title: Delayed initiation but not gradual advancement of enteral formula feeding reduces the incidence of necrotizing enterocolitis (NEC) in preterm pigs.
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.
authors.affiliation: Section of Neonatology, Texas Children's Hospital, Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Nada
authors.initials: N
authors.lastname: Ghoneim
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Texas Children's Hospital, Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bauchart-Thevret
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Texas Children's Hospital, Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Berthe
authors.initials: B
authors.lastname: Oosterloo
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Texas Children's Hospital, Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Barbara
authors.initials: B
authors.lastname: Stoll
authors.affiliation: Section of Neonatology, Texas Children's Hospital, Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Madhulika
authors.initials: M
authors.lastname: Kulkarni
authors.affiliation: Department of Neonatology, La Paz University Hospital, Madrid, Spain.
authors.forename: Miguel Saenz
authors.initials: MS
authors.lastname: de Pipaon
authors.affiliation: Texas Children's Hospital, Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Irving J
authors.initials: IJ
authors.lastname: Zamora
authors.affiliation: Texas Children's Hospital, Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Oluyinka O
authors.initials: OO
authors.lastname: Olutoye
authors.affiliation: Mead Johnson Pediatric Nutrition Institute, Evansville, Indiana, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Berg
authors.affiliation: Mead Johnson Pediatric Nutrition Institute, Evansville, Indiana, United States of America.
authors.forename: Anja
authors.initials: A
authors.lastname: Wittke
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Texas Children's Hospital, Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America; Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Texas Children's Hospital, Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Burrin
mesh_terms: D000818:Animals; D004750:Enteral Nutrition / Q000009:adverse effects / Q000379:methods*; D020345:Enterocolitis, Necrotizing / Q000453:epidemiology / Q000517:prevention & control*; D015870:Gene Expression / Q000276:immunology; D007082:Ileum / Q000378:metabolism; D015994:Incidence; D007422:Intestines / Q000473:pathology; D010289:Parenteral Nutrition, Total / Q000009:adverse effects / Q000379:methods; D047928:Premature Birth; D013552:Swine / Q000382:microbiology*