Life course epidemiology of women's reproductive health and its relation to chronic disease
Lead Research Organisation:
University of Bristol
Department Name: Social Medicine
Abstract
Reproductive health is important to a woman's overall health and well-being and is increasingly recognised as a marker for other diseases that she might experience later on in life. However there are gaps in our knowledge about what causes some women to have poorer reproductive health, for example, have highly irregular menstrual cycles, difficulties getting pregnant, or experience hot flashes and night sweats around menopause. I propose to answer these gaps. I will use information from several large studies that include many women, some of which have collected information on women since they were in the womb or since their birth. I will use this information to find out what affects their reproductive hormone levels, their menstrual patterns and how easy it is for them to get pregnant in early adulthood, and how likely they are to have complications of pregnancy. This is important as some of the causes of poor reproductive health may be preventable. Also, women are increasingly having children at older ages and it is important that we understand what affects women's chances of getting pregnant and having a healthy pregnancy. There are also gaps in our understanding of why women with poorer reproductive health, including complications of pregnancy, such as pre-eclampsia, are more likely to have other diseases later in their life such as heart disease. Here too I will use large studies of older women, to find out why some women with poorer reproductive health are more likely to have heart disease, diabetes, breast cancer and other diseases later in life. Understanding the relationship between women's reproductive health and other diseases is important as it may identify potential new treatments. I will also assess whether information about reproductive health which women accurately and easily remember can be used to accurately predict their chances of having diabetes, heart and bone disease and dementia later in life. This is important as women at high risk can then be offered advice or treatment that will lower that risk.
Technical Summary
Reproductive health is important to a woman's overall health and well-being and is increasingly recognised as a sentinel for chronic disease in later life. However important knowledge gaps in the life course epidemiology of female reproductive health and in the understanding of the nature of its relation to chronic disease remain. Here I will study multiple exposures from foetal life to adulthood in relation to reproductive health and potential as measured by reproductive hormones in early adulthood, a critical time for family planning. I will use information on multiple reproductive indicators such as menstrual cycle characteristics, parity, pregnancy complications, gynaecological disorders and their treatment, to better characterize women's reproductive health. I will study relations between these reproductive indicators (separately and in combination), reproductive hormones and major chronic disease outcomes (including breast cancer, cardiovascular disease, diabetes, osteoporotic fractures, depression, dementia, and lung disease) and disease markers to study causality and identify mechanistic pathways. Finally, I will examine whether readily available information on indicators of female reproductive health can improve risk stratification in women. I will use data from multiple complimentary studies and a variety of analytical approaches to identify causal pathways, as well as novel statistical methods to formally compare different life course models of the relationship between early life exposures, reproductive health and later disease outcomes. This work has the potential to inform preventive strategies, to identify treatment targets for female reproductive health as well as related chronic diseases, and to improve risk stratification in women at increased risk of diabetes, cardiovascular disease, osteoporosis and dementia. This is important because most are preventable or have a better prognosis if treated earlier and all are costly to health services.
Planned Impact
The aims of this research are to identify the determinants of women's reproductive health and potential in early adulthood, and to clarify whether women's reproductive health is causally related to several major diseases that are prevalent in women and if so, to identify the causal pathways. This has the potential to impact on the following groups of beneficiaries in the short to medium term, i.e. during the life of this fellowship:
1. A wide range of scientists investigating disease mechanisms. As the work proposed here aims to study the aetiology of women's reproductive health and its potential contribution to a range of major disease outcomes, findings may inform the work of colleagues investigating the aetiology of reproductive health but also of breast cancer, cardiovascular disease, diabetes, dementia, depression and lung disease using various approaches from investigations at the molecular level, through to population based approaches.
2. Researchers using a life course approach, as the work proposed here will contribute to developing novel statistical methods to compare different life course models.
3. Both myself and the appointed researcher on this project will gain immediate skills which are particularly relevant to research but that are also transferable and applicable in other contexts. These include skills in project management including people and data management, programming, and communication skills.
Beneficiaries in the medium and longer term, i.e. both during and beyond the life of the fellowship include:
4. Ultimately the goal of this research is to improve the well-being and health of women worldwide. Through better understanding of what affects women's reproductive health and potential; how their reproductive health contributes to the risk of major disease outcomes; and how readily available information on women's reproductive health can be used to identify women at risk of chronic disease, the work proposed here can inform preventive strategies, identify potential treatment targets, as well as ensure more effective provision of care. Improving our understanding of what affects reproductive health and potential in early adulthood can inform women's family planning as well as estimates of future demand for assisted reproduction technologies. By improving the accuracy and/or simplifying existing risk prediction scores, women at increased risk of a range of diseases can be identified and offered effective interventions to prevent, treat and manage their risk. By clarifying the role of pregnancy complications in shaping CVD risk, the management of women who experienced a pregnancy complication in the post-partum period can be improved and potential treatment targets can be identified. More effective risk stratification and healthcare provision is also likely to be of economic benefit to health service providers and to society in general.
5. National and international bodies responsible for issuing clinical guidance on organisation and management of care, screening policies and the use of risk prediction models, such as the UK Royal College of Obstetricians and Gynaecologists and the National Institute for Health and Care Excellence.
1. A wide range of scientists investigating disease mechanisms. As the work proposed here aims to study the aetiology of women's reproductive health and its potential contribution to a range of major disease outcomes, findings may inform the work of colleagues investigating the aetiology of reproductive health but also of breast cancer, cardiovascular disease, diabetes, dementia, depression and lung disease using various approaches from investigations at the molecular level, through to population based approaches.
2. Researchers using a life course approach, as the work proposed here will contribute to developing novel statistical methods to compare different life course models.
3. Both myself and the appointed researcher on this project will gain immediate skills which are particularly relevant to research but that are also transferable and applicable in other contexts. These include skills in project management including people and data management, programming, and communication skills.
Beneficiaries in the medium and longer term, i.e. both during and beyond the life of the fellowship include:
4. Ultimately the goal of this research is to improve the well-being and health of women worldwide. Through better understanding of what affects women's reproductive health and potential; how their reproductive health contributes to the risk of major disease outcomes; and how readily available information on women's reproductive health can be used to identify women at risk of chronic disease, the work proposed here can inform preventive strategies, identify potential treatment targets, as well as ensure more effective provision of care. Improving our understanding of what affects reproductive health and potential in early adulthood can inform women's family planning as well as estimates of future demand for assisted reproduction technologies. By improving the accuracy and/or simplifying existing risk prediction scores, women at increased risk of a range of diseases can be identified and offered effective interventions to prevent, treat and manage their risk. By clarifying the role of pregnancy complications in shaping CVD risk, the management of women who experienced a pregnancy complication in the post-partum period can be improved and potential treatment targets can be identified. More effective risk stratification and healthcare provision is also likely to be of economic benefit to health service providers and to society in general.
5. National and international bodies responsible for issuing clinical guidance on organisation and management of care, screening policies and the use of risk prediction models, such as the UK Royal College of Obstetricians and Gynaecologists and the National Institute for Health and Care Excellence.
Organisations
- University of Bristol (Fellow, Lead Research Organisation)
- Universidade de São Paulo (Collaboration)
- HARVARD UNIVERSITY (Collaboration)
- Cardiff University (Collaboration)
- University of Bath (Collaboration)
- Lund University (Collaboration)
- Federal University of Pelotas (UFPel) (Collaboration)
- Norwegian University of Science and Technology (NTNU) (Collaboration)
- University of Cape Town (Collaboration)
People |
ORCID iD |
Abigail Fraser (Principal Investigator / Fellow) |
Publications
Alsnes IV
(2017)
Hypertension in Pregnancy and Offspring Cardiovascular Risk in Young Adulthood: Prospective and Sibling Studies in the HUNT Study (Nord-Trøndelag Health Study) in Norway.
in Hypertension (Dallas, Tex. : 1979)
Anderson EL
(2015)
The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and Meta-Analysis.
in PloS one
Anderson EL
(2018)
Associations of adversity in childhood and risk factors for cardiovascular disease in mid-adulthood.
in Child abuse & neglect
Anderson EL
(2017)
Prospective associations of psychosocial adversity in childhood with risk factors for cardiovascular disease in adulthood: the MRC National Survey of Health and Development.
in International journal for equity in health
Anderson EL
(2017)
Adversity in childhood and measures of aging in midlife: Findings from a cohort of british women.
in Psychology and aging
Barnett W
(2018)
Maltreatment in childhood and intimate partner violence: A latent class growth analysis in a South African pregnancy cohort.
in Child abuse & neglect
Bell JA
(2021)
Sex differences in systemic metabolites at four life stages: cohort study with repeated metabolomics.
in BMC medicine
Carslake D
(2019)
Associations of mortality with own blood pressure using son's blood pressure as an instrumental variable.
in Scientific reports
Ejigu Y
(2020)
Differences in Growth of HIV-exposed Uninfected Infants in Ethiopia According to Timing of In-utero Antiretroviral Therapy Exposure.
in The Pediatric infectious disease journal
Ferreira DLS
(2015)
Associations of Central and Peripheral Blood Pressure With Cardiac Structure and Function in an Adolescent Birth Cohort: The Avon Longitudinal Study of Parents and Children.
in Journal of the American College of Cardiology
Foo FL
(2018)
Association Between Prepregnancy Cardiovascular Function and Subsequent Preeclampsia or Fetal Growth Restriction.
in Hypertension (Dallas, Tex. : 1979)
Fraser A
(2018)
Women's Cardiovascular Health After a Hypertensive Disorder of Pregnancy.
in Annals of internal medicine
Fraser A
(2022)
Ten-Year Cardiovascular Disease Risk Trajectories by Obstetric History: A Longitudinal Study in the Norwegian HUNT Study.
in Journal of the American Heart Association
Fraser A
(2016)
Nonlinear Exposure-Outcome Associations and Public Health Policy.
in JAMA
Fraser A
(2023)
Placental syndromes and long-term risk of hypertension.
in Journal of human hypertension
Goncalves Soares A
(2021)
Abuse in Childhood and Cardiometabolic Health in Early Adulthood: Evidence From the Avon Longitudinal Study of Parents and Children.
in Journal of the American Heart Association
Guyatt A
(2018)
Early life adiposity and telomere length across the life course: a systematic review and meta-analysis
in Wellcome Open Research
Haag K
(2020)
The emergence of sex differences in PTSD symptoms across development: evidence from the ALSPAC cohort.
in Psychological medicine
Haug EB
(2018)
Correction to: The impact of parity on life course blood pressure trajectories: the HUNT study in Norway.
in European journal of epidemiology
Haug EB
(2021)
The role of cardiovascular risk factors in maternal cardiovascular disease according to offspring birth characteristics in the HUNT study.
in Scientific reports
Haug EB
(2018)
Life Course Trajectories of Cardiovascular Risk Factors in Women With and Without Hypertensive Disorders in First Pregnancy: The HUNT Study in Norway.
in Journal of the American Heart Association
Haug EB
(2017)
Pre-pregnancy Blood Pressure and Offspring Sex in the HUNT Study, Norway.
in American journal of hypertension
Haug EB
(2018)
The impact of parity on life course blood pressure trajectories: the HUNT study in Norway.
in European journal of epidemiology
Herbert A
(2020)
Risk factors for intimate partner violence and abuse among adolescents and young adults: findings from a UK population-based cohort
in Wellcome Open Research
Herbert A
(2020)
Risk factors for intimate partner violence and abuse among adolescents and young adults: findings from a UK population-based cohort
in Wellcome Open Research
Herbert A
(2023)
Categories of Intimate Partner Violence and Abuse Among Young Women and Men: Latent Class Analysis of Psychological, Physical, and Sexual Victimization and Perpetration in a UK Birth Cohort.
in Journal of interpersonal violence
Herbert A
(2020)
Risk factors for intimate partner violence and abuse among adolescents and young adults: findings from a UK population-based cohort.
in Wellcome open research
Hiller RM
(2016)
Research Review: Changes in the prevalence and symptom severity of child post-traumatic stress disorder in the year following trauma - a meta-analytic study.
in Journal of child psychology and psychiatry, and allied disciplines
Horn J
(2020)
Life Course Trajectories of Maternal Cardiovascular Risk Factors according to Offspring Birthweight: The HUNT Study.
in Scientific reports
Howe LD
(2016)
Relationship between mediation analysis and the structured life course approach.
in International journal of epidemiology
Kurbasic A
(2019)
Maternal Hypertensive Disorders of Pregnancy and Offspring Risk of Hypertension: A Population-Based Cohort and Sibling Study.
in American journal of hypertension
Lawn RB
(2019)
Comment on the Relationship Between Common Variant Schizophrenia Liability and Number of Offspring in the UK Biobank.
in The American journal of psychiatry
Lawn RB
(2018)
Associations Between Maternal Prepregnancy Body Mass Index and Gestational Weight Gain and Daughter's Age at Menarche: The Avon Longitudinal Study of Parents and Children.
in American journal of epidemiology
Lawn RB
(2019)
Schizophrenia risk and reproductive success: a Mendelian randomization study.
in Royal Society open science
Lo CCW
(2020)
Future Cardiovascular Disease Risk for Women With Gestational Hypertension: A Systematic Review and Meta-Analysis.
in Journal of the American Heart Association
Macdonald-Wallis C
(2015)
Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: development and validation in two general population cohorts.
in BMJ (Clinical research ed.)
Magnus M
(2020)
Cardiometabolic health during early adulthood and risk of miscarriage: a prospective study
in Wellcome Open Research
Magnus MC
(2020)
Cardiometabolic health during early adulthood and risk of miscarriage: a prospective study.
in Wellcome open research
Magnus MC
(2018)
Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study.
in BMJ (Clinical research ed.)
Magnus MC
(2018)
Hypertensive Disorders During Pregnancy and Offspring Retinal Microvasculature During Adolescence.
in Journal of the American College of Cardiology
Magnus MC
(2020)
Identifying potential causal effects of age at menarche: a Mendelian randomization phenome-wide association study.
in BMC medicine
Magnus MC
(2018)
Childhood psychosocial adversity and female reproductive timing: a cohort study of the ALSPAC mothers.
in Journal of epidemiology and community health
Magnus MC
(2017)
Number of Offspring and Cardiovascular Disease Risk in Men and Women: The Role of Shared Lifestyle Characteristics.
in Epidemiology (Cambridge, Mass.)
Title | Painting depicting the link between early life trauma and health in later life |
Description | This artwork was produced by Laura Cramer (http://www.cramerpaintings.com) as part of the Creative Reactions project. It depicts Laura's representation of the potential effects of early life trauma on health in later life. |
Type Of Art | Artwork |
Year Produced | 2018 |
Impact | The artwork was displayed at the Research Without Borders festival and at an exhibition in Hamilton House in Bristol. |
Description | Alcohol in pregnancy |
Geographic Reach | National |
Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
Description | Light prenatal alcohol consumption |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
URL | https://clahrc-west.nihr.ac.uk/news-item/sobering-evidence-drinking-pregnancy-know-little-much/ |
Description | AMS GCRF |
Amount | £25,000 (GBP) |
Funding ID | GCRFNG\100313 |
Organisation | Academy of Medical Sciences (AMS) |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2018 |
End | 03/2019 |
Description | Benjamin Meaker Visiting Professorship |
Amount | £2,125 (GBP) |
Organisation | University of Bristol |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2018 |
End | 03/2018 |
Description | Benjamin Meaker Visiting Professorships |
Amount | £1,900 (GBP) |
Organisation | University of Bristol |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2017 |
End | 03/2017 |
Description | Determinants and health sequelae of intimate partner violence and abuse in young adult relationships: a mixed methods study |
Amount | £560,069 (GBP) |
Funding ID | MR/S002634/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 12/2018 |
End | 11/2021 |
Description | GW4 initiator award |
Amount | £13,483 (GBP) |
Organisation | GW4 |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2016 |
End | 04/2016 |
Description | MRC strategic skills |
Amount | £354,380 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start |
Description | MRC strategic skills fellowship |
Amount | £407,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start |
Description | Biosocial effects of trauma |
Organisation | Cardiff University |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Joint grant applications; training of PhD students and early career researchers; joint publications |
Collaborator Contribution | Joint grant applications; joint publications |
Impact | Further funding; joint publications |
Start Year | 2017 |
Description | Biosocial effects of trauma |
Organisation | Federal University of Pelotas (UFPel) |
Country | Brazil |
Sector | Academic/University |
PI Contribution | Joint grant applications; training of PhD students and early career researchers; joint publications |
Collaborator Contribution | Joint grant applications; joint publications |
Impact | Further funding; joint publications |
Start Year | 2017 |
Description | Biosocial effects of trauma |
Organisation | Universidade de São Paulo |
Country | Brazil |
Sector | Academic/University |
PI Contribution | Joint grant applications; training of PhD students and early career researchers; joint publications |
Collaborator Contribution | Joint grant applications; joint publications |
Impact | Further funding; joint publications |
Start Year | 2017 |
Description | Biosocial effects of trauma |
Organisation | University of Bath |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Joint grant applications; training of PhD students and early career researchers; joint publications |
Collaborator Contribution | Joint grant applications; joint publications |
Impact | Further funding; joint publications |
Start Year | 2017 |
Description | Biosocial effects of trauma |
Organisation | University of Cape Town |
Country | South Africa |
Sector | Academic/University |
PI Contribution | Joint grant applications; training of PhD students and early career researchers; joint publications |
Collaborator Contribution | Joint grant applications; joint publications |
Impact | Further funding; joint publications |
Start Year | 2017 |
Description | Pregnancy complications and CVD: the Swedish PACER study |
Organisation | Lund University |
Country | Sweden |
Sector | Academic/University |
PI Contribution | Expertise in the shared research agenda |
Collaborator Contribution | Expertise in the shared research agenda; data |
Impact | First manuscript submitted |
Start Year | 2014 |
Description | Pregnancy complications and future CVD: the Norwegian HUNT studies |
Organisation | Harvard University |
Country | United States |
Sector | Academic/University |
PI Contribution | Expertise in the shared research agenda and analytical skills |
Collaborator Contribution | Expertise in the shared research agenda; data |
Impact | Several conference presentations and pending publications (under revision) |
Start Year | 2014 |
Description | Pregnancy complications and future CVD: the Norwegian HUNT studies |
Organisation | Norwegian University of Science and Technology (NTNU) |
Country | Norway |
Sector | Academic/University |
PI Contribution | Expertise in the shared research agenda and analytical skills |
Collaborator Contribution | Expertise in the shared research agenda; data |
Impact | Several conference presentations and pending publications (under revision) |
Start Year | 2014 |