AbstractGlobally, pre-eclampsia is a leading cause of maternal and fetal morbidity and mortality. Approximately 2% of all pregnant women develop pre-eclampsia; women with high-risk co-morbidities are particularly at risk with reported incidences of up to 20%. Evolving evidence suggests that an integrated screening tool combining medical history, ultrasound parameters and serum biomarkers may be of use in defining the patient-specific risk for pre-eclampsia.
Against this background, this thesis examines the ability of baseline maternal characteristics, placental vascularisation indices, uterine artery Doppler and maternal serum biomarkers (Pregnancy Associated Plasma Protein-A (PAPP-A), Placental like Growth Factor (PlGF), soluble Fms-like tyrosine kinase (sFLt-1) and soluble Endoglin (sEng)) measured in the first and second trimesters of pregnancy to predict pre-eclampsia in high-risk women.
To determine the added clinical utility and predictive value of these biophysical and biochemical parameters, a prospective longitudinal observational study of high-risk women and low-risk control participants was carried out (PREDICT). Set within the context of a systematic review evaluating the ability of (first trimester) placental vascularisation indices to predict pre-eclampsia, findings from the PREDICT study demonstrate that placental vascularisation indices perform well for prediction of pre-eclampsia in the first trimester and that measurements are repeatable and reproducible within a high-risk cohort. The added clinical utility of uterine artery Doppler ultrasound for prediction of pre-eclampsia in high-risk women was not apparent, however the additional clinical utility of a number of first (sFlt-1, sFlt-1:PlGF) and second trimester biomarkers (PlGF:sEng) was demonstrated. Results from the PREDICT study indicate a potential role for a first trimester combined screening model in high-risk women incorporating information about baseline maternal characteristics, vascularisation flow index and sFlt-1. In addition, an integrated screening model combining baseline maternal characteristics and flow index is proposed for prediction of pre-eclampsia in the second trimester.
Exploratory sub-group analysis demonstrated differences in performance of placental vascularisation indices, uterine artery Doppler and serum biomarkers in prediction of pre-eclampsia. In particular, this thesis highlights the increased prevalence of obesity in pregnancy and its subsequent impact on performance of placental vascularisation indices and maternal serum biomarkers.
Future research should focus on better understanding the underlying mechanisms for pre-eclampsia in different sub-groups. Additional research is needed to extend current understanding of pre-eclampsia risk in relation to Body Mass Index trajectory and to explore suitable biomarker threshold ranges for prediction of pre-eclampsia in obese cohorts.
Adoption of a combined screening model early in pregnancy to identify those women at highest risk of pre-eclampsia has the potential to significantly improve maternal and neonatal outcomes. It is evident that supplementary research to investigate the role of combined screening models for pre-eclampsia within high-risk sub-groups is required before introduction in a clinical setting. In challenging the existing pathways of antenatal care, clinicians have an opportunity to provide personalised medical care for women at greatest risk.
|Date of Award||Jul 2018|
|Supervisor||Ian Young (Supervisor), Valerie Holmes (Supervisor) & David McCance (Supervisor)|