Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Clinical Prenatal Diagnosis Center, Women's Hospital, School of Medicine, Zhejiang University, China.
Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China; The First affiliated Hospital of Dalian Medical University, Dalian, China.
Metabolism. 2019 Jun;95:77-83. doi: 10.1016/j.metabol.2019.04.004. Epub 2019 Apr 5.
Bile acids are a group of cholesterol metabolites functioning as key regulators of glucose, lipid, and energy metabolism. Their homeostatic control is essential to the physiology of the normal pregnancy. Abnormalities of bile acids regulation in pregnancy lead to intrahepatic cholestasis of pregnancy, a serious condition associated with a number of fetal and maternal morbidities. Dysregulation of glucose and lipids is also tied to perturbations in bile acid concentrations. Changes in bile acid metabolic profiles in the second and third trimesters of pregnancy have been incompletely explored. We seek to establish pregnancy-specific normative ranges for a number of bile acids in women in the second and third trimesters and explore changes in their concentrations in the period from 12 to 40 weeks gestation.
In this cross-sectional study, a total of 782 normal pregnant women were enrolled including n = 290 in the second trimester (12-28 weeks) and n = 492 in the third trimester (29-40 weeks). The concentrations of 14 bile acids were measured by liquid chromatography and mass spectrometry (LC-MS) and compared at various time points. Reference intervals of these bile acids were calculated using standard statistical techniques.
A reference interval profile of 14 bile acids from a cohort of 782 normal pregnant women was developed. Significant differences in concentration were found between the second trimester and the third trimester. Unconjugated bile acids dominate the bile acid profile in the second trimester, while conjugated bile acids, especially (taurine-conjugated) dominate in the third trimester. 28-31 weeks gestation was the notable change period of bile acid metabolism.
This study establishes pregnancy-specific reference intervals for bile acids in the second and third trimesters. As bile acid composition changes with gestational age, this study establishes a foundation for trimester-specific clinical interpretation of bile acid metabolic profiles in pregnant women.
胆汁酸是胆固醇代谢物的一组,作为调节葡萄糖、脂质和能量代谢的关键因子。它们的稳态控制对于正常妊娠的生理学至关重要。妊娠期间胆汁酸调节异常可导致妊娠肝内胆汁淤积症,这是一种与多种胎儿和母体发病率相关的严重疾病。葡萄糖和脂质的失调也与胆汁酸浓度的波动有关。妊娠中、晚期胆汁酸代谢谱的变化尚未得到充分探讨。我们旨在为妊娠中、晚期妇女建立多种胆汁酸的妊娠特异性参考范围,并探讨 12 至 40 孕周期间其浓度的变化。
在这项横断面研究中,共纳入了 782 名正常孕妇,其中 290 名处于妊娠中期(12-28 周),492 名处于妊娠晚期(29-40 周)。采用液相色谱-质谱(LC-MS)法测定了 14 种胆汁酸的浓度,并在不同时间点进行比较。采用标准统计技术计算这些胆汁酸的参考区间。
从 782 名正常孕妇的队列中建立了 14 种胆汁酸的参考区间图谱。在妊娠中期和晚期之间发现了浓度的显著差异。未结合胆汁酸在妊娠中期主导胆汁酸谱,而结合胆汁酸,特别是(牛磺酸结合)在妊娠晚期占主导地位。28-31 孕周是胆汁酸代谢的显著变化期。
本研究为妊娠中、晚期胆汁酸建立了妊娠特异性参考区间。由于胆汁酸组成随妊娠龄而变化,本研究为妊娠妇女胆汁酸代谢谱的妊娠特异性临床解读奠定了基础。