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

Author
item GHONEIM, NADA - Texas Children'S Hospital
item BAUCHART-THEVRET, CAROLINE - Children'S Nutrition Research Center (CNRC)
item OOSTERLOO, BERTHE - Children'S Nutrition Research Center (CNRC)
item STOLL, BARBARA - Children'S Nutrition Research Center (CNRC)
item KULKARNI, MADHULIKA - Texas Children'S Hospital
item SAENZ DE PIPAON, MIGUEL - Hospital Universitario La Paz
item ZAMORA, IRVING - Texas Children'S Hospital
item OLUTOYE, OLUYINKA - Texas Children'S Hospital
item BERG, BRIAN - Mead Johnson
item WITTKE, ANJA - Mead Johnson
item Burrin, Douglas - Doug

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/3/2014
Publication Date: 9/19/2014
Citation: Ghoneim, N., Bauchart-Thevret, C., Oosterloo, B., Stoll, B., Kulkarni, M., Saenz De Pipaon, M., Zamora, I.J., Olutoye, O.O., Berg, B., Wittke, A., Burrin, D.G. 2014. Delayed initiation but not gradual advancement of enteral formula feeding reduces the incidence of necrotizing enterocolitis (NEC) in preterm pigs. PLoS One. 9(9):e106888. doi: 10.1371/journal.pone.0106888.

Interpretive Summary: Premature infants are at increased risk for an intestinal disease called necrotizing enterocolitis (NEC). Only a small percentage of infants develop NEC, but it has devastating effects on the health, and development, and can be fatal. There is uncertainty about how the mode of feeding affects the risk for NEC, such as when to start oral feedings and how much to feed to premature infants. To test this question, we used premature formula-fed, piglets as a model of human preterm infants and first fed them a high volume of formula either early or late. We then compared whether feeding early with a high volume vs. low volume and gradually increasing the volume affected the NEC incidence. The results showed that delayed formula feeding late vs. early protected against the development of NEC. We also showed that early feeding a high volume vs. low volume with a gradual increase did not increase the NEC incidence. The results supports the clinical practice of delaying enteral formula feeding with a less aggressive approach to prevent the onset of this devastating disease in premature infants.

Technical 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-1b, 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.