Kinetics of phytosterol metabolism in neonates receiving parenteral 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 and 0.8 d, 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 wk 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 d of SO lipid (AUC5) than infants born ≥ 28 wk 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.

Risks and benefits of prophylactic cyclic parenteral nutrition in surgical neonates.

BACKGROUND: Cyclic parenteral nutrition (PN) is used for both the treatment and prevention of parenteral nutrition-associated liver disease (PNALD). Early initiation of prophylactic cyclic PN may not be well tolerated in young neonates. Our objective was to test the hypothesis that prophylactic cyclic PN initiated prior to the onset of hyperbilirubinemia is associated with younger age at initiation, lower bilirubin levels, and similar rates of adverse events compared to therapeutic cyclic PN initiated after established cholestasis in surgical neonates. METHODS: A retrospective review of infants with gastrointestinal disorders requiring surgical intervention who received cyclic PN 2006-2011 was performed. RESULTS: Of the 43 infants eligible for analysis, 23 received prophylactic and 20 received therapeutic cyclic PN. Infants in both groups were comparable in demographics, surgical diagnoses, and illness severity. At initiation of cyclic PN, infants with prophylactic cyclic PN were significantly younger in chronologic (P = .003) and postmenstrual age (P = .029). Prophylactic cyclic PN was associated with a significantly lower incidence of hyperbilirubinemia (P = .001), lower maximum conjugated bilirubin (P < .0001), and lower last checked conjugated bilirubin (P = .032) compared to the therapeutic cyclic PN. The incidence of hypoglycemia, hyperglycemia, and hypertriglyceridemia was similar for the 2 groups. CONCLUSIONS: There may be a potential benefit to initiating cyclic PN prior to the development of hyperbilirubinemia in surgical neonates. Early initiation of prophylactic cyclic PN does not appear to increase the risk for adverse events.