Kinetics of phytosterol metabolism in neonates receiving parenteral nutrition

T Hang Nghiem-Rao, Ilker Tunc, Alisha M Mavis, Yumei Cao, Elizabeth M Polzin, Mary F Firary, Xujing Wang, Pippa M Simpson, Shailendra B Patel, T Hang Nghiem-Rao, Ilker Tunc, Alisha M Mavis, Yumei Cao, Elizabeth M Polzin, Mary F Firary, Xujing Wang, Pippa M Simpson, Shailendra B Patel

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.

Conflict of interest statement

Competing Interests: The authors declare that they have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Serial phytosterol levels in infants after the initiation (a–c) of SO lipid. Circles represent individual phytosterol levels. Black lines indicate model fit curve using the median of all individual kinetic parameters for the accumulation of (a) sitosterol, (b) campesterol, and (c) stigmasterol. Dashed lines represent model fit curve using the median of filtered individual fits.
Figure 2
Figure 2
Comparison of unadjusted area under the curve for each phytosterol during the first 5 days (AUC5) of SO lipid between gestational age groups. Gray boxes indicate very preterm group and white boxes indicate more mature group. Box = 25–75%; line inside box = median; error bars = minimum and maximum. *P = 0.03.
Figure 3
Figure 3
Serial phytosterol levels and conjugated bilirubin levels over time in four patients (a-d) who developed cholestasis (conjugated bilirubin > 2 mg/dL). Initiation of SO lipid is at Time=0. The arrow indicates time of discontinuation of SO lipid. Changes in sitosterol (– –), stigmasterol (• • • • ), and conjugated bilirubin (—) shown.

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