Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
Institute of Health Research, University of Exeter, Exeter, UK.
Ultrasound Obstet Gynecol. 2021 Sep;58(3):360-368. doi: 10.1002/uog.23640. Epub 2021 Jul 28.
We have proposed previously that all pregnant women should have assessment of risk for pre-eclampsia (PE) at 20 and 36 weeks' gestation and that the 20-week assessment should be used to define subgroups requiring additional monitoring and reassessment at 28 and 32 weeks. The objective of this study was to examine the potential improvement in screening at 19-24 weeks' gestation for PE with delivery at < 28, < 32, < 36 and ≥ 36 weeks' gestation by the addition of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) to the combination of maternal demographic characteristics and medical history, uterine artery pulsatility index (UtA-PI) and mean arterial pressure (MAP).
This was a prospective, non-intervention study in women attending for an ultrasound scan at 19-24 weeks as part of routine pregnancy care. Patient-specific risks of delivery with PE at < 36 weeks' gestation were calculated using the competing-risks model to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics and medical history, with multiples of the median values of UtA-PI, MAP, PlGF and sFlt-1. Different risk cut-offs were used to vary the proportion of the population stratified into each of four risk categories (very high risk, high risk, intermediate risk and low risk) with the intention of detecting about 80%, 85%, 90% and 95% of cases of delivery with PE at < 28, < 32 and < 36 weeks' gestation. The performance of screening was assessed by plotting the detection rate against the screen-positive rate and calculating the areas under these curves, and by the proportion stratified into a given group for fixed detection rates. Model-based estimates of screening performance for these various combinations of markers were also produced.
In the study population of 37 886 singleton pregnancies, there were 1130 (3.0%) that subsequently developed PE, including 160 (0.4%) that delivered at < 36 weeks' gestation. In both the modeled and empirical results, there was incremental improvement in the performance of screening with the addition of PlGF and sFlt-1 to the combination of maternal factors, UtA-PI and MAP. If the objective of screening was to identify about 90% of cases of PE with delivery at < 28, < 32 and < 36 weeks and the method of screening was a combination of maternal factors, UtA-PI and MAP, the respective screen-positive rates would be 3.1%, 8.5% and 19.1%. The respective values for screening by maternal factors, UtA-PI, MAP and PlGF were 0.2%, 0.7% and 10.6%, and for screening by maternal factors, UtA-PI, MAP, PlGF and sFlt-1 they were 0.1%, 0.4% and 9.5%. The empirical results were consistent with the modeled results. There was good agreement between the predicted risk and the observed incidence of PE at < 36 weeks' gestation for all three strategies of screening. Prediction of PE at ≥ 36 weeks was poor for all three screening methods, with the detection rate, at a 10% screen-positive rate, ranging from 33.2% to 38.4%.
The performance of screening at 19-24 weeks' gestation for PE with delivery at < 28, < 32 and < 36 weeks' gestation achieved by a combination of maternal demographic characteristics and medical history, UtA-PI and MAP is improved by the addition of serum PlGF and sFlt-1. The performance of screening for PE at ≥ 36 weeks' gestation is poor irrespective of the method of screening at 19-24 weeks. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
我们之前提出，所有孕妇应在 20 周和 36 周时评估子痫前期（PE）的风险，20 周的评估应用于定义需要在 28 周、32 周时进行额外监测和再次评估的亚组。本研究的目的是通过在 19-24 周时添加血清胎盘生长因子（PlGF）和可溶性 fms 样酪氨酸激酶-1（sFlt-1）来检查在 19-24 周时进行子痫前期筛查的潜在改善，PE 的分娩时间<28 周、<32 周、<36 周和≥36 周。
这是一项前瞻性、非干预性研究，在 19-24 周时进行超声扫描的孕妇参加了常规妊娠护理。使用竞争风险模型计算特定于患者的在<36 周时分娩的 PE 风险，该模型结合了从母亲特征和病史中获得的 PE 分娩的妊娠年龄的先验分布，以及子宫动脉搏动指数（UtA-PI）、平均动脉压（MAP）、PlGF 和 sFlt-1 的中位数倍数。使用不同的风险截止值将人群分为四个风险类别（极高风险、高风险、中风险和低风险），目的是检测<28 周、<32 周和<36 周时分娩的 PE 病例的比例约为 80%、85%、90%和 95%。通过绘制检测率与阳性检出率的关系并计算这些曲线下的面积，以及通过固定检测率对给定组的分层比例来评估筛查的性能。还生成了基于模型的这些各种标记物组合的筛查性能估计。
在 37886 例单胎妊娠的研究人群中，有 1130 例（3.0%）随后发展为 PE，其中 160 例（0.4%）在<36 周时分娩。在建模和经验结果中，添加 PlGF 和 sFlt-1 到母体因素、UtA-PI 和 MAP 的组合中，筛查性能均有改善。如果筛查的目的是识别约 90%的在<28 周、<32 周和<36 周时分娩的 PE 病例，并且筛查方法是母体因素、UtA-PI 和 MAP 的组合，相应的阳性检出率将分别为 3.1%、8.5%和 19.1%。通过母体因素、UtA-PI、MAP 和 PlGF 进行筛查的各自值分别为 0.2%、0.7%和 10.6%，而通过母体因素、UtA-PI、MAP、PlGF 和 sFlt-1 进行筛查的各自值为 0.1%、0.4%和 9.5%。经验结果与建模结果一致。对于所有三种筛查策略，预测风险与在<36 周时发生的 PE 的观察发生率之间存在良好的一致性。对于所有三种筛查方法，PE 在≥36 周时的预测都很差，在 10%的阳性检出率时，检测率范围为 33.2%至 38.4%。
通过结合母体人口统计学特征和病史、UtA-PI 和 MAP，在 19-24 周时进行子痫前期筛查的方法，<28 周、<32 周和<36 周时的 PE 分娩的筛查性能得到改善，添加血清 PlGF 和 sFlt-1 后效果更佳。无论 19-24 周时的筛查方法如何，PE 在≥36 周时的筛查性能都很差。© 2021 年国际妇产科超声学会。
