Deep Survival Analysis for Interpretable Time-Varying Prediction of Preeclampsia Risk.

Objective: Survival analysis is widely utilized in healthcare to predict the timing of disease onset. Traditional methods of survival analysis are usually based on Cox Proportional Hazards model and assume proportional risk for all subjects. However, this assumption is rarely true for most diseases, as the underlying factors have complex, non-linear, and time-varying relationships. This concern is especially relevant for pregnancy, where the risk for pregnancy-related complications, such as preeclampsia, varies across gestation. Recently, deep learning survival models have shown promise in addressing the limitations of classical models, as the novel models allow for non-proportional risk handling, capturing nonlinear relationships, and navigating complex temporal dynamics. Methods: We present a methodology to model the temporal risk of preeclampsia during pregnancy and investigate the associated clinical risk factors. We utilized a retrospective dataset including 66,425 pregnant individuals who delivered in two tertiary care centers from 2015-2023. We modeled the preeclampsia risk by modifying DeepHit, a deep survival model, which leverages neural network architecture to capture time-varying relationships between covariates in pregnancy. We applied time series k-means clustering to DeepHit's normalized output and investigated interpretability using Shapley values. Results: We demonstrate that DeepHit can effectively handle high-dimensional data and evolving risk hazards over time with performance similar to the Cox Proportional Hazards model, achieving an area under the curve (AUC) of 0.78 for both models. The deep survival model outperformed traditional methodology by identifying time-varied risk trajectories for preeclampsia, providing insights for early and individualized intervention. K-means clustering resulted in patients delineating into low-risk, early-onset, and late-onset preeclampsia groups- notably, each of those has distinct risk factors. Conclusion: This work demonstrates a novel application of deep survival analysis in time-varying prediction of preeclampsia risk. Our results highlight the advantage of deep survival models compared to Cox Proportional Hazards models in providing personalized risk trajectory and demonstrating the potential of deep survival models to generate interpretable and meaningful clinical applications in medicine.

Preeclampsia Prediction Using Machine Learning and Polygenic Risk Scores From Clinical and Genetic Risk Factors in Early and Late Pregnancies.

BACKGROUND: Preeclampsia, a pregnancy-specific condition associated with new-onset hypertension after 20-weeks gestation, is a leading cause of maternal and neonatal morbidity and mortality. Predictive tools to understand which individuals are most at risk are needed. METHODS: We identified a cohort of N=1125 pregnant individuals who delivered between May 2015 and May 2022 at Mass General Brigham Hospitals with available electronic health record data and linked genetic data. Using clinical electronic health record data and systolic blood pressure polygenic risk scores derived from a large genome-wide association study, we developed machine learning (XGBoost) and logistic regression models to predict preeclampsia risk. RESULTS: Pregnant individuals with a systolic blood pressure polygenic risk score in the top quartile had higher blood pressures throughout pregnancy compared with patients within the lowest quartile systolic blood pressure polygenic risk score. In the first trimester, the most predictive model was XGBoost, with an area under the curve of 0.74. In late pregnancy, with data obtained up to the delivery admission, the best-performing model was XGBoost using clinical variables, which achieved an area under the curve of 0.91. Adding the systolic blood pressure polygenic risk score to the models did not improve the performance significantly based on De Long test comparing the area under the curve of models with and without the polygenic score. CONCLUSIONS: Integrating clinical factors into predictive models can inform personalized preeclampsia risk and achieve higher predictive power than the current practice. In the future, personalized tools can be implemented to identify high-risk patients for preventative therapies and timely intervention to improve adverse maternal and neonatal outcomes.

An Interpretable Longitudinal Preeclampsia Risk Prediction Using Machine Learning.

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.

Prediction of Preeclampsia from Clinical and Genetic Risk Factors in Early and Late Pregnancy Using Machine Learning and Polygenic Risk Scores.

Background: Preeclampsia, a pregnancy-specific condition associated with new-onset hypertension after 20 weeks gestation, is a leading cause of maternal and neonatal morbidity and mortality. Predictive tools to understand which individuals are most at risk are needed. Methods: We identified a cohort of N=1,125 pregnant individuals who delivered between 05/2015-05/2022 at Mass General Brigham hospitals with available electronic health record (EHR) data and linked genetic data. Using clinical EHR data and systolic blood pressure polygenic risk scores (SBP PRS) derived from a large genome-wide association study, we developed machine learning (xgboost) and linear regression models to predict preeclampsia risk. Results: Pregnant individuals with an SBP PRS in the top quartile had higher blood pressures throughout pregnancy compared to patients within the lowest quartile SBP PRS. In the first trimester, the most predictive model was xgboost, with an area under the curve (AUC) of 0.73. Adding the SBP PRS to the models improved the performance only of the linear regression model from AUC 0.70 to 0.71; the predictive power of other models remained unchanged. In late pregnancy, with data obtained up to the delivery admission, the best performing model was xgboost using clinical variables, which achieved an AUC of 0.91. Conclusions: Integrating clinical and genetic factors into predictive models can inform personalized preeclampsia risk and achieve higher predictive power than the current practice. In the future, personalized tools can be implemented in clinical practice to identify high-risk patients for preventative therapies and timely intervention to improve adverse maternal and neonatal outcomes.

Complete Genome Sequences of Six Chi-Like Bacteriophages That Infect Proteus and Klebsiella.

Proteus mirabilis and Klebsiella aerogenes are Gram-negative opportunistic pathogens that are responsible for nosocomial and health care-associated infections, including urinary tract infections. Here, the full genome sequences of six Chi-like Proteus (DanisaurMW, DoubleBarrel, Inception, Jing313, and NotEvenPhaged) or Klebsiella (Phraden) bacteriophages are announced, contributing to the understanding of Chi-like phages.