Prenatal influences on childhood health: what role for mums and dads?

Lead Research Organisation: University of Bristol
Department Name: Social Medicine

Abstract

While it is widely recognised that a woman's lifestyle and experiences during pregnancy can influence the development and health of her child, remarkably little robust, scientific research supports this link. This limited evidence-base means that much of the current public health advice given to pregnant women is inconsistent, confusing and may potentially even be harmful. Additionally, there is emerging evidence that a man's behaviour can influence the health of their unborn children, but very little public health advice is currently offered to fathers-to-be, and the scientific evidence is even more scant.

This work aims to better understand how both maternal and paternal lifestyles in the prenatal period influence offspring health and social outcomes. Findings will highlight whether interventions to improve child health are best targeted at mothers, fathers or both parents.

The project makes use of detailed and diverse data that has already been collected through several large birth cohort studies from the UK, the Netherlands, Norway and Denmark; allowing access to rich data on hundreds of thousands of people.

Using these data, I will identify whether maternal and/or paternal smoking, alcohol intake, fat/sugar intake, caffeine and physical activity in the prenatal period are correlated with a range of childhood outcomes including birth weight, cleft lip/palate, body mass index, IQ and educational attainment.

I will then apply several state-of-the-art statistical methods to infer whether these parental health behaviours actually cause these offspring outcomes, or whether the observed correlations arise because of other "confounding" factors (e.g. socioeconomic position).

Where it looks like the relationship is causal, I will use several statistical methods to infer whether the outcome is caused by maternal behaviour, paternal behaviour, or a combination of the two.

Finally, I will explore the biological basis to these causal relationships by studying blood levels of DNA methylation (epigenetics), gene expression and metabolites in the children.

Findings from this work could help improve childhood health by providing better evidence about how the lifestyles of mothers and fathers shape childhood health and whether public health advice would be most effective if aimed at mothers, fathers or both parents.

Technical Summary

It is widely recognised that pregnant mothers can influence the health and characteristics of their children via non-genomic "maternal effects", but there are still gaps in our understanding regarding causality and the range and mechanism of effects. Consequently, current public health advice for women who are pregnant or looking to conceive can be inconsistent, misleading and often based on the precautionary principle rather than robust, empirical evidence of causation. Additionally, there is increasing evidence that fathers can also exert "paternal effects" on the health of their unborn children, but very little advice is currently offered to fathers-to-be.

This research will address an urgent unmet need to better understand how both maternal and paternal health behaviours in the prenatal period influence offspring health outcomes.

The four specific research questions are:
1) Which prenatal maternal and paternal health behaviours associate with offspring outcomes?
2) Which of these associations are causal?
3) How do maternal and paternal influences interact or mediate each other?
4) What are the underlying molecular mechanisms?

The project uses existing questionnaire and 'omics data (therefore representing excellent value-for-money) from six major European birth cohorts, focusing on parental exposures that might be considered modifiable (smoking, alcohol, physical activity, diet) and offspring outcomes spanning three domains of child development (anthropometry/adiposity, neurodevelopmental/psychosocial, congenital anomalies) as well as potential molecular mediators (DNA methylation, metabolites). Evidence garnered using different state-of-the-art epidemiological approaches will be triangulated to help identify and refine causal pathways.

Findings will identify the most appropriate prenatal targets (mothers, fathers or both parents) for public health advice to improve offspring outcomes.

Planned Impact

This project has the potential to have significant and far-reaching impact. It aims to produce evidence for effective advice and interventions on maternal and paternal health behaviours in the prenatal period. Ultimately, achieving this aim will lead to improved health outcomes in children.

The research focuses on health behaviours that can be considered "modifiable" in order to maximise the potential for effective interventions. The range of childhood outcomes considered is purposefully broad to reflect the potential far-reaching consequences of perturbations during development.

Beneficiaries and potential impacts of this research are outlined below:

-NATIONAL AND INTERNATIONAL POLICYMAKERS
This research will benefit policymakers (e.g. those involved with the National Institute for Health and Care Excellence, NICE) in making evidence-based policy decisions regarding prenatal public health advice. This is in line with the UK parliamentary 1001 Critical Days Campaign, a cross-party manifesto to support and establish universal and specialist provision to offer services to parents and their babies from conception to age 2, which states that "it is vital that a focus on the early years is placed at the heart of the policy making process".

-CHARITIES
Charities that support parents, particularly around pregnancy, have called for more research and more evidence-based advice to be given to parents in the prenatal period, and will therefore benefit from this research. For example: the British Pregnancy Advice Service (BPAS) invited me to a workshop in September 2017 where we discussed current prenatal advice and potential implications for the autonomy of women; "NCT" is a charity to support parents by providing them with accurate, impartial information, including research summaries; Maternity Action is the UK's leading charity committed to ending inequality and improving the health and well-being of pregnant women, partners and young children, from conception through to the child's early years; The Fatherhood Institute is a UK-based think tank whose objectives include collating, publishing and mobilising international research on fathers and their impact on children and mothers, shaping national and local policy to ensure a father-inclusive approach and producing briefs for MPs about evidence on the importance of fathers in the period from conception to age two.

-HEALTH PROFESSIONALS
Midwives, GPs, paediatricians and other allied healthcare professionals who provide support for parents and children will benefit from a better evidence-base to their clinical practice.

-THE GENERAL PUBLIC
Over 700,000 babies are conceived each year in England and Wales and at least 130 million babies are born each year worldwide. The huge number of individuals who are considering having a baby or have an unplanned pregnancy will benefit from more effective, more consistent public health advice in the prenatal period, and their offspring will benefit through enhanced health and social outcomes in childhood. This is likely to have a knock-on effect into adulthood and therefore on public health and the economy.

Publications

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Juvinao-Quintero DL (2019) DNA Methylation and Type 2 Diabetes: the Use of Mendelian Randomization to Assess Causality. in Current genetic medicine reports

 
Title EPoCH animation 
Description I created an animation to explain the aims and methods that are used in EPoCH. 
Type Of Art Film/Video/Animation 
Year Produced 2019 
Impact The animation is uploaded on YouTube and has had over 300 views. Several people have contacted me for more information about EPoCH after watching the animation. 
URL https://www.youtube.com/watch?v=-zjMVYl5R7M
 
Description 1001 Critical Days consultation
Geographic Reach National 
Policy Influence Type Participation in a national consultation
URL https://epoch.blogs.bristol.ac.uk/2020/02/04/the-1001-critical-days-movement/
 
Description Co-director of the MSc in Reproduction and Development
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Gemma Sharp is the co-director of the University of Bristol's highly successful MSc in Reproduction and Development. Students include practicing midwifes, junior doctors, researchers and embryologists. The course equips them with the necessary skills to improve their practice and critically appraise, design and conduct relevant research.
URL http://www.bristol.ac.uk/medical-school/study/postgraduate/reproduction-development/
 
Description Epigenetic Epidemiology short course
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact I developed and delivered a one week course on epigenetic epidemiology in 2019 and again in 2020. Participants ranged from masters to professorial level. The course was very well-received and participants reported feeling confident that they had achieved the intended learning outcomes. Several are now conducting their own genetic/epigenetic studies.
URL https://www.bristol.ac.uk/medical-school/study/short-courses/epigenetic-epidemiology/
 
Description Genetic and Epigenetic Epidemiology (EEPE) course
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Gemma Sharp and Rebecca Richmond (along with David Evans and Gib Hemani) co-developed and delivered a one week course on genetic and epigenetic epidemiology in Florence. Participants ranged from masters to professorial level. The course was very well-received and participants reported feeling confident that they had achieved the intended learning outcomes. Several are now conducting their own genetic/epigenetic studies.
URL https://eepe.org/courses/
 
Description Lectures at LSHTM
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Gemma Sharp was invited to give two lectures to masters students at the London School of Hygiene and Tropical Medicine: "Minimising bias and confounding in observational epidemiology" and "Mendelian Randomization". These will take place on March 17th 2020. The lectures are intended to introduce students to these important areas and methods in observational epidemiology and equip them with the skills to critically appraise, design and conduct high quality epidemiological research.
 
Description MSc in Epidemiology - unit lead of 'Molecular Epidemiology for Noncommunicable Disease'
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Gemma Sharp co-developed from scratch and now co-delivers a unit on Molecular Epidemiology as part of the University of Bristol's MSc in Epidemiology. The unit introduces masters students to molecular (genetic and epigenetic) epidemiology and equips them with the skills to critically appraise, design and conduct high quality epidemiological research.
URL https://www.bris.ac.uk/unit-programme-catalogue/UnitDetails.jsa;jsessionid=2BBAB6E8979AB5B406936FBF3...
 
Description UK Government's consultation on adding folic acid to flour
Geographic Reach National 
Policy Influence Type Participation in a national consultation
URL https://consultations.dh.gov.uk/flour/ef256a11/
 
Description WRISK project expert panel - Gemma Sharp
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL https://threadreaderapp.com/thread/1220645863577485312.html
 
Description Workshop on harmonisation of data in multicohort studies
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Gemma Sharp gave a talk as part of a half-day course on data harmonization in observational studies at the DOHaD 2019 world congress in Melbourne. Participants ranged from masters to professorial level. The course was very well-received and participants reported feeling confident that they had achieved the intended learning outcomes. Several are now conducting their own multi cohort studies.
URL http://www.cvent.com/events/2019-dohad-international/custom-132-828d23c3caf043c0ae6449de8d7bfbc3.asp...
 
Description Workshop on triangulation
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Gemma Sharp co-developed and delivered a half-day course on triangulation in observational studies at the DOHaD 2019 world congress in Melbourne. Participants ranged from masters to professorial level. The course was very well-received and participants reported feeling confident that they had achieved the intended learning outcomes. Several are now conducting their own triangulation studies.
URL http://www.cvent.com/events/2019-dohad-international/custom-132-828d23c3caf043c0ae6449de8d7bfbc3.asp...
 
Description Wellcome Trust PhD in Molecular, Genetic and Lifecourse Epidemiology - studentship to Florence Martin
Amount £130,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2020 
End 10/2024
 
Description Wellcome Trust PhD in Molecular, Genetic and Lifecourse Epidemiology - studentship to Peiyuan Huang
Amount £130,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2020 
End 10/2024
 
Description EPoCH collaboration with Born in Bradford 
Organisation Bradford Institute for Health Research (BIHR)
Department Born in Bradford
Country United Kingdom 
Sector Public 
PI Contribution We are working with Born in Bradford data, which will help highlight the use of the resource. We plan to visit Bradford to give a talk about our findings to academics and also participate in the public engagement event BIBfest.
Collaborator Contribution Our collaborators have given us access to Born in Bradford data and guidance on how to use it.
Impact No outputs yet, but we are working on an invited paper for submission in March 2020.
Start Year 2019
 
Description EPoCH collaboration with Generation R 
Organisation Erasmus MC
Country Netherlands 
Sector Academic/University 
PI Contribution A member of my research team (Kayleigh Easey) will be visiting Erasmus to work on Generation R data for the EPoCH project. This visit will help build and strengthen our collaboration and Kayleigh will present about her work and share her expertise while in Rotterdam.
Collaborator Contribution Erasmus are providing us with Generation R data, which will be a vital component of our research. They are also hosting my post-doc for the duration of her visit.
Impact We are currently sorting out the DTA and collaboration agreement with our legal departments.
Start Year 2019
 
Description EPoCH collaboration with MoBa 
Organisation Norwegian Mother and Child Cohort (MoBa)
Country Norway 
Sector Public 
PI Contribution A member of my research team (Kayleigh Easey) will be visiting Oslo to work on MoBa data for the EPoCH project. This visit will help build and strengthen our collaboration and Kayleigh will present about her work and share her expertise while in Oslo.
Collaborator Contribution Our collaborators in Oslo have helped us gain access to MoBa data through a remote system. They are guiding us through the administrative procedures. They will also host my post-doc for the duration of her stay in Oslo.
Impact The collaboration has not yet produced any outputs.
Start Year 2019
 
Description Fatherhood Institute 
Organisation Fatherhood Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Staff from the Fatherhood Institute have joined the EPoCH Research Advisory Panel after they were invited in 2019. We produced a six month progress report, which we sent to the Research Advisory Panel in December 2019. We have organised a face-to-face Advisory Panel meeting for 30/03/2020 where we will discuss the report further and show some preliminary research findings.
Collaborator Contribution The Fatherhood Institute commented on our report and plans for the future. A representative will attend our Research Advisory Panel meeting in Bristol in March 2020. By engaging the Fatherhood Institute from the beginning of this research, we ensure that they will be aware of our work (which is very relevant to their mission) and able to 1) offer their unique perspective on how our findings might be framed, and 2) help disseminate research outputs when the time comes.
Impact Establishment of a Research Advisory Panel. Production of a six month research progress report. Organisation of a Advisory Panel face-to-face meeting.
Start Year 2019
 
Description Creative Reactions 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I took part in Creative Reactions, an initiative that pairs scientists with artists to create artwork based on their academic research. I was paired with Olga Trevisan, an artist based in Venice, Italy. Based on some of my research around the Developmental Origins of Health and Disease, Olga created a piece called Beyond Question, which comments on the complexities of scientific data collection, bias and interpretation. Interesting conversations with people viewing the artwork revealed that some people's opinions (about the importance of the maternal contribution to offspring health, relative to paternal and wider societal influences) were challenged and changed. The artwork was displayed at two exhibitions at different sites in Bristol, with two separate launch events attended by the local media.
Year(s) Of Engagement Activity 2019
URL https://epoch.blogs.bristol.ac.uk/2019/12/21/beyond-question-a-collaboration-between-epoch-and-artis...
 
Description EPoCH Instagram account 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact We have a dedicated EPoCH Instagram account with >60 followers.
Year(s) Of Engagement Activity 2019,2020
URL https://www.instagram.com/epoch_study/
 
Description EPoCH Research Advisory Panel 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We want to make sure that EPoCH research findings reach the right people in the right way and we don't accidentally end up adding to the confusion around health advice during pregnancy. Therefore, we have set up a Research Advisory Panel of researchers, policy makers and people with real life experience of giving and receiving pregnancy advice.
Panel members give us feedback on our plans and tell us how they think we can best communicate our findings in the most appropriate, effective way. In return, we keep panel members up to date on our findings, and they will be invited to the academic and/or public events that we organise.
Year(s) Of Engagement Activity 2019,2020
URL https://epoch.blogs.bristol.ac.uk/2019/10/03/epoch_needs_you/
 
Description EPoCH animation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I created an animation to explain the aims and methods that will be used in EPoCH. The animation is uploaded on YouTube and has had over 300 views.
Year(s) Of Engagement Activity 2019
URL https://www.youtube.com/watch?v=-zjMVYl5R7M
 
Description EPoCH blog 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I have set up a website for the EPoCH project where I regularly post updates on the project, as well as short tutorials on some of our key research methods. The website receives a steady number of visitors and has a handful of dedicated followers. When I was recruiting for a post-doc, several candidates stated in their application that they had found out about the study through the website.
Year(s) Of Engagement Activity 2019,2020
URL https://epoch.blogs.bristol.ac.uk
 
Description EPoCH twitter account 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact We have set up a dedicated EPoCH Twitter account. We currently have >200 followers.
Year(s) Of Engagement Activity 2019,2020
URL https://twitter.com/EPoCH_study