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4-year PhD Studentship: Understanding ancestral/ethnic differences in adverse pregnancy and perinatal outcomes


   Faculty of Health Sciences

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  Prof Deborah Lawlor, Dr Carolina Borges, Dr Alice Carter  No more applications being accepted  Self-Funded PhD Students Only

About the Project

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.

Methodology

  • 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.

Keywords

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


Funding Notes

This project is open for University of Bristol PGR scholarship applications (closing date 25th February 2022)
The University of Bristol PGR scholarship pays tuition fees and a maintenance stipend (at the minimum UKRI rate) for the duration of a PhD (typically three years but can be up to four years).

References

1. Rich-Edwards JW, Fraser A, Lawlor DA, Catov JM. Pregnancy characteristics and women's future cardiovascular health: an underused opportunity to improve women's health? Epidemiology Reviews. 2014;36:57-70
2. Farrar D, Fairley L, Santorelli G, Tuffnell D, Sheldon TA, Wright J, et al. Association between hyperglycaemia and adverse perinatal outcomes in south Asian and white British women: analysis of data from the Born in Bradford cohort. Lancet Diabetes Endocrinology. 2015;3:795-804.
3. Hedderson MM, Darbinian JA, Ferrara A. Disparities in the risk of gestational diabetes by race-ethnicity and country of birth. Paediatric and Perinatal Epidemiology. 2010;24:441-448
4. Dooley SL, Metzger BE, Cho NH. Gestational Diabetes Mellitus: Influence of Race on Disease Prevalence and Perinatal Outcome in a U.S. Population. Diabetes 1991;40:25-29.
5. Yuen L, Wong VW, Simmons D. Ethnic Disparities in Gestational Diabetes. Current Diabetes Reports 2018;18:68.
6. Brand JS, West J, Tuffnell D, Bird PK, Wright J, Tilling K, et al. Gestational diabetes and ultrasound-assessed fetal growth in South Asian and White European women: findings from a prospective pregnancy cohort. BMC Medicine 2018;16:203.
7. Catov JM, Lee M, Roberts JM, Xu J, Simhan HN. Race Disparities and Decreasing Birth Weight: Are All Babies Getting Smaller? American Journal of Epidemiology 2015;183:15-23.
8. Tutlam NT, Liu Y, Nelson EJ, Flick LH, Chang JJ. The Effects of Race and Ethnicity on the Risk of Large-for-Gestational-Age Newborns in Women Without Gestational Diabetes by Prepregnancy Body Mass Index Categories. Maternal and Child Health Journal 2017;21:1643-1654.
9. Caughey AB, Stotland NE, Washington AE, Escobar GJ. Maternal Ethnicity, Paternal Ethnicity, and Parental Ethnic Discordance: Predictors of Preeclampsia. Obstetrics & Gynecology 2005;106:156-161
10. Farrar D, Santorelli G, Lawlor DA, Tuffnell D, Sheldon TA, West J, et al. Blood pressure change across pregnancy in white British and Pakistani women: analysis of data from the Born in Bradford cohort. Scientific Reports. 2019;9:13199.
11. Knnuist M, Bonsel GJ, Zondervan HA, Treffers PE. Risk factors for preeclampsia in nulliparous women in distinct ethnic groups: a prospective cohort study. Obstet Gynecol. 1998;92(2):174-8
12. Manuck TA. Racial and ethnic differences in preterm birth: A complex, multifactorial problem. Semin Perinatol. 2017;41(8):511-8.
13. Oliver-Williams CT, Steer PJ. Racial variation in the number of spontaneous abortions before a first successful pregnancy, and effects on subsequent pregnancies. Int J Gynaecol Obstet2015;129:207-12.
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