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

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.

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.

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.