J Korean Assoc Pediatr Surg.  2015 Jun;21(1):1-6. 10.13029/jkaps.2015.21.1.1.

Associated Factors with Parenteral Nutrition Associated Cholestasis in Neonates

• Kim KE
• Lee HH
• Chung ML
• Kim WW
• Nam SH

• KMID: 1804834
• DOI: http://doi.org/10.13029/jkaps.2015.21.1.1

Abstract

PURPOSE
Long time total parenteral nutrition (TPN) can induce irreversible liver damage. In this study, we investigated the associated factors of parenteral nutrition associated cholestasis (PNAC) in neonates.
METHODS
We retrospectively reviewed 227 neonates (male:female=110:117) those who had received TPN over 2 weeks from March 2010 to February 2014. PNAC was defined as direct bilirubin was higher than 2.0 mg/dL without any cause except TPN.
RESULTS
Overall incidence was 28.6%. PNAC was frequently developed in younger gestational age with lower birth weight. Episodes of sepsis, underlying bronchopulmonary dysplasia, history of necrotizing enterocolitis, and experience of gastrointestinal surgery increase the incidence of PNAC. PNAC was directly associated the duration of TPN and long period to full enteral feeding, reaching 60 and 150 mL/kg/day. Overall mortality rate was 9.7%. It was higher in PNAC group despite PNAC was not the primary cause of death. All survivors were recovered from cholestasis with encourage of enteral nutrition.
CONCLUSION
PNAC in neonate was associated with younger gestational ages and lower birth weights, duration of TPN, or who experienced sepsis, necrotizing enterocolitis, gastrointestinal surgery or bronchopulmonary dysplasia.

Keyword

Newborn infant; Parenteral nutrition; Cholestasis

MeSH Terms

Bilirubin
Birth Weight
Bronchopulmonary Dysplasia
Cause of Death
Cholestasis*
Enteral Nutrition
Enterocolitis, Necrotizing
Gestational Age
Humans
Incidence
Infant, Newborn*
Liver
Mortality
Parenteral Nutrition*
Parenteral Nutrition, Total
Retrospective Studies
Sepsis
Survivors
Bilirubin

Reference

1. Choi JS, Bae YJ, Lee YA. Comparison of total parenteral nutrition-associated cholestasis according to amino acid mixtures in very low birth weight infants. Korean J Pediatr. 2006; 49:972–976.

2. Roquete ML. Neonatal cholestasis. J Pediatr (Rio J). 2000; 76:Suppl 1. S187–S197.

3. Hsieh MH, Pai W, Tseng HI, Yang SN, Lu CC, Chen HL. Parenteral nutrition-associated cholestasis in premature babies: risk factors and predictors. Pediatr Neonatol. 2009; 50:202–207.

4. Kelly DA. Liver complications of pediatric parenteral nutrition--epidemiology. Nutrition. 1998; 14:153–157.

5. Hofmann AF. Defective biliary secretion during total parenteral nutrition: probable mechanisms and possible solutions. J Pediatr Gastroenterol Nutr. 1995; 20:376–390.

6. Quigley EM, Marsh MN, Shaffer JL, Markin RS. Hepatobiliary complications of total parenteral nutrition. Gastroenterology. 1993; 104:286–301.

7. Robinson DT, Ehrenkranz RA. Parenteral nutrition-associated cholestasis in small for gestational age infants. J Pediatr. 2008; 152:59–62.

8. Beale EF, Nelson RM, Bucciarelli RL, Donnelly WH, Eitzman DV. Intrahepatic cholestasis associated with parenteral nutrition in premature infants. Pediatrics. 1979; 64:342–347.

9. Postuma R, Trevenen CL. Liver disease in infants receiving total parenteral nutrition. Pediatrics. 1979; 63:110–115.

10. Bernstein J, Chang CH, Brough AJ, Heidelberger KP. Conjugated hyperbilirubinemia in infancy associated with parenteral alimentation. J Pediatr. 1977; 90:361–367.

11. Dahms BB, Halpin TC Jr. Serial liver biopsies in parenteral nutrition-associated cholestasis of early infancy. Gastroenterology. 1981; 81:136–144.

12. Rodgers BM, Hollenbeck JI, Donnelly WH, Talbert JL. Intrahepatic cholestasis with parental alimentation. Am J Surg. 1976; 131:149–155.

13. Whitington PF. Cholestasis associated with total parenteral nutrition in infants. Hepatology. 1985; 5:693–696.

14. Zambrano E, El-Hennawy M, Ehrenkranz RA, Zelterman D, Reyes-Múgica M. Total parenteral nutrition induced liver pathology: an autopsy series of 24 newborn cases. Pediatr Dev Pathol. 2004; 7:425–432.

15. Moss RL, Das JB, Raffensperger JG. Total parenteral nutrition-associated cholestasis: clinical and histopathologic correlation. J Pediatr Surg. 1993; 28:1270–1274.

16. Perks P, Abad-Jorge A. Nutritional management of the infant with necrotizing enterocolitis. Pract Gastroenterol. 2008; 59:46–60.

17. Chand N, Sanyal AJ. Sepsis-induced cholestasis. Hepatology. 2007; 45:230–241.

18. Northway WH Jr, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med. 1967; 276:357–368.

19. Guglielmi FW, Boggio-Bertinet D, Federico A, Forte GB, Guglielmi A, Loguercio C, et al. Total parenteral nutrition-related gastroenterological complications. Dig Liver Dis. 2006; 38:623–642.

20. Benjamin DR. Hepatobiliary dysfunction in infants and children associated with long-term total parenteral nutrition. A clinicopathologic study. Am J Clin Pathol. 1981; 76:276–283.

21. Brown MR, Putnam TC. Cholestasis associated with central intravenous nutrition in infants. N Y State J Med. 1978; 78:27–30.

22. Merritt RJ. Cholestasis associated with total parenteral nutrition. J Pediatr Gastroenterol Nutr. 1986; 5:9–22.

23. Chen CY, Tsao PN, Chen HL, Chou HC, Hsieh WS, Chang MH. Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasis. J Pediatr. 2004; 145:317–321.

24. Spiliotis JD, Kalfarentzos F. Total parenteral nutrition--associated liver dysfunction. Nutrition. 1994; 10:255–260.

25. Stormon MO, Dorney SF, Kamath KR, O'Loughlin EV, Gaskin KJ. The changing pattern of diagnosis of infantile cholestasis. J Paediatr Child Health. 2001; 37:47–50.