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      An update on necrotizing enterocolitis: pathogenesis and preventive strategies

      review-article
      , MD
      Korean Journal of Pediatrics
      The Korean Pediatric Society
      Necrotizing enterocolitis, Infant, Premature, Pathogenesis, Prevention

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          Abstract

          Necrotizing enterocolitis (NEC) is one of the most critical morbidities in preterm infants. The incidence of NEC is 7% in very-low-birth-weight infants, and its mortality is 15 to 30%. Infants who survive NEC have various complications, such as nosocomial infection, malnutrition, growth failure, bronchopulmonary dysplasia, retinopathy of prematurity, and neurodevelopmental delays. The most important etiology in the pathogenesis of NEC is structural and immunological intestinal immaturity. In preterm infants with immature gastrointestinal tracts, development of NEC may be associated with a variety of factors, such as colonization with pathogenic bacteria, secondary ischemia, genetic polymorphisms conferring NEC susceptibility, anemia with red blood cell transfusion, and sensitization to cow milk proteins. To date, a variety of preventive strategies has been accepted or attempted in clinical practice with regard to the pathogenesis of NEC. These strategies include the use of breast feeding, various feeding strategies, probiotics, prebiotics, glutamine and arginine, and lactoferrin. There is substantial evidence for the efficacy of breast feeding and the use of probiotics in infants with birth weights above 1,000 g, and these strategies are commonly used in clinical practice. Other preventive strategies, however, require further research to establish their effect on NEC.

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          Most cited references46

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          Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells

          The role of innate immune recognition by intestinal epithelial cells (IECs) in vivo is ill-defined. Here, we used highly enriched primary IECs to analyze Toll-like receptor (TLR) signaling and mechanisms that prevent inappropriate stimulation by the colonizing microflora. Although the lipopolysaccharide (LPS) receptor complex TLR4/MD-2 was present in fetal, neonatal, and adult IECs, LPS-induced nuclear factor κB (NF-κB) activation and chemokine (macrophage inflammatory protein 2 [MIP-2]) secretion was only detected in fetal IECs. Fetal intestinal macrophages, in contrast, were constitutively nonresponsive to LPS. Acquisition of LPS resistance was paralleled by a spontaneous activation of IECs shortly after birth as illustrated by phosphorylation of IκB-α and nuclear translocation of NF-κB p65 in situ as well as transcriptional activation of MIP-2. Importantly, the spontaneous IEC activation occurred in vaginally born mice but not in neonates delivered by Caesarean section or in TLR4-deficient mice, which together with local endotoxin measurements identified LPS as stimulatory agent. The postnatal loss of LPS responsiveness of IECs was associated with a posttranscriptional down-regulation of the interleukin 1 receptor–associated kinase 1, which was essential for epithelial TLR4 signaling in vitro. Thus, unlike intestinal macrophages, IECs acquire TLR tolerance immediately after birth by exposure to exogenous endotoxin to facilitate microbial colonization and the development of a stable intestinal host–microbe homeostasis.
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            Donor breast milk versus infant formula for preterm infants: systematic review and meta-analysis.

            To compare the effect of donor breast milk with infant formula in preterm infants. Separate comparisons with formula were made for donor breast milk that was: (1) given as a sole diet; (2) given as a supplement to mother's own breast milk; and (3) fortified with macronutrients and micronutrients. The main outcomes were death, necrotising enterocolitis (NEC), infection, growth and development. Electronic databases-Cochrane, CENTRAL, MEDLINE, EMBASE, CINAHL, and HMIC: DH. Systematic review and meta-analysis of trials and observational studies of preterm or low birthweight infants. Seven studies (including five randomised controlled trials), all from the 1970s and 1980s, fulfilled the inclusion criteria. All studies compared the effect of sole donor breast milk with formula (combined n = 471). One of these also compared the effect of donor breast milk with formula given as a supplement to mother's own milk (n = 343). No studies examined fortified donor breast milk. A meta-analysis based on three studies found a lower risk of NEC in infants receiving donor breast milk compared with formula (combined RR 0.21, 95% CI 0.06 to 0.76). Donor breast milk was associated with slower growth in the early postnatal period, but its long-term effect is unclear. Donor breast milk is associated with a lower risk of NEC and slower growth in the early postnatal period, but the quality of the evidence is limited. Further research is needed to confirm these findings and measure the effect of fortified or supplemented donor breast milk.
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              Necrotising enterocolitis hospitalisations among neonates in the United States.

              The objective of this study was to estimate the rate and describe the epidemiology of necrotising enterocolitis (NEC) among neonates (infants <1 month of age) hospitalised in the United States. Hospital discharge records for neonates with an NEC diagnosis and an in-hospital death or routine discharge were selected for analysis from the 2000 Kids' Inpatient Database. An estimated 4463 (SE = 219) hospitalisations associated with NEC occurred among neonates in the United States during the year 2000, resulting in a hospitalisation rate of 109.9 [95% CI 97.2, 122.6] per 100 000 livebirths. The rate of NEC hospitalisations was highest among non-Hispanic Black neonates. The median hospital length of stay was 49 days. The in-hospital fatality rate was 15.2% (SE = 1.0%). Neonates who underwent a surgical procedure during hospitalisation were more likely to have a longer length of stay and to die than were those who did not have surgical intervention. Low-birthweight (LBW) neonates with NEC were more likely than LBW neonates hospitalised with other diagnoses to be very LBW (VLBW), non-Hispanic Black and male. In addition, compared with LBW neonates hospitalised with other diagnoses, LBW neonates with NEC had higher hospital charges and longer lengths of stay, and were more likely to die during hospitalisation. This study provides the first national estimate of the rate of hospitalisation for NEC among neonates in the United States. During 2000, there was one NEC hospitalisation per 1000 livebirths, with approximately 1 in 7 NEC hospitalisations ending in death. NEC accounts for substantial morbidity; thus, the development of prevention strategies and effective therapies continues to be an important issue.
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                Author and article information

                Journal
                Korean J Pediatr
                KJP
                Korean Journal of Pediatrics
                The Korean Pediatric Society
                1738-1061
                2092-7258
                September 2011
                30 September 2011
                : 54
                : 9
                : 368-372
                Affiliations
                Department of Pediatrics, Ajou University School of Medicine, Suwon, Korea.
                Author notes
                Corresponding author: Jang Hoon Lee, MD. Department of Pediatrics, Ajou University School of Medicine, San 5 Woncheon-dong, Yeongtong-gu, Suwon 443-721, Korea. Tel: +82-31-219-5165, Fax: +82-31-219-5169, neopedlee@ 123456gmail.com
                Article
                10.3345/kjp.2011.54.9.368
                3250602
                22232629
                6266751e-1225-4045-b849-c7c72dc411fb
                Copyright © 2011 by The Korean Pediatric Society

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 July 2011
                : 28 August 2011
                Categories
                Review Article

                Pediatrics
                necrotizing enterocolitis,prevention,premature,infant,pathogenesis
                Pediatrics
                necrotizing enterocolitis, prevention, premature, infant, pathogenesis

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