Ghoneim Nada, Bauchart-Thevret Caroline, Oosterloo Berthe, Stoll Barbara, Kulkarni Madhulika, de Pipaon Miguel Saenz, Zamora Irving J, Olutoye Oluyinka O, Berg Brian, Wittke Anja, Burrin Douglas G
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.
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.
PLoS One. 2014 Sep 19;9(9):e106888. doi: 10.1371/journal.pone.0106888. eCollection 2014.
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.
肠内配方奶喂养是早产儿坏死性小肠结肠炎（NEC）的一个危险因素，但关于开始喂养和增加喂养量的最安全时机，各项研究结果存在冲突。我们的目的是测试早期与晚期开始肠内喂养以及完整蛋白配方奶与水解蛋白配方奶突然与逐渐增加喂养量对早产仔猪NEC发生率和严重程度的影响。在实验1中，早产仔猪出生时接受全胃肠外营养（TPN），在出生后第2天（EA组）或第5天（LA组）突然开始肠内配方奶喂养（达到全量摄入的50%），同时继续给予PN。仔猪还被喂食含有完整蛋白或水解蛋白的配方奶。在实验2中，早产仔猪出生时接受TPN，在出生后第2天开始给予肠内水解蛋白配方奶，要么突然增加（EA组；达到全量喂养的50%），要么逐渐增加（EG组；在5天内从10%增加到50%全量喂养），同时继续给予PN。根据宏观和组织学评分评估NEC的发生率和严重程度。在实验1中，LA组与EA组相比，NEC发生率（41%对70%，P<0.05）和严重程度降低，LA组的存活率、每日体重增加和空肠绒毛高度更高。喂食水解蛋白配方奶与完整蛋白配方奶的仔猪胃内容物重量更低，NEC发生率相似。在实验2中，EG组与EA组仔猪的NEC发生率和严重程度没有差异。LA组和EG组回肠中的促炎基因表达（IL-1β、IL-6和S100A9）均低于EA组。总之，延迟开始肠内喂养而非逐渐增加喂养量可预防早产仔猪发生NEC。喂食水解蛋白配方奶与完整蛋白配方奶可改善胃排空，而不影响NEC发生率。
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