双绒毛膜双羊膜囊双胎妊娠子痫前期与一碳代谢的相关性研究

A Study on the Correlation between Preeclampsia and Carbon Metabolism in Dichorionic Diamniotic Twin Pregnancy

目的:探索一碳代谢中甲硫氨酸循环相关代谢物胆碱、甜菜碱、二甲基甘氨酸、甲硫氨酸和氧化三甲胺与双绒毛膜双羊膜囊(DCDA)双胎妊娠子痫前期(PE)的相关性。方法:选取2017年7月至2019年4月在北京大学第三医院建档,规律产检的双胎妊娠孕妇175例为研究对象,根据是否发生PE,分为非PE组(138例)和PE组(37例)。采集孕妇孕中期空腹时外周血,应用超高效液相色谱——三重四极杆串联质谱(UHPLC-QqQ MS)进行代谢物定量分析。比较PE组与非PE组的基本特征和血浆代谢物浓度的差异。采用Poisson回归分析血浆代谢物相关的PE相对危险度(RR)并用受试者工作特征(ROC)曲线下面积(AUC)评价PE模型预测的准确性。结果:①与非PE组比较,PE组高龄孕妇比率较高,甜菜碱浓度较低,胆碱浓度较高,差异均有统计学意义(P<0.05)。②Poisson回归分析示,在校正全部混杂因素的模型中,孕妇胆碱水平与PE风险均呈正相关(RR>1,P<0.05),随胆碱水平的增加,PE发生风险呈上升趋势(P trend<0.05);甜菜碱水平与PE风险呈负相关(RR<1,P<0.05),随甜菜碱水平增加,PE发生风险呈下降趋势(P trend<0.05)。血浆二甲基甘氨酸、甲硫氨酸和氧化三甲胺水平与PE发生风险无相关性。③Poisson回归分析示,血浆甜菜碱/胆碱比值最高时,PE发生的相对风险最低(RR 0.32,95%CI 0.14~0.75)。二甲基甘氨酸/甜菜碱比值在第三分位时,孕妇发生PE的风险升高(RR 2.53,95%CI 1.01~6.32)。④PE预测方面,联合一般危险因素和甲硫氨酸代谢物的AUC为0.80。结论:孕中期母体胆碱和甜菜碱水平与DCDA双胎妊娠PE的发生有关,为早期预测及干预PE提供了新思路,但仍需扩大样本量进一步验证并探索机制。

Objective:To explore the correlation between choline,betaine,dimethylglycine,methionine and trimethylamine oxide,metabolites related to the methionine cycle in carbon metabolism,and preeclampsia(PE)in dichorionic diamniotic(DCDA)twin pregnancy.Methods:175 pregnant women with twin pregnancies who underwent regular prenatal examinations were registered in Peking University Third Hospital from July 2017 to April 2019 were included as the study subjects.According to whether PE had occurred,they were divided into non-PE group(138 cases)and PE group(37 cases).The fasting peripheral blood of pregnant women during the second trimester of pregnancy was collected,and the metabolites were quantitatively analyzed by ultra-high performance liquid chromatogrey-triple quadrupole tandem mass spectrometry(UHPLC-QqQ MS).The basic characteristics and plasma metabolite concentrations were compared between PE group and non-PE group.Poisson regression was used for plasma metabolite-related PE relative risk(RR)analysis,and receiver operating characteristic(ROC)curve was used to evaluate the accuracy of PE model prediction.Results:①Compared with the non-PE group,the rate of elderly pregnant women was higher,the concentration of betaine was lower,and the concentration of choline was higher in PE group.The differences were statistically significant(P<0.05).②Poisson regression analysis showed that in the model adjusted for all confounding factors,there was a positive correlation between maternal choline levels and PE risk(RR>1,P<0.05).The risk of PE occurrence increased as the increase of choline levels(P trend<0.05).Betaine levels were negatively associated with PE risk(RR<1,P<0.05).The risk of PE occurrence decreased as the increase of betaine level(P trend<0.05).There was no correlation between plasma levels of dimethylglycine,methionine and trimethylamine oxide and the risk of PE.③Poisson regression analysis showed that the relative risk of PE was lowest when the plasma betaine/choline ratio was highest(RR 0.32,95%CI 0.14-0.75).When the dimethylglycine/betaine ratio was in the thirdpercentile,the risk of PE was increased in pregnant women(RR 2.53,95%CI 1.01-6.32).④In terms of PE prediction,the AUC combined with general risk factors and methionine metabolites was 0.80.Conclusions:Maternal choline and betaine levels in the second trimester are related to the occurrence of PE in DCDA twin pregnancy,and provide a new idea for early prediction and intervention of PE.It is still necessary to expand the sample size to further verify and explore the mechanism.