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

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.

Keywords: biomarkers; first-trimester screening; maternal risk factors; preterm preeclampsia; twins.