The Novel Lipid Emulsion Vegaven Is Well Tolerated and Elicits Distinct Biological Actions Compared With a Mixed-Oil Lipid Emulsion Containing Fish Oil: A Parenteral Nutrition Trial in Piglets.

Background: Vegaven is a novel lipid emulsion for parenteral nutrition (PN) based on 18-carbon n-3 (ω-3) fatty acids, which elicits liver protection via interleukin-10 (IL-10) in the murine model of PN.

Objectives: In a preclinical model of PN in neonatal piglets, Vegaven was tested for efficacy and safety and compared with a mixed-oil lipid emulsion containing fish oil (SMOFlipid).

Methods: Male piglets 4-5 d old were randomly allocated to isocaloric isonitrogenous PN for 14 d, which varied only by the type of lipid emulsion (Vegaven, n = 8; SMOFlipid, n = 8).

Association between 4%-tetrasodium EDTA and sepsis in neonatal piglets: A retrospective cohort study.

Background: Central line-associated bloodstream infections are a major concern for children with intestinal failure and in animal research using parenteral nutrition (PN). In neonatal piglets receiving PN, we compared sepsis, line occlusions, line replacements, mortality, and costs with and without the use of a 4%-tetrasodium ethylenediaminetetraacetic acid (T-EDTA) locking solution.

Methods: We performed a retrospective review of piglets with a central venous jugular catheter enrolled in 14-day exclusive PN (TPN) trials or in 7-day short bowel syndrome (SBS) trials, before and after initiation of T-EDTA.

In parenteral nutrition-fed piglets, fatty acids vary by lipid emulsion and tissue sampled.

Background: Children with intestinal failure without liver disease may be given soy-based lipid emulsion (SLE) or mixed lipid emulsion (MLE; containing soy, medium-chain triglyceride, olive, and/or fish oils). Both differ in essential fatty acid content: MLE has added arachidonic acid (AA) and docosahexaenoic acid (DHA). The aim of this study, in neonatal piglets, was to compare serum and tissue fatty acid composition when the emulsions were given at unrestricted doses.

The effect of fecal microbial transplant on intestinal microbial composition in short-bowel neonatal piglets.

Background: Short-bowel syndrome (SBS) in neonates is associated with microbial dysbiosis due to intestinal surgery, prolonged hospitalization, enteral nutrition, and repeated antibiotic exposure. Sepsis and liver disease, leading causes of morbidity and mortality in SBS, may relate to such intestinal dysbiosis. We investigated the safety and feasibility of fecal microbial transplant (FMT) to alter intestinal microbial composition in SBS piglets.

Durability of Linear Small-Intestinal Growth Following Treatment Discontinuation of Long-Acting Glucagon-Like Peptide 2 (GLP-2) Analogues.

Background: Short-bowel syndrome is the leading cause of pediatric intestinal failure, resulting in dependency on long-term parenteral nutrition (PN). To promote enteral autonomy in neonates, a key outcome may be intestinal growth in length. The purpose of this study was to determine if intestinal lengthening persists following discontinuation of treatment with 1 of 2 GLP-2 analogues with different pharmacokinetic profiles.

In the Short-term, Milk Fat Globule Epidermal Growth Factor-8 Causes Site-specific Intestinal Growth in Resected Piglets.

Objectives: Short bowel syndrome (SBS) remains the leading cause of neonatal intestinal failure. Milk fat globule epidermal growth factor-8 (MFG-E8), present in human milk, has homology with epidermal growth factor (EGF), known to enhance adaptation in SBS. In this pilot study, the role of oral MFG-E8 treatment in SBS was explored in neonatal piglets.

Comparing the Intestinotrophic Effects of 2 Glucagon-Like Peptide-2 Analogues in the Treatment of Short-Bowel Syndrome in Neonatal Piglets.

Background: In treating short-bowel syndrome (SBS), autonomy from parenteral nutrition (PN) relies upon intestinal adaptation, which can be augmented by glucagon-like peptide-2 (GLP-2) analogues. In neonatal piglets with SBS, we compared intestinal adaptation following treatment with 2 GLP-2 analogues: teduglutide (TED) and apraglutide (APRA) METHODS: Following 75% distal small-intestinal resection, piglets were allocated to 4 treatment groups: saline (CON: n = 8), twice weekly APRA (5 mg/kg/dose; n = 8), and TED once daily (TED, 0.05 mg/kg/dose; n = 8) or twice daily (TEDBID, 0.

Mixed Lipid, Fish Oil, and Soybean Oil Parenteral Lipids Impact Cholestasis, Hepatic Phytosterol, and Lipid Composition.

Objectives: In parenteral nutrition-dependent infants and children, intestinal failure (IF)-associated liver disease (IFALD) remains an important problem. A comparative study was undertaken of parenteral mixed lipid (ML), ω-3 predominant fish oil (FO), and ω-6 predominant soybean oil (SO) emulsions in regards to hepatic phytosterol, neutral lipid, fatty acid (FA) content, and the relationship to cholestasis in piglets.

Methods: Neonatal piglets received parenteral nutrition, varying in lipid dose (5 or 10 g· kg · day) and formulation: SO5 (n = 5), SO10 (n = 5), FO5 (n = 5), and ML10 (n = 5).

Impact of Clinical Use of Parenteral Lipid Emulsions on Bile Acid Metabolism and Composition in Neonatal Piglets.

Background: Neonates with intestinal failure dependent on parenteral nutrition (PN) are at risk of intestinal failure-associated liver disease (IFALD). PN lipid composition relates to the risk of IFALD, but the mechanisms are poorly understood. We investigated the effects of soybean oil (SO), a mixed-lipid (ML) emulsion containing fish oil (FO), and a pure FO.

Surgical Anatomy Does Not Affect the Progression of Intestinal Failure-Associated Liver Disease in Neonatal Piglets.

Background: Intestinal failure-associated liver disease (IFALD) causes significant morbidity in neonates with short bowel syndrome (SBS) dependent on parenteral nutrition (PN). Resected ileum, with loss of the ileocecal valve (ICV), is the most common anatomy in SBS, yet its impact on IFALD has not been adequately studied.

Methods: Neonatal piglets were randomized to 75% intestinal resection with jejunocolic anastomosis (JC, n = 12), 75% resection with jejunoileal anastomosis and intact ICV (JI, n = 13), PN-fed sham (sham, n = 14), or sow-fed control (SF, n = 8).

Synergy of glucagon-like peptide-2 and epidermal growth factor coadministration on intestinal adaptation in neonatal piglets with short bowel syndrome.

Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) treatment enhance intestinal adaptation. To determine whether these growth factors exert synergistic effects on intestinal growth and function, GLP-2 and EGF-containing media (EGF-cm) were administered, alone and in combination, in neonatal piglet models of short bowel syndrome (SBS). Neonatal Landrace-Large White piglets were block randomized to 75% midintestinal [jejunoileal (JI) group] or distal intestinal [jejunocolic (JC) group] resection or sham control, with 7-day infusion of saline (control), intravenous human GLP-2 (11 nmol·kg·day) alone, enteral EGF-cm (80 μg·kg·day) alone, or GLP-2 and EGF-cm in combination.

Lipid Emulsion Formulation of Parenteral Nutrition Affects Intestinal Microbiota and Host Responses in Neonatal Piglets.

Background: Total parenteral nutrition (TPN) is a cause of intestinal microbial dysbiosis and impaired gut barrier function. This may contribute to life-threatening parenteral nutrition-associated liver disease and sepsis in infants. We compared the effects of a lipid emulsion containing long-chain ω-3 polyunsaturated fatty acids (PUFAs; SMOFlipid) and a predominantly ω-6 PUFA emulsion (Intralipid) on microbial composition and host response at the mucosal surface.

Supplemental Parenteral Vitamin E Into Conventional Soybean Lipid Emulsion Does Not Prevent Parenteral Nutrition-Associated Liver Disease in Full-Term Neonatal Piglets.

Background: Parenteral nutrition-associated liver disease (PNALD) continues to cause morbidity and mortality for neonates with intestinal failure. Lipid peroxidation is one potential etiological factor. This study was designed to test if supplementing vitamin E into conventional soy-based lipid would reduce the risk of PNALD.

Glucagon-Like Peptide-2 Alters Bile Acid Metabolism in Parenteral Nutrition--Associated Liver Disease.

Background: We aim to study the mechanisms underlying our previous finding that exogenous glucagon-like peptide-2 (GLP-2) treatment in a preclinical model of neonatal parenteral nutrition-associated liver disease (PNALD) improves cholestasis.

Methods: Neonatal piglets received 17 days of parenteral nutrition (PN) therapy and either saline control (PN/Saline n = 8) or GLP-2 treatment at 11 nmol/kg/d (PN/GLP-2, n = 7). At terminal laparotomy, bile and liver samples were collected.

Liver Disease, Systemic Inflammation, and Growth Using a Mixed Parenteral Lipid Emulsion, Containing Soybean Oil, Fish Oil, and Medium Chain Triglycerides, Compared With Soybean Oil in Parenteral Nutrition-Fed Neonatal Piglets.

Background: The optimal parenteral lipid emulsion for neonates should reduce the risk of intestinal failure-associated liver disease and inflammation, while supporting growth and development. This could be best achieved by balanced content of ω-6 and ω-3 polyunsaturated fatty acids (PUFAs). Using a neonatal piglet model of parenteral nutrition (PN), we compared a 100% soy oil-based emulsion (ω-6:ω-3 PUFA: 7:1) with a mixed lipid emulsion comprising 30% soy oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (ω-6:ω-3 PUFA: approximately 2.

Parenteral Soy Oil and Fish Oil Emulsions: Impact of Dose Restriction on Bile Flow and Brain Size of Parenteral Nutrition-Fed Neonatal Piglets.

Background: Parenteral nutrition (PN)-associated liver disease (PNALD) remains a significant cause of morbidity and mortality for neonates dependent on PN. Total fat emulsion dose and composition, particularly the large amount of ω-6 long-chain polyunsaturated fatty acids in plant oils, have been proposed as risk factors for PNALD. We hypothesized restriction of the dose of emulsion would prevent PNALD, regardless of the composition, but growth could be compromised.

Glucagon-Like Peptide 2 Improves Cholestasis in Parenteral Nutrition--Associated Liver Disease.

Background: Parenteral nutrition-associated liver disease (PNALD) remains a significant cause of morbidity and mortality in neonates with intestinal failure. Although glucagon-like peptide-2 (GLP-2) is being advanced as therapy, the effect of GLP-2 treatment on PNALD is unknown. We aim to investigate the effect of exogenous GLP-2 administration on hepatic function in a neonatal piglet model of PNALD.

Exogenous glucagon-like peptide-2 improves outcomes of intestinal adaptation in a distal-intestinal resection neonatal piglet model of short bowel syndrome.

Background: Endogenous glucagon-like peptide-2 (GLP-2) levels and intestinal adaptation are reduced in distal-intestinal resection animal models of short bowel syndrome (SBS) that lack remnant ileum. We hypothesized that exogenous GLP-2 would improve intestinal adaptation in a distal-intestinal resection neonatal piglet model of SBS.

Methods: In all, 35 piglets were randomized to 2 treatment and 3 surgical groups: control (sham), 75% mid-intestinal resection (JI), and 75% distal-intestinal resection (JC).

Effects of chronic glucagon-like peptide-2 therapy during weaning in neonatal pigs.

Background: The enteroendocrine hormone glucagon like peptide-2 (GLP-2) and its ligands are under development as therapeutic agents for a variety of intestinal pathologies. A number of these conditions occur in neonates and infants, and thus a detailed understanding of the effects of GLP-2 during the phase of rapid growth during infancy is required to guide the development of therapeutic applications. We studied the effects of GLP-2 in the neonatal pig to determine the potential effects of exogenous administration.

Effects of polymeric formula vs elemental formula in neonatal piglets with short bowel syndrome.

Background: Intestinal adaptation is important for recovery in short bowel syndrome (SBS). This process is dependent on the presence of enteral nutrition (EN) and trophic factors, such as glucagon-like peptide-2 (GLP-2). In clinical practice, elemental formula is often used to feed neonates with SBS, whereas animal studies suggest polymeric formula promotes better intestinal adaptation.

Role of glucagon-like peptide-2 deficiency in neonatal short-bowel syndrome using neonatal piglets.

Background: Short-bowel syndrome (SBS) is the most common cause of neonatal intestinal failure. Recovery requires intestinal adaptation, dependent on enteral nutrition (EN) and growth factors such as glucagon-like peptide-2 (GLP-2), which is secreted from L cells in the ileum. Neonatal SBS often results in loss of ileum; therefore, we hypothesized that without ileum, endogenous GLP-2 production would be inadequate to promote adaptation.

Hepatic ultrastructure in a neonatal piglet model of intestinal failure-associated liver disease (IFALD).

This study was designed to evaluate liver disease in neonatal piglets with surgical short bowel syndrome causing intestinal failure with partial parenteral nutrition dependence. The short bowel piglets had 75% surgical resection of distal small intestine, including all ileum and cecum, and were compared with sham controls, without resection, and to healthy sow-reared controls. After 18 days of combined parenteral and enteral nutrition in short bowel and sham piglets, liver tissue was collected for quantitative and semi-quantitative histological and ultrastructural evaluation.