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Kinetics of phytosterol metabolism in neonates receiving parenteral nutrition.

ABSTRACT: 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.

SUBMITTER: Nghiem-Rao TH

PROVIDER: S-EPMC4546827 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Kinetics of phytosterol metabolism in neonates receiving parenteral nutrition.

Nghiem-Rao T Hang TH Tunc Ilker I Mavis Alisha M AM Cao Yumei Y Polzin Elizabeth M EM Firary Mary F MF Wang Xujing X Simpson Pippa M PM Patel Shailendra B SB

Pediatric research 20150421 2

<h4>Background</h4>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.<h4>Methods</h4>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 m ...[more]

PMID: 25897540

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Project description:Manganese, an essential metal for normal growth and development, is neurotoxic on excessive exposure. Standard trace element-supplemented neonatal parenteral nutrition (PN) has a high manganese content and bypasses normal gastrointestinal absorptive control mechanisms, which places infants at risk of manganese neurotoxicity. Magnetic resonance (MR) relaxometry demonstrating short T1 relaxation time (T1R) in the basal ganglia reflects excessive brain manganese accumulation.This study tested the hypothesis that infants with greater parenteral manganese exposure have higher brain manganese accumulation, as measured by MR imaging, than do infants with lower parenteral manganese exposure.Infants exposed to parenteral manganese were enrolled in a prospective cohort study. Infants classified as having high manganese exposure received >75% of their nutrition in the preceding 4 wk as PN. All others were classified as having low exposure. Daily parenteral and enteral manganese intakes were calculated. Whole-blood manganese was measured by high-resolution inductively coupled plasma mass spectrometry. Brain MR relaxometry was interpreted by a masked reviewer. Linear regression models, adjusted for gestational age (GA) at birth, estimated the association of relaxometry indexes with total and parenteral manganese exposures.Seventy-three infants were enrolled. High-quality MR images were available for 58 infants, 39 with high and 19 with low manganese exposure. Four infants with a high exposure had blood manganese concentrations >30 ?g/L. After controlling for GA, higher parenteral and total manganese intakes were associated with a lower T1R (P = 0.01) in the globus pallidus and putamen but were not associated with whole-blood manganese (range: 3.6-56.6 ?g/L). Elevated conjugated bilirubin magnified the association between parenteral manganese and decreasing T1R.A short T1R for GA identifies infants at risk of increased brain manganese deposition associated with PN solutions commonly used to nourish critically ill infants. These trials were registered at clinicaltrials.gov as NCT00392977 and NCT00392730.

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Kinetics of phytosterol metabolism in neonates receiving parenteral nutrition.

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Kinetics of phytosterol metabolism in neonates receiving parenteral nutrition.

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