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双胎妊娠子痫前期的孕早期联合筛查——IPSISS(瑞士子痫前期筛查实施)队列纳入的前100例双胎妊娠结果

First-trimester combined screening for preeclampsia in twin pregnancies-results of the first 100 twin pregnancies included in the IPSISS (Implementing Preeclampsia Screening in Switzerland) cohort.

作者信息

Monod Cécile, Trottmann Fabienne, Raio Luigi, Challande Pauline, Amylidi-Mohr Sofia, Musik Thabea, Granado Cristina, Hildebrandt Lysann, Surbek Daniel, Martinez de Tejada Begoña, Campelo Sonia, Blume Carolin, Hänel Martin, Schäffer Leonhard, Hamza Amr, Hernadi Anett, Kohl Joachim, Hodel Markus, Ardabili Sara, Manegold-Brauer Gwendolin, Mosimann Beatrice

机构信息

Department of Obstetrics and Gynaecology, University Hospital of Basel, University of Basel, Basel, Switzerland (Monod, Musik, Granado, Hildebrandt, Manegold-Brauer, and Mosimann).

Department of Obstetrics and Gynecology, University Hospital of Bern, University of Bern, Bern, Switzerland (Trottmann, Raio, Challande, Amylidi-Mohr, and Surbek).

出版信息

Am J Obstet Gynecol MFM. 2025 Aug 17;7(10):101760. doi: 10.1016/j.ajogmf.2025.101760.

Abstract

BACKGROUND

Preeclampsia is more common in twin pregnancies than in singleton pregnancies. First-trimester combined screening, including maternal risk factors, uterine artery pulsatility index, mean arterial pressure, and placental growth factor, is possible in twin pregnancies. However, the performance is reported to be inferior compared with that in singletons.

OBJECTIVE

This study aimed to assess the performance of preeclampsia screening in the first 100 twin pregnancies included in the Implementing Preeclampsia Screening in Switzerland Study cohort in Switzerland.

STUDY DESIGN

This is a prospective multicenter registry study performed in Switzerland, including all twin and singleton pregnancies included in the registry with complete screening parameters and outcome data, between June 2020 and June 2024. A total of 3263 singleton and 104 twin pregnancies were included in this analysis. Pregnancies considered at risk for preterm preeclampsia were prescribed low-dose aspirin according to local guidelines. All parameters were converted to multiples of medians by the online calculator on the Fetal Medicine Foundation website (The Fetal Medicine Foundation, Calculators, Research Tools [https://fetalmedicine.org/research/peRisk]). Parameters were compared between singleton, monochorionic, and dichorionic twins. Statistical analysis was performed using GraphPad Prism 10.0 for Windows. Continuous variables were analyzed using the Student t test or Mann-Whitney U-test, whereas proportions were evaluated using the Fisher exact test or chi-squared test and the Kruskal-Wallis test.

RESULTS

The incidence of preterm preeclampsia in singleton pregnancies with live births was 29 of 3221 (0.9%) as opposed to 5 of 101 (5.0%) in twins. In uneventful pregnancies, median mean arterial pressure (interquartile range) was significantly higher in monochorionic twins compared with singletons, but not in dichorionic twins (88.5 [85.4-98.0] vs 86.3 [81.0-91.5] mm Hg; P=.005). Median uterine artery pulsatility index (interquartile range) was significantly lower in dichorionic twins compared with singletons and monochorionic twins (1.40 [1.05-1.65] vs 1.50 [1.20-1.9] [P=.0006] and 1.60 [1.35-1.80] [P=.022], respectively). Median PlGF (interquartile range) was significantly higher in dichorionic twins than in singletons, but not in monochorionic twins (55.0 [43.5-79.1] vs 41.0 [31.0-53.8] pg/mL; P<.0001), and median PAPP-A (interquartile range) was significantly higher in both dichorionic and monochorionic twins compared with singletons (9.72 [5.12-14.06] and 6.89 [4.13-11.59] vs 3.25 [1.81-5.15] IU/L [P<.0001], respectively). In twin pregnancies that later developed preterm preeclampsia, PlGF multiples of the median (interquartile range) were significantly lower than in uneventful twin pregnancies (0.52 [0.44-0.81] vs 0.99 [0.67-1.41]; P=.012), whereas all other markers showed no significant difference. At a fixed screen positive rate, significantly more twin pregnancies with preterm preeclampsia were screen-negative than singleton pregnancies with preterm preeclampsia.

CONCLUSION

This study demonstrated that, in our cohort, the markers performed as expected in twin compared with singleton pregnancies, and that at a fixed screen positive rate, fewer twin pregnancies with subsequent preeclampsia were detected compared with singleton pregnancies. Our preliminary results showed that a higher cutoff than 1:100, with a corresponding higher screen positive rate, must be chosen when screening for preterm preeclampsia in twin pregnancies to achieve an acceptable detection rate.

摘要

背景

双胎妊娠中先兆子痫比单胎妊娠更常见。孕早期联合筛查,包括孕妇风险因素、子宫动脉搏动指数、平均动脉压和胎盘生长因子,在双胎妊娠中是可行的。然而,据报道其筛查效能低于单胎妊娠。

目的

本研究旨在评估瑞士“瑞士实施先兆子痫筛查研究队列”中纳入的前100例双胎妊娠的先兆子痫筛查效能。

研究设计

这是一项在瑞士进行的前瞻性多中心登记研究,纳入了2020年6月至2024年6月登记的所有双胎和单胎妊娠,且有完整的筛查参数和结局数据。本分析共纳入3263例单胎妊娠和104例双胎妊娠。根据当地指南,将有早产先兆子痫风险的妊娠给予低剂量阿司匹林治疗。所有参数通过胎儿医学基金会网站(胎儿医学基金会,计算器,研究工具[https://fetalmedicine.org/research/peRisk])上的在线计算器转换为中位数倍数。对单胎、单绒毛膜双胎和双绒毛膜双胎的参数进行比较。使用适用于Windows的GraphPad Prism 10.0进行统计分析。连续变量采用Student t检验或Mann-Whitney U检验进行分析,而比例采用Fisher精确检验或卡方检验以及Kruskal-Wallis检验进行评估。

结果

单胎活产妊娠中早产先兆子痫的发生率为3221例中的29例(0.9%),而双胎妊娠中为101例中的5例(5.0%)。在正常妊娠中,单绒毛膜双胎的平均动脉压中位数(四分位间距)显著高于单胎,但双绒毛膜双胎中则不然(88.5[85.4 - 98.0]与86.3[81.0 - 91.5]mmHg;P = 0.005)。双绒毛膜双胎的子宫动脉搏动指数中位数(四分位间距)显著低于单胎和单绒毛膜双胎(分别为1.40[1.05 - 1.65]与1.50[1.20 - 1.9][P = 0.0006]和1.60[1.35 - 1.80][P = 0.022])。双绒毛膜双胎的胎盘生长因子中位数(四分位间距)显著高于单胎,但单绒毛膜双胎中则不然(55.0[43.5 - 79.1]与41.0[31.0 - 53.8]pg/mL;P < 0.0001),并且双绒毛膜双胎和单绒毛膜双胎的妊娠相关血浆蛋白-A中位数(四分位间距)均显著高于单胎(分别为9.72[5.12 - 14.06]和6.89[4.13 - 11.59]与3.25[1.81 - 5.15]IU/L[P < 0.0001])。在后来发生早产先兆子痫的双胎妊娠中,胎盘生长因子中位数倍数(四分位间距)显著低于正常双胎妊娠(0.52[0.44 - 0.81]与0.99[0.67 - 1.41];P = 0.012),而所有其他标志物无显著差异。在固定的筛查阳性率下,与单胎妊娠发生早产先兆子痫相比,双胎妊娠发生早产先兆子痫时筛查为阴性的显著更多。

结论

本研究表明,在我们的队列中,与单胎妊娠相比,这些标志物在双胎妊娠中的表现符合预期,并且在固定的筛查阳性率下,与单胎妊娠相比,后续发生先兆子痫的双胎妊娠被检测到的更少。我们的初步结果表明,在双胎妊娠中筛查早产先兆子痫时,必须选择高于1:100的更高截断值以及相应更高的筛查阳性率,以获得可接受的检测率。

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