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. 2020 Sep;56(3):400-407. doi: 10.1002/uog.22093. Epub 2020 Aug 5.
First-trimester screening for pre-eclampsia (PE) is useful because treatment of the high-risk group with aspirin reduces the rate of early PE with delivery at < 34 weeks' gestation by about 80% and that of preterm PE with delivery at < 37 weeks by 60%. In previous studies, we reported that the best way of identifying the high-risk group is by a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). An alternative biochemical marker is pregnancy-associated plasma protein-A (PAPP-A), which is used widely as part of early screening for trisomy. The objective of this study was to examine the additive value of PlGF and PAPP-A in first-trimester screening for preterm PE by maternal factors, MAP and UtA-PI and define the risk cut-off and screen-positive rate to achieve a desired detection rate of PE if PAPP-A rather than PlGF was to be used for first-trimester screening.
This was a non-intervention screening study. The data were derived from prospective screening for adverse obstetric outcomes in women with singleton pregnancy attending for a routine first-trimester hospital visit. Patient-specific risks of delivery with PE at < 37 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 (MoM) values of MAP, UtA-PI, PlGF and PAPP-A. The performance of screening in the total population and in subgroups of women of white and black racial origin was estimated. McNemar's test was used to compare the detection rate, for a fixed screen-positive rate, of screening with and without PlGF and PAPP-A. Risk cut-offs and screen-positive rates to achieve desired detection rates of preterm PE were determined in screening with and without PlGF and PAPP-A.
The study population was composed of 60 875 singleton pregnancies, including 1736 (2.9%) that developed PE. There are three main findings of this study. First, the performance of first-trimester screening for PE by a combination of maternal factors, MAP, UtA-PI and PlGF is superior to that of screening by maternal factors, MAP, UtA-PI and PAPP-A; for example, in screening by maternal factors, MAP, UtA-PI and PlGF, at a screen-positive rate of 10%, the detection rate of PE with delivery at < 37 weeks' gestation was 74.1%, which was 7.1% (95% CI, 3.8-10.6%) higher than in screening by maternal factors, MAP, UtA-PI and PAPP-A. Second, addition of serum PAPP-A does not improve the prediction of PE provided by maternal factors, MAP, UtA-PI and PlGF. Third, the risk cut-off and screen-positive rate to achieve a given fixed detection rate of preterm PE vary according to the racial composition of the study population and whether the biomarkers used for screening are MAP, UtA-PI and PlGF or MAP, UtA-PI and PAPP-A. For example, in screening by a combination of maternal factors, MAP, UtA-PI and PlGF in white women, if the desired detection rate of preterm PE was 75%, the risk cut-off should be 1 in 136 and the screen-positive rate would be 14.1%; in black women, to achieve a detection rate of 75%, the risk cut-off should be 1 in 29 and the screen-positive rate would be 12.5%. In screening by a combination of maternal factors, MAP, UtA-PI and PAPP-A in white women, if the desired detection rate of preterm PE was 75%, the risk cut-off should be 1 in 140 and the screen-positive rate would be 16.9%; in black women, to achieve a detection rate of 75%, the risk cut-off should be 1 in 44 and the screen-positive rate would be 19.3%.
In first-trimester screening for PE, the preferred biochemical marker is PlGF rather than PAPP-A. However, if PAPP-A was to be used rather than PlGF, the same detection rate can be achieved but at a higher screen-positive rate. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
早孕期子痫前期（PE）筛查具有重要意义，因为对高危人群使用阿司匹林治疗可将<34 孕周的早产 PE 发生率降低约 80%，将<37 孕周的早产 PE 发生率降低 60%。在之前的研究中，我们报告说，确定高危人群的最佳方法是结合母体因素、平均动脉压（MAP）、子宫动脉搏动指数（UtA-PI）和血清胎盘生长因子（PlGF）。另一种生化标志物是妊娠相关血浆蛋白-A（PAPP-A），它作为唐氏综合征早期筛查的一部分被广泛应用。本研究的目的是探讨 PlGF 和 PAPP-A 在早孕期筛查早产 PE 中的附加价值，方法是通过母体因素、MAP 和 UtA-PI 进行筛查，并确定风险临界值和筛查阳性率，以实现如果使用 PAPP-A 进行早孕期筛查，PE 的检测率。
这是一项非干预性筛查研究。数据来源于对单胎妊娠女性进行的不良产科结局的前瞻性筛查，这些女性在常规的早孕期医院就诊。通过竞争风险模型计算特定患者在<37 孕周时发生 PE 的分娩风险，将获得的母体特征和病史中 PE 的分娩时孕龄的先验分布与 MAP、UtA-PI、PlGF 和 PAPP-A 的中位数倍数（MoM）值相结合。估计了在总人群和白人和黑人群体亚组中的筛查表现。使用 McNemar 检验比较有无 PlGF 和 PAPP-A 筛查时的检测率和固定筛查阳性率。在有和没有 PlGF 和 PAPP-A 的筛查中确定了达到预期早产 PE 检测率的风险临界值和筛查阳性率。
研究人群包括 60875 例单胎妊娠，其中 1736 例（2.9%）发生了 PE。本研究有三个主要发现。首先，通过母体因素、MAP、UtA-PI 和 PlGF 结合进行早孕期 PE 筛查的性能优于通过母体因素、MAP、UtA-PI 和 PAPP-A 进行的筛查；例如，在通过母体因素、MAP、UtA-PI 和 PlGF 进行筛查时，筛查阳性率为 10%时，<37 孕周时 PE 的检测率为 74.1%，比通过母体因素、MAP、UtA-PI 和 PAPP-A 进行筛查时高 7.1%（95%CI，3.8-10.6%）。其次，添加血清 PAPP-A 并不能提高由母体因素、MAP、UtA-PI 和 PlGF 提供的 PE 预测。第三，达到特定固定早产 PE 检测率的风险临界值和筛查阳性率因研究人群的种族构成以及用于筛查的生物标志物是 MAP、UtA-PI 和 PlGF 还是 MAP、UtA-PI 和 PAPP-A 而有所不同。例如，在通过母体因素、MAP、UtA-PI 和 PlGF 结合进行筛查的白人女性中，如果预期的早产 PE 检测率为 75%，则风险临界值应为 1/136，筛查阳性率应为 14.1%；在黑人女性中，要达到 75%的检测率，风险临界值应为 1/29，筛查阳性率应为 12.5%。在通过母体因素、MAP、UtA-PI 和 PAPP-A 结合进行筛查的白人女性中，如果预期的早产 PE 检测率为 75%，则风险临界值应为 1/140，筛查阳性率应为 16.9%；在黑人女性中，要达到 75%的检测率，风险临界值应为 1/44，筛查阳性率应为 19.3%。
在早孕期 PE 筛查中，首选的生化标志物是 PlGF，而不是 PAPP-A。但是，如果要使用 PAPP-A 而不是 PlGF，则可以达到相同的检测率，但筛查阳性率更高。 © 2020 作者。超声在妇产科由约翰威利父子有限公司出版代表国际妇产科超声学会。
