**3. Etiology and risk factors**

The exact etiology of NEC is undetermined and multiple risk factors have been forwarded. NEC occurs in a stereotypic relation at chronological age of onset to the gestational age at birth, the younger the gestation, the later the onset; and requires that the infant be fed [1, 11]. In one study the median age at onset in infants with a GA of less than 26 weeks was 23 days compared to a median age of 11 days for more mature infants with a GA of greater than 31 weeks [17]. Prematurity is the single greatest risk factor with almost 90% patients being premature. Enteral feeding is the second most common feature with over 98% of cases having a history of feeding. However, rate of advancement unless excessive, trophic, and early versus late and colostrum feeding are not conclusively proven to have any effect on the occurrence of NEC [18]. Other suggested risk factors are the 5 min Apgar score < 7, outborn status, body temperature 0f 36°C at 1 h of age, cesarean section, use of indomethacin with or without dexamethasone, sepsis, use of inotropes, severe metabolic acidosis, patent ductus arteriosus (PDA), gastroschisis, severe anemia, polycythemia, packed red blood cell (PRBC) transfusion, use of H2 antagonist, exposure to empirical antimicrobials, and black and Hispanic ethnicity [19]. Approximately 10% of cases occur in term and late preterm infants. Risk factors for NEC in term infants are nonhuman milk feeding; preexisting illnesses, such as congenital heart disease; primary gastrointestinal disorders; sepsis; polycythemia; respiratory disease; hypotension; neonatal

abstinence; fetal growth restriction; and perinatal hypoxia [20]. Despite the fact that no predilection for sex, race, or ethnicity has been conclusively established, a higher incidence is observed in male African American infants than in any other single demographic. This could be related to the higher incidence of prematurity in this ethnic group than in the general US population. Hypoxic ischemic injury is no longer considered a major predisposing factor in the development of NEC except in term babies [21].
