孕早期血清同型半胱氨酸、25-羟维生素D联合子宫动脉血流参数对子痫前期的预测价值

Predictive value of serum homocysteine and 25-hydroxy vitamin D combined with uterine artery blood flow parameters for preeclampsia during early pregnancy

目的:探讨孕早期血清同型半胱氨酸(homocysteine,Hcy)、25-羟维生素D(25-hydroxy vitamin D,25-OHD)联合子宫动脉血流参数对子痫前期(preeclampsia,PE)的预测价值。方法:本研究为前瞻性队列研究。纳入2021年11月—2023年5月于徐州医科大学附属连云港医院产前检查并分娩的2200例孕妇,于孕11~13周+6常规产前检查时检测血清Hcy、25-OHD水平,同时超声检测子宫动脉血流参数——收缩期峰值血流速度/舒张期峰值血流速度(peak systolic velocity/end diastolic velocity,S/D)、搏动指数(pulsatility index,PI)和阻力指数(resistance index,RI)。根据孕20周后是否发生PE,分为PE组(141例)和对照组(2059例)。采用两独立样本t检验和χ2检验比较2组孕妇的一般临床资料和妊娠结局、Hcy、25-OHD及子宫动脉血流参数,采用多因素Logistic回归分析PE的独立危险因素;采用受试者工作特征(receiver operating characteristic,ROC)曲线分析各项指标及联合指标对PE的预测价值;采用R软件构建PE风险列线图预测模型,校正曲线对列线图预测模型进行内部验证。结果:PE组和对照组孕妇年龄、检测孕周、生育史及PE病史等差异均无统计学意义(P>0.05)。PE组收缩压及舒张压均高于对照组,分娩孕周及新生儿体重均低于对照组(P<0.05)。PE组血清Hcy水平、S/D、PI和RI均高于对照组,25-OHD水平低于对照组(P均<0.001)。多因素Logistic回归分析显示,Hcy(OR=2.58,95%CI:2.03~3.27)、S/D(OR=1.56,95%CI:1.33~1.84)、PI(OR=2.06,95%CI:1.45~2.94)和RI(OR=2.97,95%CI:1.68~5.24)均是PE的独立危险因素,而25-OHD是独立保护因素(OR=0.80,95%CI:0.72~0.88)。ROC曲线分析显示,血清Hcy、25-OHD、S/D、PI和RI界值分别为6.65μmol/L、23.43μg/L、2.93、1.26和0.85时,预测PE的灵敏度分别为0.908、0.699、0.752、0.844和0.589,特异度分别为0.783、0.915、0.574、0.578和0.891;上述指标联合预测效能更佳,曲线下面积为0.967(95%CI:0.956~0.979),灵敏度为0.969,特异度为0.865。内部验证显示,列线图预测模型的校正曲线与原始曲线及理想曲线接近,一致性指数为0.966(95%CI:0.656~0.993),模型拟合度高。结论:基于孕早期血清Hcy、25-OHD以及子宫动脉血流参数S/D、PI、RI构建的PE风险列线图对PE具有较好的预测价值,可为临床早期筛查或预测PE提供参考。

Objective:To explore the predictive value of serum homocysteine(Hcy),25-hydroxy vitamin D(25-OHD),and uterine artery blood flow parameters for preeclampsia(PE)during early pregnancy.Methods:In this prospective cohort study,2200 pregnant women who underwent prenatal examinations and delivered at the Affiliated Lianyungang Hospital of Xuzhou Medical University between November 2021 and May 2023 were included.Serum Hcy and 25-OHD levels were measured during regular prenatal examination at 11-13+6 weeks of gestation,along with ultrasound assessment of uterine artery blood flow parameters,such as peak systolic velocity/end diastolic velocity(S/D),pulsatility index(PI),and resistance index(RI).These participants were categorized into a PE group(141 cases)and a control group(2059 cases)according to whether developed PE by the 20th week of gestation.Two independent sample student’s t-test and Chi-square test were used to compare the general clinical and pregnancy outcomes data,Hcy,25-OHD,and uterine artery blood flow parameters between the two groups.The multivariate logistic regression analysis was employed to identify independent risk factors for PE.The receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of the markers used along or in combination for PE.A PE risk nomogram was developed using R software,with calibration curves internally validating the nomogram prediction model.Results:There was no statistically significant difference in the maternal age,gestational weeks of detection,reproductive history,and PE history between the PE group and the control group(P>0.05).Both the systolic blood pressure and diastolic blood pressure in the PE group were higher than those in the control group,while both the gestational week of delivery and the neonatal weight were lower than those in the control group(P<0.05).Serum Hcy levels,S/D,PI,and RI were higher in the PE group than in the control group,whereas the levels of 25-OHD were lower in the PE group than in the control group(all P<0.001).The multivariate logistic regression analysis indicated that Hcy(OR=2.58,95%CI:2.03-3.27),S/D(OR=1.56,95%CI:1.33-1.84),PI(OR=2.06,95%CI:1.45-2.94)and RI(OR=2.97,95%CI:1.68-5.24)were independent risk factors for PE,while 25-OHD was an independent protective factor(OR=0.80,95%CI:0.72-0.88).The ROC curve analysis showed that the optimal cut-off values for predicting PE were 6.65μmol/L for Hcy,23.43μg/L for 25-OHD,2.93 for S/D,1.26 for PI,and 0.85 for RI,with the sensitivity of 0.908,0.699,0.752,0.844,and 0.589,respectively,and the specificity of 0.783,0.915,0.574,0.578,and 0.891,respectively.The performance of these markers used in combination for predicting PE was superior,with an area under the curve of 0.967(95%CI:0.956-0.979),the sensitivity of 0.969,and the specificity of 0.865.The internal validation showed that the calibration curve of the nomogram approximated both the original curve and the ideal curve,with a concordance index of 0.966(95%CI:0.656-0.993),suggesting a high model fit.Conclusion:The PE risk nomogram,constructed based on serum Hcy,25-OHD,and the uterine artery blood flow parameters of S/D,PI and RI in early pregnancy,provides a good predictive value for PE and may offer guidance for early clinical screening or prediction of PE.