Supplementary Material for: Added value in low-risk pregnancies of longitudinal changes in uterine Doppler and circulating angiogenic factors during the third trimester in predicting term preeclampsia

Introduction: To assess the relationship between longitudinal changes in the uterine Doppler velocimetry and the maternal profile of angiogenic factors in the third trimester of pregnancy and to assess their ability to predict term preeclampsia.
Methods: A cohort of low-risk pregnant women was constructed at second trimester routine scan and scheduled for a uterine Doppler evaluation and measurement of the circulating levels of angiogenic factors at ~30 and ~36 weeks. The performance of both parameters at both time-points and their change over time from the first to the second measurement in predicting term preeclampsia was evaluated by logistic regression and receiver operating characteristic curve (ROC) analyses.
Results: A total of 1172 women were analyzed, of which 28 (2.4%) women developed term preeclampsia. At ~30 weeks, a model including the ratio sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) and the uterine Doppler explained 16.2% of the uncertainty of developing term preeclampsia, while at ~36 weeks the same variables explained 25.2% [p<0.001]. A model including the longitudinal changes of both predictors had an R2 of 26.8%, which was not significantly different from that of the ~36 weeks evaluation [p=0.45]. The area under the curve (AUC) of the ~36 weeks sFlt-1/PlGF ratio was significantly higher than at ~30 weeks (0.86 [0.77-0.94] vs. 0.81 [0.73-0.9]; p=0.043). The AUC of the 30-to-36 week change of the sFlt-1/PlGF ratio (0.85 [0.77-0.94]) did not significantly differ from that of at ~36 weeks (p=0.82). At ~36 weeks, for a 10% of false positives, the sFlt-1/PlGF ratio had a detection rate of 71.4%, with positive and negative likelihood ratios of 7.3 and 0.32, respectively.
Conclusion: A cross-sectional measurement of the sFlt-1/PlGF ratio outperforms uterine Doppler in predicting term preeclampsia. The combination of both markers does not improve such prediction, nor the evaluation of the longitudinal changes between ~30 and ~36 weeks.

引言：本研究旨在评估妊娠晚期子宫多普勒测速的纵向变化与孕产妇血管生成因子谱之间的关联，并探究二者对足月子痫前期的预测效能。
研究方法：于孕中期常规超声检查时纳入低危妊娠妇女队列，分别于妊娠约30周及约36周时安排子宫多普勒评估，并检测其循环中血管生成因子水平。采用logistic回归及受试者工作特征曲线（receiver operating characteristic curve, ROC）分析，评估两个时间点下两项指标单独应用、以及两次测量间的纵向变化对足月子痫前期的预测性能。
研究结果：共纳入1172例妊娠妇女进行分析，其中28例（2.4%）发生足月子痫前期。在妊娠约30周时，包含sFlt-1/PlGF比值（fms样酪氨酸激酶1/胎盘生长因子，fms-like tyrosine kinase-1/placental growth factor）与子宫多普勒指标的模型可解释足月子痫前期发生风险的16.2%变异；而在妊娠约36周时，同一模型的解释度达25.2%（p<0.001）。纳入两项预测指标纵向变化的模型其R²为26.8%，与妊娠约36周时的检测结果无显著差异（p=0.45）。妊娠约36周时sFlt-1/PlGF比值的曲线下面积（area under the curve, AUC）显著高于约30周时（0.86 [0.77-0.94] vs. 0.81 [0.73-0.9]; p=0.043）。sFlt-1/PlGF比值在30周至36周间的纵向变化的AUC为0.85（0.77-0.94），与约36周时的检测结果无显著差异（p=0.82）。在妊娠约36周时，当假阳性率为10%时，sFlt-1/PlGF比值的检出率为71.4%，其阳性似然比与阴性似然比分别为7.3与0.32。
研究结论：单项横断面检测sFlt-1/PlGF比值在预测足月子痫前期方面的效能优于子宫多普勒超声；联合两项指标并不能提升预测效能，同样，检测妊娠约30周至约36周间的纵向变化也无法改善预测效果。