464 - Reduced Parenteral Lipid on Bilirubin Neurotoxicity in Extremely Premature Infants: A Randomized Controlled Trial

Poster Number: 464
Publication Number: 464.1120

Background: Parenteral lipids displace bilirubin from albumin, allowing passage of unbound bilirubin into the brain, and may result in unrecognized bilirubin neurotoxicity and lifelong neurodevelopmental impairment in extremely preterm infants. This risk may be influenced by phototherapy (Hegyi, 2017). Brainstem auditory evoked response (BAER) wave V latency is an early marker of bilirubin neurotoxicity.

Objective: Determine whether a reduced parenteral lipid dose reduces bilirubin neurotoxicity compared to a usual lipid dose.

Design/Methods: Randomized controlled trial with factorial design. Eligible infants were < 27 week gestation or ≤750g at birth and were enrolled in the NICHD Neonatal Research Network Cycled Phototherapy Trial of cycled versus continuous phototherapy. Infants were enrolled within 36 postnatal hours and randomized 1:1 to reduced or usual lipid dose until 14 postnatal days. The reduced lipid arm received starting soy-based lipid emulsion of 0.5 g/kg/d advanced to maximum of 1.5 g/kg/d. The usual lipid arm received 1 g/kg/d advanced to 3 g/kg/d. Unbound bilirubin and free fatty acids were measured (in duplicate with a fluorescently labelled probe with variation coefficient of 6%) daily for 6 days after achieving maximal lipid dose. BAER was performed between 36 week postmenstrual age and discharge. Primary outcome was BAER wave V latency (adjudicated independently by 2 study investigators) with test for interaction based on randomly assigned phototherapy method. Pre-specified secondary outcomes include additional BAER and bilirubin measures, growth, neonatal morbidities, and neurodevelopmental exams at 2 years. Analyses will be conducted using pre-specified Bayesian intention-to-treat framework (Holzapfel, 2023).

Results: A total of 113 infants of 121 eligible infants (93%) have enrolled over 30 months (January 2021-July 2023) with planned sample size of 120 (Figure 1). BAERs have been performed and adjudicated in 96 surviving infants. Characteristics of infants enrolled in each group are shown in Table 1. Target enrollment completion date is January 2024 with final BAER obtained in March 2024. Final analysis awaits pending BAERs, growth and morbidity measures at 36 week postmenstrual age.

Conclusion(s): This is the first randomized trial evaluating the safety of parenteral lipid dosing—a decision made daily in all neonatal intensive care units—on bilirubin neurotoxicity in extremely preterm infants. Primary outcome and pre-selected secondary outcomes by treatment group will be available for PAS presentation.