Safety and Efficacy of a Composite Lipid Emulsion with Fish Oil in Hospitalized Neonates and Infants Requiring Prolonged Parenteral Nutrition - A Randomized, Double-Blind, Multicenter, Controlled Trial

Steven A Abrams; Kimberly D Ernst; Joern-Hendrik Weitkamp; Maria Mascarenhas; Ann Anderson-Berry; Jeffrey Rudolph; Con Y Ling; Daniel T Robinson; Darla Shores; Amy B Hair; Joanne Lai; Brian Lane; Katherine R McCallie; Orly Levit; Jae H Kim

doi:10.1016/j.tjnut.2024.10.005

Safety and Efficacy of a Composite Lipid Emulsion with Fish Oil in Hospitalized Neonates and Infants Requiring Prolonged Parenteral Nutrition - A Randomized, Double-Blind, Multicenter, Controlled Trial

J Nutr. 2024 Oct 5:S0022-3166(24)01072-1. doi: 10.1016/j.tjnut.2024.10.005. Online ahead of print.

Authors

Steven A Abrams¹, Kimberly D Ernst², Joern-Hendrik Weitkamp³, Maria Mascarenhas⁴, Ann Anderson-Berry⁵, Jeffrey Rudolph⁶, Con Y Ling⁷, Daniel T Robinson⁸, Darla Shores⁹, Amy B Hair¹⁰, Joanne Lai¹¹, Brian Lane¹², Katherine R McCallie¹³, Orly Levit¹⁴, Jae H Kim¹⁵

Affiliations

¹ Department of Pediatrics, Dell Medical School at the University of Texas-Austin, Austin, TX, USA. Electronic address: sabrams@austin.utexas.edu.
² Division of Neonatal-Perinatal Medicine, The University of Oklahoma Children's Hospital, Oklahoma City, USA.
³ Department of Pediatrics, Mildred Stahlman Divison of Neonatology, Vanderbilt University Medical Center, Monroe Carrol Jr. Children's Hospital, Nashville, TN, USA.
⁴ Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, and Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA.
⁵ Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.
⁶ Department of Pediatrics, Division of Gastroenterology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
⁷ Department of Pediatrics, University of Utah, Salt Lake City, UT, USA; Division of Neonatology at Primary Children's Hospital, Salt Lake City, UT, USA.
⁸ Department of Pediatrics, Northwestern University Feinberg School of Medicine; Division of Neonatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
⁹ Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹⁰ Department of Pediatrics, Division of Neonatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
¹¹ Department of Pediatric Gastroenterology, Susan and Leonard Feinstein Ibd Clinical Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹² Division of Neonatology, Departments of Pediatrics, University of California, San Diego and Rady Children's Hospital San Diego, San Diego, CA, USA.
¹³ Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University, Palo Alto, CA, USA.
¹⁴ Neonatal-Perinatal Medicine, General Neonatology, Yale New Haven Children's Hospital, New Haven, CT, USA.
¹⁵ Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

PMID: 39374788
DOI: 10.1016/j.tjnut.2024.10.005

Abstract

Background: Intravenous lipids are critical to the care of extremely premature and other high-risk infants.

Objective: The study evaluated safety and efficacy of parenteral nutrition (PN) with composite intravenous lipid emulsion (CO-ILE) with fish oil compared to pure soybean oil lipid emulsion (SOLE).

Methods: Randomized, controlled, double-blind, multicenter study (NCT02579265) in neonates/ infants anticipated to require ≥28 days of PN due to gastrointestinal malformations or injury. Duration of the initial and extended treatment phase was 28 days and 84 days (for patients with PN indication after day 28).

Results: 83/ 78 patients (mean postnatal age: 11.4/ 8.3 days, 54/ 59 preterm) received CO-ILE and SOLE, respectively. 33 patients per group completed 28 days on treatment. Risk of having conjugated bilirubin values > 2 mg/dL confirmed by a second sample 7 days after the first during the initial treatment phase (primary outcome) was 2.4% (2 of 83) with CO-ILE and 3.8% (3 of 78) with SOLE (risk ratio 0.59 [95% CI: 0.09, 3.76]). Between days 29 and 84, the number of patients with confirmed conjugated bilirubin values > 2 mg/dL did not increase in the CO-ILE group (n=2) and increased in the SOLE group (n=9). At the end of the initial treatment phase, conjugated bilirubin concentrations were 45.6% lower under CO-ILE than under SOLE (p=0.006). There was no clinical or laboratory evidence of essential fatty acid deficiency in patients in the CO-ILE group. Median time to discharge alive was 56.7 and 66.4 days with CO-ILE and SOLE, respectively (hazard ratio: 1.16; 95% CI: 0.81, 1.68).

Conclusions: CO-ILE was associated with a possible lower risk of cholestasis and significantly lower conjugated bilirubin at the end of the initial treatment phase in high-risk neonates and infants as compared to patients treated with SOLE. In summary, these data indicate that CO-ILE can be considered safe and may be preferable over SOLE in high-risk neonates.

Clinical trial registry number: Clinicaltrials.gov, study ID NCT02579265.

Keywords: cholestasis; fish oil; infants; lipids; neonates; parenteral nutrition.

Associated data

ClinicalTrials.gov/NCT02579265