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Epidemiology
Cohort profile
Human Early Life Exposome (HELIX) study: a European population-based exposome cohort
  1. Léa Maitre1,2,3,
  2. Jeroen de Bont1,2,3,
  3. Maribel Casas1,2,3,
  4. Oliver Robinson1,2,3,4,
  5. Gunn Marit Aasvang5,
  6. Lydiane Agier6,
  7. Sandra Andrušaitytė7,
  8. Ferran Ballester3,8,9,
  9. Xavier Basagaña1,2,3,
  10. Eva Borràs2,10,
  11. Céline Brochot11,
  12. Mariona Bustamante1,2,3,10,
  13. Angel Carracedo12,13,
  14. Montserrat de Castro1,2,3,
  15. Audrius Dedele7,
  16. David Donaire-Gonzalez1,2,3,
  17. Xavier Estivill14,15,
  18. Jorunn Evandt5,
  19. Serena Fossati1,2,3,
  20. Lise Giorgis-Allemand6,
  21. Juan R Gonzalez1,2,3,
  22. Berit Granum5,
  23. Regina Grazuleviciene7,
  24. Kristine Bjerve Gützkow5,
  25. Line Småstuen Haug5,
  26. Carles Hernandez-Ferrer1,2,3,
  27. Barbara Heude16,
  28. Jesus Ibarluzea3,17,18,19,
  29. Jordi Julvez1,2,3,4,
  30. Marianna Karachaliou20,
  31. Hector C Keun21,
  32. Norun Hjertager Krog5,
  33. Chung-Ho E Lau21,22,
  34. Vasiliki Leventakou20,
  35. Sarah Lyon-Caen6,
  36. Cyntia Manzano1,2,3,
  37. Dan Mason23,
  38. Rosemary McEachan23,
  39. Helle Margrete Meltzer5,
  40. Inga Petraviciene7,
  41. Joane Quentin6,
  42. Theano Roumeliotaki20,
  43. Eduard Sabido2,
  44. Pierre-Jean Saulnier24,
  45. Alexandros P Siskos21,
  46. Valérie Siroux6,
  47. Jordi Sunyer1,2,3,4,
  48. Ibon Tamayo1,3,25,
  49. Jose Urquiza1,2,3,
  50. Marina Vafeiadi20,
  51. Diana van Gent1,2,3,
  52. Marta Vives-Usano1,2,3,10,
  53. Dagmar Waiblinger23,
  54. Charline Warembourg1,2,3,
  55. Leda Chatzi26,27,
  56. Muireann Coen22,
  57. Peter van den Hazel28,
  58. Mark J Nieuwenhuijsen1,2,3,
  59. Rémy Slama6,
  60. Cathrine Thomsen5,
  61. John Wright23,
  62. Martine Vrijheid1,2,3
  1. 1 ISGlobal, Institute for Global Health, Barcelona, Spain
  2. 2 Universitat Pompeu Fabra (UPF), Barcelona, Spain
  3. 3 CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
  4. 4 Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain
  5. 5 Norwegian Institute of Public Health, Oslo, Norway
  6. 6 Team of Environmental Epidemiology, IAB, Institute for Advanced Biosciences, Inserm, CNRS, CHU-Grenoble-Alpes, University Grenoble-Alpes, CNRS, Grenoble, France
  7. 7 Department of Environmental Sciences, Vytautas Magnus University, Kaunas, Lithuania
  8. 8 Nursing School, Universitat de València, Valencia, Spain
  9. 9 FISABIO–Universitat Jaume I–Universitat de València Joint Research Unit of Epidemiology and Environmental Health, Valencia, Spain
  10. 10 Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
  11. 11 Unité Modèles pour l’Ecotoxicologie et la Toxicologie (METO), Institut National de l’Environnement Industriel et des Risques (INERIS), Verneuil en Halatte, France
  12. 12 Fundación Pública Galega de Medicina Xenómica (SERGAS), Santiago, Spain
  13. 13 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universidad de Santiago de Compostela, Santiago, Spain
  14. 14 Research Department, Sidra Medicine, Doha, Qatar
  15. 15 Genomics Unit, Dexeus Woman’s Health, Barcelona, Spain
  16. 16 Inserm UMR 1153—Centre de Recherche Epidémiologie et Biostatistique Sorbonne Paris Cité (CRESS), Equipe de recherche sur les origines précoces de la santé et du développement de l’enfant (ORCHAD), Villejuif, France
  17. 17 School of Psychology, University of the Basque Country UPV/EHU, San Sebastian, Spain
  18. 18 Biodonostia Health Research Institute, San Sebastian, Spain
  19. 19 Department of Health, Public Health of Gipuzkoa, Government of the Basque Country, San Sebastian, Spain
  20. 20 Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
  21. 21 Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
  22. 22 Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
  23. 23 Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
  24. 24 Centre d’Investigation Clinique CIC1402, Inserm, Université de Poitiers, CHU Poitiers, Poitiers, France
  25. 25 Department of Statistics, Faculty of Arts and Sciences, Harvard University, Cambridge, Massachusetts, USA
  26. 26 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
  27. 27 Department of Genetics and Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
  28. 28 Veiligheids- en Gezondheidsregio Gelderland Midden (VGGM), Arnhem, The Netherlands
  1. Correspondence to Professor Martine Vrijheid; martine.vrijheid{at}isglobal.org

Abstract

Purpose Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations.

Participants The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31 472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6–11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level).

Findings to date Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6–11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder.

Future plans HELIX study results will inform on the early life exposome and its association with molecular omics signatures and child health outcomes. Cohort data are accessible for future research involving researchers external to the project.

  • birth cohort
  • exposome
  • epidemiology
  • omics
  • public health
  • community child health

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2017-021311

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    Footnotes

    • Contributors LM coordinated the collection and harmonisation of the data as the HELIX project scientific coordinator (2016–2018) and drafted the first draft of the manuscript. JdB performed the panel study fieldwork, data harmonisation and data description and assisted in drafting the manuscript. MCasas coordinated field work in the INMA Sabadell cohort, designed the biomarker database, coordinated sample collection and assisted in drafting the manuscript. OR prepared fieldwork protocols and questionnaires and supervised the fieldwork across all cohorts as the HELIX project coordinator (2013–2016). The following authors contributed to the collection of data on chemical contaminants: CT led the workpackage and oversaw all aspects of the work on the biomarker measurements of chemical contaminants; LSH performed the biological sample management and biomarker analysis; CB conducted the pharmacokinetics models data collection and protocols preparation. The following authors contributed to the collection of data on outdoor exposures: MJN led the workpackage and oversaw all aspects of the work on outdoor exposures; MdC conducted the outdoor exposure calculations; DDG conducted the exposure monitoring of panel children and physical activity; IT conducted the outdoor exposome data harmonisation and modelled indoor air pollution and water contamination exposures. The following authors contributed to the omics data collection, analysis and interpretation: MCoen led the omics workpackage, designed the study and oversaw the metabolomics data collection; HCK designed the study and oversaw the metabolomics data collection; CEL performed the NMR metabolite quantification; APS performed the MS metabolite quantification; EB conducted the proteomics analysis; ES designed the proteomics study and oversaw the proteomics data collection; MB designed the study and conducted the analysis for the DNA methylation and transcriptomics (gene expression and miRNAs); MVives conducted the gene expression and miRNA analysis; AC facilitated the analysis and oversaw research for DNA methylation data; XE coordinated the analysis and oversaw research for transcriptomics (gene expression and miRNAs) data collection; JRG designed the omics and exposome bioinformatics and statistical analyses; CHF programmed the R package and contributed to the design of the omics and exposome bioinformatics and statistical analyses. The following authors contributed to data analysis and interpretation: RS led the workpackage and oversaw the preparation of statistical analysis protocols; XB led the statistical analysis working group and prepared statistical analysis protocols; LC led a workpackage, prepared clinical examination protocols and contributed to the clinical data harmonisation and interpretation; SF prepared clinical examination protocols and contributed to the clinical data harmonisation and interpretation; JJ prepared the neurodevelopment protocols and coordinated the neurodevelopment data preparation and interpretation. VS and BG led the allergy and respiratory health data collection, harmonisation and interpretation. VS also assisted in the preparation of statistical analysis protocols. LA conducted the spirometry data harmonisation and contributed to the statistical protocol preparation. CW checked pooled data for accuracy of information and revised the manuscript critically. The following authors contributed to the cohort data collection. MoBa cohort: HMM designed the study and oversaw all aspects of subcohort and panel study data collection. KBG coordinated the subcohort fieldwork; BG coordinated the pregnancy panel fieldwork; GMA constructed and harmonised the MoBa existing database; JE was responsible for the neurological testing in the subcohort, NHK collected GIS input data and prepared routine monitoring data;. KANC cohort: RG (PI of the KANC cohort) designed the study and oversaw all aspects of KANC data collection. SA coordinated the fieldwork for subcohort and panel study and checked pooled data for accuracy of information; AD conducted fieldwork and GIS work; IP revised KANC data and revised the manuscript critically. INMA cohort: MVrijheid designed the study and oversaw all aspects of INMA subcohort and panel study data collection. FB (PI of the INMA-Valencia cohort) oversaw data collection in Valencia; JI (PI of the INMA-Gipuzkoa cohort) oversaw data collection in Gipuzkoa; JS (PI of the INMA-Sabadell cohort and of the entire INMA study) oversaw all previous INMA data collections; CM coordinated the Barcelona pregnant woman panel fieldwork and data preparation. EDEN cohort: RS designed the study and oversaw all aspects of EDEN subcohort and panel study data collection and critically reviewed the manuscript. BH (PI of the EDEN cohort) oversaw previous follow-ups of EDEN population; SLC coordinated the pregnant women panel fieldwork; JQ co-coordinated the children subcohort fieldwork and database integration; PJS was responsible for the subcohort fieldwork in Poitiers; LGA co-coordinated the children panel follow-up, checked pooled data for accuracy of information, conducted the ESCAPE data harmonisation and prepared GIS data. RHEA cohort: LC (PI of the RHEA cohort) designed the study and oversaw all aspects of RHEA subcohort and panel study data collection. JMK carried out the field work and helped design the clinical examination protocols, VL coordinated and carried out the fieldwork; TR checked pooled data for accuracy of information, prepared GIS data and conducted the clinical data harmonisation; MVafeiadi coordinated fieldwork and sample management. BiB cohort: JW designed and oversaw all aspects of BiB subcohort and panel study data collection data; DM constructed the database; RMc designed and oversaw all aspects of BiB subcohort and panel study data collection data; DW coordinated the fieldwork. PvH was responsible for dissemination aspects of the HELIX project. JU constructed and managed the HELIX database and performed data harmonisation, cleaning and validation. DvG is the HELIX project coordinator; she drafted the ethical and data protection and sharing proposal. Finally, the following authors designed the HELIX study and supervised all aspects of the work as members of the HELIX Project Executive Committee: LC, MCoen, PvdH, MJN, RS, CT and JW. MVrijheid coordinated the HELIX project, supervised all data collection, supervised all work related to the manuscript and drafted the manuscript. All authors read and approved the final manuscript. ISGlobal is a member of the Agency for the Research Centres of Catalonia (CERCA) Programme, Generalitat de Catalunya. MC is a member of the MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, UK. ISGlobal is a member of the Agency for the Research Centres of Catalonia (CERCA) Programme, Generalitat de Catalunya. MC is a member of the MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, UK.

    • Funding The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-206) under grant agreement no 308333—the HELIX project. Dr Maribel Casas and Dr Jordi Julvez received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (MS16/00128, MS14/00108). INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, the Conselleria de Sanitat, Generalitat Valenciana, Department of Health of the Basque Government; the Provincial Government of Gipuzkoa, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Norwegian Mother and Child Cohort Study (MoBa) is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, NIH/NIEHS (contract no. N01-ES-75558), and NIH/NINDS (grant no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1). The Rhea project was financially supported by European projects, and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion district, Crete, Greece: 2011–2014; ’Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–2015). The work was also supported by MICINN (MTM2015-68140-R) and Centro Nacional de Genotipado-CEGEN-PRB2-ISCIII. CW received funding from the Fondation de France.

    • Competing interests None declared.

    • Patient consent Parental/guardian consent obtained.

    • Ethics approval Comité Ético de investigación Clínica Parc de Salut MAR.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement The data warehouse has been established in a format that allows future use beyond the project lifespan (2013–2017) as an accessible resource for collaborative research involving researchers external to the project. Access to HELIX data is based on approval by the HELIX Project Executive Committee and by the individual cohorts, who will evaluate potential overlap with ongoing work, adequacy of data protection plans, logistic and financial consequences and adequacy of authorship and acknowledgement plans. Further details on the content of the data warehouse (data catalogue) and procedures for external access are described on the project website (http://www.projecthelix.eu/index.php/es/data-inventory). The authors encourage interested researchers to contact them to set up collaborations.