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Intravenous lipid emulsions in pediatrics: time for a change?

For the past few decades, intravenous lipid emulsions have been accepted as a key component of parenteral nutrition in infants and children. As a calorie-dense nutrient and provider of essential fatty acids, they have been effective and have contributed substantially to the better outcomes of low birth weight and very low birth weight infants, the critically ill child, and, more recently bone marrow transplant patients. In the last decade studies have proven that lipids can be major biologic modulators, not just a good source of calories (1). The traditional lipid emulsion for children and adults are produced mainly from soy oil triglycerides. There has been little impetus to change the type of lipid emulsion administered to children because of the general belief that soy oil-based emulsions have served us well. In fact, the only major recent change in pediatric parenteral nutrition practice has been the replacement of 10% lipid emulsions by 20% emulsions (10 g vs. 20 g triglyceride per 100 mL) after it was realized that excess liposomal phospholipid in the former led to slower emulsion clearance and increased accumulation of phospholipid in plasma of low birth weight infants (2). Nevertheless, concerns have been raised about providing infants and children with soy oil-based emulsions as their sole lipid intake (3,4). Soy oil contains 50% or more of its triglyceride fatty acids as linoleic acid. This may represent a “linoleic acid overload” that may compete for and inhibit synthesis of longer chain -3 fatty acids such as eicosapentaenoic acid and docosahexanoic acid. High conversion of linoleic acid to arachidonate acid may lead to overproduction of proinflammatory cytokines; in contrast, the cytokines derived from -3 fatty acids generally are considered to be anti-inflammatory (3). Especially important to the growing infant is adequate provision of docosahexanoic acid for normal retinal and brain development (5). Thus, there has been interest in substituting triglycerides with lesser amounts of linoleic acid in intravenous lipid emulsions. One approach has been the widespread use in Europe, and likely soon in the United States, of emulsions containing 50% of their triglyceride as medium-chain triglyceride (MCT). These emulsions have been shown to be more rapidly cleared and are used in both adults and children (4,6,7) because of the ability of MCT to be more rapidly hydrolyzed by lipoprotein lipases (8). Emulsions containing MCT and long train triglyceride (LCT) at 1:1 weight ratios are well tolerated and safe in low birth weight and older children (9–12). Some reports suggest metabolic advantages of the MCTcontaining emulsions over LCT emulsions. Of interest, there are indications that using emulsions containing MCT not only are advantageous in increasing lipid utilization, but also in decreasing the severity of chronic cholestasis syndromes and other hepatotoxicities that have been linked to parenteral nutrition (13,14). Fish oil triglycerides are also now being considered for parenteral nutrition either as pure fish oil particles or incorporated into MCT/LCT emulsions, and are currently under clinical evaluation in adults and children (3,4,15). Early data suggest that these emulsions are well tolerated even in preterm infants, where they enhanced high density lipoprotein phospholipids and red cell content of eicosapentaenoic acid (15). Lipid emulsions consisting entirely of fish oil triglyceride also are available as an adjunct to intravenous nutrition therapy in Europe and elsewhere (but not the United States), although they have not been approved yet for pediatric use. Another approach to diminishing the intake of linoleic acid is by replacing soy oil with olive oil in lipid emulsions. Evaluation of this approach in preterm infants is described in the report of Göbel et al. in this issue of JPGN. The olive oil-based emulsion contained approximately 18% and 2% of total triglyceride fatty acids as linoleic acid and -linolenic acid compared with the control soy oil emulsion, which had values of approximately 50% and 7% for these fatty acids, respectively. Compared with the soy oil emulsion, the olive oil emulsion contained twice the amount of -tocopherol. There were no adverse clinical or biochemical effects associated with the infusion of the olive oil emulsion, suggesting similar safety parameters to soy oil in this high-risk group. As anticipated by the relatively high level of oleic Journal of Pediatric Gastroenterology and Nutrition 37:112–114 © August 2003 Lippincott Williams & Wilkins, Inc., Philadelphia