Organ-system-based subclassification of preeclampsia using machine learning predicts pregnancy outcomes

Abstract Background Preeclampsia (PE) is a complex disorder with significant variability in organ involvement. It remains unclear whether machine learning can identify organ-system-based subclasses of PE. This study aimed to identify novel subclasses of PE using organ-system biomarkers to improve pregnancy outcome prediction. Methods We retrospectively analyzed clinical data from PE patients at Fujian Maternity and Child Health Hospital. K-means clustering was applied using organ system function indicators, with 10-fold cross-validation. Functional indicators and pregnancy outcomes were compared across subclasses. Heatmap and sankey diagrams were used to reveal the distribution of patients across combined organ system clusters. Results The analysis included 7,531 PE patients treated between 2013 and 2023. 10-fold cross-validation confirmed clustering robustness with mean ARI of 0.8806 ± 0.0099 and NMI of 0.7800 ± 0.0123. Three heart function clusters were identified using five indicators, with H-Cluster 1 showing the poorest heart function and the highest complication rates. Five kidney clusters were determined from ten indicators. K-Cluster 1 and K-Cluster 5 showed distinct biomarker patterns but similar complication rates (P > 0.05). Liver function analysis using thirteen indicators revealed four clusters. L-Cluster 1 exhibited elevated liver enzymes and bilirubin with higher severe PE and intrahepatic cholestasis rates, whereas L-Cluster 3 had lower protein levels but higher anemia, fetal distress and hemorrhage incidence (P < 0.05). Five coagulation clusters were determined from nine indicators, showing significant differences in indicators and complication rates (P < 0.05). Heatmap and sankey diagram analyses revealed significant overlap between high-risk clusters, with the most frequent combination being H-Cluster 1, K-Cluster 1, L-Cluster 1 and C-Cluster 5. Conclusions Machine learning identified distinct PE subclasses based on organ system dysfunction patterns, each demonstrating unique pregnancy outcomes. This suggests potential clinical utility of computational approaches for PE subclassification and generates hypotheses for further investigation of its biological mechanisms.