Compassionate Use of Omegaven in Preterm Neonates with Parenteral Nutrition Associated Direct Hyperbilirubinemia

Abstract

Background: Intravenous fish-oil-based fat emulsions enriched with omega 3 fatty acids, such as Omegaven, are available through investigational new drug (IND) and emergency IND (eIND) applications to ameliorate parenteral nutrition associated liver disease (PNALD).Objective: To describe changes in conjugated, direct bilirubin in the cohort of preterm neonates before and after continuous Omegaven administration.Design/Methods: Between April 2009 and July 2011, under compassionate use protocols at St Louis University/Cardinal Glennon Children's Medical Center and George Washington University/Children's National Medical Center, preterm neonates receiving parenteral nutrition (PN) with soybean emulsions were treated with Omegaven and prospectively followed. Eligibility requirements included serum direct bilirubin levels ≥ 3 mg/dL and predicted PN duration of > 21 days. Omegaven stopping criteria were either the serum direct bilirubin level < 1 mg/dL or sufficient tolerance of enteral nutrition, prompting PN discontinuation. To assure sufficient Omegaven therapeutic exposure, only neonates receiving Omegaven for ≥ 30 days were included in the data analysis. Wilcoxon signed-rank test was used to assess serum direct bilirubin change.Results: Data of 17 very low birth weight preterm neonates were analysed: over a median of 64 days of Omegaven therapy, serum direct bilirubin level decreased significantly (6.16 mg/dl vs 4.82 mg/dl, p=0.035). Importantly, followed safety markers were unchanged during therapy. Conclusions:Modest, yet statistically significant decrease in serum direct bilirubin levels was associated with fish-oil based lipid emulsions use in our cohort of cholestatic preterm neonates.