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HELIX Sintesi della relazione

Project ID: 308333
Finanziato nell'ambito di: FP7-ENVIRONMENT
Paese: Spain

Periodic Report Summary 2 - HELIX (The Human Early-Life Exposome – novel tools for integrating early-life environmental exposures and child health across Europe)

Project Context and Objectives:
Major environmental hazards may lead to serious, chronic pathologies with large societal and economic costs, especially when exposed during critical developmental periods in pregnancy or early life. Special susceptibility during these times requires special protection through public health action and environmental legislation. Many associations between early-life exposures and health remain poorly characterised, giving rise to uncertain health risk and impact assessments due to lack of comprehensive data on exposure to multiple environmental hazards in early life, the large degree of exposure misclassification and uncertainties, and lack of integrated multiple environmental hazards and individual variability to estimate combined effects on health. Focus has almost uniquely been on single exposure-health effect relationships, lacking a global view of how various types of exposures co-exist and jointly impact on health during critical developmental periods.
The “exposome” encompasses the totality of human environmental exposures from conception onwards; key focus is its epidemiological applications for prevention of human disease. The HELIX (Human Early-Life Exposome) concept is built around these needs in human population studies (Annex I, Figure 1). HELIX relies on six longitudinal cohorts for collection of individual information on exposures, behaviours and health.
HELIX will develop an early-life exposome toolkit and database in three overlapping steps, each focusing on the development of specific tools and methods to obtain and analyse exposome data.
1. Measuring the external exposome:
• Develop and apply tools and methods to obtain robust estimates of exposures to persistent and non-persistent pollutants in food, consumer products, water and indoor air, in pregnancy and early childhood.
• Develop and apply tools and methods to obtain robust estimates of chemical and physical exposures in the outdoor environment during pregnancy and early childhood: ambient air pollution, ambient noise, green space/built environment, ultra-violet radiation.
Fieldwork associated with the above has been carried out in six European cohorts: BiB (UK), EDEN (France), INMA (Spain), KANC (Lithuania), MoBa (Norway) and Rhea (Greece).
2. Integrating the external and internal exposome:
• Develop tools to integrate data on multiple exposures, exposure predictors, and individual exposure variability (temporal, behavioural, toxicokinetic), in order to define multiple exposure patterns and describe exposure uncertainties.
• Measure molecular signatures associated with environmental exposures through analysis of profiles of metabolites, proteins, RNA transcripts, and DNA methylation.
The -omics data generation will be completed in June 2016, with the data warehouse to be presented in December 2016.
3. Impact of the early-life exposome on child health:
• Develop novel statistical approaches for the analysis of the association of patterns of multiple and combined exposures and child health outcomes.
• Provide exposure-response estimates for the association between multiple and combined exposures, and child health. Focussing on foetal and childhood growth and obesity, neurodevelopment, and immune system-mediated outcomes.
• Estimate the burden of common childhood diseases that may be attributed to multiple environmental exposures in Europe. Using integrated health impact assessment tools, prevalence data from over 35 European birth cohorts (>300,000 subjects) and surveys, and exposure-response results from HELIX.
• Strengthen the knowledge base for European policy in the area of child and environmental health. Through engaging with, and effectively disseminating HELIX knowledge to, stakeholders including those responsible for risk management and mitigation and prevention strategies. This will provide guidance on priority areas for action with respect to monitoring and limiting pregnancy and childhood exposures.

Project Results:
WP1 is applying novel tools and methods to obtain robust estimates of exposures to persistent and non-persistent pollutants in food, consumer products, water and indoor air, during pregnancy and early childhood. Collection of biological samples and exposure data for the Helix subcohort, children panel and pregnancy panel studies has now been completed. Health examinations, personal monitoring kits and covariate questions were integrated into the fieldwork. Chemical analyses to determine biomarkers of exposure to persistent and non-persistent pollutants are underway. Work is ongoing to build predictive models of indoor air pollutants based on the measurements from the panel studies.

WP2 is developing novel tools and methods to obtain robust estimates of chemical and physical exposures in the outdoor environment, focusing on key outdoor exposures. The focus has been on obtaining the required data from the relevant municipal authorities, building the GIS environment and geocoding address history where necessary. Exposures estimates were obtained for the subjects using the personal assessment kit developed for this purpose.

WP3 aims to integrate data on multiple exposures, exposure determinants, and exposure variability, to define multiple exposure patterns and describe exposure uncertainties. A PBPK modeling test run was realized with INMA and Barcelona pregnancy panel study samples. Exposure determinants have been identified, already collected from the cohorts at different time points, and new data collected in the HELIX subcohort, including parental socio-demographic characteristics, parental and child life style characteristics, maternal diet during pregnancy and childhood, physical activity in pregnancy and childhood. Factor Analysis of multiple exposure patterns and the model-based clustering approach are under development in the R package in progress.

WP4 has worked on the optimization of the study design, assessing detectability and analytical variability of the omics methodologies and defining quality control strategies. In addition, metabolomics data was generated for the panel study which enabled assessment of both the analytical and biological variability of metabolomic urinary profiles from 20 children across one week in the first season of the panel study. This data also enabled a decision to be made for all future analyses that is to use the pooled urinary samples to generate metabolomic profiles for the remainder of the panel study samples and for the subcohort samples. For the proteomic and transcriptomics/epigenomic parts, methods have been assessed, developed and optimized, with quality control strategies. Analyses of all HELIX subcohort and panel samples are ongoing and expected to be finished in June 2016.

WP5 characterizes the short- and medium-term effect of the exposome on specific highly prevalent child health outcomes. Health outcome examinations have finished and the design of the HELIX data warehouse are ongoing. A simulation study was carried out to compare the efficiency of various statistical approaches considered to assess the impact of the Exposome on human health.

WP6 aims to estimate the burden of common childhood diseases that may be attributed to multiple environmental exposures in Europe. Work focused on obtaining exposure estimates and exposure-response data available in the scientific literature on environmental risk factors related to childhood health in 28 European countries. Scenarios for health impact assessment (HIA) have been identified on active transportation in children, that will integrate multiple exposures and outcomes. This includes the design and development of a quantitative model to estimate the risks and benefits of the active transportation in children.

The project maintains a framework of communication, dissemination and engagement with stakeholders. Tools and activities include a website, social media, webinars, interviews and scientific publications.

Potential Impact:
HELIX will 1) exploit available or to-be-developed novel tools and methods to integrate and link environmental data with health data and information, and apply them to (large-scale) population studies; 2) contribute to the definition of an integrated exposure concept and prediction of individual disease risks related to environment; 3) reduce uncertainty in risk assessments of chemicals; 4) provide a better understanding of the effect of multiple exposures, such as to mixtures of chemicals, behaviour, and the physical environment; 5) improve preventive strategies to lower health costs; 6) increase EU competitiveness, especially that of SME's that may find new business sectors in exposure characterisation and modelling; 7) address the priority goals of the Parma Declaration on Environment and Health (2010) and contribute to EU policies on Environment and Health, and above all, 8) lead to a reduction of the environmental burden of disease.
So far, most previous EU-funded research projects have focused on single pollutants. HELIX will make major breakthroughs by proposing a more integrated, holistic, way of studying the environment and linking with health data during early life. It will provide the new tools and methods to do this and carefully evaluate their use and impact by applying them to (large-scale) population studies. HELIX will thus contribute to:
Definition of an integrated exposure concept
Prediction of individual disease risks related to environment
Reduce the uncertainty in risk assessments of chemicals
Better understanding of the effect of multiple exposures, such as to mixtures of chemicals and behaviour/physical environment
Improve preventive strategies to lower health costs
Increased EU competitiveness, especially that of SME's that may find new business sectors in exposure characterisation and modelling
Added value at European level
The exposome concept calls for an integrated approach to environmental exposure. This is only possible by pooling expertise and research resources across countries. Furthermore, only through this European dimension can we take full advantage of the ongoing effort in other EU FP7 Environment and Health projects. The project includes cohorts from all parts of Europe: North, East, South and West and will thus address pan European problems and promote a truly pan-European partnership. It will improve generalizability and increase power of analysis through multi-centre sampling. The health impact scenarios developed by HELIX will take account of all available information in European birth cohorts and other data sources. The main reasons for carrying out the work on a European level are:
1) Health benefits by improving environment through exposure reduction is a truly international topic, but the current tool base is limited;
2) The economic, social, cultural and historical aspects of the environmental exposures to children differ substantially within Europe and an integrated exposure concept can thus only be achieved by basing this on data from different European countries;
3) Research and centres of expertise are distributed across the countries of Europe, and only a European level project will achieve the required multi disciplinary expertise;
4) Environmental policy making has an important European dimension; the added value of gathering data in multiple European countries is important to impact for the development of European policies and regulations by taking into account different country scenarios.

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