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Early-life stressors and LifeCycle health

Periodic Reporting for period 3 - LIFECYCLE (Early-life stressors and LifeCycle health)

Reporting period: 2020-01-01 to 2021-06-30

Early life is an important window of opportunity to improve health across the full lifecycle. Exposure to stressors just before or during pregnancy or during early childhood leads to developmental adaptations, which subsequently affect life course and disease risk. Optimising early-life conditions has the yet unfulfilled potential to improve life course health trajectories for individuals themselves and also their offspring through transgenerational effects. Therefore, novel strategies for optimising early life will help to maximize the human developmental potential for current and future European generations. Prospective cohort studies starting from pregnancy or childhood provide the opportunity to study the effects of early-life stressors in relation to lifecycle health trajectories, and their potential for targeted prevention or intervention strategies. Europe has a strong tradition in population-based prospective cohort studies from pregnancy or childhood onwards. These cohorts are invaluable resources to identify a wide range of early-life stressors in connection with individual biological, developmental and health trajectory variations related to the onset and evolution of non-communicable diseases.

The LifeCycle Project (www.lifecycle-project.eu) is designed to establish the EU Child Cohort Network, which brings together existing, successful pregnancy and child cohorts and biobanks, by developing a governance structure taking account of national and European ethical, legal and societal implications, a shared data-management platform and data-harmonisation strategies. LifeCycle enriches this EU Child Cohort Network by generating new integrated data on early life stressors related to socio-economic, migration, urban environment and life-style determinants, and capitalise on these data by performing hypothesis-driven research on early life stressors influencing cardio-metabolic, respiratory and mental health trajectories during the full lifecycle, and the underlying epigenetic mechanisms. LifeCycle translates these results into recommendations for targeted strategies and personalised prediction models to improve health trajectories for current and future Europeans generations by optimising their earliest phase of life. To strengthen this long-term collaboration, LifeCycle organises yearly international meetings open to pregnancy and child cohort researchers, introduces a Fellowship Training Programme for exchange of junior researchers between European pregnancy or child cohorts, and develops e-learning modules for researchers performing life course health studies. Ultimately, LifeCycle will lead to a unique sustainable EU Child Cohort Network, and provide recommendations for targeted prevention strategies by identification of novel markers of early life stressors related to health trajectories throughout the lifecycle.
LifeCycle management was performed according to the plan. The COVID-19 pandemic led to delays in reporting which have all been submitted now. An non-addititional cost extenstion amendment has been submitted and approved.

Major achievements for the first 54 months
- Establishment of the EU Child Network with:
- Harmonization of more than 800 variables between 19 cohorts for approximately 250,000 children and their parents;
- Enrichment of existing cohorts by new integrated exposure and exposome variables;
- Harmonization protocols available for other cohorts (https://lifecycle-project.eu);
- YouTube channel with freely accessible instruction videos for setting op the cohort specific data-infrastructure;
- An up to date registry of European pregnancy and child cohort studies (www.birthcohorts.net);
- A new catalogue showing the available variables (EU Child Cohort Network Variable Catalogue);
- A GDPR proof and federated infrastructure for data-management and analysis using Opal severs and DataSHIELD;
- A governance infrastructure for performing shared analyses between cohorts;
- Strategies for sustainability after the LifeCycle duration reflected by use of this network in already four recently Horizon2020 funded projects (EUCAN-Connect, ATHLETE, LongiTools, EndObesity);
- A successful programme funding LifeCycle fellowships for 11 junior researchers;

Almost 200 published papers related to the associations of early life stressors and cardio-metabolic, respiratory and mental health trajectories during the life course, of which most are based on multi-cohorts collaborations.

Organization of nine successful workshops open for external researchers on Causal inference, Epigenetic programming, Approaches and methods in pregnancy and child cohort studies, DataSHIELD Analyses, Mendelian Randomization, Impact, Exposome analyses, and Transportability.
LIFECYCLE has the following key expected results:

The EU Child Cohort Network brings together data of more than 250,000 European children and their parents and enables optimal exploitation of available research and biobank data. This network will enable long-term exploitation of the enormous potential of European pregnancy and child cohort studies, and within this project, use these cohorts to generate novel findings and translate these into practical applications for use by healthcare professionals and European citizens.

Novel markers for integrated adverse early-life stressors and the early-life exposome, which will be derived from European pregnancy and child cohort studies participating in the EU Child Cohort Network. These integrated data will be harmonized between European pregnancy and child cohorts and enable comparison studies between European populations and countries and etiological research.

Personalized prediction models to predict the onset and evolution of risk factors for cardio-metabolic, respiratory and mental outcomes throughout the life course from individual pregnancy and infancy early-life stressor data, taking account for baseline risk estimation from socio-economic, migration and urban environmental stressors.

Mobile eHealth applications for individually customised counselling for pregnant women and young children based on personalised prediction models.

Tutorials and e-learning modules for researchers focused on “Early-life programming of non-communicable diseases”. LifeCycle will develop e-learning modules conceptualised for training of healthcare professionals and investigators. E-learning modules will provide effective dissemination by digital information sharing with a broad global outreach.
LifeCycle concept