Necrotizing Enterocolitis

https://doi.org/10.1016/j.clp.2007.11.009Get rights and content

In necrotizing enterocolitis (NEC) the small (most often distal) and/or large bowel becomes injured, develops intramural air, and may progress to frank necrosis with perforation. Even with early, aggressive treatment, the progression of necrosis, which is highly characteristic of NEC, can lead to sepsis and death. This article reviews the current scientific knowledge related to the etiology and pathogenesis of NEC and discusses some possible preventive measures.

Section snippets

Epidemiology and risk factors

NEC is a disease familiar to all practitioners who care for very low birth weight (VLBW) babies. It also can be considered a disease of medical progress, because the routine use of antenatal steroids and prophylactic surfactant has resulted in higher survival of preterm infants, and it is this group that is most susceptible to this potentially devastating disease [2]. There is a well-known inverse relationship between the incidence of NEC and gestational age at birth, with extremely premature

Etiology and pathogenesis

Although extensive research has investigated the pathophysiology of NEC, a complete understanding has not been elucidated fully. The most accepted epidemiologic precursors for NEC are prematurity [3], [39] and gastrointestinal feeding [39].

Santulli and colleagues [40] described the classic triad of pathologic events in the pathogenesis of NEC: (1) intestinal ischemia (2) colonization by pathogenic bacteria, and (3) excess protein substrate in the intestinal lumen. Subsequently Kosloske [41]

Prevention

Because the onset of NEC often is abrupt and overwhelming, with rapid progression, it seems unlikely that intervention strategies to halt the progression will succeed after the presentation of clinical signs and symptoms. In contrast, preventive approaches have had some success, and clinical trials have reported reduction of disease with the use of breast-milk feeding [34], [116], [117], [131], [132], enteral antibiotic prophylaxis [133], probiotics [134], [136], and arginine supplements [137].

Summary

The incidence of neonatal NEC and the mortality stemming from this disease have not improved significantly during the last 40 years. Still, many animal and human studies have emerged to help clinicians unfold numerous pathophysiologic abnormalities at the cellular level. A better understanding of this basic information may improve significantly the outcomes of patients who have this potentially devastating disease. One of the more promising of the various strategies proposed for the prevention

Acknowledgments

The authors thank Rita Maier, Director, Health Education Library, New York Hospital Queens, and her staff for their timely help in providing the necessary resources related to literature search.

References (154)

  • R.M. Kliegman et al.

    Necrotizing enterocolitis

    N Engl J Med

    (1984)
  • P. Srinivasan et al.

    Necrotizing Enterocolitis

  • B.J. Stoll et al.

    Epidemiology of necrotizing enterocolitis: a case control study

    J Pediatr

    (1980)
  • W. Hsueh et al.

    Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts

    Pediatr Dev Pathol

    (2003)
  • A.R. Llanos et al.

    Epidemiology of neonatal necrotising enterocolitis: a population-based study

    Paediatr Perinat Epidemiol

    (2002)
  • S.O. Guthrie et al.

    Necrotizing enterocolitis among neonates in the United States

    J Perinatol

    (2003)
  • P.W. Lin et al.

    Necrotising enterocolitis

    Lancet

    (2006)
  • K. Sankaran et al.

    Variations in incidence of necrotizing enterocolitis in Canadian neonatal intensive care units

    J Pediatr Gastroenterol Nutr

    (2004)
  • S.K. Lee et al.

    Variations in practice and outcomes in the Canadian NICU network: 1996–1997

    Pediatrics

    (2000)
  • R. Guillet et al.

    Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants

    Pediatrics

    (2006)
  • J.D. Horbar et al.

    Trends in mortality and morbidity for very low birth weight infants, 1991–1999

    Pediatrics

    (2002)
  • M. Luig et al.

    Epidemiology of necrotizing enterocolitis–part I: changing regional trends in extremely preterm infants over 14 years

    J Paediatr Child Health

    (2005)
  • R.G. Harper et al.

    Neonatal outcome of infants born at 500 to 800 grams from 1990 through 1998 in a tertiary care center

    J Perinatol

    (2002)
  • M. Luig et al.

    Epidemiology of necrotizing enterocolitis–part II: risks and susceptibility of premature infants during the surfactant era: a regional study

    J Paediatr Child Health

    (2005)
  • A.A. Fanaroff et al.

    The NICHD Neonatal Research Network: changes in practice and outcomes during the first 15 years

    Semin Perinatol

    (2003)
  • A.A. Fanaroff et al.

    Trends in neonatal morbidity and mortality for very low birthweight infants

    Am J Obstet Gynecol

    (2007)
  • J.A. Lemons et al.

    Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996. NICHD Neonatal Research Network

    Pediatrics

    (2001)
  • R.C. Holman et al.

    Necrotising enterocolitis hospitalisations among neonates in the United States

    Paediatr Perinat Epidemiol

    (2006)
  • R.C. Holman et al.

    The epidemiology of necrotizing enterocolitis infant mortality in the United States

    Am J Public Health

    (1997)
  • P.F. Ehrlich et al.

    Outcome of perforated necrotizing enterocolitis in the very low-birth weight neonate may be independent of the type of surgical treatment

    Am Surg

    (2001)
  • M.C. Henry et al.

    Surgical therapy for necrotizing enterocolitis: bringing evidence to the bedside

    Semin Pediatr Surg

    (2005)
  • M.L. Blakely et al.

    Postoperative outcomes of extremely low birth-weight infants with necrotizing enterocolitis or isolated intestinal perforation: a prospective cohort study by the NICHD Neonatal Research Network

    Ann Surg

    (2005)
  • B. Warner et al.

    The effect of birth hospital type on the outcome of very low birth weight infants

    Pediatrics

    (2004)
  • D. Roberts et al.

    Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth

    Cochrane Database Syst Rev

    (2006)
  • R.D. Uauy et al.

    Necrotizing enterocolitis in very low birth weight infants: biodemographic and clinical correlates. National Institute of Child Health and Human Development Neonatal Research Network

    J Pediatr

    (1991)
  • G.D. Grave et al.

    New therapies and preventive approaches for necrotizing enterocolitis: report of a research planning workshop

    Pediatr Res

    (2007)
  • A.R. Gerber et al.

    Increased risk of illness among nursery staff caring for neonates with necrotizing enterocolitis

    Pediatr Infect Dis

    (1985)
  • D. Boccia et al.

    Nosocomial necrotising enterocolitis outbreaks: epidemiology and control measures

    Eur J Pediatr

    (2001)
  • I. Banyasz et al.

    Genetic polymorphisms for vascular endothelial growth factor in perinatal complications

    Eur Cytokine Netw

    (2006)
  • A. Treszl et al.

    Genetic basis for necrotizing enterocolitis—risk factors and their relations to genetic polymorphisms

    Front Biosci

    (2006)
  • A. Treszl et al.

    Lower prevalence of IL-4 receptor alpha-chain gene G variant in very-low-birth-weight infants with necrotizing enterocolitis

    J Pediatr Surg

    (2003)
  • D.J. Ostlie et al.

    Necrotizing enterocolitis in full-term infants

    J Pediatr Surg

    (2003)
  • S. Ng

    Necrotizing enterocolitis in the full-term neonate

    J Paediatr Child Health

    (2001)
  • D.K. Lambert et al.

    Necrotizing enterocolitis in term neonates: data from a multihospital health-care system

    J Perinatol

    (2007)
  • D.B. McElhinney et al.

    Necrotizing enterocolitis in neonates with congenital heart disease: risk factors and outcomes

    Pediatrics

    (2000)
  • A. Maayan-Metzger et al.

    Necrotizing enterocolitis in full-term infants: case-control study and review of the literature

    J Perinatol

    (2004)
  • T.E. Wiswell et al.

    Necrotizing enterocolitis in full-term infants. A case-control study

    Am J Dis Child

    (1988)
  • S. Bolisetty et al.

    A regional study of underlying congenital diseases in term neonates with necrotizing enterocolitis

    Acta Paediatr

    (2000)
  • R.M. Kliegman et al.

    Necrotizing enterocolitis: research agenda for a disease of unknown etiology and pathogenesis

    Pediatr Res

    (1993)
  • T.V. Santulli et al.

    Acute necrotizing enterocolitis in infancy: a review of 64 cases

    Pediatrics

    (1975)
  • A.M. Kosloske

    Pathogenesis and prevention of necrotizing enterocolitis: a hypothesis based on personal observation and a review of the literature

    Pediatrics

    (1984)
  • W.A. Ballance et al.

    Pathology of neonatal necrotizing enterocolitis: a ten-year experience

    J Pediatr

    (1990)
  • C. Hammerman et al.

    Probiotics and neonatal intestinal infection

    Curr Opin Infect Dis

    (2006)
  • L. Dunn et al.

    Beneficial effects of early hypocaloric enteral feeding on neonatal gastrointestinal function: preliminary report of a randomized trial

    J Pediatr

    (Apr 1988)
  • R.E. McKeown et al.

    Role of delayed feeding and of feeding increments in necrotizing enterocolitis

    J Pediatr

    (1992)
  • E.F. LaGamma et al.

    Failure of delayed oral feedings to prevent necrotizing enterocolitis. Results of study in very-low-birth-weight neonates

    Am J Dis Child

    (1985)
  • C.L. Berseth et al.

    Prolonging small feeding volumes early in life decreases the incidence of necrotizing enterocolitis in very low birth weight infants

    Pediatrics

    (2003)
  • S.F. Rayyis et al.

    Randomized trial of “slow” versus “fast” feed advancements on the incidence of necrotizing enterocolitis in very low birth weight infants

    J Pediatr

    (1999)
  • D.M. Anderson et al.

    The relationship of neonatal alimentation practices to the occurrence of endemic necrotizing enterocolitis

    Am J Perinatol

    (1991)
  • B.A. Bhat et al.

    Effects of human milk fortification on morbidity factors in very low birth weights infants

    Ann Saudi Med

    (2001)
  • Cited by (55)

    • Racial disparities in the development of comorbid conditions after preterm birth: A narrative review

      2022, Seminars in Perinatology
      Citation Excerpt :

      Building on this work, Guthrie et al. used an administrative database for births across 24 states between 1998-2000 among neonates between 23-34 weeks GA, and found that Black infants developed NEC more often than other infants.90 Several studies followed with similar findings that non-Hispanic Black infants were more likely to develop NEC and experienced higher rates of NEC-associated mortality, compared to infants of other races even after adjusting for birthweight and other clinical and demographic characteristics.91–93 When stratifying by GA, Anderson et al. found that Black infants born between 32-34 weeks (OR 1.49; 95%CI 1.03, 2.16) and 34-36 weeks (OR 2.29 95%CI 1.14, 4.58) were more likely to develop NEC than non-Black infants, however no difference was found in the <32 week GA stratification groups, suggesting that differential care practices for older infants may modulate the inherent risk based on immaturity.11

    • The Neonate

      2016, Obstetrics: Normal and Problem Pregnancies
    • Dual purpose use of preterm piglets as a model of pediatric GI disease

      2014, Veterinary Immunology and Immunopathology
    • Anesthesia Outside the Operating Room

      2023, Neonatal Anesthesia, Second Edition
    View all citing articles on Scopus
    View full text