Delayed initiation but not gradual advancement of enteral formula feeding reduces the incidence of necrotizing enterocolitis (NEC) in preterm pigs.

Nada Ghoneim,Berthe Oosterloo,Douglas G Burrin,Miguel Saenz De Pipaon,Oluyinka O Olutoye,Anja Wittke,Caroline Bauchart-Thevret,Irving J Zamora,Barbara Stoll,Madhulika Kulkarni,Brian Berg,Edgardo Szyld

doi:10.1371/journal.pone.0106888

Abstract

Enteral formula feeding is a risk factor for necrotizing enterocolitis (NEC) in premature infants, yet studies are conflicting regarding the safest timing for introduction and advancement of feeds. Our aim was to test the effects of early vs. late initiation and abrupt vs. gradual advancement of enteral feeding of an intact vs. hydrolyzed protein formula on NEC incidence and severity in preterm pigs. In Experiment 1, preterm pigs received total parenteral nutrition (TPN) at birth with abrupt initiation of enteral formula feeds (50% full intake) on d of life (DOL) 2 (EA) or 5 (LA) while PN continued. Pigs were also fed formula containing either intact or hydrolyzed protein. In Experiment 2, preterm pigs received TPN at birth with enteral, hydrolyzed-protein formula feeds introduced on DOL 2 either abruptly (EA; 50% full feeds) or gradually (EG; 10–50% full feeds over 5 d) while PN continued. NEC incidence and severity were assessed based on macroscopic and histological scoring. In Experiment 1, NEC incidence (41% vs. 70%, P<0.05) and severity were reduced in LA vs. EA groups and LA was associated with a higher survival rate, daily weight gain and jejunum villus height. Piglets fed hydrolyzed vs. intact protein formula had lower stomach content weights and similar NEC incidence. In Experiment 2, NEC incidence and severity were not different between pigs the EG vs. EA group. Proinflammatory gene expression (IL-1β, IL-6 and S100A9) in the ileum was lower in both LA and EG vs. EA groups. In conclusion, delayed initiation but not gradual advancement of enteral feeding is protective against NEC in preterm pigs. Feeding hydrolyzed vs. intact protein formula improved gastric transit without affecting the NEC incidence.

Highlights

Necrotizing enterocolitis (NEC) remains the most common gastrointestinal disease in preterm neonates and has devastating complications
Abdominal distension was evident in up to 30–45% of the pigs after 2–3 days of enteral feeding without any difference between the 2 treatment groups (Figure S1B) but with a high occurrence with the intact protein diet compared to the hydrolyzed protein diet (P,0.001, intact vs. hydrolyzed protein)
The first major finding in this study is that delayed initiation of enteral feeding for 3 days was protective against NEC in the preterm pig

Summary

Introduction

Necrotizing enterocolitis (NEC) remains the most common gastrointestinal disease in preterm neonates and has devastating complications It occurs in 5–10% of very low birth weight (VLBW, ,1500 g) infants [1] with a mortality rate of 15–25%, which has not improved appreciably in the past 30 years [2]. While mild cases may lead to delayed feeding and growth with reliance on parenteral nutrition for a defined period, severe cases require surgery with bowel resection and can result in death in 30–40% [2] Those that survive may end up with short bowel syndrome with lifelong dependence on parenteral nutrition, as well as other complications of surgery such as strictures and infection. These patients are at risk for adverse neurodevelopmental outcomes [3]

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