Nghiem-Rao T Hang, Tunc Ilker, Mavis Alisha M, Cao Yumei, Polzin Elizabeth M, Firary Mary F, Wang Xujing, Simpson Pippa M, Patel Shailendra B
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
Bioinformatics and Systems Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Pediatr Res. 2015 Aug;78(2):181-9. doi: 10.1038/pr.2015.78. Epub 2015 Apr 21.
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.
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.
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.
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.
大豆油(SO)脂质中的植物甾醇可能导致婴儿发生肠外营养相关肝病(PNALD)。尚未对接受SO脂质的婴儿的植物甾醇代谢进行特征描述。
在一项前瞻性队列研究中,45名新生儿(36名接受SO脂质,9名作为对照)接受了系列血液样本检测,以测定其谷甾醇、菜油甾醇和豆甾醇水平。采用数学建模来确定植物甾醇代谢的药代动力学参数以及植物甾醇暴露情况。
与对照组相比,接受SO脂质的婴儿的谷甾醇和菜油甾醇水平显著更高(P < 0.01)。在输注SO脂质期间,谷甾醇和菜油甾醇分别在1.5天和0.8天内达到稳态血浆水平的一半。稳态水平以谷甾醇最高(1.68mg/dl),其次是菜油甾醇(0.98mg/dl),豆甾醇最低(0.01mg/dl)。胎龄<28周的婴儿在接受SO脂质的前5天(AUC5),其谷甾醇稳态水平更高(P = 0.03),谷甾醇曲线下面积也更大(P = 0.03),高于胎龄≥28周的婴儿。
SO脂质中的植物甾醇在新生儿体内迅速蓄积。接受SO脂质的极早产儿有更高的谷甾醇暴露,且可能存在清除植物甾醇的机制发育不完善的情况,这可能导致他们易患PNALD。