Low Dose Parenteral Fat for Prevention of Parenteral Nutrition Associated Cholestasis in Preterm Neonates
Condition: Parenteral Nutrition-Associated Liver Disease
MeSH terms: Liver Diseases; Cholestasis
Study type: Interventional

Summary: 
      The goal of the study is to determine if parenteral nutrition-associated cholestasis (PNAC)
      is related to the amount of parenteral (intravenous) fat administered to premature babies
      until full enteral nutrition is achieved.
    

Detailed description: 
      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).

      Current Nutritional Management for VLBW infants in the NBSCU:

      The administration of parenteral nutrition to all the preterm babies with a gestational age
      less than or equal to 29 weeks' is standard practice in the NBSCU for infants not receiving
      full enteral nutrition. Fat, as an integral part of the intravenous alimentation, is started
      in the first day of life at a dose of 0.5 grams/kg/day of an 20% fat emulsion(eg, Lyposyn II,
      Abbott Laboratories Chicago, IL). The amount of fat is then gradually increased by 0.5-1
      grams/kg/day to total amount of 3 grams/kg/day as tolerated. The tolerance is checked by
      measuring serum triglyceride level the morning after 3 grams/kg/day has been reached for the
      first time serum triglyceride level ≤200 mg/dl are accepted for infants ≤52 weeks
      postmenstrual age. If the serum triglyceride level is >200 mg/dL, the intravenous fat
      emulsion is reduced for 24 hours, then the triglyceride level is checked again to ensure that
      it has dropped below 200 mg/dL. The fat emulsion is then restarted at 1-1.5 grams/kg/day and
      the serum triglyceride level is monitored as it is slowly increased.

      Enteral nutrition is started initially as minimal enteral feedings, also called non-nutritive
      feedings, usually by 48±12 hours of age with about 12 ml/kg/day. The feedings are then
      advanced as tolerated with the goal to reach full enteral nutrition (>120 ml/kg/day) between
      14-21days of life. As the enteral volumes reach 1/3, 1/2, and 2/3 of the total daily fluid
      volume, the rate of administration of the lipid emulsion is decreased in steps (ie, from 2
      grams/kg/day to 1.5 to 1.0) , until the intravenous fat emulsion is stopped.

      As part of standard NBSCU management guidelines screening of liver function consists of
      measuring serum direct bilirubin level after the baby has been on TPN for 10 days to two
      weeks and then biweekly, if PN continues. In addition, if the direct bilirubin level is
      greater than 2.5mg/dL, then liver enzymes will be checked .

      Study Procedure:

      All preterm babies with a gestational age less than or equal to 29 weeks' born at YNHH who
      will receive intravenous fat emulsion as part of their nutrition management are eligible to
      participate in the study. The parents of these babies will be approached during the first 24
      hours of life, regarding the possible participation in the study. After informed consent will
      be obtained, the subjects will be randomized by YNHH Investigator pharmacy to one of the two
      groups: intervention (restricted intravenous fat intake) and control (standard intravenous
      fat intake).

      Therefore, the purpose of this study will be to determine if PNAC is related to the amount of
      parenteral fat administered to premature babies until full enteral nutrition is reached.
    

Intervention name(s): Intravenous fat emulsion; Restriction of intravenous fat emulsion to 1 gm/kg/d
Intervention type(s): Other; Other
Intervention description(s): An infusion of intravenous fat will start at 0.5 grams/kg on the first day of life, with increments of 0.5 -1.0 grams/kg every day, until a total dose of 3 grams/kg is reached.; Intravenous fat will be started at 0.5 grams/kg on the first day of life and then increase to a dose of 1gram/kg/day the next day. There will be no further increase in the amount of intravenous fat.
Intervention MeSH terms: Soybean oil, phospholipid emulsion; Fat Emulsions, Intravenous
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Parenteral nutrition associated liver disease; Direct bilirubin; Intravenous fat emulsion; Very low birth weight infants; PNAC