Plasma Phytosterol Half-Life and Levels Are Increased in Very Low Birth Weight Preterm Infants with Parenteral Nutrition-Associated Cholestasis

Parenteral nutrition-associated cholestasis (PNAC) has been linked to plasma accumulation of phytosterols in infants receiving vegetable-oil-based lipid emulsions (LE). To date, information on the ability of infants with PNAC to metabolize intravenous (IV) phytosterols has been very limited. We characterized plasma phytosterol half-life in very low birth weight (VLBW) preterm infants with PNAC. As part of a prospective cohort study, VLBW infants with PNAC underwent serial blood sample measurements of sitosterol (Sito), campesterol (Camp), and stigmasterol (Stigma). Infants without PNAC served as controls (CTRL, control infants). Thirty-seven PNAC infants and 14 CTRL were studied. On PN day 7 and PN day 14, PNAC infants had higher plasma phytosterol concentrations compared to those of CTRL (p < 0.05). A significant and positive correlation was found between plasma Camp, Stigma, Sito concentrations, and IV phytosterol intake from birth to PN day 7 (p = 0.001, p = 0.001, and p = 0.005, respectively). Stigma concentration was positively correlated with conjugated bilirubin on PN day 7 (p = 0.012). After stopping IV LE, half-lives of Camp, Stigma, and Sito became significantly longer in PNAC infants than in CTRL (Camp: 18.8 +/- 6.2 vs 11.8 +/- 3.0 days, p = 0.001; Stigma: 13.8 +/- 5.8 vs 9.4 +/- 3.4 days, p = 0.023; Sito: 15.3 +/- 5.0 vs 9.8 +/- 3.0 days, p = 0.002). In conclusion, phytosterols increased earlier during PN and were eliminated slowly after stopping IV LE in PNAC infants than in CTRL. The Stigma concentration on PN day 7 could represent an early marker of cholestasis. Our results provide additional evidence on the relationship between IV phytosterols and PNAC.