Soy-based vs Soy-MCT-Olive-Fish Oil-Based Lipid Infusions: Effects on Unbound Bilirubin and Response to Phototherapy in Preterm Infants--A Pilot Study

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 Background: Bilirubin-induced neurotoxicity (BIND) is mediated by the fraction of total serum bilirubin (TSB) that is not bound to albumin ("free bilirubin", or Bf). Intravenous lipid emulsions increase unbound free fatty acids (FFAu) in the blood, which compete with bilirubin for albumin binding and increase Bf relative to TSB. Previous studies have confirmed that soy-based lipid (IL) increases Bf in preterm infants and that Bf levels are unresponsive to phototherapy at high IL doses. The effects of soy-MCT-olive-fish oil-based lipid (SMOF) on Bf and its responsiveness to phototherapy are not known.
The goals of the study were to compare Bf levels, the response of Bf to phototherapy, and FFAu profiles in very preterm infants receiving IL vs SMOF infusions. We hypothesized that Bf will 1) increase significantly in infants receiving increasing doses of IL, but not SMOF, and 2) decrease on phototherapy for those receiving SMOF, but not IL.
Preterm infants (< 1500 g, < 32 wks) were infused with IL (n=14) or SMOF (n=8) at clinician discretion, and phototherapy was prescribed using standard practice guidelines based on TSB levels. TSB, Bf, and FFAu profiles were measured while on 0, 1, 2, and 3 g/kg/day of lipid, and at the times of initiation and termination of phototherapy. TSB was analyzed in the clinical laboratory; Bf, total FFAu, and FFAu profiles were measured using novel fluorescent probes.
The IL and SMOF groups were similar in gestational age and birth weight. Increasing doses of IL, but not SMOF, resulted in increased Bf levels (p=0.008) (Table 1). TSB was not affected by either lipid. Higher doses of IL infusion led to markedly increased FFAu levels (p<0.001), while SMOF did not result in increased FFAu (p=0.054). Phototherapy was not effective for lowering Bf for infants receiving IL, but may have been effective for those receiving SMOF (p=0.15) (Table 2). Serum unbound linoleic acid was significantly higher in IL- than SMOF-treated infants (p<0.05).
The results of this pilot study suggest that SMOF displaces less bilirubin than IL, leading to lower Bf levels and better response to phototherapy. We speculate that the mechanism for this finding may be related to differences in serum FFAu profiles and albumin binding affinities. Consequently, infants receiving SMOF may be at lower risk of BIND than those receiving IL, even with similar TSB concentrations.

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Cohen Children's Medical Center, Northwell Health
Fluoresprobe Sciences
Women and Infants Hospital and AdventHealth for Children
Pediatrics, Rutgers Robert Wood Johnson Medical School
Cohen Children's Medical Center, Northwell Health

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