胎盘血流动力学特征联合母体血清学指标预测胎儿生长受限及子痫前期的应用研究

Application study of placental hemodynamic characteristics combined with maternal serum biomarkers in predicting fetal growth restriction and preeclampsia

摘要:

目的应用三维超声评估胎盘体积及胎盘血流参数变化，结合早孕期母体血清学指标，评估预测胎儿生长受限(fetal growth restriction, FGR)及子痫前期(preeclampsia, PE)的临床应用价值。 方法前瞻性搜集临床资料完整、符合纳排标准的孕妇264例，分为子痫前期和胎儿生长受限的病例组(FGR亚组、PE亚组、PE+FGR亚组)以及正常对照组。于妊娠11~13周+6进行超声检查，应用三维容积模式慢速扫描整个胎盘，获得胎盘容积(placenta volume, PV)、血管指数(vascular index, VI)、血流指数(blood flow index, FI)及血管血流指数(vascular blood flow index, VFI)。同时检测孕妇血清胎盘生长因子(placental growth factor, PIGF)、妊娠相关血浆蛋白-A(pregnancy associated plasma protein-A, PAPP-A)和游离雌三醇(unconjugated estriol, uE3)含量。采用受试者工作特征(receiver operating characteristics, ROC)曲线，计算ROC曲线下面积(AUC)以评价上述超声和血清学指标对PE和FGR的预测价值。 结果264例孕妇中，病例组孕妇血清PIGF和PAPP-A的含量低于对照组，差异具有统计学意义(P＜0.05)。FGR亚组孕妇血清PIGF和PAPP-A的含量低于对照组(P＜0.05)，但PE亚组与正常对照组、PE亚组与FGR亚组的孕妇血清含量差异无统计学意义(P＞0.05)。病例组、FGR亚组的PV、VI、VFI低于正常对照组，PE亚组的PV、VFI低于正常对照组(P＜0.05)。多因素二元Logistic回归分析显示，PV(OR=0.959，95%CI: 0.936~0.982)、VFI(OR=0.691，95%CI: 0.489~0.976)、PAPP-A(OR=0.995,95%CI: 0.993~0.998)、PIGF(OR=0.798,95%CI: 0.702~0.908)是FGR的独立危险因素；ROC曲线分析显示，PV、VFI与PAPP-A、PIGF联合对FGR具有较好的预测价值，AUC为0.875，灵敏度为81.6%，特异度为78.3%。 结论早孕期胎盘血流参数PV、VFI和血清学指标PAPP-A、PIGF是FGR的独立危险因素；上述指标联合应用对FGR具有较好的预测价值。

Abstract:

ObjectiveTo evaluate the clinical value of combining three-dimensional ultrasound assessment of placental volume and hemodynamic parameters with first trimester maternal serum biomarkers in predicting fetal growth restriction(FGR) and preeclampsia(PE) at early pregnancy. MethodsA total of 264 pregnant women with complete clinical data and meeting the inclusion and exclusion criteria were prospectively collected, and they were divided into the case groups of preeclampsia and fetal growth restriction(FGR subgroup, PE subgroup, PE+FGR subgroup), and the normal control group. Ultrasound examination was performed at 11-13+6 weeks of gestation, adjusting the area of interest to the entire placenta and scanning the whole placenta slowly to obtain placenta volume(PV), vascular index(VI), blood flow index(FI) and vascular blood flow index(VFI). Meanwhile, the serum placental growth factor(PIGF), pregnancy associated plasma protein-A(PAPP-A) and unconjugated estriol(uE3) in the pregnant women were detected. The receiver operating characteristics(ROC) curve was used to evaluate the predictive value of the ultrasound parameters and maternal serum biomarkers by calculating the area under the curve(AUC). ResultsOf the 264 pregnancy women, the PIGF and PAPP-A in the case group and in the FGR subgroup were all lower than those in the control group, the difference was statistically significant(all P＜0.05), but there was no significant differences in those indices between PE subgroup and the control group and between the PE and FGR subgroup(all P>0.05). And the PV, VI, VFI were lower in case group and FGR subgroup, the PV, VFI were lower in PE subgroup than those in the control group(all P＜0.05). Multivariate binary Logistic regression analysis revealed that PV(OR=0.959, 95%CI: 0.936-0.982), VFI(OR=0.691, 95%CI: 0.489-0.976), PAPP-A(OR=0.995, 95%CI: 0.993-0.998), PIGF(OR=0.798, 95%CI: 0.702-0.908) were independent risk factors for FGR. The ROC curve analysis showed that the combination of PV, VFI with PAPP-A and PIGF had better predictive value for FGR, with an AUC of 0.875, a sensitivity of 81.6%, and a specificity of 78.3%. ConclusionAt the first trimester, placental hemodynamic parameters PV, VFI and maternal serum biomarkers PAPP-A, PIGF are identified as independent risk factors for FGR. The combined application of these parameters demonstrates a significant predictive value for FGR.