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)
- University of Bath (Collaboration)
- Cardiff University (Collaboration)
- Lund University (Collaboration)
- Federal University of Pelotas (UFPel) (Collaboration)
- Norwegian University of Science and Technology (NTNU) (Collaboration)
- University of Cape Town (Collaboration)
Publications
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
O'Keeffe L
(2019)
Accounting for height in indices of body composition during childhood and adolescence
in Wellcome Open Research
Anderson EL
(2017)
Adversity in childhood and measures of aging in midlife: Findings from a cohort of british women.
in Psychology and aging
Magnus MC
(2018)
Age at Menarche and Cardiometabolic Health: A Sibling Analysis in the Scottish Family Health Study.
in Journal of the American Heart Association
O'Keeffe LM
(2020)
Age at period cessation and trajectories of cardiovascular risk factors across mid and later life.
in Heart (British Cardiac Society)
Martin FZ
(2022)
Alcohol Intake and Hypertensive Disorders of Pregnancy: A Negative Control Analysis in the ALSPAC Cohort.
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.)
Regan AK
(2019)
Association between interpregnancy interval and adverse birth outcomes in women with a previous stillbirth: an international cohort study.
in Lancet (London, England)
Foo FL
(2018)
Association Between Prepregnancy Cardiovascular Function and Subsequent Preeclampsia or Fetal Growth Restriction.
in Hypertension (Dallas, Tex. : 1979)
Magnus MC
(2018)
Association of Maternal Psychosocial Stress With Increased Risk of Asthma Development in Offspring.
in American journal of epidemiology
Marinovich ML
(2021)
Associations between interpregnancy interval and preterm birth by previous preterm birth status in four high-income countries: a cohort study.
in BJOG : an international journal of obstetrics and gynaecology
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
Anderson EL
(2018)
Associations of adversity in childhood and risk factors for cardiovascular disease in mid-adulthood.
in Child abuse & neglect
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
Carslake D
(2019)
Associations of mortality with own blood pressure using son's blood pressure as an instrumental variable.
in Scientific reports
O'Keeffe LM
(2018)
Associations of Y chromosomal haplogroups with cardiometabolic risk factors and subclinical vascular measures in males during childhood and adolescence.
in Atherosclerosis
Barnes M
(2022)
Being silenced, loneliness and being heard: understanding pathways to intimate partner violence & abuse in young adults. a mixed-methods study.
in BMC public health
Timpka S
(2019)
Birth weight and cardiac function assessed by echocardiography in adolescence: Avon Longitudinal Study of Parents and Children.
in Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology
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
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
Kilpi F
(2022)
Changes in women's physical function in mid-life by reproductive age and hormones: a longitudinal study.
in BMC women's health
Anderson EL
(2015)
Childhood energy intake is associated with nonalcoholic fatty liver disease in adolescents.
in The Journal of nutrition
Magnus MC
(2018)
Childhood psychosocial adversity and female reproductive timing: a cohort study of the ALSPAC mothers.
in Journal of epidemiology and community health
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
Simpson J
(2016)
Cord Blood Adipokines and Lipids and Adolescent Nonalcoholic Fatty Liver Disease.
in The Journal of clinical endocrinology and metabolism
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
Fraser A
(2024)
Correction: Placental syndromes and long-term risk of hypertension.
in Journal of human hypertension
O'Keeffe LM
(2019)
Data on trajectories of measures of cardiovascular health in the Avon Longitudinal Study of Parents and Children (ALSPAC).
in Data in brief
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 | 11/2022 |
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 |