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 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 try 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 epigenetics (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 (DII) and dietary quality scores (DASH)

4: Determine maternal diet effects on offspring health and epigenetics

Results: Our findings from a series of individual participant data meta-analyses suggest that suboptimal maternal diet (low quality/pro-inflammatory diet) in pregnancy is i) associated with lower birth size and increased risk of delivering a small-for-gestational-age baby (n=24, 861 mother-child pairs), ii) greater risk of late childhood overweight and obesity (n=16,295 mother-child pairs), iii) moderate increased risk of childhood anxiety, aggression, depressive and ADHD symptoms (n= 11,870 mother-child pairs), iv) negatively associated with offspring bone outcomes (n=7,780 mother-child pairs) and v) not linearly associated with child's wheezing or asthma (n=18,326 mother-child pairs), with limited evidence of maternal diet influence on epigenetics. Impact: Our results may have public health implications in terms of informing the development of more effective evidence-based public health strategies with an emphasis on advocating a healthy/less pro-inflammatory diet in pregnancy to optimise fetal growth, reduce obesity and attenuate development of a range of adverse childhood health outcomes.

Highlights from the ALPHABET project include the following publications:

Associations of maternal dietary inflammatory potential and quality with offspring birth outcomes: An individual participant data pooled analysis of 7 European cohorts in the ALPHABET consortium. Chen LW, Aubert AM, Shivappa N, Bernard JY, Mensink-Bout SM, Geraghty AA, Mehegan J, Suderman M, Polanska K, Hanke W, Trafalska E, Relton CL, Crozier SR, Harvey NC, Cooper C, Duijts L, Heude B, Hébert JR, McAuliffe FM, Kelleher CC, Phillips CM.PLoS Med. 2021 Jan 21;18(1):e1003491. doi: 10.1371/journal.pmed.1003491.

Maternal dietary quality, inflammatory potential and childhood adiposity: an individual participant data pooled analysis of seven European cohorts in the ALPHABET consortium. Chen LW, Aubert AM, Shivappa N, Bernard JY, Mensink-Bout SM, Geraghty AA, Mehegan J, Suderman M, Polanska K, Hanke W, Jankowska A, Relton CL, Crozier SR, Harvey NC, Cooper C, Hanson M, Godfrey KM, Gaillard R, Duijts L, Heude B, Hébert JR, McAuliffe FM, Kelleher CC, Phillips CM.BMC Med. 2021 Feb 22;19(1):33. doi: 10.1186/s12916-021-01908-7.

Dietary Quality and Dietary Inflammatory Potential During Pregnancy and Offspring Emotional and Behavioral Symptoms in Childhood: An Individual Participant Data Meta-analysis of Four European Cohorts. Polanska K, Kaluzny P, Aubert AM, Bernard JY, Duijts L, El Marroun H, Hanke W, Hébert JR, Heude B, Jankowska A, Mancano G, Mensink-Bout SM, Relton C, Shivappa N, Suderman M, Trafalska E, Wesolowska E, Garcia-Esteban R, Guxens M, Casas M, Phillips CM.Biol Psychiatry. 2021 Mar 15;89(6):550-559. doi: 10.1016/j.biopsych.2020.10.008.

Maternal diet in pregnancy and child's respiratory outcomes: an individual participant data meta-analysis of 18 000 children. Mensink-Bout SM, van Meel ER, de Jongste JC, Annesi-Maesano I, Aubert AM, Bernard JY, Chen LW, Cooper C, Crozier SR, Hanke W, Harvey NC, Hébert JR, Heude B, Jerzynska J, Kelleher CC, Mehegan J, McAuliffe FM, Phillips CM, Polanska K, Relton CL, Shivappa N, Suderman M, Jaddoe VWV, Duijts L. Eur Respir J. 2021 Sep 9:2101315. doi: 10.1183/13993003.01315-2021.

Deriving the Dietary Approaches to Stop Hypertension (DASH) Score in Women from Seven Pregnancy Cohorts from the European ALPHABET Consortium. Aubert AM, Forhan A, de Lauzon-Guillain B, Chen LW, Polanska K, Hanke W, Jankowska A, Mensink-Bout SM, Duijts L, Suderman M, Relton CL, Crozier SR, Harvey NC, Cooper C, McAuliffe FM, Kelleher CC, Phillips CM, Heude B, Bernard JY. Nutrients. 2019 Nov 8;11(11):2706. doi: 10.3390/nu11112706.

These publications, in high impact journals, have been highlighted in press releases and invited commentaries.

The results from this series of individual participant data meta-analyses suggest that suboptimal maternal diet (low quality/pro-inflammatory diet) in pregnancy is:

i) associated with lower birth size and increased risk of delivering a small-for-gestational-age baby (n=24, 861 mother-child pairs),

ii) greater risk of late childhood overweight and obesity (n=16,295 mother-child pairs),

iii) moderate increased risk of childhood anxiety, aggression, depressive and ADHD symptoms (n= 11,870 mother-child pairs),

iv) not linearly associated with child's wheezing or asthma (n=18,326 mother-child pairs).