Enhancing TSH-based congenital hypothyroidism screening using machine learning and resampling algorithms.

purposeCongenital hypothyroidism (CH) is a common cause of severe intellectual disability, affecting approximately 1 in 2,000 newborns globally. Treatable with early intervention, congenital hypothyroidism has long been a target of newborn screening programs. Current thyroid stimulating hormone (TSH) based programs suffer from low positive predictive value, resulting in unnecessary diagnostic investigations. Congenital hypothyroidism screening has proven challenging for machine learning previously due to massive class imbalance and having a single well known predictor, preventing acceptable screening sensitivity. This study represents the most comprehensive evaluation of machine learning for congenital hypothyroidism screening to date.

methodsAnalyzing data from 616,910 infants screened by Newborn Screening Ontario between 2019 and 2024. 12 classification and 12 resampling algorithms were trained using 4 different optimization metrics, for a total of 576 distinct models evaluated using stratified 5-fold cross-validation to ensure robustness. Models were optimized for sensitivity and then positive predictive value using various metrics. Model explainability was assessed using SHAP values and feature importances.

resultsWe were able to create a model achieving 16.8% PPV while maintaining 100% sensitivity using a RUSBoost classifier and Gaussian Noise resampling. This represents a 60% improvement in positive predictive value over the current approach. TSH remained the dominant predictor as in current screening, but our model was able to include minor amounts of additional information from other features to improve performance.

conclusionThese machine learning algorithms show no missed cases of CH and are able to significantly improve performance across robust testing. The findings suggest that machine learning offers a promising avenue for refining TSH-based CH screening processes, reducing false positives, and alleviating unnecessary stress and costs associated with current methods used by the majority of newborn screening programs globally.