Date of Award

2019

Degree Name

Doctor of Philosophy (College of Medicine)

Schools and Centres

Medicine

First Supervisor

Professor Sarah Lord

Second Supervisor

Professor Lisa Askie

Abstract

My thesis aims to improve pre-eclampsia prevention and outcomes in Australian women by providing evidence that can be used to enhance pre-eclampsia risk assessment in broad antenatal settings. I conducted the thesis in three stages. In stage 1, a systematic review identified major limitations in the existing evidence for current guideline approaches and ‘simple’ risk models incorporating maternal characteristics to identify women at increased risk of pre-eclampsia in early pregnancy. While the review demonstrated models including specialised tests such as uterine artery Doppler and serum biomarkers improved sensitivity to predict pre-eclampsia compared to simple models, there was insufficient evidence to compare the performance of simple models versus clinical guideline decision rules; and few simple models had been externally validated. To address these gaps, I conducted studies with the aim to validate current guideline approaches and published simple models; and to develop and validate a simple risk model for predicting pre-eclampsia in settings where specialised tests are not available. Studies were undertaken using the Perinatal Antiplatelet Review of International Studies (PARIS) clinical trials dataset (Stage 2); and the Western Sydney Local Health District’s ObstetriX database (Stage 3). The findings support the use of current guideline approaches to offer a simple and specific approach for predicting pre-eclampsia. Analysis of the PARIS dataset demonstrated the methodological challenges for developing and validating simple risk models to improve on guideline approaches. The PARIS model supported the value of including maternal mean arterial pressure (MAP) in simple models for pre-eclampsia prediction. Analysis of Western Sydney data demonstrated ethnic variation in the risk of preeclampsia independent of established clinical risk factors. These findings support the inclusion of ethnicity for pre-eclampsia risk assessment in Australia’s diverse multiethnic population. Further research is needed to understand the underlying causes for the reduced risk of preeclampsia observed for immigrant women. The Western Sydney (WS) risk model achieved modest performance for prediction of pre-eclampsia in nulliparous women. The model did not outperform the current antenatal guidelines; but has the advantage of providing individualised risk estimates to better inform patient counselling and guide decisions for further testing and prophylaxis. Further research is needed to assess the impact of adding MAP to the WS model. These findings can inform the development of Australian antenatal guidelines for the preeclampsia risk assessment and contribute towards the development of an improved nation-wide pre-eclampsia preventive strategy.

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