Improved Prediction Tools for Preeclampsia, Renal Dysfunction and Foetal Growth Restriction in Pregnancy, Using Advanced Statistical Techniques

Lead Supervisor
Dr Salma Ayis
Senior Lecturer in Medical Statistics
School of Population Health and Environmental Sciences, King’s College London
salma.ayis@kcl.ac.uk

Co-supervisor
Nick Kametas, MD, MRCOG
Consultant in Maternal-Fetal Medicine and Obstetrics Honorary Reader, University of London Training Program Director St 1-2, South London; King’s College Hospital Foundation Trust, Women’s Health Academic Centre, King’s Health Partner’s

Partner
Dr Elizabeth Ball MD, PhD
Consultant Gynaecologist; NHS Consultant, Obstetrician and Gynaecologist at the Royal London Hospital, Barts Health NHS Trust. Hon. Senior Lecturer Queen Mary University of London

Project Details

Background

Hypertensive disorders of pregnancy (HDP) and foetal growth restriction (FGR) are major causes of maternal and perinatal morbidity both within the United Kingdom and worldwide, affecting 8% and 10% of pregnancies, respectively. HDP comprise of women with pre-existing (chronic) hypertension (CH) and women with gestational hypertension (GH). Pre-eclampsia (PE) is the newly diagnosed GH with evidence of maternal or fetal compromise. PE includes, over and above hypertension, the development of maternal renal or liver dysfunction, thrombocytopenia and /or the development of FGR. To ensure appropriate management, monitoring, and timely interventions, it is essential to be able to predict women at high risk of these outcomes.   

A primary tool for the diagnosis of preeclampsia is blood pressure (BP). Systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) are all potential markers for pregnancy complications in women with hypertensive disorders. MAP is estimated by adding one third of the pulse pressure (PP) to diastolic blood pressure. Furthermore, it is unclear whether one BP reading is enough, and many societies recommend repeat readings with averaging all or the last two readings.  There is evidence however, to suggest that mean arterial pressure (MAP) that wasn’t considered by MAP tool, is more so than SBP or DBP that were considered in predicting preeclampsia in both high and low risk pregnant women. 

This study aims to derive and validate a risk calculator, for Preeclampsia (PE) and the most important of its constituents, namely maternal renal dysfunction, and FGR. Furthermore, we aim to assess 

  • Whether SBP, DBP or MAP have different performance for the prediction of each of the outcomes.
  • Whether the first, second or average of two BP readings are more predictive, of any outcome. 

Study Plan

This project will use routinely collected data between 2009 and 2019, of around 3000 participants, in a dedicated maternal-foetal medicine clinic at Kings College Hospital, London, for the management of pregnancies at risk of or complicated by hypertension. The data comprised women with chronic hypertension, a history of gestational hypertension, and those with normal BP, who were followed longitudinally according to local protocols. 

A systematic review will be conducted on the performance and accuracy of MAP, and modified versions of MAP, for the detection of pregnancy outcomes.

The review will be reported in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-analysis. Quality appraisal will be completed using the Quality in Prognostic Studies Tool, Cochrane Risk of Bias Tool. 

Findings will be publicised through posters, research papers, and conferences presentations. 

Specific objectives:

  1. Conduct a systematic review on the performance and accuracy of MAP, and modified versions of MAP, for the detection of pregnancy outcomes, and a meta-analysis if appropriate.
  2. Detect heterogenous trajectories of hypertension in pregnant women, using Group Based Trajectory Models (GBTM) and develop a risk calculator of outcomes for each.
  3. Investigate associations between trajectories and hypertension drugs use. 
  4. Assess differential measures of hypertension (first, second, average) and how these relate to the prediction of pregnancy outcomes. 

Datasets

Routinely collected data between 2009 and 2019, of around 3000 participants, in a dedicated maternal-foetal medicine clinic at Kings College Hospital, London. Collected longitudinally based on local protocols.

Keywords

Hypertensive disorders of pregnancy (HDP); Mean Arterial Pressure (MAP);  Pre-eclampsia (PE); foetal growth restriction (FGR); Group Based Trajectory Models (GBTM); Risk Calculator