An Interpretable Longitudinal Preeclampsia Risk Prediction Using Machine Learning

SUMMARY Background Preeclampsia is a pregnancy-specific disease characterized by new onset hypertension after 20 weeks of gestation that affects 2-8% of all pregnancies and contributes to up to 26% of maternal deaths. Despite extensive clinical research, current predictive tools fail to identify up to 66% of patients who will develop preeclampsia. We sought to develop a tool to longitudinally predict preeclampsia risk. Methods In this retrospective model development and validation study, we examined a large cohort of patients who delivered at six community and two tertiary care hospitals in the New England region between 02/2015 and 06/2023. We used sociodemographic, clinical diagnoses, family history, laboratory, and vital signs data. We developed eight datasets at 14, 20, 24, 28, 32, 36, 39 weeks gestation and at the hospital admission for delivery. We created linear regression, random forest, xgboost, and deep neural networks to develop multiple models and compared their performance. We used Shapley values to investigate the global and local explainability of the models and the relationships between the predictive variables. Findings Our study population (N=120,752) had an incidence of preeclampsia of 5.7% (N=6,920). The performance of the models as measured using the area under the curve, AUC, was in the range 0.73-0.91, which was externally validated. The relationships between some of the variables were complex and non-linear; in addition, the relative significance of the predictors varied over the pregnancy. Compared to the current standard of care for preeclampsia risk stratification in the first trimester, our model would allow 48.6% more at-risk patients to be identified. Interpretation Our novel preeclampsia prediction tool would allow clinicians to identify patients at risk early and provide personalized predictions, as well as longitudinal predictions throughout pregnancy. Funding National Institutes of Health, Anesthesia Patient Safety Foundation. RESEARCH IN CONTEXT Evidence before this study Current tools for the prediction of preeclampsia are lacking as they fail to identify up to 66% of the patients who develop preeclampsia. We searched PubMed, MEDLINE, and the Web of Science from database inception to May 1, 2023, using the keywords “deep learning”, “machine learning”, “preeclampsia”, “artificial intelligence”, “pregnancy complications”, and “predictive models”. We identified 13 studies that employed machine learning to develop prediction models for preeclampsia risk based on clinical variables. Among these studies, six included biomarkers such as serum placental growth factor, pregnancy-associated plasma protein A, and uterine artery pulsatility index, which are not routinely available in our clinical practice; two studies were in diverse cohorts of more than 100 000 patients, and two studies developed longitudinal predictions using medical records data. However, most studies have limited depth, concerns about data leakage, overfitting, or lack of generalizability. Added value of this study We developed a comprehensive longitudinal predictive tool based on routine clinical data that can be used throughout pregnancy to predict the risk of preeclampsia. We tested multiple types of predictive models, including machine learning and deep learning models, and demonstrated high predictive power. We investigated the changes over different time points of individual and group variables and found previously known and novel relationships between variables such as red blood cell count and preeclampsia risk. Implications of all the available evidence Longitudinal prediction of preeclampsia using machine learning can be achieved with high performance. Implementation of an accurate predictive tool within the electronic health records can aid clinical care and identify patients at heightened risk who would benefit from aspirin prophylaxis, increased surveillance, early diagnosis, and escalation in care. These results highlight the potential of using artificial intelligence in clinical decision support, with the ultimate goal of reducing iatrogenic preterm birth and improving perinatal care.