Plasma Fatty Acids in Premature Infants With Hyperbilirubinemia

Abstract

Infants who are dependent on parenteral nutrition (PN) sometimes develop PN-associated cholestasis (PNAC). A compassionate use protocol, approved by the U.S. Food and Drug Administration and the institutional review board, guided enrollment of hospitalized infants with PNAC (<1 year of age, PN dependence for >3 weeks). Plasma concentrations of essential fatty acids were monitored before and after a soybean-based PN lipid, infused at 3 g/kg body weight/d, was replaced by an experimental fish oil-based intravenous fat emulsion (FO-IVFE) at 1.0 g/kg/d. All participants were born premature (n = 10; 20% male). At enrollment, infants were (mean ± SD) 86.5 ± 53.5 days of life and weighed 2.24 ± 0.87 kg; direct bilirubin was 5.5 ± 1.3 mg/dL. After treatment, blood concentrations significantly increased from baseline (P < .017) for circulating eicosapentaenoic acid (6.3 ± 3.0 to 147.8 ± 53.1 µg/mL), docosahexaenoic acid (20.7 ± 6.5 to 163.7 ± 43.4 µg/mL), pristanic acid (0.01 ± 0.01 to 0.17 ± 0.03 µg/mL), and phytanic acid (0.06 ± 0.03 to 0.64 ± 0.15 µg/mL). In contrast, total plasma ω-6 fatty acids (including linoleic acid) decreased (P < .017). The triene/tetraene ratio remained below the threshold value of 0.2 that defines ω-6 deficiency. No adverse effects were observed attributable to FO-IVFE. Discontinuation of FO-IVFE was typically due to infants (body weight 3.76 ± 1.68 kg) transitioning to enteral feeding rather than for resolution of hyperbilirubinemia (direct bilirubin 7.9 ± 4.8 mg/dL). These exploratory results suggest that FO-IVFE raises circulating ω-3 fatty acids in premature infants without development of ω-6 deficiency in the 8.3 ± 5.8-week time frame of this study.