Parenteral Nutrition–Associated Cholestasis in Neonates: Multivariate Analysis of the Potential Protective Effect of Taurine

Abstract

Background: Neonates receiving parenteral nutrition (PN) are at risk for PN-associated cholestasis (PNAC); however, no preventive factors for PNAC have been clearly identified. Despite reports suggesting that taurine may prevent PNAC in neonates, such an effect of taurine has not yet been definitively demonstrated. We determined whether taurine supplementation reduces the incidence of PNAC in premature or critically ill neonates. Methods: This study was part of a prospective, randomized, multi-institutional trial designed to assess cholecystokinin vs placebo as a potential preventive therapy of PNAC. Taurine supplementation of PN varied between institutions. The presence or absence of taurine in PN was analyzed by multivariate analysis, with a primary outcome measure of serum conjugated bilirubin (CB) as a measure of PNAC. Results: Taurine reduced PNAC in premature infants (estimated maximum CB [95% confidence interval] 0.50 mg/dL [–0.17 to 1.18] for those receiving taurine, vs 3.45 mg/dL [1.79–5.11] for neonates not receiving taurine, approaching significance, p = .07). Taurine significantly reduced PNAC in infants with necrotizing enterocolitis (NEC; estimated maximum CB 4.04 mg/dL [2.85–5.23], NEC infants receiving taurine, vs 8.29 mg/dL [5.61–10.96], NEC infants not receiving taurine, p < .01). There were too few neonates with surgical anomalies to evaluate the effect of taurine in this group. Conclusions: Within specific subgroups of neonatal patients, taurine supplementation does offer a very significant degree of protection against PNAC. Patients with NEC or severe prematurity are most likely to benefit substantially from taurine supplementation.

Neonates receiving parenteral nutrition (PN) are at risk for PN-associated cholestasis. Whether taurine supplementation reduces the risk of cholestasis has not been proven clinically. Multivariate analysis of 236 neonates receiving PN with or without taurine demonstrated a clear reduction in conjugated bilirubin in neonates with prematurity or necrotizing enterocolitis receiving taurine.

Get full access to this article

View all access options for this article.

References

Wilmore DW, Dudrick SJ. Growth and development of an infant receiving all nutrients exclusively by vein. JAMA. 1968 ;203:140– 144.

Kubota A, Yonekura T, Hoki M, et al. Total parenteral nutrition-associated intrahepatic cholestasis in infants: 25 years' experience. J Pediatr Surg. 2000 ;35:1049– 1051.

Ginn-Pease ME, Pantalos D, King DR. PN-associated hyperbilirubinemia: a common problem in newborn surgical patients. J Pediatr Surg. 1985;20:436– 439.

Beath SV, Davies P, Papadopoulou A, et al. Parenteral nutrition-related cholestasis in postsurgical neonates: multivariate analysis of risk factors. J Pediatr Surg. 1996 ;31:604– 606.

Meehan JJ, Georgeson KE. Prevention of liver failure in parenteral nutrition-dependent children with short bowel syndrome. J Pediatr Surg. 1997;32:473– 475.

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

Teitelbaum DH, Han-Markey T, Drongowski RA, et al. Use of cholecystokinin to prevent the development of parenteral nutrition-associated cholestasis. JPEN J Parenter Enteral Nutr. 1997 ;21:100– 103.

Kubota A, Okada A, Imura K, et al. The effect of metronidazole on PN-associated liver dysfunction in neonates. J Pediatr Surg. 1990 ;25:618– 621.

Cooper A, Betts JM, Pereira GR, Ziegler MM. Taurine deficiency in the severe hepatic dysfunction complicating total parenteral nutrition.J Pediatr Surg. 1984;19:462– 466.

10.

Sweeny DJ, Barnes S, Diasio RB. Bile acid conjugation pattern in the isolated perfused rat liver during infusion of an amino acid formulation.JPEN J Parenter Enteral Nutr. 1991 ;15:303– 306.

11.

Guertin F, Roy CC, Lepage G, et al. Effect of taurine on total parenteral nutrition-associated cholestasis. JPEN J Parenter Enteral Nutr. 1991;15:247– 251.

12.

Vinton NE, Laidlaw SA, Ament ME, Kopple JD. Taurine concentrations in plasma, blood cells, and urine of children undergoing long-term total parenteral nutrition. Pediatr Res. 1987 ;21:399– 403.

13.

Dahlstrom KA, Ament ME, Laidlaw SA, Kopple JD. Plasma amino acid concentrations in children receiving long-term parenteral nutrition. J Pediatr Gastroenterol Nutr. 1988 ;7:748– 754.

14.

Heird WC, Dell RB, Helms RA, et al. Amino acid mixture designed to maintain normal plasma amino acid patterns in infants and children requiring parenteral nutrition. Pediatrics. 1987 ;80:401– 408.

15.

Adamkin DD, Radmacher P, Rosen P. Comparison of a neonatal versus general-purpose amino acid formulation in preterm neonates. J Perinatol. 1995;15:108– 113.

16.

Cooke RJ, Whitington PF, Kelts D. Effect of taurine supplementation on hepatic function during short-term parenteral nutrition in the premature infant. J Pediatr Gastroenterol Nutr. 1984 ;3:234– 238.

17.

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

18.

Teitelbaum DH, Tracy T, Auothmany M, et al. Use of cholecystokinin-octapeptide for the prevention of parenteral nutrition-associated cholestasis. Pediatrics. 2005 ;115:1132– 1140.

19.

Bell MJ, Kosloske AM, Benton C, Martin LW. Neonatal necrotizing enterocolitis: prevention of perforation. J Pediatr Surg. 1973 ;8:601– 605.

20.

Touloukian RJ, Smith GJ. Normal intestinal length in preterm infants. J Pediatr Surg. 1983 ;18:720– 723.

21.

Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988;16:128– 140.

22.

Garland J, Henrickson K, Maki D. The 2002 Hospital Infection Control Practices Advisory Committee Centers for Disease Control and Prevention guideline for prevention of intravascular device-related infection.Pediatrics. 2002;110:1009– 1013.

23.

Escobar G, Fischer A, Li D, Kremers R, Armstrong M. Score for neonatal acute physiology: validation in three Kaiser Permanente neonatal intensive care units. Pediatrics. 1995 ;96:918– 922.

24.

Brown MR, Thunberg BJ, Golub L, Maniscalco WM, Cox C, Shapiro DL. Decreased cholestasis with enteral instead of intravenous protein in the very low-birth-weight infant. J Pediatr Gastroenterol Nutr. 1989 ;9:21– 27.

25.

Gaull G, Sturman JA, Raiha NCR. Development of mammalian sulfur metabolism: absence of cystathionase in human fetal tissues. Pediatr Res. 1972;6:538 .

26.

Imura K, Okada A. Amino acid metabolism in pediatric patients.Nutrition. 1998;14:143– 148.

27.

Rassin DK, Gaull GE, Jarvenpaa A-L, Raiha NCR. Feeding the low-birth-weight infant, II: effects of taurine and cholesterol supplementation on amino acids and cholesterol. Pediatrics. 1983 ;71:179 .

28.

Helms RA, Storm MC, Christensen ML, Hak EB, Chesney RW. Cysteine supplementation results in normalizations of plasma taurine concentrations in children receiving home parenteral nutrition. J Pediatr. 1999 ;134:358– 361.

29.

Geggel HS, Ament ME, Heckenlively JR, Martin DA, Kopple JD. Nutritional requirement for taurine in patients receiving long-term parenteral nutrition. N Engl J Med. 1985 ;312:142– 146.

30.

Rascher K, Sevos G, Berthold G, et al. Light deprivation slows but does not prevent the loss of photoreceptors in taurine transporter knockout mice. Vision Res. 2004;44:2091– 2100.

31.

Tazuke Y, Kiristioglu I, Heidelberger KP, Eisenbraun MD, Teitelbaum DH. Hepatic P-glycoprotein changes with total parenteral nutrition administration. JPEN J Parenter Enteral Nutr. 2004 ;28:1– 7.

32.

Zelikovic I, Chesney RW, Friedman AL, Ahlfors CE. Taurine depletion in very low birth weight infants receiving prolonged total parenteral nutrition: role of renal immaturity. J Pediatr. 1990 ;116:301– 306.

33.

Redmond HP, Stapleton PP, Neary P, Bouchier-Hayes D. Immunonutrition: the role of taurine. Nutrition. 1998 ;14:599– 604.

34.

Haber LR, Vaupshas V, Vitullo BB, Seemayer TA, deBelle RC. Bile acid conjugation in organ culture of human fetal liver.Gastroenterology. 1978;74:1214– 1223.

35.

Adamkin DH, McClead RE, Desai NS, McCulloch KM, Marchildon MB. Comparison of two neonatal intravenous amino acid formulations in preterm infants: a multicenter study. J Perinatol. 1991 ;11:375– 382.