From Point Estimates to Distributions: GMM Pooling for MIL in Preterm Birth Prediction

Preterm birth is associated with significant mortality and a risk for lifelong morbidity. The complex multifactorial aetiology hampers accurate prediction and thus optimal care. A pipeline consisting of bespoke machine learning methods for data imputation, feature selection, and regression models to predict gestational age (GA) at birth was developed and evaluated from comprehensive multi-modal morphological and functional fetal MRI data from 333 control cases and 93 preterm birth cases. The GA at birth predictions were classified into term and preterm categories and their accuracy, sensitivity, and specificity were reported. An ablation study was performed to further validate the design of the pipeline. Performance was evaluated using stratified 10-fold cross-validation. The pipeline achieves an R2 score of 0.13 and a mean absolute error of 2.74 weeks. It also achieves a 0.77 accuracy, 0.59 sensitivity, and 0.82 specificity across folds. The predominant features selected by the pipeline include cervical length and statistics derived from placental T2* values. The confluence of fast, motion-robust and multi-modal fetal MRI techniques and machine learning prediction allowed the prediction of the gestation at birth. This information is essential for any pregnancy. To the best of our knowledge, preterm birth had only been addressed as a classification problem in the literature. Therefore, this work provides a proof of concept. Future work will increase the cohort size to allow for finer stratification within the preterm birth cohort. Our code is available at https://github.com/dfajardorojas/ml-for-preterm-birth-.

Background: Pregnancy-associated thrombotic microangiopathy (P-TMA) is rare but life-threatening. Early risk prediction before overt clinical presentation remains challenging, as the associated laboratory abnormalities are subtle, multidimensional, and frequently masked by common physiological changes such as gestational thrombocytopenia and pregnancy-related proteinuria, thus overlapping heavily with benign obstetric and renal conditions. This complexity is poorly captured by univariate or rule-based approaches; however, it is addressable by machine learning, which can extract latent, time-dependent risk signatures from longitudinal clinical tests. Methods: This retrospective study included 300 pregnancies comprising 142 P-TMA cases and 158 controls. After exclusion of identifiers and non-informative variables, 146 longitudinal laboratory predictors were retained. Participants were divided into a training cohort (80%) and a held-out test cohort (20%) using stratified sampling. Five algorithms were evaluated: logistic regression, support vector machine with radial basis function kernel, random forest, extra trees, and gradient boosting. The final model was selected by mean cross-validated AUROC, refitted on the full training cohort, and evaluated once in the held-out test cohort. Interpretability analyses examined global feature importance and distributional patterns of leading predictors. Results: Gradient boosting was prespecified by cross-validation in the training cohort. The model achieved an AUROC of 0.872 (95% CI: 0.769-0.952) and an AUPRC of 0.883 (95% CI: 0.780-0.959) in a held-out test cohort, with sensitivity of 0.750 and specificity of 0.812. Conclusions: Longitudinal clinical laboratory tests obtained during routine care contained informative and clinically plausible signals for P-TMA risk. Notably, cystatin C at week 6 showed promise as an early monitoring indicator.

Existing computational pathology methods predominantly operate within whole-slide image (WSI)-level multiple instance learning (MIL) paradigms, while patient-level modeling remains underexplored. In routine pathological practice, however, pathologists derive diagnostic and prognostic conclusions by integrating evidence across multiple WSIs rather than relying on any single slide. This discrepancy creates a fundamental misalignment when patient-level supervision is directly imposed on conventional MIL frameworks, often leading to unstable optimization and degraded predictive reliability. To address this issue, we propose Anchor-Guided Evidence MIL (AGE-MIL), a weakly supervised framework for patient-level prediction. AGE-MIL constructs a patient-level anchor from slide representations to capture global pathological context and guide the retrieval and integration of diagnostically relevant local patches, enabling robust patient-level modeling. Patient-level risk is further modeled as an evidence accumulation process, promoting stable optimization under weak supervision. AGE-MIL is evaluated on six clinically relevant patient-level prediction tasks from two independent cohorts. Experimental results show that the proposed framework consistently outperforms eight state-of-the-art MIL methods. Code is available at https://github.com/wodeniua/AGE-MIL.