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Parenteral nutrition associated cholestasis

Parenteral nutrition (PN) is life saving for many preterm infants and other neonates with severe illness, but prolonged use of PN can lead to intrahepatic cholestasis, referred to as parenteral nutrition–associated cholestasis (PNAC). It is defined as direct bilirubin greater than 2.0 mg/dL persistent for at least 2 consecutive tests duringthe administration of PN, not associated with other known causes of cholestasis [13].

With the increasing survival of preterm infants and neonates requiring intensive care, PNAC has become a more common clinical challenge. The incidence of PNAC varywidely depending on the population studied, with high incidencein populations carrying several risk factors for PNAC. It increases with duration of PN and ranges from 10% to 85% in infants [48].

A multifactorial aetiology has been proposed for the development of PNAC. Recognized risk factors for PNAC include low birth weight, low gestational age, necrotizing enterocolitis, intestinal malformations, and intestinal surgery. A further risk factor is the occurrence ofsevere infections, due to the requirement for central line for infusion of PN, and bacterial overgrowth caused by enteralstarvation and immature immune function[913].

However, exposure to PN is demonstratedas the main factor in the development of PNAC. Intravenous hyper-alimentationhas been implicated, such as thetotal caloric overload, the quality of aminoacid solutions, the cumulative amount and the quality of lipid infusion, the presence of excessivealuminium in the PN solution, and the high manganese intake with PN [1, 1417].

Ursodeoxycholic acid, cyclic PN, light protection for PN, tapering the soybean-based lipid emulsion, and antibiotics to decontaminate bacterial overgrowth are used to treat PNAC [1821].

In recent years, increasing attention has been paid to the lipid content in PN. It has been found that fish oil–containing lipid emulsions could be useful in infants to reverse PNAC for whom enteral feeding is intolerable. However, no evidence supports the use of fish oil–containing lipid emulsions to prevent PNAC in neonates, including preterm infants [22].

Enteral feeding remains the best strategy to reverse and prevent PNAC, with as little as 10% of caloric intake showing beneficial effects [5, 22].


  1. 1.

    Kubota A, Okada A, Nezu R, Kamata S, Imura K, Takagi Y: Hyperbilirubinemia in neonates associated with total parenteral nutrition. JPEN J Parenter Enteral Nutr. 1988, 12: 602-606. 10.1177/0148607188012006602.

  2. 2.

    Teitelbaum DH: Parenteral nutrition-associated cholestasis. Curr Opin Pediatr. 1997, 9: 270-275. 10.1097/00008480-199706000-00016.

  3. 3.

    McLin VA, Balistreri WF: Approach to neonatal cholestasis. Pediatric gastrointestinal disease. Edited by: Walker WA, Goulet O, Kleinman RE, Sherman PM, Shneider BL, Sanderson IR. 2004, Ontario, Canada: B. C. Decker, 2: 1079-1093. 4th ed

  4. 4.

    de Meijer VE, Gura KM, Le HD, Meisel JA, Puder M: Fish oil-based lipid emulsions prevent and reverse parenteral nutrition-associated liver disease: the Boston experience. JPEN J Parenter Enteral Nutr. 2009, 33: 541-547. 10.1177/0148607109332773.

  5. 5.

    Costa S, Maggio L, Sindico P, Cota F, De Carolis MP, Romagnoli C: Preterm small for gestational age infants are not at higher risk for parenteral nutrition-associated cholestasis. J Pediatr. 2010, 156: 575-579. 10.1016/j.jpeds.2009.10.038.

  6. 6.

    Xu ZW, Li YS: Pathogenesis and treatment of parenteral nutrition-associated liver disease. Hepatobiliary Pancreat Dis Int. 2012, 11: 586-593. 10.1016/S1499-3872(12)60229-X.

  7. 7.

    Angsten G, Finkel Y, Lucas S, Kassa AM, Paulsson M, Lilja HE: Improved outcome in neonatal short bowel syndrome using parenteral fish oil in combination with omega-6/9 lipid emulsions. JPEN J Parenter Enteral Nutr. 2012, 36: 587-955. 10.1177/0148607111430507.

  8. 8.

    Nandivada P, Carlson SJ, Chang MI, Cowan E, Gura KM, Puder M: Treatment of parenteral nutrition-associated liver disease: the role of lipid emulsions. Adv Nutr. 2013, 4: 711-717. 10.3945/an.113.004770.

  9. 9.

    Kaufman SS, Gondolesi GE, Fishbein TM: Parenteral nutrition associatedliver disease. Sem Neonatol. 2003, 8: 375-381. 10.1016/S1084-2756(03)00094-0.

  10. 10.

    Drongowski RA, Coran AG: An analysis of factors contributing to thedevelopment of total parenteral nutrition-induced cholestasis. JPEN J Parenter Enteral Nutr. 1989, 13: 586-589. 10.1177/0148607189013006586.

  11. 11.

    Kelly DA: Liver complications of pediatric parenteral nutrition-epidemiology. Nutrition. 1998, 14: 153-157. 10.1016/S0899-9007(97)00232-3.

  12. 12.

    Kaufman SS, Gondolesi GE, Fishbein TM: Parenteral nutrition associatedliver disease. Semin Neonatol. 2003, 8: 375-581. 10.1016/S1084-2756(03)00094-0. (Nota bibliografica ripetuta due volte: vedi num. 9),

  13. 13.

    Moss RL, Das JB, Raffensperger JG: Necrotizingenterocolitis andtotal parenteral nutrition-associated cholestasis. Nutrition. 1996, 12: 340-343. 10.1016/S0899-9007(96)80057-8.

  14. 14.

    Wright K, Ernst KD, Gaylord MS, Dawson JP, Burnette TM: Increasedincidence of parenteral nutrition-associated cholestasis with AminosynPF compared to Trophamine. J Perinatol. 2003, 23: 444-450. 10.1038/

  15. 15.

    Shin JI, Namgung R, Park MS, Lee C: Could lipid infusion be a risk forparenteral nutrition-associated cholestasis in low birth weight neonates?. Eur J Pediatr. 2008, 167: 197-202. 10.1007/s00431-007-0454-7.

  16. 16.

    Von Stockhausen HB, Schrod L, Bratter P, Rosick U: Aluminium loadingin premature infants during intensive care as related to clinical aspects. J Trace Elem Electrolytes Health Dis. 1990, 4: 209-213.

  17. 17.

    Fok TF, Chui KKM, Cheung R, Ng PC, Cheung KL, Hjelm M: Manganese intake and cholestatic jaundice in neonates receiving parenteralnutrition: a randomized controlled study. Acta Pediatr. 2001, 90: 1009-1015. 10.1111/j.1651-2227.2001.tb01356.x.

  18. 18.

    Chien-Yi Chen, Po-Nien Tsao, Huey-Ling Chen, Hung-Chieh Chou, Wu-Shiun Hsieh, Mei-Hwei Chang: Ursodeoxycholic acid (udca) therapy in very-low-birthweight Infants with parenteral nutrition associated Cholestasis. J Pediatr. 2004, 145: 317-321. 10.1016/j.jpeds.2004.05.038.

  19. 19.

    Thibault M, McMahon J, Faubert G, Charbonneau J, Malo J, Ferreira E, Mohamed I: Parenteral nutrition-associated liver disease: a retrospective study of ursodeoxycholic Acid use in neonates. J Pediatr Pharmacol Ther. 2014, 19: 42-48.

  20. 20.

    Miloudi K, Comte B, Rouleau T, Montoudis A, Levy E, Lavoie JC: The mode of administration of total parenteral nutrition and nature of lipid content influence the generation of peroxides and aldehydes. Clin Nutr. 2012, 31: 526-534. 10.1016/j.clnu.2011.12.012.

  21. 21.

    Carter BA, Karpen SJ: Intestinal failure-associated liver disease: management and treatment strategies past, present, and future. Semin Liver Dis. 2007, 27: 251-258. 10.1055/s-2007-985070.

  22. 22.

    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: 277-283. 10.3945/jn.114.204974.

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Correspondence to Simonetta Costa.

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Costa, S., Barone, G., Catenazzi, P. et al. Parenteral nutrition associated cholestasis. Ital J Pediatr 41, A4 (2015).

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  • Preterm Infant
  • Parenteral Nutrition
  • Cholestasis
  • Enteral Feeding
  • Ursodeoxycholic Acid