ERA-HDHL cofunded call “Biomarkers for Nutrition and Health” (BioNH 2016)

Early life programming of childhood health: a nutritional and epigenetic investigation of adiposity and bone, cardiometabolic, neurodevelopmental and respiratory health
ALPHABET
2017-01-01
2019-11-30
Dr Catherine Phillips
Partner Organization Partner Country

1. Overall project description


1.1 Summary

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.


1.2 Highlights

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.


 


4. Impact


4.1 List of publications

AuthorsTitleYear, Issue, PPDoiPdf
Chen L-W*, Murrin CM, Mehegan J, Kelleher CK, Phillips CMMaternal, but not paternal or grandparental, caffeine intake is associated with childhood obesity and adiposity: The Lifeways Cross-Generation Cohort Study. 2019, 109(6), 1648-165510.1093/ajcn/nqz019
Wesołowska E*, Jankowska A, Trafalska E, Kałużny P, Grzesiak M, Dominowska J, Hanke W, Calamandrei G, Polańska K*.Sociodemographic, Lifestyle, Environmental and Pregnancy-Related Determinants of Dietary Patterns during Pregnancy2019, 16(5) , E754doi: 10.3390/ijerph16050754.
Chen L-W*, Navarro P, Murrin CM, Mehegan J, Kelleher CK, Phillips CMMaternal Dietary Glycemic and Insulinemic Indexes Are Not Associated with Birth Outcomes or Childhood Adiposity at 5 Years of Age in an Irish Cohort Study 2019, 149(6), 1037–1046doi.org/10.1093/jn/nxz025
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 Study2018, 108(6), 1301-130810.1093/ajcn/nqy219
Curtis E*, Suderman M*, Phillips CM*, Relton C*, Harvey N*.Early‐life dietary and epigenetic influences on childhood musculoskeletal health: Update on the UK component of the ALPHABET project2018, 43(2), 158-17310.1111/nbu.12322
Mensink-Bout SM*, van Meel ER, de Jongste JC, Voortman T, Reiss IK, De Jong NW, Jaddoe VWV, Duijts L*. Maternal and neonatal 25-hydroxyvitamin D concentrations and school-age lung function, asthma and allergy. The Generation R Study. 2019 10.1111/cea.13384
Hu C, Duijts L*, Erler NS, Elbert NJ, Piketty C, Bourdès V, Blanchet-Réthoré S, de Jongste JC, Pasmans SGMA, Felix JF, Nijsten T. Most associations of early life environmental exposures and genetic risk factors poorly differentiate between eczema phenotypes. The Generation R study. 2019 10.1111/bjd.17879
den Dekker HT, Burrows K, Felix JF, Salas LA, Nedeljkovic I, Yao J, Rifas-Shiman SL, Ruiz-Arenas C, Amin N, Bustamante M, DeMeo DL, Henderson AJ, Howe CG, Hivert MF, Ikram MA, de Jongste JC, Lahousse L, Mandaviya PR, van Meurs JB, Pinart M, Sharp GC, Stolk L, Uitterlinden AG, Anto JM, Litonjua AA, Breton CV, Brusselle GG, Sunyer J, Smith GD, Relton CL*, Jaddoe VWV, Duijts L*. Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course. 2019 10.1183/13993003.01795-2018

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
Scientists, public health professionals and cliniciansChen 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, 2018Poster presentation
Scientists, nutritional professionals and policy makersChen 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, 2018Oral presentation
Scientists, clinicians, studentsN 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, 2017Oral presentation
Scientists, clinicians, studentsCurtis 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, 2017Oral presentation
Scientists, clinicians, studentsCurtis 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, 2018Oral presentation
Public (school children)Bone Research Society event at annual conference (Lifelab). N Harvey*, E Curtis* June 26th 2018Workshop
Scientists, clinicians, studentsH.T. den Dekker, Newborn DNA- methylation, childhood lung function, and the risk of asthma and COPD across the life course, DOHaD, Rotterdam, 2017Oral presentation
Scientists, clinicians, studentsS.M. Mensink-Bout*, Influence of maternal and fetal 25-hydroxyvitamin D levels on lung function and atopic disease development, DOHaD, Rotterdam, 2017Poster presentation
Scientists, clinicians, studentsS.M. Mensink-Bout, Vitamin D levels during pregnancy and respiratory health in childhood, International Conference on Nutrition&Growth, Paris, 2018Oral presentation
Scientists, clinicians, studentsC. Hu, Eczema phenotypes in childhood, DOHaD, Rotterdam, 2017Poster presentation
Scientists, clinicians, studentsC. Hu, Phenotypes of childhood eczema, EAACI Skin Allergy Club, 2018Oral presentation
Scientists, clinicians, studentsC. Hu, Eczema phenotypes in childhood, DOHaD, Rotterdam, 2017Poster presentation
ScientistsS.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, 2018Poster presentation
Scientists, clinicians and policy makersS.M. Mensink-Bout*, Early life vitamin D levels and childhood respiratory morbidity and allergic sensitization, European Respiratory Society International Congress, Paris, 2018Oral presentation
Scientists, cliniciansC. Hu, Associations of early life environmental exposures and genetic risk factors with eczema phenotypes, Annual meeting of Dutch Society for Experimental Dermatology 2019Oral presentation
Scientists, cliniciansC. Hu, Eczema phenotypes and risk of allergic and respiratory conditions in school age children, European Society for Pediatric Dermatology Congress, 2019Oral presentation
Scientists, cliniciansC. Hu, Associations of early life environmental exposures and genetic risk factors with eczema phenotypes, European Society for Pediatric Dermatology Congress, 2019Poster presentation
Scientists, clinicians, studentsS.M. Mensink-Bout, General and organ fat measures and respiratory outcomes at the age of 10 years, Sophia Research Day, Rotterdam, 2019Oral 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.

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf

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