A novel approach to joint prediction of preeclampsia and delivery timing using semicompeting risks

Abstract

Background: Preeclampsia is a pregnancy complication that contributes substantially to perinatal morbidity and mortality worldwide. Existing approaches to modeling and prediction of preeclampsia typically focus either on predicting preeclampsia risk alone, or on the timing of delivery following a diagnosis of preeclampsia. As such, they are misaligned with typical healthcare interactions during which the 2 events are generally considered simultaneously.

Objective: This study aimed to describe the "semicompeting risks" framework as an innovative approach for jointly modeling the risk and timing of preeclampsia and the timing of delivery simultaneously. Through this approach, one can obtain, at any point during the pregnancy, clinically relevant summaries of an individual's predicted outcome trajectories in 4 risk categories: not developing preeclampsia and not having delivered, not developing preeclampsia but having delivered because of other causes, developing preeclampsia but not having delivered, and developing preeclampsia and having delivered.

Study design: To illustrate the semicompeting risks methodology, we presented an example analysis of a pregnancy cohort from the electronic health record of an urban, academic medical center in Boston, Massachusetts (n=9161 pregnancies). We fit an illness-death model with proportional-hazards regression specifications describing 3 hazards for timings of preeclampsia, delivery in the absence of preeclampsia, and delivery following preeclampsia diagnosis.

Results: The results indicated nuanced relationships between a variety of risk factors and the timings of preeclampsia diagnosis and delivery, including maternal age, race/ethnicity, parity, body mass index, diabetes mellitus, chronic hypertension, cigarette use, and proteinuria at 20 weeks' gestation. Sample predictions for a diverse set of individuals highlighted differences in projected outcome trajectories with regard to preeclampsia risk and timing, and timing of delivery either before or after preeclampsia diagnosis.

Conclusion: The semicompeting risks framework enables characterization of the joint risk and timing of preeclampsia and delivery, providing enhanced, meaningful information regarding clinical decision-making throughout the pregnancy.

Keywords: clinical risk prediction; gestational hypertension; medically-indicated preterm birth; preeclampsia; semicompeting risks.