Adverse pregnancy and perinatal outcomes (APPOs), including miscarriage, stillbirth, gestational diabetes (GD), hypertensive disorders of pregnancy (HDP), preterm birth (PTB), and small and large for gestational age (SGA/LGA) together affect over 40% of pregnancies, and are associated with poor future health for mother and offspring.1 The risk of APPOs varies by ancestry.
South Asian women have twice the risk of GD compared with white-Europeans,2 with other ancestries having rates between South Asian and Europeans.3-5 Non-Europeans are more at risk of SGA than white-Europeans.6-8 HDP are most common in African origin women compared with all ancestries, with South and East Asian, and US Hispanic women having similar or lower risk than white-Europeans.9-11 PTB, and pregnancy loss, are more common in African and South Asian women compared with white-Europeans.12,13
Causes of ancestry differences in APPOs are unclear. Some differences mirror differences in related conditions (e.g. type 2 diabetes and hypertension) in the population. There is evidence that ancestral differences change over time,7 suggesting potentially modifiable causes and opportunities to improve pregnancy health for all women. Differences in genetics and factors such as body composition, diet, smoking and antenatal care are plausible, but the underrepresentation of non-European populations in research limits robust exploration.
Aims and Objectives
To use multiple methods and data sources to explore the causes of ancestral differences in APPOs, including (i) using record linkage to explore differences in pre-conceptual and antenatal monitoring and care, (ii) undertaking novel or adding to existing trans-ancestral genome-wide association studies (GWAS) of APPOs, and (iii) using multivariable regression and Mendelian randomization (MR) to explore potential ancestral differences in causes of APPOs.
- Use linked hospital and primary care data from the UK (CPRD, Scottish and Welsh), US and Scandinavian countries to explore ancestral/ethnic differences in attendance for a provision of pre-conception and antenatal care, including adherence to country specific clinical guidelines.
- Use pregnancy/birth cohorts (e.g. LifeCycle cohort collaboration) to compare distributions of established risk factors for APPOs (e.g. maternal age, parity, smoking, BMI, consanguineous partnership) and explore possible ancestral differences in the associations of these risk factors with APPOs.
- Undertake new, or add to existing/on-going trans-ancestral GWAS of APPOs. We anticipate that this will be most likely for South Asian, East Asian, and African groups in addition to white-Europeans.
- Use results from (3), MR-PREG (a collaboration of cohorts with genetic and APPOs data) to explore causes of APPOs and the extent to which they vary by ethnicity, using MR in subgroups stratified by ethnicity. Currently data from Born in Bradford, UK Biobank, China Kadoorie biobank and Japanese biobank would support differences between white-European, South Asian and East Asian women to be compared. A current application that is being reviewed for access to 23andMe data would enhance this to larger numbers and African ancestral data.
ancestry, ethnicity, pregnancy
How to apply for this project
This project will be based in Bristol Medical School - Population Health Sciences in the Faculty of Health Sciences at the University of Bristol.
Please visit the Faculty of Health Sciences website for details of how to apply