Part 1. Current Controversies in the Understanding of Necrotizing Enterocolitis

Barbara Noerr, RNC, MSN, CRNP


Adv Neonatal Care. 2003;3(3) 

In This Article

Feedings and NEC

The GI tract is an active organ in utero. The fetus swallows amniotic fluid composed of nutrients, growth factors, and immunoglobulins.[8] Although occasionally NEC occurs in neonates who have never been fed, more frequently it occurs in preterm infants on enteral feedings. Aggressive feeding advancement, often defined as greater than 20 kcal/kg/d, has been implicated.[8] See Table 4 for feeding factors that have potential associations with NEC.

The delay of enteral feedings in sick preterm neonates may decrease the normal GI functional adaptation, resulting in subsequent feeding intolerance. Delayed feedings and/or starvation are associated with the following[35,42,43,44]:

  • Fewer mucosal antibody cells due to limited exposure to gut antigens

  • Reduction in the local immune response to foreign organisms

  • Decreased enzyme levels (eg, disaccharidases)

  • Damage to mucosal barriers

  • Increased susceptibility to infections

  • Morphologic injury

  • Decreased secretion of immunoglobulin A (IgA)

  • Bacterial overgrowth

Early enteral feedings have been proposed to avoid the anatomic and physiologic alternations associated with delayed enteral feedings.[35,42] A recent systematic review of the literature found few randomized studies addressing the role of early or minimal enteral feedings in preterm neonates.[43,44] Based on the limited results available, early feedings had no significant effect on weight gain, NEC, mortality, and age at discharge. Although no increase in NEC was found with early feedings, it remains unclear if early or delayed feedings are of benefit in high-risk neonates.[43]

Others have proposed the use of minimal enteral feedings or subnutritional feedings in premature infants. A meta-analysis of minimal enteral feedings showed an overall decrease in days to full enteral feedings, total days that feedings were held, and total length of stay in the hospital, with no perceptible effect on NEC.[44] The reviewers concluded that the evidence for benefit of minimal enteral feedings was not convincing because of the small number of available studies and limitations of study methods.[44]

The relationship between the rate of advancement of feedings and NEC remains controversial. Although some retrospective case control studies suggest that rapid advancement of feedings is linked to NEC,[45,46,47] a recently published prospective randomized controlled trial provides contrary evidence.[48] A total of 185 neonates with birth weights 501 to 1,500 g (gestational age ≤34 weeks) were randomized according to weight stratification into 2 groups. The fast group started feedings at 35 mL/kg/d with incremental advancements of 35 mL/kg/d (5-day schedule to full feedings). The slow group had feedings started at 20 mL/kg/d with advancements of 15 mL/kg/d (10-day schedule to full feedings). Both groups received a 20-cal/oz commercial formula initially and were advanced to a 24-cal/oz product when full feedings were reached (160 mL/kg/d).

No difference in the incidence of NEC (stage ≥II), intestinal perforation, mortality from NEC, age at NEC diagnosis, or feeding intolerance between groups was found.[48] The study incidence did not differ significantly from historical data from the same NICU. Although birth weight in the fast group was regained more rapidly, this did not translate to earlier discharge from the hospital. A small sample size leading to a type II error (failure to reject a false null hypothesis) existed in this study, warranting cautious interpretation. Feeding increments >35 mL/kg/d do have the potential to alter the risk for NEC and require further study.

The incidence of NEC before and after introduction of a standardized feeding protocol was recently reported.[5] Before standardization, the incidence of NEC was 4.8% (n = 477 infants 1,250 to 2,500 g). After introduction of the standardized protocol, the incidence declined to 1.1% (n = 467 matched cohorts). The protocol consisted of feedings of 3 to 4 mL, initiated at 24 to 72 hours after birth, and advanced by no more than 20 mL/kg/d. The exclusive use of breast-milk was approximately 35% in the standardized group compared with 20.5% in the nonprotocol group (P = 0.002).

Multivariate analysis confirmed that the change in feeding protocols was an independent variable for the decreased incidence of NEC.[5] The risk of NEC decreased by 60% in neonates fed only breastmilk, although this did not reach statistical significance. Encouraging mothers to provide breastmilk for the baby's initial feedings, even if they do not wish to continue breastfeeding during infancy, is essential. Not only does this foster active participation in care and decision making, but it also may lessen the risk of NEC.


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