate of progression of enteral feeding, the direct-breastfeeding policy, and the onset of NEC using general linear mixed models to account for clustering by the NICU. An ancillary propensity-matched case-control study, EPIFLORE (Etude Epidémiologique de la flore), in 20 of the 64 NICUs, analyzed the intestinal microbiota by culture and 16S ribosomal RNA gene sequencing.Results: Among the 3161 enrolled preterm infants, 106 (3.4%; 95% CI: 2.8%, 4.0%) developed NEC. Individual characteristics were significantly associated with NEC. Slower and intermediate rates of progression of enteral feeding strategies were associated with a higher risk of NEC, with an adjusted OR of 2.3 (95% CI: 1.2, 4.5; P = 0.01) and 2.0 (95% CI: 1.1, 3.5; P = 0.02), respectively. Less favorable and intermediate direct-breastfeeding policies were associated with higher NEC risk as well, with an adjusted OR of 2.5 (95% CI: 1.1, 5.8; P = 0.03) and 2.3 (95% CI: 1.1, 4.8; P = 0.02), respectively. Microbiota analysis performed in 16 cases and 78 controls showed an association between Clostridium neonatale and Staphylococcus aureus with NEC (P = 0.001 and P = 0.002).Conclusions: A slow rate of progression of enteral feeding and a less favorable direct-breastfeeding policy are associated with an increased risk of developing NEC. For a given level of risk assessed by propensity score, colonization by C. neonatale and/or S. aureus is significantly associated with NEC. This trial (EPIFLORE study) was registered at clinicaltrials.gov as NCT01127698. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is a frequent complication occurring in extremely preterm infants. Despite recent advances in newborn medicine, the incidence of BPD does not appear to have changed markedly, and specific treatments and prevention strategies are still lacking. Nutrition plays an important role in normal lung development and maturation. Malnutrition may delay somatic growth and new alveoli development, thus aggravating pulmonary injury involved in the pathogenesis of BPD. However, few nutrients have been investigated for their potential to mitigate the pathogenesis of BPD. In this article, we reviewed the recent progress in research on potential nutrients useful for the prevention or treatment of BPD, including glutamine, cysteine and N-acetylcysteine, L-arginine and L-citrulline, long chain polyunsaturated fatty acids (LCPUFAs), inositol, selenium, and some antioxidant vitamins including vitamin A. Current evidence shows that vitamin A and LCPUFA can prevent BPD, and that L-citrulline might provide a new method to treat chronic pulmonary hypertension associated with BPD in premature infants. The effects of other nutrients on BPD prevention need to be further studied. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC), a disease most commonly seen in preterm infants, often presents without warning and is associated with very high mortality and morbidity. Progress in the prevention and treatment of NEC has been slow. In this article, we will discuss some of the reasons as to why this progress has been slow. We will describe some of the factors that appear to be highly associated and important components in the pathophysiology of NEC. We will discuss the intestinal microbial environment of the fetus as well as the preterm infant and how interaction of dysbiosis with an immature gastrointestinal tract combined with dietary factors play a role in the pathogenesis of NEC. Testable hypotheses are discussed as well as how these may lead to not only a better understanding of the pathophysiology of the disease but also the preventative strategies. [ABSTRACT FROM AUTHOR]

We are changing our concept that the newborn infant emerges from a sterile environment. In-utero colonization may have major impacts on the developing mammal in terms of development of immunity and metabolism that, with epigenetic modifications, will lead to diseases in later life. In addition, the microbial profile that develops during and after birth depends on mode of delivery, type of feeding (human milk versus formula) and various other environmental factors to which the newborn is exposed. The goal of this review is to clarify that the microbiome in the maternal fetal unit as well as the immediate changes that occur as new microbes are acquired postnatally play major roles in subsequent health and disease. Rapidly developing technologies for multi-omic analyses and systems biology are shifting paradigms in both scientific knowledge and clinical care. [ABSTRACT FROM AUTHOR]

The "Evaluation of the Evidence to Support Practice Guidelines for the Nutritional Care of Preterm Infants: The Pre-B Project" is the first phase in a process to present the current state of knowledge and to support the development of evidence-informed guidance for the nutritional care of preterm and high-risk newborn infants. The future systematic reviews that will ultimately provide the underpinning for guideline development will be conducted by the Academy of Nutrition and Dietetics' Evidence Analysis Library (EAL). To accomplish the objectives of this first phase, the Pre-B Project organizers established 4 working groups (WGs) to address the following themes: 1) nutrient specifications for preterm infants, 2) clinical and practical issues in enteral feeding of preterm infants, 3) gastrointestinal and surgical issues, and 4) current standards of infant feeding. Each WG was asked to 1) develop a series of topics relevant to their respective themes, 2) identify questions for which there is sufficient evidence to support a systematic review process conducted by the EAL, and 3) develop a research agenda to address priority gaps in our understanding of the role of nutrition in health and development of preterm/neonatal intensive care unit infants. This article is a summary of the reports from the 4 Pre-B WGs. [ABSTRACT FROM AUTHOR]

Obesity is a major public health problem in the United States and many other countries. Childhood obesity rates have risen extensively over the last several decades with the numbers continuing to rise. Obese and overweight children are at high risk of becoming overweight adolescents and adults. The causes are multifactorial and are affected by various genetic, behavioral, and environmental factors. This review aims to discuss a previously under-recognized antecedent of obesity and related chronic metabolic diseases such as heart disease and diabetes. Specifically, we highlight the relationship of the microbial ecology of the gastrointestinal tract during early development and the consequent effects on metabolism, epigenetics, and inflammatory responses that can subsequently result in metabolic syndrome. Although studies in this area are just beginning, this area of research is rapidly expanding and may lead to early life interventions that may have significant impacts in the prevention of obesity. [ABSTRACT FROM AUTHOR]

Appropriate nutrition is essential for optimal development and growth of preterm infants. Infants less than 25 weeks corrected gestational age are frequently the most difficult group for which to provide adequate nutrition due to minimal energy stores and high fluid losses. Nutrient delivery becomes an integral, but also very challenging part in their management. Early administration of intravenous nutrients provides a critical bridge to full enteral nutrition. However, enteral feeding is challenging due to immaturities of the intestinal tract, feeding intolerance and the risk of catastrophic gastrointestinal disease such as necrotizing enterocolitis (NEC). Decreased gastric acid production, increased gut permeability, reduced immunoglobulins, immature intestinal epithelia and a decreased mucin barrier all contribute to weakness to gastrointestinal insult. This review aims to illustrate the importance of enteral feeding and the common challenges and approaches in the nutrition of infants born at this age. [ABSTRACT FROM AUTHOR]

Abstract: During the course of mammalian evolution there has been a close relationship between microbes residing in the gastrointestinal (GI) tract and the mammalian host. Interactions of resident intestinal microbes with the luminal contents and the mucosal surface play important roles in normal intestinal development‚ nutrition and adaptive innate immunity. The GI tract of the premature infant has a large but fragile surface area covered by a thin monolayer of epithelial cells that overlies a highly immunoreactive submucosa. Interactions in the lumen between microbes, nutrients and the intestinal mucosa can range from a healthy homeostasis to an uncontrolled systemic inflammatory response syndrome (SIRS) that leads to multiple organ system failure and death. Recent advances in molecular microbiota analytic methodology that stem from advances in high throughput sequencing technology have provided us with the tools to determine the GI microbiota in great depth, including the nearly 80% of microbes in the intestine that are very difficult if not impossible to culture by current methodology. Application of these techniques to derive a better understanding of the developing intestinal ecosystem in the premature neonate may hold the key to understand and eventually prevent several important diseases including necrotizing enterocolitis (NEC) and late onset neonatal sepsis that may be acquired via translocation through the GI tract. [ABSTRACT FROM AUTHOR]

Objectives: To use high throughput techniques to analyze intestinal microbial ecology in premature neonates, who are highly susceptible to perturbations of the luminal environment associated with necrotizing enterocolitis (NEC) and late-onset sepsis.Study Design: With non-culture-based techniques, we evaluated intestinal microbiota shortly after birth and during hospitalization in 23 neonates born at 23 to 32 weeks gestational age. Microbiota compositions were compared in 6 preterm infants in whom NEC, signs of systemic inflammation, or both developed with matched control subjects by using 16S ribosomal RNA pyrosequencing.Results: Microbial DNA was detected in meconium, suggesting an intrauterine origin. Differences in diversity were detected in infants whose mothers intended to breast feed (P = .03), babies born to mothers with chorioamnionitis (P = .06), and in babies born at <30 weeks gestation (P = .03). A 16S ribosomal RNA sequence analysis detected Citrobacter-like sequences only in cases with NEC (3 of 4) and an increased frequency of Enterococcus-like sequences in cases and Klebsiella in control subjects (P = .06). The overall microbiota profiles in cases with NEC were not distinguishable from that in control subjects.Conclusions: Microbial DNA in meconium of premature infants suggests prenatal influences. [ABSTRACT FROM AUTHOR]

Glutamine (GIn) is important for intestinal barrier function and regulation of tight junction (TJ) proteins, but the intracellular mechanisms of action remain undefined. The purpose of this study was to test the hypothesis that GIn regulates intercellular junction integrity and TJ proteins through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in Caco-2 cells. Deprivation of exogenous and endogenous glutamine decreased transepithelial electrical resistance (TER) (P< 0.01) and increased permeability (P < 0.01). Both wortmannin and LY294002, PI3K inhibitors, prevented the TER decrease and the permeability increase induced by Gin deprivation (P < 0.001). GIn deprivation also caused decreased TJ protein claudin-1 (P < 0.001). Both wortmannin and LY294002 treatment prevented this effect lP < 0.001). Deprivation of GIn increased phosphor-Akt protein. Gin supplementation reversed this effect. Decreased TER and increased permeability associated with GIn deprivation were not observed in small interfering RNA for p85 transfected Caco-2 cells. In conclusion, GIn regulates intercellular junction integrity and TJ proteins through the P13-Kinase/Akt pathway. [ABSTRACT FROM AUTHOR]

Probiotics are widely used in the treatment and prevention of gastrointestinal problems. However, in some immune- compromised populations, the administration of live microorganisms may not be appropriate. A potential alternative to live microorganisms is to inactivate them as long as the beneficial function is retained. We hypothesized that UV-inactivated Lactobacillus rhamnosus GG (LGG) could downregulate interleukin-8 (IL-8) production in intestinal epithelial cells stimulated by the pathogenic ligand, flagellin, using similar mechanisms as live LGG. Caco-2 cells were pretreated with live or UV- inactivated LGG at 1011 colony-forming units/L and stimulated by flagellin at a dose of 500 μg/L. lL-8 production was measured by ELISA, inhibitor of κB (IκB) and ubiquitinated-lκB (Ub-lκB) expression by immunoblotting and nuclear factor (NF) κB localization by immunofluorescence staining. Flagellin induced a 17-fold increase in lL-8 production compared with control (P < 0.05), whereas pretreatment with either live LGG or UV-inactivated LGG resulted in 66 and 59% decreases, respectively, compared with the flagellin group(P< 0.05). Flagellin-induced NFκB nuclear translocation was prevented by both live and UV-inactivated LGG. Flagellin decreased IκB, which was reversed by either live or UV-inactivated LGG (P < 0.05). UV-inactivated LGG decreased Ub-lκB expression (P < 0.051, although live LGG had no effect. This study supports the concept that UV-inactivated and live LGG are equally effective in decreasing lL-8 production in the intestinal epithelium. Although the mechanism involves different pathways, both alter cytoplasmic IκB, thereby inhibiting NFκB nuclear translocation. [ABSTRACT FROM AUTHOR]

The maternal microbiome has emerged as an important area of investigation. While birth is a critical timepoint for initial colonization of the newborn, the fetus resides in the womb surrounded by multiple unique colonized niches. The maternal microbiome has recently been shown to be associated with several morbidities in offspring. Understanding the multiple bacterial niches within the pregnant woman and how they interact with the fetus in-utero can lead to novel therapies to improve the health of offspring. In this review, we provide an overview of the available literature on normal bacterial colonization within the individual niches of the pregnant woman and the known associations with outcomes in offspring, including a discussion of the controversy of in-utero colonization. [ABSTRACT FROM AUTHOR]

Abstract: The level of gastrointestinal (GI) maturity of an individual infant is a major determinant of whether the infant will be able to meet nutritional needs by sole use of the GI tract or if parenteral means will be necessary. The GI tract is not only an organ for digestion and absorption of nutrients; it also performs major endocrine, neural and immunologic functions. In this review, anatomic, functional and biochemical development will be described and related to means by which enteral nutrition can be used in the prematurely born infant to optimize health and prevent disease. [Copyright &y& Elsevier]

Summary: The early postnatal interplay between nutrition, growth patterns, and metabolic and epigenetic phenomena is crucial in determining subsequent health; health that extends through the lifetime of the individual and very likely even into subsequent generations. Recent research in the area of postnatal nutrition and its relationship to adult health, with an emphasis on the appropriate-for-gestational-age infant who is born prematurely and who undergoes growth delays, is presented. Select studies in animals, pertinent to understanding the mechanisms of how early postnatal under- and overnutrition might affect adult health and propagate to subsequent generations, are reviewed. Scientifically based approaches to administering postnatal nutrition designed to improve outcomes and areas where future investigations are needed are presented. [Copyright &y& Elsevier]

The intestine serves not only as a digestive absorptive organ, it is also one of the largest immune organs of the body, has a huge endocrine and exocrine role, and also encompasses neural tissue equivalent to that of the entire spinal cord. The microbial microenvironment also plays a critical role in development. This brief overview of developmental aspects of these intestinal functions will be related to clinical problems in the neonatal period and subsequent health. [Copyright &y& Elsevier]

The pathogenesis of necrotizing enterocolitis (NEC) is poorly understood, but appears to be multifactorial and highly associated with immaturity of the gastrointestinal tract, colonization of the intestinal microbiota, and immature innate immune system. The goal of this review is to provide an overview of some of these risk factors and how they might lead to the genesis of NEC. A better understanding of these factors should help us prevent and treat this devastating disease. [Copyright &y& Elsevier]

Certain probiotic bacteria show anti-inflammatory activity after being heat killed, whereas others do not, suggesting that the gastrointestinal environment may alter the activity of probiotic bacteria. Occasionally, probiotics are provided when a patient is also being treated with oral antibiotics; this may have an effect on the probiotic activity. We hypothesized that Lactobacillus rhamnosus GG (LGG) are capable of downregulating tumor necrosis factor-α (TNFα)-induced interleukin (IL)-8 production under all 3 of these conditions, and that LGG act through the nuclear factor κB (NFκB)/inhibitor of κB (lκB) pathway. Caco-2 cells were treated with live or heat-killed LGG in doses ranging from 104 to 1010 cfu/L, in the presence or absence of antibiotics and TNFα in the media. TNFα-induced production of IL-8 by Caco-2 cells was modulated by LOG under all 3 conditions. However, higher doses of live LOG without TNFα in the presence or absence of antibiotics in vitro induced the production of IL-8 (P = 0.001). Heat-killed LGG also blunted the TNFα-induced IL-8 production (P < 0.01), but by itself did not increase IL-8 production at higher doses as markedly as live LGG (P < 0.05). LOG reduced the TNFα-induced NFκB translocation to the nucleus and lessened the decrease in lκB in the cytoplasm (P < 0.05). LGG reduced TNFα-induced IL-8 production by affecting the NFκB/lκB pathway in Caco-2 cells. High doses of live LOG markedly increased lL-8 production, but heat-killed LGG caused only a slight increase in IL-8. Thus, heat-killed LGG may effectively ameliorate inflammation with a lower potential than live LGG at high doses to cause inflammation. [ABSTRACT FROM AUTHOR]

The intestinal epithelium may serve as a nidus for inflammation that can cause local and systemic organ dysfunction. Relative to the adult, the immature intestine is exquisitely sensitive to inflammatory agents. Glutamine (Gln), an amino acid that is rapidly depleted during critical illness, modulates intestinal inflammation in vitro and in vivo. Here we relate Gln status to activation of the inhibitor of kappaB (IkappaB)/nuclear factor (NF)-kappaB signaling pathway in fetal-derived (H4) and adult (Caco-2) enterocytes. In the absence of Gln with or without LPS, H4 cells expressed more interleukin (IL)-8) than Caco-2 cells. Gln supplementation partially prevented the LPS-induced elevation of IL-8 in both cell types. IkappaBalpha was significantly decreased in both H4 and Caco-2 cells with Gln deprivation, and this was followed by an increase in NF-kappaB p65 in the nucleus. DNA binding of NF-kappaB was increased in both H4 and Caco-2 cells with Gln deprivation. IkappaBalpha phosphorylation was not altered by Gln status in either H4 or Caco-2 cells. Proteasomal inhibition after Gln depletion in Caco-2 cells was associated with an increase in the IkappaB-ubiquitin complex, but a decrease in complex formation in H4 cells, indicating that Gln deprivation alters IkappaBalpha through a pathway that differs from Caco-2 cells. We speculate that a reduced capacity of the immature enterocyte (H4) to respond to Gln deprivation with increased synthesis of IkappaBalpha rather than increased proteolysis as seen in the Caco-2 cells is the underlying mechanism. [ABSTRACT FROM AUTHOR]

The intestinal epithelium may serve as a nidus for inflammation that can cause local and systemic organ dysfunction. Relative to the adult, the immature intestine is exquisitely sensitive to inflammatory agents. Glutamine (Gln), an amino acid that is rapidly depleted during critical illness, modulates intestinal inflammation in vitro and in vivo. Here we relate Gin status to activation of the inhibitor of κB (IκB)/nuclear factor (NF)-κB signaling pathway in fetal-derived (H4) and adult (Caco-2) enterocytes. In the absence of Gin with or without LPS, H4 cells expressed more interleukin (IL)-8) than Caco-2 cells. Gln supplementation partially prevented the LPS-induced elevation of IL-8 in both cell types. IκBα was significantly decreased in both H4 and Caco-2 cells with Gin deprivation, and this was followed by an increase in NF-κB p65 in the nucleus. DNA binding of NF-κB was increased in both H4 and Caco-2 cells with Gin deprivation. IκBα phosphorylation was not altered by Gin status in either H4 or Caco-2 cells. Proteasomal inhibition after Gin depletion in Caco-2 cells was associated with an increase in the IκB-ubiquitin complex, but a decrease in complex formation in H4 cells, indicating that Gin deprivation alters IκBα through a pathway that differs from Caco-2 cells. We speculate that a reduced capacity of the immature enterocyte (H4) to respond to Gln deprivation with increased synthesis of IκBα rather than increased proteolysis as seen in the Caco-2 cells is the underlying mechanism. [ABSTRACT FROM AUTHOR]

Dietary glutamine (Gln) has been shown to be important for maintenance of the intestinal barrier. To investigate the role of the epithelium in this Gln dependence, Caco-2 cells were raised on semipermeable membranes under conditions that model different regions of the crypt and villus. Gln availability was controlled by addition to the medium and treatment with methionine sulfoximine to inhibit Gln synthetase (GS). Barrier function was assayed by measuring transepithelial electrical resistance and fluxes of [(14)C]mannitol and fluorescein isothiocyanate-dextran. The barrier function of these monolayers was found to require the Gln provided either in the medium at the apical or basal surface or via GS. However, the barrier was no more sensitive to Gln deprivation than it was to accumulation or maintenance of total protein. These results suggest that the in vivo dependence of the gut mucosal barrier on Gln likely involves roles separate from maintenance of the epithelial barrier per se. [ABSTRACT FROM AUTHOR]

Of all the amino acids, glutamine is the most versatile. Studies in the maternal-fetal-placental unit demonstrate that both glutamine and glutamate play an important role in fetal and placental metabolism. If an infant is born very prematurely, the supply of glutamine from the mother is suddenly interrupted. The infant is dependent on endogenous synthesis or an exogenous supply of glutamine to meet the challenges of the external environment and a tripling of body weight in the first 3-4 mo of life. Studies of glutamine supplementation in low birth weight infants and critically ill adults suggest benefits, especially in terms of decreased nosocomial infections. Two large multicenter trials are currently underway that are designed to address these potential benefits in very low birth weight infants. These trials will not explain the mechanism of action. This review raises hypotheses about the role of the amide nitrogen of glutamine for nucleotide and glucosamine synthesis in the small intestine and how this might relate to greater integrity of the intestinal mucosa, hence preventing bacterial translocation and/or the subsequent proinflammatory response that might lead to multiorgan failure. [ABSTRACT FROM AUTHOR]

Concentrations of prostaglandin E2, prostaglandin F2α (PGF2α), and its metabolite 13, 14-dihydro-15-keto prostaglandin F2α (DHKF2α) were measured in human milk at three different stages of lactation in mothers of premature and term infants. Before radioimmunoassay, our samples were purified by solid-phase extraction with C,8 Sep-Pak cartridges and reverse-phase high-performance liquid chromatography. When concentrations of the three prostaglandins were compared in the milk of mothers delivering prematurely and at term, very low concentrations were measured and no differences were observed. Concentrations of prostaglandins also remained essentially the same at the various stages of lactation. However, the mean ratio of DHKF2α to PGF2α was higher in samples from mothers who delivered early than in samples from those who delivered at term. These ratios were comparable to those reported in the literature for human plasma. The functional significance of these compounds in human milk remains undetermined. [ABSTRACT FROM AUTHOR]

We enrolled 98 infants (gestational age <33 weeks) in a pilot randomized trial of antibiotics vs no antibiotics; 55 were randomized (lower maternal infectious risk; symptoms expected for gestation). Adverse events did not differ significantly between the randomization arms. This trial establishes a framework for a larger multicentered trial. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of gastric residual aspiration and evaluation on preterm very low birth weight infants' gastrointestinal function, intestinal inflammation, and gastrointestinal mucosal bleeding.Study Design: This single-center, randomized trial compared omission of gastric residuals vs prefeed gastric residuals in 143 infants ≤32 weeks of gestation with a birthweight of ≤1250 g for 6 weeks after birth. Serum levels of gastrin and motilin were collected between 14 and 21 days of life. Stools were collected at 3 and 6 weeks of age and analyzed for calprotectin and S100A12 levels. All stools were tested for occult blood for 6 weeks.Results: Means for gastrin (P = .999) and motilin (P = .694) were similar between groups and there were no statistically significant differences in adjusted means for transformed calprotectin (P = .580), and S100A12 (P = .212). Both calprotectin (P = .003) and S100A12 (P = .002) increased from week 3 to week 6. The mean percentage of stools positive for occult blood (P = .888) were similar between the groups.Conclusions: Gastrointestinal function, intestinal inflammation, and gastrointestinal mucosal bleeding were similar whether aspiration and evaluation of gastric residuals were eliminated or not, suggesting routinely evaluating gastric residuals before every feeding may be unnecessary. TRIAL REGISTRATION CLINICALTRIALS.GOV:: NCT01863043. [ABSTRACT FROM AUTHOR]

Designing an optimal feeding program for preterm infants is particularly challenging. These infants require individualized feeding plans and frequent medical interventions, and their health status and physical limitations necessitate specialized products. This review highlights the challenges of translating new understandings into practical application and, specifically, the challenges of translating scientific knowledge into available nutritional products that can be used to meet the special needs of preterm infants. All infant formula products are developed for use in a heavily regulated environment, which is not integrated internationally. The regulatory framework for preterm nutrition products can be particularly complex in the areas of composition and the degree of scientific and clinical support required across countries. Registration and approval of products for preterm infants in most countries must address the complexities for a population for which no well-recognized nonclinical safety or efficacy models exist. Mandatory regulatory review for science-based innovative product improvements may require two or more years. In addition, throughout years of development, industry must justify the financial support of programs that serve a small specialty segment of the market. These industry-specific challenges may be neither visible nor appreciated by the general public or health care professionals, and, yet, they are integral to the development process. Effective collaborations among academic scientists, regulatory authorities, and the industry are essential to bring science to the bedside. Without such collaborations, preterm infants, and particularly very low birth weight infants, in the neonatal intensive care unit will not be able to benefit from innovative nutrition interventions designed to improve short- and long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

The interplay between microorganisms and the intestine of newborn infants is associated with diverse functional and clinical outcomes that result from the specific interactions among microbial communities, their products, and the unique characteristics of the gastrointestinal tract. Multiple mechanisms of action for infant formula ingredients with probiotic activity appear to exist. These mechanisms are thought to protect the host not only from intestinal diseases but also from systemic infection. However, questions about the safety of probiotics for preterm infants remain unanswered, particularly with regard to sepsis, immunomodulatory effects, and microbial resistance. Few well-designed studies have been conducted to evaluate the effects of probiotic, prebiotic, and synbiotic ingredients on relevant clinical outcomes in preterm infants. Although existing data are encouraging, there is insufficient evidence to recommend the routine use of these ingredients in all preterm infants. [ABSTRACT FROM AUTHOR]

When microbial communities colonize in the developing intestinal tract after birth, microrganisms interact with specific apical surface receptors on the enterocytes. This interaction triggers a response that prevents overexpression of inflammatory cytokines, thus providing protection from pathogen-induced mucosal damage. Multiple immune modulatory factors in human milk and innate humoral factors also control inflammatory responses, providing additional protective effects. Our understanding of the role of the luminal microbial communities or microbiota is growing rapidly as novel technologies provide new insights into their taxonomy, function during early development, and impact on life-long health. Multiple studies have evaluated the effects of the specific nutrients, glutamine, arginine, nucleotides, polyunsaturated fatty acids, and lactoferrin, on disease outcomes in premature infants. These studies support a role for nutrients to modulate host defense mechanisms in premature infants, to develop normal digestive function, to protect from bacterial translocation, and to preserve mucosal barrier integrity. These effects are clearly important. However, not enough is yet known to design specific clinical care practices that support a healthy microbiota. [ABSTRACT FROM AUTHOR]

We review research relating ischemia/reperfusion to injury in the neonatal intestine. Epidemiologic evidence suggests that the most common form of necrotizing enterocolitis is not triggered by a primary hypoxic-ischemic event. Its late occurrence, lack of preceding ischemic events, and evidence for microbial and inflammatory processes preclude a major role for primary hypoxic ischemia as the sentinel pathogenic event. However, term infants, especially those with congenital heart disease who have development of intestinal necrosis, and those preterm infants with spontaneous intestinal perforations, are more likely to have intestinal ischemia as a primary component of their disease pathogenesis. [ABSTRACT FROM AUTHOR]

Initial bacterial colonization, including colonization with health-positive bacteria, such as bifidobacteria and lactobacilli, is necessary for the normal development of intestinal innate and adaptive immune defenses. The predominance of beneficial bacteria in the gut microflora of breast-fed infants is thought to be, at least in part, supported by the metabolism of the complex mixture of oligosaccharides present in human breast milk, and a more adult-type intestinal microbiota is found in formula-fed infants. Inadequate gut colonization, dysbiosis, may lead to an increased risk of infectious, allergic, and autoimmune disorders later in life. The addition of appropriate amounts of selected prebiotics to infant formulas can enhance the growth of bifidobacteria or lactobacilli in the colonic microbiota and, thereby, might produce beneficial effects. Among the substrates considered as prebiotics are the oligosaccharides inulin, fructo-oligosaccharides, galacto-oligosaccharides, and lactulose. There are some reports that such prebiotics have beneficial effects on various markers of health. For example, primary prevention trials in infants have provided promising data on prevention of infections and atopic dermatitis. Additional well-designed prospective clinical trials and mechanistic studies are needed to advance knowledge further in this promising field. [Copyright &y& Elsevier]

Abstract: Necrotizing enterocolitis (NEC) is a devastating disease affecting primarily premature infants. Despite advances in neonatal care, the mortality rate following NEC has not changed significantly in the past 30 years. New preventative measures are needed. In this review, we will provide information to assess the possible role of probiotics, prebiotics and related agents in the prevention of this devastating disease. We will also discuss short and long term safety issues as well as potential alternatives. Although it is tempting to rebuild the intestinal microbiota using the agents such as pro and prebiotics during infancy, routine use is not yet warranted a cautious approach on the basis of sounds scientific data is needed. [Copyright &y& Elsevier]