EpiFASSTT: Epigenetic effects on children's psychosocial development in a randomised trial of Folic Acid Supplementation in Second and Third Trimester

Increasingly accurate surveys of human health throughout the course of life has led experts to propose that stresses on the child while still in the mother's womb can affect its health much later in life. While many factors can potentially act as stressors, the majority of these are difficult to examine thoroughly in human populations and so findings are based largely on observational work. Among concrete factors known to affect child health is the essential nutrient folate, which has been proven to play a role in preventing neural tube closure defects (e.g. Spina bifida) when deficient during the first three months (first trimester) of pregnancy. Current UK guidance is therefore to supplement with folate during first trimester only. However other observational studies suggest that folate deficiency in trimesters two and three also affects children's brain development. Proof for this can only be provided by the gold standard test which is a Randomised Control Trial, where half the participants take folate in trimesters 2 and 3 and half do not, with participants assigned randomly to supplement or no supplement. We recently conducted such a trial (Folic Acid Supplementation in the Second and Third Trimester (FASSTT)) and showed that folate levels in blood were substantially improved in mothers receiving the supplement and in their children. Follow-up work with the children at age seven showed improved outcomes with regard to several measures of intellectual and emotional development, including verbal reasoning ability and emotional resilience. Such long-term effects on health are thought to be mediated by a semi-permanent trace on the genes of the affected person called an epigenetic mark (from epi- (above) and gene). Here we plan to do a thorough search for possible epigenetic marks in the children from the FASSTT trial and their mothers. The levels of such marking detected, and the genes affected by it, will tell us much about the extent to which environmental stressors can affect a person's future health. Likewise it will give us concrete markers for assessing the impact of factors such as nutritional inputs on the health of the child. The results of our study will also inform policy regarding food supplements and pregnancy/early life social care, with tangible benefits for children, their mums, and in the wider sphere the social and health services which provide them with support.

First and foremost, we will address the scope of the call, by combining psychological and biological approaches to investigate the underlying epigenetic changes linking early life experiences with later psychological and physical health outcomes. The overall outcome of the proposed project will be the scientific evidence needed to inform future health policy in relation to nutrition, pregnancy and early life psychosocial development. This will be achieved through an in-depth investigation combining expertise from psychology, nutrition, epigenetics and computing, and applying innovative and emerging technologies to generate new knowledge in an area of current public health importance. We will actively engage with key stakeholders to ensure that we maximise the opportunity for our project outcomes to influence policy and alter behaviour. This includes initiatives such as an Advisory Board for our trial consisting of participants and members of the public; engagement with policy makers at regional government level and in NGOs and use of Open days and Public Lectures. Enhanced multidisciplinary capacity will be built which will extend well beyond the lifetime of the current project. Each project outcome will also be reported as a paper for submission to high impact factor journals in the relevant disciplines, including those focused on public health, as well as presentations at prestigious international conferences and workshops. The excellent training opportunities afforded by this interdisciplinary project in the emerging area of early life influences and epigenetics are further enhanced by a clear program of training for staff and students, such as the Masterclass, as well as events with broader appeal like the Open Day. Participants and public on the Advisory Board will also receive training and gain experience in research studies, and interaction with the Board will be invaluable for the academic staff. The combined expertise described in this proposal will provide added value and considerably enhance the overall impact achievable by any one group alone.
We represent a multidisciplinary team involving three distinct Research Institutes (Biomedical Sciences, Psychology and Intelligent Systems), each with a strong track record of scientific excellence and published work. Of note the current proposal builds substantially on an long history of successful folate research at Ulster, which was recently the focus of a Research Impact Case Study in REF2014 on Folate (folic acid), health policy and the consumer http://ulster.ac.uk/ref2014/Impact/3B_5.pdf This is one demonstration of how international outputs for some of the team to date have provided a scientific foundation for developing evidence-based policy in this area and its translation to consumers. This new proposal has the potential for further concrete impact in terms of influencing policy on food fortification, dietary recommendations and support during pregnancy. Our findings are likely to have a real chance of improving the cognitive and socio-emotional development of children during the first years of life and the quality of life and well-being for mothers. Given the strength of the evidence that childhood development has significant impacts for adult health and well-being the outcomes of this study have major implications for long term impact. Further, the potential benefits to children in general if this work is supported could have a major public health impact within a relatively short timescale. Early intervention and prevention also has economic implications for health care.