Download PDF
Am J Perinatol 2019; 36(13): 1382-1386
DOI: 10.1055/s-0038-1676977
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

SMOFlipid Protects Preterm Neonates against Perinatal Nutrition–Associated Cholestasis

Yair Kasirer   *
1   Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
,
Alona Bin-Nun   *
1   Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
2   Department of Pediatrics, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
,
Ateret Raveh
1   Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
,
Irina Schorrs
1   Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
,
Francis B. Mimouni
1   Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
3   Department of Pediatrics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Cathy Hammerman
1   Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
2   Department of Pediatrics, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
› Author Affiliations Funding None.
Further Information

Publication History

04 October 2018

25 November 2018

Publication Date:
08 January 2019 (online)

    Permissions and Reprints

Abstract

Objective Intravenous lipid infusions improve both short- and long-term outcomes of premature neonates. However, prolonged infusion of lipids has been implicated in the development of parenteral nutrition-associated cholestasis (PNAC). We speculated that the multicomponent SMOFlipid would be hepatoprotective against PNAC.

Study Design This is a retrospective review comparing the incidence and severity of direct hyperbilirubinemia in preterm infants <1,500 g who were hospitalized for a minimum of 2 weeks during a 20-month period in which all preterm infants on total parenteral nutrition (TPN) received fat as Lipofundin with the following 20-month period in which all preterm infants on TPN received SMOFlipid.

Results Infants in the SMOFlipid period had a lower incidence of PNAC (6 vs. 13%; p = 0.022), lower peak direct bilirubin levels (3.2 vs. 7.1 mg/dL; p = 0.018), and a shorter length of stay (51 vs. 60 days; p = 0.019). The relative risk of developing direct hyperbilirubinemia during the Lipofundin period was 2.22 (1.1–4.3) as compared with period 1; p = 0.018; NNT-14.

Conclusion SMOFlipid was hepatoprotective in our population of preterm neonates <1,500 g receiving long-term TPN as compared with those receiving Lipofundin, despite similar levels of exposure to both intravenous lipid load and duration in the two groups.

Keywords

perinatal nutrition - cholestasis - long chain polyunsaturated fatty acids

* Contributed equally as first authors.


 

  • References

  • 1 Burrin DG, Ng K, Stoll B, Sáenz De Pipaón M. Impact of new-generation lipid emulsions on cellular mechanisms of parenteral nutrition-associated liver disease. Adv Nutr 2014; 5 (01) 82-91
    CrossrefPubMedGoogle Scholar
  • 2 Carter BA, Shulman RJ. Mechanisms of disease: update on the molecular etiology and fundamentals of parenteral nutrition associated cholestasis. Nat Clin Pract Gastroenterol Hepatol 2007; 4 (05) 277-287
    CrossrefPubMedGoogle Scholar
  • 3 Calder PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans 2017; 45 (05) 1105-1115
    CrossrefPubMedGoogle Scholar
  • 4 Zhang P, Lavoie PM, Lacaze-Masmonteil T, Rhainds M, Marc I. Omega-3 long-chain polyunsaturated fatty acids for extremely preterm infants: a systematic review. Pediatrics 2014; 134 (01) 120-134
    CrossrefPubMedGoogle Scholar
  • 5 Pichler J, Simchowitz V, Macdonald S, Hill S. Comparison of liver function with two new/mixed intravenous lipid emulsions in children with intestinal failure. Eur J Clin Nutr 2014; 68 (10) 1161-1167
    CrossrefPubMedGoogle Scholar
  • 6 Skouroliakou M, Konstantinou D, Agakidis C. , et al. Parenteral MCT/ω-3 polyunsaturated fatty acid-enriched intravenous fat emulsion is associated with cytokine and fatty acid profiles consistent with attenuated inflammatory response in preterm neonates: a randomized, double-blind clinical trial. Nutr Clin Pract 2016; 31 (02) 235-244
    CrossrefPubMedGoogle Scholar
  • 7 Martin CR. Fatty acid requirements in preterm infants and their role in health and disease. Clin Perinatol 2014; 41 (02) 363-382
    CrossrefPubMedGoogle Scholar
  • 8 Wanten GJ, Calder PC. Immune modulation by parenteral lipid emulsions. Am J Clin Nutr 2007; 85 (05) 1171-1184
    CrossrefPubMedGoogle Scholar
  • 9 Martin CR, Dasilva DA, Cluette-Brown JE. , et al. Decreased postnatal docosahexaenoic and arachidonic acid blood levels in premature infants are associated with neonatal morbidities. J Pediatr 2011; 159 (05) 743-749
    CrossrefPubMedGoogle Scholar
  • 10 Dupont IE. Peroxidation of lipid emulsions: effects of changes in fatty acid pattern and alpha-tocopherol content on the sensitivity to peroxidative damage. Clin Nutr 1999; 18 (02) 113-116
    CrossrefPubMedGoogle Scholar
  • 11 Chen WY, Lin SY, Pan HC. , et al. Beneficial effect of docosahexaenoic acid on cholestatic liver injury in rats. J Nutr Biochem 2012; 23 (03) 252-264
    CrossrefPubMedGoogle Scholar
  • 12 Diamond IR, Sterescu A, Pencharz PB, Kim JH, Wales PW. Changing the paradigm: Omegaven for the treatment of liver failure in pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr 2009; 48 (02) 209-215
    CrossrefPubMedGoogle Scholar
  • 13 Fallon EM, Le HD, Puder M. Prevention of parenteral nutrition-associated liver disease: role of omega-3 fish oil. Curr Opin Organ Transplant 2010; 15 (03) 334-340
    CrossrefPubMedGoogle Scholar
  • 14 Gura KM, Lee S, Valim C. , et al. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics 2008; 121 (03) e678-e686
    CrossrefPubMedGoogle Scholar
  • 15 Puder M, Valim C, Meisel JA. , et al. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg 2009; 250 (03) 395-402
    CrossrefPubMedGoogle Scholar
  • 16 Vlaardingerbroek H, Ng K, Stoll B. , et al. New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs. J Lipid Res 2014; 55 (03) 466-477
    CrossrefPubMedGoogle Scholar
  • 17 Repa A, Binder C, Thanhaeuser M. , et al. 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
    CrossrefPubMedGoogle Scholar
  • 18 Goulet O, Antébi H, Wolf C. , et al. A new intravenous fat emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil: a single-center, double-blind randomized study on efficacy and safety in pediatric patients receiving home parenteral nutrition. JPEN J Parenter Enteral Nutr 2010; 34 (05) 485-495
    CrossrefPubMedGoogle Scholar
  • 19 Diamond IR, Grant RC, Pencharz PB. , et al. 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 (05) 866-877
    CrossrefPubMedGoogle Scholar
  • 20 Beken S, Dilli D, Fettah ND, Kabataş EU, Zenciroğlu A, Okumuş N. The influence of fish-oil lipid emulsions on retinopathy of prematurity in very low birth weight infants: a randomized controlled trial. Early Hum Dev 2014; 90 (01) 27-31
    CrossrefPubMedGoogle Scholar
  • 21 D'Ascenzo R, Savini S, Biagetti C. , et al. Higher docosahexaenoic acid, lower arachidonic acid and reduced lipid tolerance with high doses of a lipid emulsion containing 15% fish oil: a randomized clinical trial. Clin Nutr 2014; 33 (06) 1002-1009
    CrossrefPubMedGoogle Scholar
  • 22 Vlaardingerbroek H, Vermeulen MJ, Carnielli VP, Vaz FM, van den Akker CH, van Goudoever JB. Growth and fatty acid profiles of VLBW infants receiving a multicomponent lipid emulsion from birth. J Pediatr Gastroenterol Nutr 2014; 58 (04) 417-427
    CrossrefPubMedGoogle Scholar
  • 23 Savini S, D'Ascenzo R, Biagetti C. , et al. The effect of 5 intravenous lipid emulsions on plasma phytosterols in preterm infants receiving parenteral nutrition: a randomized clinical trial. Am J Clin Nutr 2013; 98 (02) 312-318
    CrossrefPubMedGoogle Scholar
  • 24 Ng K, Stoll B, Chacko S. , et al. Vitamin E in new-generation lipid emulsions protects against parenteral nutrition-associated liver disease in parenteral nutrition-fed preterm pigs. JPEN J Parenter Enteral Nutr 2016; 40 (05) 656-671
    CrossrefPubMedGoogle Scholar
  • 25 Kapoor V, Glover R, Malviya MN. Alternative lipid emulsions versus pure soy oil based lipid emulsions for parenterally fed preterm infants. Cochrane Database Syst Rev 2015; (12) CD009172
    PubMedGoogle Scholar
  • 26 Tomsits E, Pataki M, Tölgyesi A, Fekete G, Rischak K, Szollár L. Safety and efficacy of a lipid emulsion containing a mixture of soybean oil, medium-chain triglycerides, olive oil, and fish oil: a randomised, double-blind clinical trial in premature infants requiring parenteral nutrition. J Pediatr Gastroenterol Nutr 2010; 51 (04) 514-521
    CrossrefPubMedGoogle Scholar
  • 27 Park HW, Lee NM, Kim JH, Kim KS, Kim SN. Parenteral fish oil-containing lipid emulsions may reverse parenteral nutrition-associated cholestasis in neonates: a systematic review and meta-analysis. J Nutr 2015; 145 (02) 277-283
    CrossrefPubMedGoogle Scholar
  • 28 Hojsak I, Colomb V, Braegger C. , et al; ESPGHAN Committee on Nutrition. ESPGHAN Committee on Nutrition Position Paper. Intravenous lipid emulsions and risk of hepatotoxicity in infants and children: a systematic review and meta-analysis. J Pediatr Gastroenterol Nutr 2016; 62 (05) 776-792
    CrossrefPubMedGoogle Scholar
  • 29 D'Ascenzo R, D'Egidio S, Angelini L. , et al. Parenteral nutrition of preterm infants with a lipid emulsion containing 10% fish oil: effect on plasma lipids and long-chain polyunsaturated fatty acids. J Pediatr 2011; 159 (01) 33-38
    CrossrefPubMedGoogle Scholar