Adverse pregnancy outcomes and maternal cardiometabolic health: an observational cohort study using electronic medical records

Study type
Protocol
Date of Approval
Study reference ID
20_145
Lay Summary

Women who have experienced an adverse pregnancy outcome (APO) such as preeclampsia, gestational diabetes, stillbirth, miscarriage, or preterm delivery are more likely to have heart disease and stroke in later life compared to women without pregnancy APOs.

We aim to find out whether APOs lead to heart disease and stroke or simply ‘reveal’ women who are already prone to heart disease even before pregnancy. This study will demonstrate whether cardiovascular health profiles are different in women with a history of an APO to those without and when these differences emerge. We will also determine whether having information about APOs helps to better classify women at increased risk of heart disease and stroke in older age so that they can be offered advice or preventative treatment as early as possible. We will answer these questions using routinely collected GP and linked hospital data. We will compare profiles of risk factors for heart disease such as body mass index (BMI), blood pressure, lipids and glucose over time, from before to many years after pregnancy. This work has the potential to shape clinical practice and ultimately reduce the risk of cardiovascular disease (CVD) in women.

Technical Summary

Adverse pregnancy outcomes (APOs: still birth, miscarriage, hypertensive disorders of pregnancy, gestational diabetes, pre-term delivery and delivering a small- or large-for gestational-age baby) are associated with an approximate doubling of maternal cardiovascular disease (CVD) risk in later life. Clinical guidelines recommend referring women with a past APO for monitoring and control of CVD risk factors. However, clinicians lack guidance on what to monitor and when.

We aim to understand the role of APOs on women’s cardiometabolic health, to (i) determine when women with APOs cross established treatment thresholds (e.g. with statins), (ii) whether APOs improve the accuracy of predicting incident CVD in women beyond established tools (QRISK3), (iii) whether differences in cardiometabolic health already exist before pregnancy or emerge post-pregnancy.

We will conduct a prospective cohort study using primary care data from the Clinical Practice Research Datalink (CPRD), linked to information on incident fatal and nonfatal CVD from Hospital Episodes Statistics (HES) and Office of National Statistics (ONS) Mortality Database. Will use multi-level models to account for clustering of repeated measures within individuals to estimate trajectories of cardiovascular risk factors and 10-year cardiovascular risk (according to QRISK3) for women with and without APOs. As part of this, we will also study in detail the relationship between pre-pregnancy cardiovascular risk factors and risk of APOs in order to (i) determine the extent to which differences in risk profiles exist prior to pregnancy and (ii) allow for accurate modelling of confounders in the analysis.

This work will inform CVD screening and prevention strategies in women and shed light on the role of APOs in the aetiology of CVD.

Health Outcomes to be Measured

Primary outcomes: CVD risk scores and CVD events: BMI; systolic blood pressure; diastolic blood pressure; total cholesterol; HDL cholesterol; glucose; HbA1c or diabetes as a categorical variable; QRISK3 scores will be generated.

Collaborators

Abigail Fraser - Chief Investigator - University of Bristol
Kate Birnie - Corresponding Applicant - University of Bristol
Alun Hughes - Collaborator - University College London ( UCL )
Deborah Anne Lawlor - Collaborator - University of Bristol
Kate Tilling - Collaborator - University of Bristol
Laura Howe - Collaborator - University of Bristol
Maria Christine Magnus - Collaborator - Norwegian Institute of Public Health
Neil Davies - Collaborator - University of Bristol
Rosie Cornish - Collaborator - University of Bristol
Theresa Redaniel - Collaborator - University of Bristol

Linkages

CPRD Mother-Baby Link;HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Townsend Score;Practice Level Index of Multiple Deprivation;Pregnancy Register