Clinical utility of 3D power doppler ultrasound and maternal biomarkers in the prediction of pre-eclampsia in high-risk pregnancies

Globally, 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.<br/><br/>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.<br/><br/>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.<br/><br/>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.<br/><br/>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.<br/><br/>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.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

Queen's University Belfast

Year dc:date.issued

2018

Author dc:creator

• Eastwood, Kelly-Ann

Advisors dc:contributor.advisor

• Young, Ian
• Holmes, Valerie

Language dc:language

eng

Identifier

oai:pure.qub.ac.uk/portal:studenttheses/f7d39c9c-b4b4-4e3a-987d-859731a2851e

OAI identifier oai:identifier

oai:pure.qub.ac.uk/portal:studenttheses/f7d39c9c-b4b4-4e3a-987d-859731a2851e