Rethinking preeclampsia: six paradigm shifts in placental pathophysiology for maternal–foetal medicine

Preeclampsia affects 2–4% of all pregnancies worldwide and remains one of the leading causes of maternal and neonatal morbidity and mortality. The article presents six inter-related paradigm shifts in understanding this disease, emerging from a research programme between 2020 and 2026. These shifts include: the origin of the problem in the first trimester rather than the second trimester, increased oxygen levels in intervillous spaces instead of oxygen deficiency in early-onset disease, metabolic and glycocalyx-based causes rather than pure angiogenic imbalance, the role of the placenta as a source of extracellular vesicles, steroid imbalance and alternative signalling pathways, and reduced immune tolerance. The research suggests the need for earlier and multimodal risk assessment in the first trimester using biomarkers that capture senescence and metabolic changes. However, some of these findings require independent verification in other research groups before clinical application.