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Necrotizing enterocolitis (NEC) remains one of the most devastating diagnoses in the neonatal intensive care unit. Primarily affecting preterm infants, it is a leading cause of death and lifelong gastrointestinal and neurodevelopmental morbidities in the very low birth weight (VLBW) (birth weight < 1500 g) population. Despite decades of research, the specific etiology for NEC remains unknown. NEC appears to be precipitated by an insult that leads the immature neonatal immune system to mount an abnormal and deleterious inflammatory response. Since many neonates die or suffer unfavorable outcomes despite maximal medical and surgical therapy, a preventive strategy is greatly needed. This chapter reviews the epidemiology, pathophysiology, diagnostic criteria, and supportive treatment of NEC, as well as promising novel, preventive strategies currently under investigation.


Necrotizing enterocolitis is estimated to occur in 1 per 1000 US live births each year.1 Its annual rate in the highest-risk population, VLBW infants born prior to 29 weeks, is much higher (10%–15%). NEC frequency is inversely related to birth weight and gestational age in a nonlinear fashion, with a marked increase in NEC incidence as birth weight decreases below 1500 g.2 In the United States, the incidence rate in the VLBW population has remained stable at 11% in recent years.3 Despite this stability, the proportion of neonatal deaths secondary to NEC has actually increased over the past 2 decades, as preterm deaths from other causes have fallen due to advances in neonatal care.4

Although NEC is predominantly a disease of VLBW infants, it is occasionally seen in term infants following other illnesses. Concurrent diagnoses of congenital heart disease, bacterial sepsis, polycythemia, and hypotension are associated with NEC in term and late-preterm infants.5

Patient Demographics

Necrotizing enterocolitis is reported more frequently in male infants and non-Hispanic infants of African descent.1 Timing of onset is inversely related to gestational age, with a median onset of nearly 4 postnatal weeks in infants born at less than 25 weeks’ gestation, 2 weeks at 27–29 weeks’ gestation, and within the first week in term infants.6 Most NEC cases present sporadically, although temporal, nonseasonal clustering of NEC cases within neonatal intensive care units has been reported.7

Antenatal Risk Factors

The main antenatal risk factors for NEC are those associated with preterm birth, the leading risk factor for NEC.8 Thus, at birth it is nearly impossible to predict which VLBW infants will be at higher risk for NEC. Recent investigations have reported an association between antenatal indomethacin administration for tocolysis and NEC.9, 10

Postnatal Risk Factors

Prematurity is the leading postnatal risk factor for NEC, which only rarely occurs in term infants. The association between preterm birth and NEC has been consistently verified over time in numerous investigations.1, 3, ...

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