Kinetics of Phytosterol Metabolism in Neonates Receiving Parental Nutrition

BACKGROUND: Phytosterols in soybean oil (SO) lipids likely contribute to parenteral nutrition-associated liver disease (PNALD) in infants. No characterization of phytosterol metabolism has been done in infants receiving SO lipids. METHODS: In a prospective cohort study, 45 neonates (36 SO lipid vs 9 control) underwent serial blood sample measurements of sitosterol, campesterol, and stigmasterol. Mathematical modeling was used to determine pharmacokinetic parameters of phytosterol metabolism and phytosterol exposure. RESULTS: Compared to controls, SO lipid-exposed infants had significantly higher levels of sitosterol and campesterol (p<0.01). During SO lipid infusion, sitosterol and campesterol reached half of steady-state plasma levels within 1.5 days and 0.8 days, respectively. Steady-state level was highest for sitosterol (1.68 mg/dL), followed by campesterol (0.98 mg/dL), and lowest for stigmasterol (0.01 mg/dL). Infants born < 28 weeks gestational age had higher sitosterol steady-state levels (p=0.03) and higher area under the curve for sitosterol (p=0.03) during the first 5 days of SO lipid (AUC(5)) than infants born ≥ 28 weeks gestational age. CONCLUSION: Phytosterols in SO lipid accumulate rapidly in neonates. Very preterm infants receiving SO lipid have higher sitosterol exposure, and may have poorly developed mechanisms of eliminating phytosterols that may contribute to their vulnerability to PNALD.