Parenteral nutrition (PN) is a lifesaving means of nutritional support for thousands of hospitalized infants who cannot tolerate normal oral feeding due to the immaturity or surgical removal of the intestine due to congenital or disease-related causes. PN is a method of delivering nutrients directly into the bloodstream via an intravenous catheter, bypassing the digestive system entirely.
A serious complication of PN is the risk for a metabolic condition called parenteral nutrition-associated liver disease (PNALD), which leads to cholestasis, or impaired bile flow in the liver, and scarring of liver tissue. These conditions can lead to liver failure if not managed. PNALD can affect up to 50% of premature infants given total PN for prolonged periods, creating a significant clinical burden and the urgent need for safer nutritional strategies for these fragile patients.
Dr. Gregory Guthrie
“Preventing PNALD in critically ill infants who cannot be fed normally poses a significant clinical challenge,” said Dr. Gregory Guthrie, assistant professor of pediatrics at the USDA-ARS Children’s Nutrition Research Center at Baylor College of Medicine and first and corresponding author of a recent paper on this topic.
“To study PNALD in a way that is clinically relevant to human infants, we worked with a neonatal piglet model, a powerful tool that closely mimics the biology of preterm infants,” Guthrie said. “This model is indispensable for developing and testing new therapies that could one day be translated to the neonatal intensive care unit.”
In this study, published in the Journal of Clinical Investigations Insight, the Guthrie lab and colleagues investigated a way to protect the liver from long-term injury that occurs when bile flow from the liver is obstructed. This condition occurs in infants with a congenital condition called biliary atresia, the most common cause for liver transplant in pediatrics.
The Guthrie lab developed a novel model of biliary obstruction in neonatal pigs to test whether new-generation lipid emulsions can protect from liver injury. Previous studies have shown that parenteral administration of lipid emulsions made of multiple oil components can prevent cholestasis in preterm infants.
“We investigated whether new-generation mixed oil-lipid emulsions could protect the liver,” Guthrie said. “We found that while these newly FDA approved lipid emulsions significantly improved infant’s growth compared to older soy-based emulsions, they failed to prevent the progression of liver injury caused by bile flow obstruction. This highlights a critical limitation of current nutritional support in the most severe cases of obstructive cholestasis.”
Dr. Douglas Burrin
Ultimately, this research paves the way for new clinical interventions that could dramatically improve outcomes, preventing both liver injury and intestinal dysfunction in this vulnerable pediatric population,” said co-author Dr. Douglas Burrin, professor of pediatrics and the USDA-ARS Children’s Nutrition Research Center at Baylor.
Other contributors to this work include Caitlin Vonderohe, Valeria Meléndez Hebib and Barbara Stoll, all in the Department of Pediatrics and the USDA-ARS Children’s Nutrition Research Center at Baylor College of Medicine.
This project was supported in part by federal funds from the USDA, Agricultural Research Service under cooperative agreement no. 3092-51000-060-01, Texas Medical Center Digestive Disease Center’s Pilot Feasibility Grant DK056338 and their core facilities for Tissue Analysis and Molecular Imaging, the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants DK129408, DK13584, and DK094616) and a Research Scientist Development Award (K01) from the NIDDK.
