Gastric Residual to Predict Necrotizing Enterocolitis in Preterm Piglets As Models for Infants

Kappel, Susanne Soendergaard; Sangild, Per Torp; Hilsted, Linda; Hartmann, Bolette; Thymann, Thomas; Aunsholt, Lise

doi:10.1002/jpen.1814

Cited by 6 publications

(12 citation statements)

References 46 publications

(88 reference statements)

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“…The preterm piglet model has been used to study gut maturation and necrotizing enterocolitis (NEC) in relation to diet. Recently, it was shown that aspects of feeding tolerance can also be evaluated in this model, using gastric residual measurements and X-ray contrast imaging [21].…”

Section: Introductionmentioning

confidence: 99%

Mildly Pasteurized Whey Protein Promotes Gut Tolerance in Immature Piglets Compared with Extensively Heated Whey Protein

et al. 2020

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Human milk is the optimal diet for infant development, but infant milk formula (IMF) must be available as an alternative. To develop high-quality IMF, bovine milk processing is required to ensure microbial safety and to obtain a protein composition that mimics human milk. However, processing can impact the quality of milk proteins, which can influence gastro-intestinal (GI) tolerance by changing digestion, transit time and/or absorption. The aim of this study was to evaluate the impact of structural changes of proteins due to thermal processing on gastro-intestinal tolerance in the immature GI tract. Preterm and near-term piglets received enteral nutrition based on whey protein concentrate (WPC) either mildly pasteurized (MP-WPC) or extensively heated (EH-WPC). Clinical symptoms, transit time and gastric residuals were evaluated. In addition, protein coagulation and protein composition of coagulates formed during in vitro digestion were analyzed in more detail. Characterization of MP-WPC and EH-WPC revealed that mild pasteurization maintained protein nativity and reduced aggregation of β-lactoglobulin and α-lactalbumin, relative to EH-WPC. Mild pasteurization reduced the formation of coagulates during digestion, resulting in reduced gastric residual volume and increased intestinal tract content. In addition, preterm piglets receiving MP-WPC showed reduced mucosal bacterial adherence in the proximal small intestine. Finally, in vitro digestion studies revealed less protein coagulation and lower levels of β-lactoglobulin and α-lactalbumin in the coagulates of MP-WPC compared with EH-WPC. In conclusion, minimal heat treatment of WPC compared with extensive heating promoted GI tolerance in immature piglets, implying that minimal heated WPC could improve the GI tolerance of milk formulas in infants.

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Section: Introductionmentioning

confidence: 99%

Mildly Pasteurized Whey Protein Promotes Gut Tolerance in Immature Piglets Compared with Extensively Heated Whey Protein

et al. 2020

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“…Traditionally, the severity of NEC in piglets has been assessed using gross injury scoring which depicts macroscopic damage of the intestine, or histologic injury scoring, or a combination of both ( 18 , 24 – 26 , 29 – 31 , 37 , 59 , 61 – 63 , 65 , 68 ). During our study, it was common to find piglets with high gross injury and high histologic injury scores that appeared clinically healthy throughout the entire experiment and did not show bacterial translocation to internal organs.…”

Section: Discussionmentioning

confidence: 99%

Development of a novel definitive scoring system for an enteral feed-only model of necrotizing enterocolitis in piglets

et al. 2023

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IntroductionNecrotizing enterocolitis (NEC) is a complex inflammatory disorder of the human intestine that most often occurs in premature newborns. Animal models of NEC typically use mice or rats; however, pigs have emerged as a viable alternative given their similar size, intestinal development, and physiology compared to humans. While most piglet NEC models initially administer total parenteral nutrition prior to enteral feeds, here we describe an enteral-feed only piglet model of NEC that recapitulates the microbiome abnormalities present in neonates that develop NEC and introduce a novel multifactorial definitive NEC (D-NEC) scoring system to assess disease severity.MethodsPremature piglets were delivered via Caesarean section. Piglets in the colostrum-fed group received bovine colostrum feeds only throughout the experiment. Piglets in the formula-fed group received colostrum for the first 24 h of life, followed by Neocate Junior to induce intestinal injury. The presence of at least 3 of the following 4 criteria were required to diagnose D-NEC: (1) gross injury score ≥4 of 6; (2) histologic injury score ≥3 of 5; (3) a newly developed clinical sickness score ≥5 of 8 within the last 12 h of life; and (4) bacterial translocation to ≥2 internal organs. Quantitative reverse transcription polymerase chain reaction was performed to confirm intestinal inflammation in the small intestine and colon. 16S rRNA sequencing was performed to evaluate the intestinal microbiome.ResultsCompared to the colostrum-fed group, the formula-fed group had lower survival, higher clinical sickness scores, and more severe gross and histologic intestinal injury. There was significantly increased bacterial translocation, D-NEC, and expression of IL-1α and IL-10 in the colon of formula-fed compared to colostrum-fed piglets. Intestinal microbiome analysis of piglets with D-NEC demonstrated lower microbial diversity and increased Gammaproteobacteria and Enterobacteriaceae.ConclusionsWe have developed a clinical sickness score and a new multifactorial D-NEC scoring system to accurately evaluate an enteral feed-only piglet model of NEC. Piglets with D-NEC had microbiome changes consistent with those seen in preterm infants with NEC. This model can be used to test future novel therapies to treat and prevent this devastating disease.

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“…We used preterm piglets as a model for preterm infants because they show many similarities to infants in their complications after preterm birth, including maldigestion, poor respiration, brain defects, high NEC sensitivity and a degree of feeding intolerance with large gastric residuals (16,20,33,34). The model has translational limitations, not only because preterm piglet anatomy and physiology may differ from infants (e.g., a relatively long small intestine and high NEC sensitivity) but also because serial X-rays are required to accurately assess the passage of contrast through the entire gut.…”

Section: Discussionmentioning

confidence: 99%

Radiographic Imaging to Evaluate Food Passage Rate in Preterm Piglets as a Model for Preterm Infants

et al. 2021

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Objectives and study: Gut motility in infants mature with increasing post-menstrual age and is affected by numerous hormonal, immunological and nutritional factors. However, it remains unclear how age and diet influence gut motility and its relation to feeding intolerance and gastric residuals in preterm neonates. Using preterm piglets as a model for infants, we investigated if contrast passage rate, as determined by X-ray contrast imaging, is affected by gestational age at birth, advancing postnatal age and different milk diets.Methods: Contrast passage rate was evaluated using serial abdominal X-ray imaging on postnatal day 4 and 18 in preterm and near-term piglets fed infant formula, colostrum or intact bovine milk, with or without added fortifier (total n = 140).Results: Preterm piglets had a faster small intestinal passage rate of contrast solution at day 4 of life than near-term piglets (SIEmpty, hazard ratio (HR): 0.52, 95%CI [0.15, 0.88], p < 0.01). Formula fed piglets at day 4 had a faster passage rate of contrast to caecum (ToCecum, HR: 0.61, 95%CI [0.25,0.96], p = 0.03), and through the colon region (CaecumToRectum, p < 0.05, day 4) than colostrum fed preterm piglets. The time for contrast to leave the stomach, and passage through the colon in day 4 preterm piglets were slower than in older piglets at day 18 (both, p < 0.05). Adding a nutrient fortifier increased body growth, gastric residuals, intestinal length and weight, but did not affect any of the observed passage rates of the contrast solution.Conclusion: Serial X-ray contrast imaging is a feasible method to assess food passage rate in preterm piglets. Contrast passage rate through different gut segments is affected by gestational age at birth, postnatal age, and milk diet. The preterm piglet could be a good model to investigate clinical and dietary factors that support maturation of gut motility and thereby feeding tolerance and gut health in preterm infants.

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Gastric Residual to Predict Necrotizing Enterocolitis in Preterm Piglets As Models for Infants

Cited by 6 publications

References 46 publications

Mildly Pasteurized Whey Protein Promotes Gut Tolerance in Immature Piglets Compared with Extensively Heated Whey Protein

Mildly Pasteurized Whey Protein Promotes Gut Tolerance in Immature Piglets Compared with Extensively Heated Whey Protein

Development of a novel definitive scoring system for an enteral feed-only model of necrotizing enterocolitis in piglets

Radiographic Imaging to Evaluate Food Passage Rate in Preterm Piglets as a Model for Preterm Infants

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