Unbound free fatty acids from preterm infants treated with intralipid decouples unbound from total bilirubin potentially making phototherapy ineffective.

Extremely low birth weight (ELBW; <1,000 g) infants have poor outcomes, often compromised by bilirubin neurotoxicity. We measured unbound bilirubin (Bf) and unbound free fatty acid (FFAu) levels in 5 ELBW infants in a trial examining the effects of pharmacologic ductal closure on infants treated with Intralipid infusion (3 g/kg/day). The levels for all infants (mean ± SD) were: total serum bilirubin (TSB) 4.6 ± 1.7 mg/dl, FFAu 376 ± 496 nM, and Bf 42 ± 30 nM. Of the 3 infants who died, 2 had TSB <5.9 mg/dl but FFAu >580 nM and Bf >75 nM. Multiple regression revealed a major effect on Bf levels due to FFAu, indicating that Intralipid elevated levels of FFAu and Bf. Indomethacin or ibuprofen reduced Bf levels, most likely by reducing FFAu levels through lipase inhibition. Because displacement of Bf by FFAu decouples Bf from TSB, phototherapy may not reduce the risk of bilirubin or FFAu toxicity in Intralipid-treated ELBW infants.