According to the Developmental Origins of Health and Disease hypothesis early life exposure to environmental factors plays a critical role in defining offspring health in childhood and later life. Thus adaptation to suboptimal nutrition during pregnancy or early childhood may perpetuate intergenerational transmission of a range of adverse health outcomes. Epigenetic phenomena have been proposed as potential mediating mechanisms. Novel associations between selected early life exposures (e.g. maternal intake of certain micronutrients) and offspring epigenome and health have been reported. However the complexity of intergenerational whole diet-health-epigenome associations is not fully understood.

The ALPHABET project aims to address this gap. This consortium brings together 7 partners from Ireland, UK, France, The Netherlands, Poland and the US and 8 European longitudinal birth cohorts which are at the international forefront of lifecourse epidemiology.This project will allow us to go beyond the limits of individual cohorts to identify and validate diet-health-epigenome relationships across multiple populations. Using dietary, clinical and epigenetic data and biological samples from these cohorts, this project will advance the state-of-the-art by significantly expanding the knowledge base regarding the relationships between maternal dietary environment (defined by dietary quality and inflammatory potential), offspring health outcomes (including adiposity, bone, cardiometabolic, respiratory and neurodevelopmental health) and offspring epigenetic age and patterns (DNA methylation) from birth throughout childhood. The main objectives are to:

1: Harmonise data from participating birth cohorts

2: Perform epigenetic profiling of archived samples

3: Generate dietary inflammatory indices and dietary quality scores

4: Determine maternal diet effects on offspring epigenetic age/patterns and health

5: Identify and validate epigenetic patterns associated with offspring health

6: Investigate gestational weight gain/maternal adiposity effects on offspring health and epigenome

7: Test potential intra-uterine influences by comparing maternal and paternal dietary effects

8: Examine identified diet-health-epigenome associations throughout childhood

Achievements thus far include data harmonisation, extraction and sharing between partners. New dietary variables, reflecting dietary quality and dietary inflammatory index, have been generated for all cohorts. The current focus is on diet-health-epigenome analyses. Impact: Our results may have public health implications in terms of refining dietary exposure measures and informing the development of more effective evidence-based public health strategies with an emphasis on advocating a healthy diet in pre-pregnancy, pregnancy and early postnatal life, to reduce obesity, improve health and attenuate development of a range of adverse health outcomes in future generations.

Preliminary findings from the project suggest that a more pro-inflammatory and low quality maternal diet are associated with suboptimal offspring birth outcomes and higher risk of late childhood overweight/obesity. Abstracts based on that work have been accepted for oral presentation at 2 international conferences during October 2019. These include the European Nutrition Conference, Federation of European Nutrition Societies (FENS) conference in Dublin, Ireland and at the Developmental Origins of Health and Disease (DOHaD) conference, Melbourne, Australia. Analysis of associations with epigenetic profiles and other offspring outcomes is underway.