浙江地区健康孕妇中孕期和晚孕期胆汁酸谱特征及院内参考区间建立

Characteristics and reference interval of bile acid profile of healthy pregnant women in second and third trimesters of pregnancy in Zhejiang Province

目的观察健康孕妇在妊娠中晚期的胆汁酸谱变化, 并建立院内参考区间。方法选取2019年7月至2020年8月在浙江省人民医院产科进行产前检查怀有健康单胎的孕妇共298名, 分别在中孕期(T_(2))和晚孕期(T_(3))采集早晨隔夜空腹静脉血, 纳入自身对照研究组, 采用液相色谱串联质谱法检测15种胆汁酸(包括胆酸、鹅脱氧胆酸、脱氧胆酸、熊脱氧胆酸、石胆酸及其甘氨酸和牛磺酸结合型)浓度, 分析其妊娠中晚期的变化特征并确定其参考区间。15种胆汁酸和总胆汁酸浓度均为偏态分布数据, 采用第99百分位数(P_(99))表示参考区间单侧上限。根据以上数据结果建立本院健康孕妇不同孕期胆酸谱参考区间。结果健康孕妇血清甘氨胆酸、牛磺胆酸、甘氨熊脱氧胆酸和石胆酸的水平在T_(2)和T_(3)差异有统计学意义(P<0.05), 其他11种胆汁酸亚型在不同孕周间差异无统计学意义(P均>0.05)。不同孕期总胆汁酸、初级或次级胆汁酸、游离或结合型胆汁酸(包括甘氨酸结合型或牛磺酸结合型)水平均保持稳定, 且各种胆汁酸在T_(2)和T_(3)呈正相关(P<0.05)。结论健康孕妇的初级、次级或游离型、结合型胆汁酸在T_(2)和T_(3)保持稳定, 仅少数亚型胆汁酸差异有统计学意义, 且甘氨酸结合型与牛磺酸结合型胆汁酸在T3期呈弱相关(P<0.05)。本研究通过液相色谱串联质谱技术定量检测并建立本院亚型胆汁酸的健康孕妇参考区间, 为今后的相关疾病研究提供数据支持。

Objective To investigate the changes and to establish a reference interval of bile acid profile of healthy pregnant women in the second and third trimesters of pregnancy in our hospital.Methods A total of 298 healthy singleton pregnant women who underwent prenatal examination in the Department of Obstetrics of Zhejiang Provincial People′s Hospital from July 2019 to August 2020 were enrolled in this study.The overnight fasting serum samples were collected from all subjects during their second and third trimesters of pregnancy.The concentrations of 15 bile acids(cholic acid,chenodeoxycholic acid,deoxycholic acid,ursodeoxycholic acid,lithocholic acid and their glycine-and taurine-conjugated types)were analyzed by liquid chromatography tandem mass spectrometry(LC-MS/MS).The characteristics of changes were analyzed and the reference intervals were determined for the second and third trimesters.The concentrations of 15 bile acids and total bile acids were skewed-distributed,and 99 percentiles(P_(99))were used to represent the unilateral upper limit of the reference interval.Results There was significant difference in the serum levels of glycine cholic acid(GCA),taurocholic acid(TCA),glycine ursodeoxycholic acid(GUDCA)and lithocholic acid(LCA)between the second and third trimesters healthy pregnant females(P<0.05).For other 11 bile acids,there was no significant difference.The levels of total bile acids,primary or secondary bile acids,free or conjugated bile acids(glycine-bound and taurine-bound bile acids)were stable with gestation.Conclusion Primary,secondary or free,and conjugated bile acids in healthy pregnant women remained stable at T_(2) and T_(3),with significant differences in only a few subtypes of bile acids.While the correlation between glycine-bound and taurine-bound bile acids showed a weakening trend at T_(3)(P<0.05).It is necessary to establish reference intervals of bile acids for healthy pregnant women in this area.This study provided data support for future research on related diseases during pregnancy.