ALPHABET
Early life programming of childhood health: a nutritional and epigenetic investigation of adiposity and bone, cardiometabolic, neurodevelopmental and respiratory health
Background and aim
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:
- Harmonise data from participating birth cohorts
- Perform epigenetic profiling of archived samples
- Generate dietary inflammatory indices (DII) and dietary quality scores (DASH)
- Determine maternal diet effects on offspring health and epigenetics
Expected impact
Given the research focus, the expected scientific, health and socio-economic impacts of the project results may be significant considering the health service and societal costs associated with obesity alone, currently and for future generations.
- For the scientific community
Our results will make a significant contribution to the knowledge base regarding the developmental origins of health/disease, specifically highlighting the importance and increasing awareness of the role of maternal dietary quality and inflammatory potential during pregnancy in influencing both offspring birth and childhood outcomes.
- Health-related applications or new products
Improving our understanding of the relationships between maternal nutrition, pregnancy outcome and subsequent child health may help inform public health policy and potentially development of functional foods or new dietary guidelines/recommendations. For example improved dietary quality and/or reduced pro-inflammatory dietary status achieved through revision of existing guidelines or development of new guidelines for optimal nutrition in pregnancy or development of functional foods may lead to beneficial health effects in women of reproductive years and their offspring which may have long term effects on their health into adulthood, with associated socioeconomic benefits.
Consortium
| Partner Organization | Partner Country |
|---|---|
| Nofer Institute of Occupational Medicine | Poland |
| Erasmus University Rotterdam | The Netherlands |
| National Institute of Health and Medical Research (INSERM) | France |
| University of Bristol | United Kingdom |
| University of Southampton | United Kingdom |
Highlights
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:
- associated with lower birth size and increased risk of delivering a small-for-gestational-age baby (n=24, 861 mother-child pairs),
- greater risk of late childhood overweight and obesity (n=16,295 mother-child pairs),
- moderate increased risk of childhood anxiety, aggression, depressive and ADHD symptoms (n= 11,870 mother-child pairs),
- not linearly associated with child's wheezing or asthma (n=18,326 mother-child pairs).
Reports
Endreport
The main findings of the ALPHABET project are that suboptimal maternal diet (ie having a low quality or a pro-inflammatory diet) in pregnancy is:
- asociated with lower birth size and increased risk of delivering a small-for-gestational-age baby (n=24, 861 mother-child pairs),
- may adversely influence offspring body composition and risk of overweight and obesity, especialy during late childhood. (n=16,295 mother-child pairs),
- associated with moderate increased risk of childhood anxiety, agression, depressive and ADHD symptoms (n= 11,870 mother-child pairs),
- negatively associated with offspring bone outcomes (n=7,780 mother-child paris)
- not linearly associated with child's wheezing or asthma (n=18,326 mother-child pairs).
- associated with subtle epigenetic modifications in the offspring.
This collective body of research highlights the importance of improving and promoting an overall maternal dietary pattern based on predefined criteria (specifically dietary quality and reducing dietary inflammatory potential) to optimise fetal and childhood growth, bone development, emotional and behavioural symptoms and avert adverse birth and childhood outcomes (including obesity) and associated substantial healthcare burden. These findings are of direct relevance to the aims of the JPI HDHL BioNH call “to focus on the identification and validation of biomarkers that are modulated by diet and that indicate a change in health status and/or the risk of developing diet-related diseases” and 2) the JPI HDHL strategic goal to “change dietary patterns based on developments in food, nutritional and health sciences, and to develop evidence-based recommendations that will, together with concomitant changes in physical activity, have a major impact on improving public health, increasing the quality of life and prolonging productive life”.
Outcome
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.
Communication & Dissemination Activities
| Target group | Authors | Means of communication |
|---|---|---|
| Scientists, public health professionals and clinicians | Chen L-W*, Navarro P, Murrin CM, Mehegan J, Kelleher CK*, Phillips CM*. Prospective associations of maternal glycaemic insulin index and load with birth outcomes and weight status at age 5 years: results from the Lifeways Cross Generation Cohort Study. Public Health Science Conference, Belfast, UK, 2018 | Poster presentation |
| Scientists, nutritional professionals and policy makers | Chen L-W*, Fitzgerald R, Murrin CM, Mehegan J, Kelleher CK*, Phillips CM* Associations of maternal caffeine intake with birth outcomes: Results from the Lifeways Cross Generation Cohort Study. International Conference on Nutrition and Growth, Paris, France, 2018 | Oral presentation |
| Scientists, clinicians, students | N Harvey*. Gestational vitamin D supplementation and offspring bone development: translation from observation to intervention. World Congress in the Developmental Origins of Adult Health and Disease, Rotterdam, 2017 | Oral presentation |
| Scientists, clinicians, students | Curtis E*, Harvey N* et al., RXRA promoter DNA methylation at birth is associated with gestational vitamin D supplementation: results from the MAVIDOS trial. World Congress in the Developmental Origins of Adult Health and Disease, Rotterdam, 2017 | Oral presentation |
| Scientists, clinicians, students | Curtis E*, Harvey N* et al, Maternal urinary beta-C-terminal telopeptide of type I collagen (CTX) in pregnancy, and response to cholecalciferol supplementation: findings from the MAVIDOS trial. World Congress in Osteoporosis, Krakow, 2018 | Oral presentation |
| Public (school children) | N Harvey*, E Curtis* Bone Research Society event at annual conference (Lifelab). June 26th 2018 | Workshop |
| Scientists, clinicians, students | H.T. den Dekker, Newborn DNA- methylation, childhood lung function, and the risk of asthma and COPD across the life course, DOHaD, Rotterdam, 2017 | Oral presentation |
| Scientists, clinicians, students | S.M. Mensink-Bout*, Influence of maternal and fetal 25-hydroxyvitamin D levels on lung function and atopic disease development, DOHaD, Rotterdam, 2017 | Poster presentation |
| Scientists, clinicians, students | S.M. Mensink-Bout, Vitamin D levels during pregnancy and respiratory health in childhood, International Conference on Nutrition&Growth, Paris, 2018 | Oral presentation |
| Scientists, clinicians, students | C. Hu, Eczema phenotypes in childhood, DOHaD, Rotterdam, 2017 | Poster presentation |
| Scientists, clinicians, students | C. Hu, Phenotypes of childhood eczema, EAACI Skin Allergy Club, 2018 | Oral presentation |
| Scientists, clinicians, students | C. Hu, Eczema phenotypes in childhood, DOHaD, Rotterdam, 2017 | Poster presentation |
| Scientists | S.M. Mensink-Bout*, Influence of maternal and fetal 25-hydroxyvitamin D levels on lung function and atopic disease development, Conference on Epidemiological Birth Cohort and Longitudinal Studies – 3rd Paula Rantakallio Symposium, Oulu, 2018 | Poster presentation |
| Scientists, clinicians and policy makers | S.M. Mensink-Bout*, Early life vitamin D levels and childhood respiratory morbidity and allergic sensitization, European Respiratory Society International Congress, Paris, 2018 | Oral presentation |
| Scientists, clinicians | C. Hu, Associations of early life environmental exposures and genetic risk factors with eczema phenotypes, Annual meeting of Dutch Society for Experimental Dermatology 2019 | Oral presentation |
| Scientists, clinicians | C. Hu, Eczema phenotypes and risk of allergic and respiratory conditions in school age children, European Society for Pediatric Dermatology Congress, 2019 | Oral presentation |
| Scientists, clinicians | C. Hu, Associations of early life environmental exposures and genetic risk factors with eczema phenotypes, European Society for Pediatric Dermatology Congress, 2019 | Poster presentation |
| Scientists, clinicians, students | S.M. Mensink-Bout, General and organ fat measures and respiratory outcomes at the age of 10 years, Sophia Research Day, Rotterdam, 2019 | Oral presentation |
| Generation R Study participants | Study participants are kept informed of updates/news from the cohort studies | Newsletters (usually annual, but up to 4 times/year for Generation R) Social media including cohort websites and facebook. Press releases. |
| Scientists, public health professionals and clinicians | 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* Influence of maternal dietary inflammatory potential and quality on offspring birth outcomes: a pooled analysis of 7 European cohorts in the ALPHABET consortium. 11th World Congress on Developmental Origins of Health and Disease, Melbourne, Australia. October 20-23, 2019. | Oral |
| Scientists, public health professionals and clinicians | 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* Maternal dietary quality, inflammatory potential and offspring adiposity throughout childhood: a pooled analysis of 7 European cohorts (ALPHABET consortium). 13th Federation of European Nutrition Societies (FENS) European Nutrition Conference 2019, Dublin, Ireland. October 15-18, 2019. | Oral |
| Scientists, public health professionals and clinicians | Chen LW, Lyons B, Navarro P, Shivappa N, Mehegan J, Murrin CM, Hébert JR, Kelleher CC, Phillips CM* Maternal Dietary Inflammatory Potential and Quality Are Associated with Offspring Asthma Risk over 10-year Follow-up: The Lifeways Cross-Generation Cohort Study. Nutrition 2019 by the American Society of Nutrition, Baltimore, USA. June 8-11, 2019 | |
| Scientists, public health professionals and clinicians | Marion Lecorguillé, Pilar Navarro, Ling-Wei Chen, Celine Murrin, Karien Viljoen, John Mehegan, Nitin Shivappa, James R Hébert, Cecily C. Kelleher, Matthew Suderman* and Catherine M Phillips* Maternal and paternal dietary quality and dietary inflammation associations with offspring DNA methylation and epigenetic biomarkers of aging, European Public Health Conference, Dublin (online) Nov 10th-14th, 2021 | Oral |
| Scientists, public health professionals and clinicians | Polańska K*, Trafalska E, Hanke W, Wesołowska E, Jankowska A, Kałużny P, Janasik B, Gromadzinska J, Wasowicz W, Calamandrei G. Sociodemographic, lifestyle, environmental and pregnancy-related determinants of the micronutrients status during pregnancy. 31st annual conference of the International Society for Environmental Epidemiology (ISEE 2019) 25-28 August 2019, Utrecht, The Netherlands | Oral |
| Scientists, public health professionals and clinicians | Polańska K*, Trafalska E, Hanke W, Wesołowska E, Jankowska A, Kałużny P, Janasik B, Gromadzinska J, Wasowicz W, Calamandrei G. Sociodemographic, lifestyle, environmental and pregnancy-related determinants of the micronutrients status during pregnancy. 12th European Public Health Conference Building bridges for solidarity and public health. 20 - 23 November 2019, Marseille, France | Oral |
| Scientists, public health professionals and clinicians | Matthew Suderman*. Prenatal nutrition, DNA methylation and offspring health outcomes. European Association for the Study or Obesity and the World Obesity Federation joint congress, 2020, | Oral |
| Scientists and clinicians | E Curtis, N Harvey* MAVIDOS 4 year bone outcomes at American Society for Bone and Mineral Research Annual Scientific Meeting, Orlando, Florida, USA, September 2019. | Oral |
| Scientists and clinicians | E Curtis*, N Harvey* MAVIDOS maternal bone turnover markers at World Congress in Osteoporosis, Paris, France, April 2019. | Oral |
| Scientists and clinicians | E Curtis: Mechanisms of maternal and offspring bone health in MAVIDOS; UK Association of Physicians, Oxford, UK April 2019. | Oral |
| Scientists and clinicians | N Harvey*: Developmental contribution to bone health in peak bone mass debate, 6th European Calcified Tissue Society Congress, Budapest 2019 | Oral |
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