Necrotizing enterocolitis: A multifactorial disease with no cure

Abstract

INTRODUCTIONNecrotizing enterocolitis (NEC) is an inflammatory bowel disease of neonates and remains one of the most common gastrointestinal emergencies in newborn infants [1] . Onset of NEC is often within the first three months of life and neonates who are of extremely low birth weight (< 1000 g) and under 28 wk gestation are the most susceptible [2] . Full term neonates account for 10% of all NEC cases while premature infants account for 90% [3] . With an incidence rate of 1%-5% for all newborns admitted to the NICU [1] , a prevalence of 7%-14% of very low birth weight infants (VLBW, 500-1500 g) [4] and a mortality rate approaching 20%-50% [5] , NEC continues to represent a significant clinical problem. In Canada, the incidence rate is 1.8 per 100 live births with a prevalence of 7% of VLBW infants [1] . Advances in obstetric and neonatal care have improved survival rates for smaller, more immature infants, and as more VLBW preterm infants survive the neonatal period, the population at risk for NEC increases [1] .No consistent association between sex, race, and rates of NEC has been identified. However, male VLBW infants and black infants are at greater risk of death [6] . Due to inadequate treatments and no effective preventative strategy, an estimated 20%-40% of babies with NEC require surgery [1] and 10%-30% experience significant morbidity including neurodevelopmental impairment, vision and hearing impairment, failure to thrive, feeding abnormalities, diarrhea, bowel obstruction, and short bowel syndrome [1,2,7] . The case fatality rate with surgical intervention is as high as 50% [1] . NEC is also a financial burden to the health care system with yearly hospital charges reported to be as high as $6.5 million in the US [8] . Thus, NEC continues to be an important health issue for preterm neonates. DIAGNOSIS Clinical signs and symptomsThe onset of NEC can occur suddenly within a few AbstractNecrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature of the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events, formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear. Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Development of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

Investigation of the early intestinal microflora in premature infants with/without necrotizing enterocolitis using two different methods

“…It is known that any abnormality in the ecosystem of the gastrointestinal tract may result in a pathological process potentially leading to NEC (3). It is suspected that abnormal colonization of the gastrointestinal tract or an unfavorable balance between commensal and pathogenic bacteria is part of the pathogenesis of NEC (4)(5)(6). It has been suggested that the ability of microflora to invade the epithelium and ferment unabsorbed nutrients (7), and the colonization by various bacterial pathogens in a sufficiently vulnerable host (8) could promote the development of NEC.…”

Neonatal necrotizing enterocolitis rat model attenuated by a remote ischemic preconditioning in the pregnant

“…Necrotizing enterocolitis (NEC) is the main cause of morbidity and mortality in very low birth weight neonates 1,2 . Due to an unsatisfactory response to treatment and lack of effective prevention, it is estimated that 20% to 40% of newborns with NEC require surgical treatment 2 .…”

C5a, A Complement Activation Product, Is a Useful Marker in Predicting the Severity of Necrotizing Enterocolitis

“…Ninety percent of cases occur in preterm infants, with the greatest risk in the smaller, more premature infants (Lin et al 2008;Thompson and Bizzarro 2008;Schnabl et al 2008). Compared with an overall incidence rate of 1% to 7.7%, up to 7% to 14% of very-low-birth-weight infants (< 1,500 g) are diagnosed with NEC (Kosloske 1994;Neu 2005).…”