Minimization of IntraLipid Versus Omegaven (MILOve)

• Feasibility [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
  "Success" of the pilot trial will be determined by reaching the following criteria: 98.5% of subjects receive the modified lipid therapy within 12 to 24h of randomization; and/or 90% of subjects had their labs taken at the appropriate times as detailed by the study protocol.
• Clinical endpoint [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
  The proportion of subjects in each group that have a rise in conjugated bilirubin to or over 100 after randomization

• Feasibility [ Time Frame: study end ] [ Designated as safety issue: No ]
  "Success" of the pilot trial will be determined by reaching the following criteria: 98.5% of subjects receive the modified lipid therapy within 12 to 24h of randomization; and/or 90% of subjects had their labs taken at the appropriate times as detailed by the study protocol.
• Clinical endpoint [ Time Frame: during study treatment ] [ Designated as safety issue: No ]
  The proportion of subjects in each group that have a rise in conjugated bilirubin to or over 100 after randomization

• Total duration of parenteral nutrition [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
• Growth [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]

• Total duration of parenteral nutrition [ Time Frame: study end ] [ Designated as safety issue: No ]
• Growth [ Time Frame: study end ] [ Designated as safety issue: Yes ]

Prolonged use of parenteral nutrition can lead to parenteral nutrition associated liver disease (PNALD). The purpose of this study is to determine the effect of treatment with a smaller amount lipid minimization) of our standard soybean oil based intravenous lipid emulsion (Intralipid) versus a fish-oil based lipid emulsion (Omegaven) in infants with severe cholestasis.

Infants meeting eligibility will be randomized to receive either 1g/kg/day of Intralipid® 20% or 1g/kg/day Omegaven® 10%. Infants randomized to Intralipid® whose conjugated bilirubin level rises >100umol/L will be crossed over to receive 1g/kg/day Omegaven®. Monitoring includes liver function tests (AST, ALT,ALP, GGT, Conjugated Bilirubin), Fatty Acid Profile (RBC and serum fatty acids; triene/tetraene ratio), INR (coagulation profile) and cytokine measure (inflammatory markers).

• Cholestasis
• Parenteral Nutrition Associated Liver Disease (PNALD)

• Dietary Supplement: Omegaven
  Omegaven 1g/kg/day until infant receiving full enteral feeds
• Dietary Supplement: Lipid minimization

  1g/kg/day daily until infant receiving full enteral feeds

  IF conjugated bili rises above 100, crossover to Omegaven (1gram/kg/day)

• Active Comparator: Lipid minimization
  Intervention: Dietary Supplement: Lipid minimization
• Experimental: Omegaven
  Intervention: Dietary Supplement: Omegaven

Inclusion Criteria:

• infants admitted to neonatal intensive care unit
• severe cholestasis, defined as conjugated bilirubin greater than 35
• receiving at least 60% calories by IV infusion and expected to require intravenous nutrition for at least an additional 28 days
• signed consent

Exclusion Criteria:

• hepatitis (TORCH or other viral infection)
• primary liver disease as etiology of cholestasis
• clinically severe bleeding not able to be managed with routine measures
• lethal congenital abnormalities
• congenital heart disease associated with right heart dysfunction