Published online July 27, 2009
PEDIATRICS Vol. 124 No. 2 August 2009, pp. 710-716 (doi:10.1542/peds.2008-1765)

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ARTICLE

Use of Di(2-Ethylhexyl)Phthalate–Containing Infusion Systems Increases the Risk for Cholestasis

Heike von Rettberg, MD^a, Torsten Hannman, MD^b, Ulrike Subotic, MD^c, Joachim Brade, PhD^d, Thomas Schaible, MD^e, Karl Ludwig Waag, MD^a and Steffan Loff, MD^b

^a Department of Pediatric Surgery
^d Institute of Biometrics
^e Department of Pediatrics, University Hospital Mannheim, Mannheim, Germany
^b Department of Pediatric Surgery, Klinikum Stuttgart, Stuttgart, Germany
^c Department of Pediatric Surgery, Inselspital Bern, University of Bern, Bern, Switzerland

INTRODUCTION: Most polyvinylchloride infusion systems are plasticized with up to 60% of di(2-ethylhexyl)phthalate (DEHP). DEHP is easily extracted from the tubing by total parenteral nutrition (TPN) solutions and has been shown to have toxic effects on various organ systems including the liver in animals and humans. A role was postulated for DEHP in the development of hepatobiliary dysfunction in premature and newborn infants receiving parenteral nutrition, and the incidence of cholestasis was investigated after changing from polyvinylchloride infusion systems to polyvinylchloride-free infusion systems.

MATERIALS AND METHODS: Two 3-year periods from 1998 to 2004 were investigated retrospectively before and after changing from polyvinylchloride to polyvinylchloride-free infusion systems in our department. This resulted in 1 group of 30 patients treated with polyvinylchloride lines and a second group of 46 patients treated with polyvinylchloride-free lines. The 2 groups were examined for the incidence of cholestasis and other possible contributing factors. Statistics were performed by using SAS software (SAS Institute, Cary, NC).

RESULTS: After changing infusion systems, the incidence of cholestasis dropped from 50% to 13%. Using DEHP-plasticized polyvinylchloride infusion systems for TPN increased the risk for cholestasis by a factor of 5.6. The use of polyvinylchloride lines correlated strongly with the development of TPN-associated cholestasis (P = .0004).

CONCLUSIONS: Using DEHP-containing polyvinylchloride infusions systems contributes to the development of cholestasis. Therefore, the use of DEHP-free infusion systems for TPN is recommended, especially in premature and newborn infants.

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Key Words: di(2-ethylhexyl) phthalate • DEHP • parenteral nutrition • liver function • cholestasis • total parenteral nutrition associated cholestasis • TPNAC • infants

Abbreviations: TPN—total parenteral nutrition • TPNAC—total parenteral nutrition–associated cholestasis • DEHP—di(2-ethylhexyl)phthalate • PPAR—peroxisome proliferation activating receptors

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Accepted Feb 10, 2009.

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