Predictive performance of Fetal Medicine Foundation first-trimester screening algorithm for pre-eclampsia according to conception mode

Abstract

Objective: To investigate the incidence of pre-eclampsia (PE) and the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester PE screening algorithm across pregnancies conceived using assisted reproductive technology (ART), after ovulation induction (OI) and through spontaneous conception (SC). Methods: This prospective multicenter study included women with a singleton pregnancy undergoing routine combined first-trimester screening for aneuploidies at six Danish university hospitals from May 2019 to December 2020. Data on maternal characteristics, including mode of conception, medical history, mean arterial pressure (MAP), uterine artery pulsatility index, serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor, were collected to calculate an individual risk of PE using the FMF algorithm, without any clinical intervention based on the risk estimate. Obstetric outcomes, including PE diagnosis, were collected from the national birth registry. Women were categorized into three conception groups: ART, OI and SC. The ART group was further subdivided into ART using frozen embryo transfer (FET), fresh embryo transfer (fresh ET) or oocyte donation (OD). Detection rates (DRs) of the FMF algorithm were calculated using the risk cut-off that defined a screen-positive rate of 10% in the overall population and compared across conception groups. Differences in screen-positive rates and individual risk markers were further investigated. Results: Of the 8157 women included in the study, 535 conceived using ART, 235 after OI and 7387 through SC. The incidence of PE was highest in the ART group (7.3%) compared with the OI (5.1%; P = 0.34) and SC (3.4%; P < 0.001) groups. Among ART subgroups, the incidence of PE was 8.3% in FET, 6.4% in fresh ET and 12.3% in OD pregnancies (P > 0.05). However, the distribution of preterm vs term PE differed significantly across ART subgroups, with FET pregnancies showing a larger proportion of term PE (preterm, 11.1%; term, 88.9%) and OD pregnancies a larger proportion of preterm PE (preterm, 57.1%; term, 42.9%) (P = 0.03). The DR for preterm PE was 81.8% (95% CI, 48.2–97.7%) in ART pregnancies and 64.3% (95% CI, 48.0–78.4%) in SC pregnancies (P = 0.47). For overall PE, the DR was significantly higher in ART pregnancies (69.2% (95% CI, 52.4–83.0%)) than in SC pregnancies (35.7% (95% CI, 29.8–42.0%)) (P < 0.001). There was no significant difference in DRs for overall PE across ART subgroups. The corresponding screen-positive rates for PE varied significantly across conception groups: 22.8% in ART, 14.5% in OI and 8.9% in SC pregnancies (P < 0.01 for all). Significant differences in individual risk markers were observed across the ART subgroups, with higher MAP in OD pregnancies and higher PAPP-A in FET pregnancies. Conclusions: A higher incidence of PE was observed in women who conceived using ART and notable differences in the distribution of preterm and term PE were observed among the ART subgroups. The FMF first-trimester PE screening algorithm showed high DRs across all conception groups. However, differences in screen-positive rates and individual risk marker profiles suggest that the incorporation of ART-subgroup-specific adjustments could improve the predictive performance of the model in ART pregnancies, and underscore the need for tailored clinical management and patient communication. Given the high incidence of term PE in FET pregnancies, alternative interventions to acetylsalicylic acid may be necessary, given that this primarily prevents preterm PE. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.