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Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease

Journal of Perinatology volume 27, pages 284–290 (2007)Cite this article

Abstract

Background:

Prolonged use of parenteral nutrition (PN) in neonates can lead to parenteral nutrition-associated liver disease (PNALD), manifested by elevated direct bilirubin concentrations, and in some cases progressing to hepatic failure. When new potential means of preventing PNALD in the neonatal intensive care unit (NICU), such as Omegaven usage, are tested in clinical trials, the studies should enroll neonates at a very high risk of developing PNALD. However, it is not always clear, in the first days of life, which neonates are most likely to develop PNALD. Therefore, preparatory to devising studies of prophylaxis against PNALD, we conducted an evaluation of all NICU patients who received PN for ⩾14 day, assessing their likelihood of developing PNALD.

Methods:

We performed an historic cohort analysis of all neonates in the Intermountain Healthcare system, receiving PN for 14 days or more during their stay, with dates of birth between 1 January, 2002 and 30 June, 2006.

Results:

During the 4½-year period, 9861 neonates were cared for in the Intermountain Healthcare NICUs. Of these, 9547 (96.8%) survived for at least 28 days, and of these 6543 (68.5%) received PN. Twenty-one percent (1366 patients) of those receiving PN, received it for ⩾14 days. PNALD was ascertained in this group by a direct bilirubin ⩾2.0 mg/dl. Neonates receiving PN for 14–28 days had a 14% incidence of PNALD, those receiving PN for 29–56 days had a 43% incidence, those receiving PN for 57–100 days had a 72% incidence and those receiving PN for >100 days had a 85% incidence. Groups of patients identifiable on the first day of life as having the highest risk of developing PNALD were birth weight <500 g (odds ratio (OR), 30.7), birth weight 500–749 g (OR, 13.1), gastrochisis (OR, 20.3) and jejunal atresia (OR, 24.0). Among 357 patients who developed PNALD, the highest direct bilirubin concentrations correlated with the highest serum alkaline phosphatase and transaminase concentrations. Deaths after 28 days were much more common in those with the highest direct bilirubin and transaminase concentrations (P<0.0001).

Conclusions:

In the first days of life, certain NICU patients can be identified as being at very high risk for developing PNALD. These are patients <750 g birth weight, those with gastrochisis and those with jejunal atresia. We speculate that these groups would be reasonable subjects for including in a PNALD prophylaxis trial, testing new preventative strategies such as Omegaven usage.

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Abbreviations

NICU:

neonatal intensive care unit

PN:

parenteral nutrition

PNALD:

parenteral nutrition-associated liver disease.

References

  1. Thureen PJ, Hay Jr WW . Early aggressive nutrition in preterm infants. Semin Neonatol 2001; 6: 403–415.

    Article  CAS  Google Scholar 

  2. Ziegler EE, Thureen PJ, Carlson SJ . Aggressive nutrition of the very low birthweight infant. Clin Perinatol 2002; 29: 225–244.

    Article  Google Scholar 

  3. Teitlebaum DH . Parenteral nutrition-associated cholestasis. Curr Opin Pediatr 1997; 9: 270–275.

    Article  Google Scholar 

  4. Kelly DA . Intestinal failure-associated liver disease: what do we know today? Gastroenterology 2006; 130 (2 Suppl 1): S70–S77.

    Article  CAS  Google Scholar 

  5. Heubi JE, Wiechmann DA, Creutzinger V, Setchell KD, Squires Jr R, Couser R et al. Tauroursodeoxycholic acid (TUDCA) in the prevention of total parenteral nutrition-associated liver disease. J Pediatr 2002; 141: 237–242.

    Article  CAS  Google Scholar 

  6. Teitelbaum DH, Tracy Jr TF, Aouthmany MM, Llanso A, Brown MB, Yu S et al. Use of cholecystokinin–octapeptide for the prevention of parenteral nutrition-associated cholestasis. Pediatrics 2005; 115: 1332–1340.

    Article  Google Scholar 

  7. Tietelbaum DH, Han-Markey T, Drongowski RA, Coran AG, Bayar G, Geiger JD et al. Use of cholecystokinin to prevent the development of parenteral nutrition-associated cholestasis. JPEN J Parenter Enteral Nutr 1997; 21: 100–103.

    Article  Google Scholar 

  8. Spencer AU, Yu S, Tracy TF, Aouthmany MM, Llanos A, Brown MB et al. Parenteral nutrition-associated cholestasis in neonates: multivariate analysis of the potential protective effect of taurine. JPEN J Parenter Enteral Nutr 2005; 29: 337–343.

    Article  CAS  Google Scholar 

  9. Gleghorn EE, Merritt RJ, Subramanian N, Ramos A . Phenobarbital does not prevent total parenteral nutrition-associated cholestasis in noninfected neonates. JPEN J Parenter Enteral Nutr 1986; 10: 282–283.

    Article  CAS  Google Scholar 

  10. Blaszyk K, Wild PJ, Olivera A, Kelly DG, Burgart LJ . Hepatic copper in patients receiving long-term total parenteral nutrition. J Clin Gastroenterol 2005; 39: 318–320.

    Article  Google Scholar 

  11. Yip YY, Lim AK, Tan KL . A multivariate analysis of factors predictive of parenteral nutrition-related cholestasis (TPN cholestasis) in VLBW infants. J Singapore Paediatr Soc 1990; 32: 144–148.

    CAS  PubMed  Google Scholar 

  12. Van Aerde JE, Duerksen DR, Gramlich L, Meddings JB, Chan G, Thomson AB et al. Intravenous fish oil emulsion attenuates total parenteral nutrition-induced cholestasis in newborn piglets. Pediatr Res 1999; 45: 202–208.

    Article  CAS  Google Scholar 

  13. Alwayn IP, Gura K, Nose V, Zausche B, Javid P, Garza J et al. Omega-3 fatty acid supplementation prevents hepatic steatosis in a murine model of nonalcoholic fatty liver disease. Pediatr Res 2005; 57: 445–452.

    Article  CAS  Google Scholar 

  14. Gura KM, Duggan CP, Collier SB, Jennings RW, Folkman J, Bistrian BR et al. Reversal of parenteral nutrition-associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management. Pediatrics 2006; 118: e197–e201.

    Article  Google Scholar 

  15. Gura KM, Parsons SK, Bechard LJ, Henderson T, Dorsey M et al. Use of a fish oil-based lipid emulsion to treat essential fatty acid deficiency in a soy allergic patient receiving parenteral nutrition. Clin Nutr 2005; 24: 839–847.

    Article  CAS  Google Scholar 

  16. Marcus AD . A doctor's push for drug pits him against its maker. T Wall Street J 2006; 248: 1–15.

    Google Scholar 

  17. Mullick FG, Moran CA, Ishak KG . Total parenteral nutrition: a histopathologic analysis of the liver changes in 20 children. Mod Pathol 1994; 7: 190–194.

    CAS  PubMed  Google Scholar 

  18. Zambrano E, El-Hennawy M, Ehrenkranz RA, Zelterman D, Reyes-Mugica M . Total parenteral nutrition induced liver pathology: an autopsy series of 24 newborn cases. Pediatr Dev Pathol 2004; 5: 425–432.

    Article  Google Scholar 

  19. Kobuta A, Yonekura T, Oyanagi H, Kawahara H, Yagi M et al. Total parenteral nutrition-associated intrahepatic cholestasis in infants: 25 years' experience. J Pediatr Surg 2000; 35: 1049–1051.

    Article  Google Scholar 

  20. Wales PW, de Sliva N, Kim JH, Lecce I, Sandhu A, Moore AM . Neonatal short bowel syndrome: a cohort study. J Pediatr Surg 2005; 40: 755–762.

    Article  Google Scholar 

  21. Weinberger B, Watorek K, Strauss R, Witz G, Hiatt M, Hegyi T . Association of lipid peroxidation with hepatocellular injury in preterm infants. Crit Care 2002; 6: 521–525.

    Article  Google Scholar 

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Authors and Affiliations

  1. Intermountain Healthcare, Salt Lake City, UT, USA

    R D Christensen, E Henry, S E Wiedmeier, J Burnett & D K Lambert

  2. Neonatology, McKay-Dee Hospital Center, Ogden, UT, USA

    R D Christensen & D K Lambert

  3. The Institute for Healthcare Delivery Research, Salt Lake City, UT, USA

    E Henry

  4. Neonatology, LDS Hospital, Salt Lake City, UT, USA

    S E Wiedmeier & J Burnett

  5. Primary Children's Medical Center and the University of Utah School of Medicine, Salt Lake City, UT, USA

    S E Wiedmeier

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  1. R D Christensen
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  2. E Henry
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  5. D K Lambert
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Correspondence to R D Christensen.

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Christensen, R., Henry, E., Wiedmeier, S. et al. Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease. J Perinatol 27, 284–290 (2007). https://doi.org/10.1038/sj.jp.7211686

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