Marina Vafeiadi, Raquel Soler-Blasco, Mariza Kampouri, Mònica Guxens, Martine Vrijheid, Johanna Lepeule, Llúcia González-Safont, Mark J. Nieuwenhuijsen, Mark Mon-Williams, John Wright, Rosie McEachan, Anne-Claire Binter, Claire Philippat, Jonathan Y. Bernard, Jordi Sunyer, Loreto Santa-Marina, Leda Chatzi, Lucia Alonso, Ainara Andiarena, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Agency for science, technology and research [Singapore] (A*STAR), University of South-Eastern Norway (USN), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), CIBER de Epidemiología y Salud Pública (CIBERESP), Universitat Jaume I, University of Crete [Heraklion] (UOC), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), University of Bradford, University of Southern California (USC), Universitat Pompeu Fabra [Barcelona] (UPF), Erasmus University Medical Center [Rotterdam] (Erasmus MC), This work was supported by funding from the European Community’s Seventh Framework Programme [FP7/2007–206 n◦308333, the HELIX project]. This INMA cohort was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, PI041436, PI081151 incl. FEDER funds, FIS PI06/0867, FIS-PI09/00090, FIS and FIS-PI18/01142 incl. FEDER funds, FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI16/00118 and PI17/00663, FIS-FSE: 17/00260, Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051, and CPII18/00018), from UE (FP7-ENV-2011 cod 282957, HEALTH.2010.2.4.5-1, and H2020 n◦824989), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249), Alicia Koplowitz Foundation 2017, CIBERESP, Department of Health of the Basque Government (2013111089, 2009111069, 2013111089, 2015111065 and 2018111086), Provincial Government of Gipuzkoa (DFG06/002, DFG08/001, DFG15/221 and DFG 89/17) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu , Legazpi, Azkoitia y Azpeitia y Beasain). We acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the 'Centro de Excelencia Severo Ochoa 2019-2023' Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. The work was also supported by MICINN [MTM2015-68140- R] and Centro Nacional de Genotipado- CEGEN- PRB2- ISCIII (Spain). 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: 2012–15). This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Collaboration for Applied Health Research and Care (CLAHRC) for Yorkshire and Humber (UK). The EDEN study was supported by Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A), and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programs (ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety and French National Agency for Food Security (now ANSES), Mutuelle Générale de l’Education Nationale a complementary health insurance (MGEN), French-speaking association for the study of diabetes and metabolism (ALFEDIAM). Core support for Born in Bradford is also provided by the Wellcome Trust (WT101597MA, UK). Born in Bradford (BiB) is only possible because of the enthusiasm and commitment of the children and parents in BiB. We are grateful to all the participants, health professionals, schools and researchers who have made BiB happen. BiB receives funding from the ESRC/MRC, the Wellcome Trust (WT101597MA) and the National Institute for Health Research Yorkshire and Humber ARC (reference: NIHR20016). M. Mon-Williams was supported by a Fellowship from the Alan Turing Institute. Additional funding from the National Institute of Environmental Health Science supported Dr Chatzi (R01ES030691, R01ES029944, R01ES030364, R21ES029681, and P30ES007048). The views expressed are those of the authors, and not necessarily those of the NHS or the NIHR. None of the funders were involved in designing the study, collecting the data, analyzing or interpreting the data, deciding to submit the article for publication, or the writing of the report., HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Singapore Institute for Clinical Sciences [Singapour] (SICS), Bradford Institute for Health Research [Bradford, UK], Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), University of Leeds, Universitat de València (UV), Karolinska Institutet [Stockholm], Binter, Anne-Claire, Child and Adolescent Psychiatry / Psychology, Erasmus MC other, European Commission, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
[EN]Background: The urban environment may influence neurodevelopment from conception onwards, but there is no evaluation of the impact of multiple groups of exposures simultaneously. We investigated the association between early-life urban environment and cognitive and motor function in children. Methods: We used data from 5403 mother-child pairs from four population-based birth-cohorts (UK, France, Spain, and Greece). We estimated thirteen urban home exposures during pregnancy and childhood, including: built environment, natural spaces, and air pollution. Verbal, non-verbal, gross motor, and fine motor functions were assessed using validated tests at five years old. We ran adjusted multi-exposure models using the Deletion-Substitution-Addition algorithm. Results: Higher greenness exposure within 300 m during pregnancy was associated with higher verbal abilities (1.5 points (95% confidence interval 0.4, 2.7) per 0.20 unit increase in greenness). Higher connectivity density within 100 m and land use diversity during pregnancy were related to lower verbal abilities. Childhood exposure to PM2.5 mediated 74% of the association between greenness during childhood and verbal abilities. Higher exposure to PM2.5 during pregnancy was related to lower fine motor function (-1.2 points (-2.1, -0.4) per 3.2 mu g/m3 increase in PM2.5). No associations were found with non-verbal abilities and gross motor function. Discussion: This study suggests that built environment, greenness, and air pollution may impact child cognitive and motor function at five years old. This study adds evidence that well-designed urban planning may benefit children's cognitive and motor development. Acknowledgements We are grateful to all the participating children, parents, practi-tioners and researchers in the four countries who took part in this study. This work was supported by funding from the European Community's Seventh Framework Programme [FP7/2007-206 n 308333; the HELIX project] . This INMA cohort was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds, FIS PI06/0867, FIS-PI09/00090, FIS and FIS-PI18/01142 incl. FEDER funds, FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI16/00118 and PI17/00663; FIS-FSE: 17/00260; Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051, and CPII18/00018) , from UE (FP7-ENV-2011 cod 282957, HEALTH.2010.2.4.5-1, and H2020 n 824989) , Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundacio La marato de TV3 (090430) , Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249) , Alicia Koplowitz Foundation 2017, CIBERESP, Department of Health of the Basque Government (2013111089, 2009111069, 2013111089, 2015111065 and 2018111086) , Provincial Government of Gipuzkoa (DFG06/002, DFG08/001, DFG15/221 and DFG 89/17) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu , Legazpi, Azkoitia y Azpeitia y Beasain) . We acknowledge support from the Spanish Ministry of Science and Inno-vation and the State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S) , and support from the Generalitat de Catalunya through the CERCA Program. The work was also supported by MICINN [MTM2015-68140-R] and Centro Nacional de Genotipado-CEGEN-PRB2-ISCIII (Spain) . 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: 2012-15) . This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Collaboration for Applied Health Research and Care (CLAHRC) for Yorkshire and Humber (UK) . The EDEN study was supported by Foundation for medical research (FRM) , National Agency for Research (ANR) , National Institute for Research inPublic health (IRESP: TGIR cohorte sante 2008 program) , French Min-istry of Health (DGS) , French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) , and Human Nutrition Na-tional Research Programs, Paris-Sud University, Nestle, French National Institute for Population Health Surveillance (InVS) , French National Institute for Health Education (INPES) , the European Union FP7 pro-grams (ESCAPE, ENRIECO, Medall projects) , Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients (AFD) ) , French Agency for Environmental Health Safety and French National Agency for Food Security (now ANSES) , Mutuelle Generale de l'Education Nationale a complementary health insurance (MGEN) , French-speaking association for the study of diabetes and metabolism (ALFEDIAM) . Core support for Born in Bradford is also provided by the Wellcome Trust (WT101597MA, UK) . Born in Bradford (BiB) is only possible because of the enthusiasm and commitment of the children and parents in BiB. We are grateful to all the participants, health professionals, schools and researchers who have made BiB happen. BiB receives funding from the ESRC/MRC, the Wellcome Trust (WT101597MA) and the National Institute for Health Research York-shire and Humber ARC (reference: NIHR20016) . M. Mon-Williams was supported by a Fellowship from the Alan Turing Institute. Additional funding from the National Institute of Environmental Health Science supported Dr Chatzi (R01ES030691, R01ES029944, R01ES030364, R21ES029681, and P30ES007048) . The views expressed are those of the authors, and not necessarily those of the NHS or the NIHR. None of the funders were involved in designing the study, collecting the data, analyzing or interpreting the data, deciding to submit the article for publication, or the writing of the report. Data sharing statement The HELIX data warehouse has been established 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. Further details on the content of the data warehouse (data catalogue) and procedures for external access are described on the project website (http:// www.proj-ecthelix.eu/index.php/es/data-inventory) .