Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

de Vrijer, Barbra

2nd Supervisor

Regnault, Timothy RH

Co-Supervisor

Abstract

Hypertensive disease of pregnancy (HDP) is a serious cardiometabolic pregnancy complication. Early onset HDP (EO-HDP) is more severe but rare, whereas late onset HDP (LO-HDP) is milder but common. Current disease markers, including placental growth factor (PlGF), are reasonable predictors of EO-HDP but poor predictors of LO-HDP. We sought to assess the performance of metabolomic biomarkers in HDP through a scoping review and primary analysis of plasma from symptomatic patients. Review of 31 studies indicated better prediction of all HDP and EO-HDP than LO-HDP using metabolomic biomarkers. Due to substantial heterogeneity in reported metabolites, no set of reliable biomarkers have been consolidated. The primary metabolomic analysis identified a panel of five metabolites that outperformed PlGF (p

Summary for Lay Audience

Hypertensive disease of pregnancy (HDP) is a serious pregnancy complication characterized by high blood pressure. The only known cure is delivery, which can happen prematurely. Two types of HDP exist. Early onset HDP, caused by the placenta not developing properly in early pregnancy, is more severe but less common. Late onset HDP is less severe but more common and is associated with the mother’s metabolic health. Due to their different disease origins, predictive tools are good at predicting early onset HDP, but not late onset HDP. This study aimed to investigate whether metabolomic biomarkers, the measurement of various metabolites in the blood to find markers of disease, could improve the prediction and early diagnosis of HDP. Firstly, we reviewed 31 previous studies on the topic and found that metabolomic markers can be good early predictors of all HDP and early onset HDP. Early prediction of late onset HDP was relatively poor. Unfortunately, there was little overlap between the biomarkers reported across studies which limits their clinical translatability. Secondly, we analyzed blood samples from patients with early and late onset HDP, who were admitted with early signs of HDP. Combining metabolites into multi-marker panels greatly improved the detection of late onset HDP compared to other validated biomarkers. However, the proposed metabolomic biomarkers in this study need to be externally validated to obtain a more accurate representation of their performance. We further identified several disrupted metabolic pathways in both early and late onset HDP, providing more insight into underlying disease mechanisms. These preliminary data suggests that metabolomic biomarkers may aid in the early diagnosis of HDP, particularly for late onset disease. This is important due to the high prevalence of late onset HDP and the low accuracy of current tools for its prediction. Ultimately, improving early detection of HDP can help doctors better monitor patients, plan deliveries, and allocate hospital resources.

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