Phenotyping Preeclampsia Using Unsupervised Machine Learning: A Prospective Cohort Study

Objective To explore clinically meaningful phenotypes of preeclampsia using unsupervised machine learning. Design Prospective cohort study. Setting BCNatal, a tertiary maternal‐foetal medicine centre (Barcelona, Spain). Population A total of 482 pregnant women diagnosed with preeclampsia between August 2013 and April 2024. Methods Maternal demographic, clinical, ultrasound and laboratory data were prospectively collected, together with delivery details and maternal and neonatal complications. We generated a patient representation using maternal age, height, weight, body‐mass index, blood pressure, angiogenic factors, urinary albumin/creatinine ratio, gestational age at birth and birthweight centile. Dimensionality reduction was performed using Uniform Manifold Approximation and Projection, followed by k ‐means clustering to identify phenotypes. Main Outcome Measures Maternal and neonatal characteristics and complication rates were compared across clusters to evaluate the clinical significance of the data‐driven phenotypes. Results Three phenotypes were identified. Cluster A ( n = 223; 46.2%) showed earlier delivery (mean 33.1 ± SD 3.3 weeks), marked angiogenic imbalance, prevalent foetal growth restriction (64%) and the highest rates of maternal (23%) and neonatal (41%) complications. Cluster B ( n = 147; 30.5%) had later delivery (37.0 ± 2.1 weeks), moderate angiogenic imbalance and intermediate birthweight centiles (15.5 ± 9.7). Cluster C ( n = 112; 23.2%) comprised mostly term cases (38.2 ± 1.5 weeks) with the lowest angiogenic imbalance and the highest birthweight centile (67.9 ± 27.3); obesity (31%) and diabetes (15%) were most prevalent and maternal (4%) and neonatal (9%) complications were least frequent. Conclusions Unsupervised learning delineated three preeclampsia phenotypes. These phenotypes could support the need for future risk stratification and more personalised management; prospective external validation is warranted.