Low Dose Parenteral Fat for Prevention of Parenteral Nutrition Associated Cholestasis in Preterm Neonates

In the neonatal intensive care unit, parenteral nutrition is widely used to provide protein, energy, vitamins and minerals to infants who cannot accept enteral feeds.

Intravenous fat emulsion is an important component of parenteral nutrition because of the important caloric supply that it brings, but also for the essential fatty acids (linoleic and linolenic acid) that it provides. Because intravenous fat emulsion is the only supply of essential fatty acids, at least until the enteral feeds are established, there is a minimum of fat that has to be administered with at least 0.25g/kg /day for preterm babies and 0.1g/kg/day for term infants (Lee EJ, 1993). The maximal dose of intravenous fat safe to administer is difficult to determine. Although in larger preterm infants intravenous fat is tolerated well based on measurement of serum triglycerides, there are still question regarding tolerance in extremely low birth weight infants.

Parenteral nutrition has been associated with the development of liver disease-parenteral nutrition associated liver disease (PNALD). PNALD can range from cholestasis and a transient elevation of liver enzymes to more severe forms including fibrosis, liver cirrhosis and hepatic failure. Cholestasis, defined as hyperbilirubinemia with a direct bilirubin above 2 mg/dL or more than 15% of total bilirubin, is a hepatocellular injury of the liver that manifests after the administration of parenteral nutrition for at least two weeks. The mechanism by which the liver injury occurs is unknown and probably multifactorial. Risk factors associated with the development of PNAC include: prematurity, low birth weight, absence of enteral feeds, bacterial sepsis, necrotizing enterocolitis, prolonged use of parenteral nutrition, and multiple surgical procedures on the gastro-intestinal tract. In addition, many of the nutrients contained in parenteral nutrition, have been linked with the development of cholestasis.

Specific factors associated with intravenous fat emulsions that have been related to PNAC include : phytosterols, the rate of administration of the intravenous emulsion, the total amount of fat administered and toxic metabolites of intravenous fat emulsions.

The total amount of lipids was found to be a risk factor for cholestasis in children on long-term parenteral nutrition and decreased amount of fat was recommended for the prevention of this hepatic complication (Colomb V, 2000). In the adult population parenteral lipid intake of less than 1gr/kg of body weight decreased the risk of cholestasis in parenteral nutrition treated patients (Cavicchi, 2000).