Necrotising Enterocolitis: Newer Insights

Abstract

Necrotising enterocolitis is the most common gastrointestinal emergency of the neonates with high mortality and morbidity. Despite 3 decades of extensive research and animal studies etio-pathogenesis, early diagnosis, preventive strategies and management options remain controversial. The present article reviews the literature for recent advances and newer insights for changing epidemiological trends, pathogenesis, role of inflammatory cytokines and various preventive and management strategies.

Necrotising, enterocolitis, neonates

Introduction
Necrotising enterocolitis is the most common acquired gastrointestinal disease in the newborn infants, affecting 1-3 cases per 1000 live births, 2-5% of very low birth (VLBW) infants and 1-8% of all Neonatal Intensive care unit admissions (1). The term ‘Necrotisingenterocolitis’ first appeared in the European literature in the early 1950s in articles by Schmid and Quaiser who described infants dying from necrotic lesions of the gastrointestinal tract(2). Infants with NEC represent some of the sickest infants in the NICU and exhibit a high mortality rate ranging from 20-50%. Futhermore, once an infant is diagnosed with definite NEC, with the exception of supportive care, there is little one can do to alter the course of the disease. NEC is almost exclusively a disease of prematurity, with >90% of all cases occurring in premature infants and in infants less than 2000 gms (3), (4). The disease is rare in countries where prematurity is uncommon such as Japan and Sweden (5).

The lack of improvement in the mortality rate for NEC over the past 10 years has prompted the investigators to re-examine the epidemiologic and risk factors and search for strategies to prevent the disease. This article reviews the latest epidemiological trends and pathogenesis and preventive and management options reported in the literature by searching MEDLINE (1996-2006), EMBASE (1996-2006), CINAHAL, Cochrane reviews and hand search of major neonatal and perinatal journals.

NEC has emerged as a disease of NICU survivors. The overall incidence is 1-3 cases per 1000 live births, with considerable variation observed among institutions and even within an institution. Hack et al and Uauy et al have reported an incidence of NEC varying from 4% to 19% among seven tertiary academic NICUs in USA (6),(7). Similar variations have been reported from India and Australia (8), (9). Analysis of data from 17 Canadian NICU’s have however, not shown any significant variation in the risk-adjusted incidence of NEC with exception at one center (10). The majority of NEC cases are endemic, however clustering and epidemics have also been reported. In most studies, male and female infants are equally affected. NEC when occurs in term neonates is a different disease from preterm infants (Table/Fig 1) highlights the differences between NEC in term and preterm infants (10),(11), (12), and (13).
Recently Luig,Lui, the New South Wales (NSW) and Australian Capital Territory (ACT) NICUS group have reported an encouraging reduction in the incidence of NEC from 12% in 1986-87 and 1992-1993 to 6% in 1998-1999 for all infants born in NSW at 24-28 weeks gestation. However, the mortality rate remains unchanged at 27-37% as did requirement for surgical intervention at 41-57% (14). Similar reduction in incidence from 5.3% to 3.2% for infants less than 32 weeks is also reported from the Australian and New Zealand Neonatal Network (ANZNN) (15). This is however not supported from other large Neonatal databases.

The Oxford – Vermont Network with 362 NICU’sreported proven NEC cases varying from 6.2%- 8.4% (16). The National Institute of Child Health and Human Development Neonatal research network (NICHD) have reported rates increasing from 5% in 1991-1992 to 7 % in 1995-1996(17). Various hypothesis suggested for the decline in the incidence of NEC in Australia (NSW) such as increased usage of antenatal steroids(88%

Conclusion

With the advances in perinatal care there are changing epidemiological terns for NEC with increasing number of ELBW neonates surviving. Research for understanding of pathogenesis is focused on molecular mechanisms and unifying concept of pathogenesis is emerging. Various preventive strategies for NEC remain inconclusive with utilization of potentially better feeding practices suggested as a global approach for prevention. It remains a disease of high morbidity and mortality with adverse long term outcomes. Future research needs to direct towards clinically useful preventive and diagnostic strategies based on recent emerging concepts of pathogenic mechanisms (role of cytokines, nitric oxide, cyclo-oxygenases, etc).



Conflict of Interest: None