This is a multicenter, open-label, randomized controlled clinical trial designed to evaluate whether incorporating maternal angiogenic markers into clinical decision-making improves outcomes in early-onset severe preeclampsia. The study will include 386 singleton pregnancies diagnosed with preeclampsia with severe features according to ACOG criteria between 30+0 and 33+6 weeks of gestation across 11 tertiary referral centers in Spain. At inclusion, the maternal plasma sFlt-1/PlGF ratio will be measured in all participants. Women will then be randomly assigned (1:1) to either standard expectant management (control group) or angiogenic marker-guided management (intervention group) using a centralized REDCap randomization system that will generate the allocation sequence in blocks of 10, stratified by participating center. In the control group, clinical management will follow current standard practice, with planned delivery at 34 weeks if maternal and fetal conditions remain stable, and sFlt-1/PlGF results will be masked to treating clinicians. In the intervention group, timing of delivery will be guided by predefined sFlt-1/PlGF thresholds: \>655 from 30+0 weeks, \>110 from 34+0 weeks, and ≤110 allowing expectant management up to 37 weeks, provided no other obstetric indication for delivery arises. The primary objective is to evaluate whether the use of an algorithm based on the sFlt-1/PlGF ratio to guide the timing of delivery in women with early-onset severe preeclampsia with severe features improves maternal and neonatal outcomes compared with standard management. Secondary objectives include evaluating the predictive value of baseline and longitudinal sFlt-1/PlGF measurements, assessing the association between angiogenic marker abnormalities and disease progression, determining their relationship with placental dysfunction assessed by Doppler and histopathological examination, and evaluating the impact of the algorithm on maternal and neonatal healthcare resource utilization. Analyses will follow the intention-to-treat principle and will account for the multicenter design of the study.
