双胎妊娠孕妇血浆甲基供体及相关代谢物水平与胎儿生长的关系研究  

Association between maternal plasma one-carbon biomarkers during pregnancy and fetal growth in twin pregnancies

作　　者：宫晓丽 杜雨峰 赵扬玉[1] 吴天晨 石慧峰 王晓莉[3] 魏瑗[1] Gong Xiaoli;Du Yufeng;Zhao Yangyu;Wu Tianchen;Shi Huifeng;Wang Xiaoli;Wei Yuan(Department of Obstetrics and Gynecology,National Clinical Research Center for Obstetrics and Gynecology,National center for Healthcare Quality Management in Obstetrics,Peking University Third Hospital,Beijing 100191,China;Department of Epidemiology and Statistics,School of Public Health,Lanzhou University,Lanzhou 730000,China;Department of Maternal and Child Health,School of Public Health,Peking University,Beijing 100191,China)

机构地区：[1]北京大学第三医院妇产科、国家妇产疾病临床医学研究中心、国家产科专业医疗质量控制中心,北京100191 [2]兰州大学公共卫生学院流行病与卫生统计学研究所,兰州730000 [3]北京大学公共卫生学院妇幼卫生学系,北京100191

出　　处：《中华妇产科杂志》2023年第10期774-782,共9页Chinese Journal of Obstetrics and Gynecology

基　　金：国家重点研发计划(2016YFC1000400);兰州大学中央高校基本科研业务费专项资金(lzujbky-2020-8)。

摘　　要：目的研究双胎妊娠孕妇血浆甲基供体及相关代谢物(胆碱、甜菜碱、蛋氨酸、二甲基甘氨酸和同型半胱氨酸)的水平与胎儿生长的关系。方法采用以医院为基础的队列研究,收集2017年3月至2018年1月间在北京大学第三医院就诊的双胎妊娠孕妇92例及其胎儿的临床资料,采集双胎妊娠孕妇的空腹血(采血孕周中位数为18.9周),使用高效液相色谱联合质谱仪对血浆中的甲基供体及相关代谢物水平进行定量分析。使用广义估计模型分析孕妇血浆甲基供体及相关代谢物水平与双胎新生儿结局之间的关系,使用广义可加混合效应模型分析孕妇血浆甲基供体及相关代谢物水平与胎儿生长超声指标之间的关系。结果(1)一般临床资料:92例双胎妊娠孕妇中,66例(72%)为双绒毛膜双羊膜囊(双绒双羊)双胎妊娠,26例(28%)为单绒毛膜双羊膜囊(单绒双羊)双胎妊娠。5种血浆甲基供体及相关代谢物水平在各基本特征分层的双胎妊娠孕妇中的比较显示,≥35岁孕妇的血浆胆碱和甜菜碱水平均较高,与<35岁的孕妇比较,差异均有统计学意义(P均<0.05)。(2)双胎妊娠孕妇血浆甲基供体及相关代谢物水平与新生儿生长指标的相关性:校正混杂因素后,双胎妊娠孕妇血浆同型半胱氨酸水平与新生儿出生体重呈显著负相关(β=-47.9,95%CI为-94.3~-1.6;P=0.043);蛋氨酸水平升高与小于胎龄儿(SGA;OR=0.5,95%CI为0.3~0.9;P=0.021)以及低出生体重儿(OR=0.6,95%CI为0.4~0.9;P=0.020)的风险降低显著相关;同型半胱氨酸水平升高与SGA(OR=1.5,95%CI为1.0~2.2;P=0.029)和双胎儿生长不一致(OR=1.9,95%CI为1.0~3.7;P=0.049)的风险增加显著相关。(3)双胎妊娠孕妇血浆甲基供体及相关代谢物水平与双胎儿宫内生长相关指标的相关性:双胎妊娠孕妇血浆胆碱水平每增加1个标准差,妊娠中期胎儿的头围、腹围、股骨长和估测胎儿体重分别增加1.9 mm、2.6 mm、0.5 mm和20.1 g;�Objective To characterize the relationship between the levels of plasma methyl donor and related metabolites(including choline,betaine,methionine,dimethylglycine and homocysteine)and fetal growth in twin pregnancies.Methods A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018.Fasting blood was collected from the pregnant women with twin pregnancies(median gestational age:18.9 weeks).The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry.The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins,and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators.Results(1)General clinical data:of the 92 women with twin pregnancies,66 cases(72%)were dichorionic diamniotic(DCDA)twin pregnancies,and 26 cases(28%)were monochorionic diamniotic(MCDA)twin pregnancies.The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women≥35 years old were higher than those in pregnant women<35 years old,and the differences were statistically significant(all P<0.05).(2)Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators:after adjusting for confounding factors,plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight(β=-47.9,95%CI:-94.3--1.6;P=0.043).Elevated methionine level was significantly associated with decreased risks of small for gestational age infants(SGA;OR=0.5,95%

关 键 词：妊娠 双胎 胎儿发育 DNA甲基化 胆碱 高半胱氨酸 甲硫氨酸 队列研究 

分 类 号：R714.2[医药卫生—妇产科学]