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Parenteral Plant Sterols and Intestinal Failure–associated Liver Disease in Neonates

Kurvinen, Annika*; Nissinen, Markku J.; Andersson, Sture; Korhonen, Päivi§; Ruuska, Tarja§; Taimisto, Mari§; Kalliomäki, Marko||; Lehtonen, Liisa||; Sankilampi, Ulla; Arikoski, Pekka; Saarela, Timo#; Miettinen, Tatu A.**; Gylling, Helena**; Pakarinen, Mikko P.*

Journal of Pediatric Gastroenterology and Nutrition: June 2012 - Volume 54 - Issue 6 - p 803–811
doi: 10.1097/MPG.0b013e3182474118
Original Articles: Hepatology and Nutrition

Objectives: We prospectively evaluated incidence of prolonged (>28 days) parenteral nutrition (PN), associated complications, and significance of parenteral plant sterols (PS) in neonatal intestinal failure–associated liver disease (IFALD) compared with children.

Methods: We recruited 28 neonates (mean age 50 days, range 28–126) and 11 children (6.9 y, 2.1–16.6) in all of Finland. Patients underwent repeated measurements of serum cholesterol, noncholesterol sterols, including PS, cholestanol and cholesterol precursors, and liver biochemistry during and 1 month after discontinuation of PN. Healthy matched neonates (n = 10) and children (n = 22) served as controls.

Results: IFALD occurred more frequently among neonates (63%) than children (27%; P < 0.05). Ratios of serum PS, including stigmasterol, sitosterol, avenasterol, and campesterol, and total PS were increased among neonates compared with healthy controls and children on PN by 2- to 22- and 2- to 5-fold (P < 0.005), respectively. Neonates with IFALD had significantly higher ratios of serum PS and cholestanol compared with neonates without IFALD (P < 0.05). Total duration of PN associated with serum cholestanol, stigmasterol, avenasterol, alanine aminotransferase, and aspartate aminotransferase (r = 0.472–0.636, P < 0.05). Cholestanol and individual serum PS, excluding campesterol, reflected direct bilirubin (r = 0.529–0.688, P < 0.05). IFALD persisted after discontinuation of PN in 25% of neonates with 4.2- and 2.2-times higher ratios of serum stigmasterol and cholestanol compared with neonates without IFALD (P < 0.05).

Conclusions: Frequent occurrence of IFALD among neonates on PN displays an association to duration of PN and markedly increased serum PS, especially stigmasterol, in comparison to healthy neonates and children on PN. Striking accumulation of parenteral PS may contribute to IFALD among neonates.

*Section of Pediatric Surgery, Children's Hospital

Department of Medicine, Division of Gastroenterology

Childrens Hospital, University Central Hospital, University of Helsinki, Helsinki

§Department of Pediatrics, Tampere University Hospital, University of Tampere, Tampere

||Department of Pediatrics, Turku University Hospital, Turku

Department of Pediatrics, Kuopio University Hospital, University of Eastern Finland, Kuopio

#Department of Pediatrics, Oulu University Hospital, University of Oulu, Oulu

**Division of Internal Medicine, University Central Hospital, Helsinki, Finland.

Address correspondence and reprint requests to Annika Kurvinen, Section of Pediatric Surgery, Children's Hospital, University Central Hospital, University of Helsinki, Tukholmankatu 8C, PO Box 705, 00029 HUS, Helsinki, Finland (e-mail:

Received 6 October, 2011

Accepted 19 December, 2011

This work was supported by the Sigrid Juselius Foundation and the Sohlberg Foundation.

The authors report no conflicts of interest.

Copyright 2012 by ESPGHAN and NASPGHAN