Parenteral Lipid Dose and Bilirubin Neurotoxicity in Extremely Preterm Infants: A Factorial Randomized Trial.

OBJECTIVE

To assess whether a lower maximum dose of soybean oil lipid emulsion reduces bilirubin neurotoxicity measured by brainstem auditory evoked response wave V latency.

STUDY

DESIGN

Single-center Bayesian randomized trial (January 2021-January 2024) in a level IV neonatal intensive care unit. Infants born at <27 weeks or ≤750 g were stratified by phototherapy regimen, randomized to 1.5 vs 3.0 g/kg/day maximum soybean oil lipid emulsion (Intralipid) doses through day 14.

RESULTS

Of 143 eligible infants, 134 were enrolled (67 lower dose, 65 higher dose). Mean [SD] daily lipid administration was 1.1 [0.3] vs 1.96 [0.58] g/kg/day. Unbound bilirubin levels were similar between groups although values ≥ 30 and ≥ 40 nM occurred more often in the higher dose group (14.5% vs 28.6% and 6.5% vs 16.1%), even at low total serum bilirubin levels (3-8 mg/dL). Adjusted wave V latency did not differ between groups (7.36 ms [0.53] vs 7.22 ms [0.57], aMD: -0.14 [95% CrI -0.34, 0.06]), with no interaction with phototherapy dose. Clinical outcomes and growth were comparable.

CONCLUSIONS

The lower maximum lipid dose did not reduce brainstem auditory evoked response wave V latency. Elevated unbound bilirubin levels occurred at the higher dose, suggesting the need for a multicenter safety trial in extremely preterm infants.

TRIAL REGISTRATION: ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04584983.