Pediatric Surgery| Volume 287, P1-7, July 2023

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Neonatal Intensive Care Unit Mixed Lipid Emulsion Use Associated With Reduced Cholestasis at Discharge in Surgical Patients

Published:February 22, 2023DOI:



      Parenteral nutrition associated cholestasis (PNAC) is a common morbidity in neonates requiring total parenteral nutrition (TPN). Previous studies in infants with intestinal failure have shown a benefit of mixed lipid emulsion (MLE) in reducing PNAC. It is not known whether this benefit extends to a general neonatal intensive care unit (NICU) population, where MLE is used on a selective basis. The objective of this study is to examine associations between MLE use and PNAC rate in the general NICU setting.


      This is a retrospective review of NICU patients who received TPN for 7 or more days. We compared patients born between 1/1/2014 and 12/31/2015 (pre-MLE) to patients born between 7/1/2017 and 12/31/2018 (post-MLE). Fisher's exact test and two-sample t-test were used to compare the two groups.


      There were 353 patients in 2014-2015 and 271 patients in 2017-2018. Demographics were similar between the two groups, but there were more patients with congenital heart disease in the MLE era (P < 0.001). Mortality was similar (6.2% pre-MLE versus 6.3% post-MLE). There was no significant difference in PNAC rate between the pre-MLE (11.5%) and post-MLE (14.1%) patient cohorts (P = 0.342). Among patients receiving MLE (n = 38), 58% developed PNAC, while only 6.4% of the post-MLE cohort not receiving MLE developed PNAC. Of the patients coded with a surgical diagnosis, there was no significant difference in PNAC rates between pre-MLE and post-MLE groups. Discharge rates of PNAC did differ between pre-MLE surgical patients (13.0%) and post-MLE surgical patients (8.2%). In the subgroup of post-MLE surgical patients, PNAC rate differed significantly between those receiving MLE (43.5%) and not receiving MLE (15.4%). However, this difference was resolved by discharge (8.7% versus 7.7%).


      There were no significant differences in PNAC rates between the pre-MLE and post-MLE cohorts. However, in surgical patients, MLE was associated with reduced PNAC at discharge, with levels equivalent to those seen in neonates receiving TPN for 7 or more days, despite having a higher starting rate of PNAC. Further studies are needed to determine whether the general NICU population may benefit from MLE or certain selective subpopulations like surgical patients.


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        • Carlson S.J.
        Parenteral Nutrition.
        in: Groh-Wargo S. Thompson M. Hovasi Cox J. ADA Pocket Guide to Neonatal Nutrition. American Dietetic Association, Chicago, IL2009: 29-63
        • Wales P.W.
        • Allen N.
        • Worthington P.
        ASPEN clinical guidelines: support of pediatric patients with intestinal failure at risk of parenteral nutrition-associated liver disease.
        JPEN J Parenter Enteral Nutr. 2014; 38: 538-557
        • Orso G.
        • Mandato C.
        • Veropalumbo C.
        Pediatric parenteral nutrition-associated liver disease and cholestasis: novel advances in pathomechanisms-based prevention and treatment.
        Dig Liver Dis. 2016; 48: 215-222
        • Dai Y.J.
        • Sun L.L.
        • Li M.Y.
        Comparison of formulas based on lipid emulsions of olive oil, soybean oil, or several oils for parenteral nutrition: a systematic review and meta-analysis.
        Adv Nutr. 2016; 7: 279-286
        • Kasirer Y.
        • Bin-Nun A.
        SMOFlipid protects preterm neonates against perinatal nutrition-associated cholestasis.
        Am J Perinatol. 2019; 36: 1382-1386
        • Jackson R.L.
        • White P.Z.
        • Zalla J.
        SMOFlipid vs Intralipid 20%: effect of mixed-oil vs soybean-oil emulsion on parenteral nutrition-associated cholestasis in the neonatal population.
        JPEN J Parenter Enteral Nutr. 2021; 45: 339-346
        • Diamond I.R.
        • Grant R.C.
        • Pencharz P.B.
        • de Silva N.
        Preventing the progression of intestinal failure-associated liver disease in infants using a composite lipid emulsion: a pilot randomized controlled trial of SMOFlipid.
        JPEN J Parenter Enteral Nutr. 2017; 41: 866-877
        • Hill N.S.
        • Cormack B.E.
        • Little B.S.
        • Bloomfield F.H.
        Growth and clinical outcome in very low-birth-weight infants after the introduction of a multicomponent intravenous lipid emulsion.
        JPEN J Parenter Enteral Nutr. 2020; 44: 1318-1327
        • Wang Y.L.
        • Chen L.I.
        • Tsao L.Y.
        Parenteral nutrition with fish oil-based lipid emulsion reduces the risk of cholestasis in preterm infants.
        J Int Med Res. 2021; 49
        • Glenn J.O.
        • Wischmeyer P.E.
        Enteral fish oil in critical illness: perspectives and systematic review.
        Curr Opin Clin Nutr Metab Care. 2014; 17: 116-123
        • Casson C.
        • Nguyen V.
        • Nayak P.
        • Channabasappa N.
        A comparison of Smoflipid® and Intralipid® in the early management of infants with intestinal failure.
        J Pediatr Surg. 2020; 55: 153-157
        • Hudgins D.K.
        • Holmes A.P.
        • Parman M.G.
        • Harris J.B.
        Comparison of neonatal outcomes with use of a soybean oil-based injectable lipid emulsion vs a 4-oil emulsion product.
        Am J Health Syst Pharm. 2021; 78: 210-215
        • Repa A.
        • Binder C.
        • Thanhaeuser M.
        A mixed lipid emulsion for prevention of parenteral nutrition associated cholestasis in extremely low birth weight infants: a randomized clinical trial.
        J Pediatr. 2018; 194: 87-93