Each year, more than half-a-million infants are born prematurely and have immature guts that cannot absorb enough food to sustain life. In order to nourish these babies, physicians use a life-saving therapy called total parenteral nutrition in which an emulsion of fluid containing electrolytes, glucose, amino acids, vitamins, minerals and often fats is introduced into the infant’s body intravenously.
In this country, the only such lipid emulsion approved for use in infants is based on soybean oil, called Intralipid®. Unfortunately, if the babies remain on this emulsion for a long period, they develop what is called parenteral nutrition-associated liver disease (PNALD), which can be life-threatening. New emulsions are approved in Europe and may provide a healthier alternative to soybean oil for premies.
“We knew using a fish-based oil could reverse the liver disease in children, but we do not know if it can prevent it,” Dr. Douglas G. Burrin, professor of pediatrics – nutrition at Baylor College of Medicine and physiologist at the USDA/ARS Children’s Nutrition Research Center at Baylor. In a study in the Journal of Lipid Research, he and colleagues tested two new lipid emulsions in premature, newborn piglets. One group received the soybean-oil based emulsion, while the others got either an emulsion based on pure-fish oil and a third a mixture that contained soybean oil, medium chain triglycerides and olive and fish oils.
They found that the pigs on the two new emulsions – one containing pure fish oil and the other with 15 percent fish oil – were less likely to develop PNALD. The authors state in the article that: “The data provide strong support for the idea that the composition of the lipid emulsion is a significant determinant of PNALD, even when the lipid load is held constant.”
“These new emulsions have been in development for several years,” said Burrin. “They are an important source of nutrition in the form of fat for adults and babies who cannot eat by mouth. There is a large population of babies who need this for optimal growth. Only one is approved by the (U.S.) FDA (Food and Drug Administration).” The fish oil supplement called Omegaven® has limited approval for use in the U.S., but is only available for “compassionate use” on a case by case basis in infants who develop the liver disease. The blended mixture emulsion (also known as SMOFlipid®) is approved for pediatric use in Europe.
Doctors at Texas Children’s Hospital have been treating dozens of babies with liver disease using the pure fish oil emulsion (Omegaven®) for compassionate use. According to Dr. Steven Abrams, professor of pediatrics-nutrition and neonatal expert at Texas Children’s Hospital, “Our results have been excellent with most of the babies doing very well and having an almost complete recovery of their liver disease”.
The new emulsions are caught in a catch-22 situation in this country. Many physicians do not feel they can be approved without a “gold standard” randomized controlled trial that compares the newer forms against the approved version. Others physicians, however, feel that a randomized trial (in which neither the physician nor the patients knows who is getting which emulsion) would be unethical because the new emulsions have been so effective in compassionate use, after children have developed liver disease.
Burrin’s team was awarded a new NIH grant recently to investigate how the newer emulsions prevent liver disease using their premie piglet model.
Others who took part in this research include: Kenneth Ng, Barbara Stoll, Nancy Benight and Shaji Chacko, all of the USDA/ARS Children’s Nutrition Research Center at Baylor as well as the department of pediatrics at Baylor; Deborah Schady and Milton L. Finegold of the Baylor department of pathology; Oluyinka Olutoye of the department of pediatric surgery at Baylor; Hester Vlaardingerbroek and Johannes B. van Goudoever of Sophia Chidlren’s Hospital in Rotterdam, The Netherlands; Leo A.J. Kluijtmans of Radboud University Nijmegen Medical Centre in The Netherlands; Wim Kulik of the University of Amsterdam in The Netherlands; and E. James Squires of the University of Guelph in Guelph, Ontario.
Funding for this came from the U.S. Department of Agriculture, Agricultural Research Service (Cooperative Agreement Number 58-6250-6-001), the American Society for Parenteral and Enteral Nutrition, the Texas Medical Center Digestive Diseases Center (NIH Grant P30 DK-56338), Ter Meulen Fund of the Royal Netherlands Academy of Arts and Sciences, a grant from the Young Investigator Exchange Program of the International Pediatric Research Foundation, and a research fellowship grant of the Sophia Kinderziekenhuis Fonds, Rotterdam, The Netherlands and the American Liver Foundation.