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Background Early-life environmental exposures are suspected to be involved in the development of chronic diseases later in life. Most studies conducted so far considered single or few exposures and single-health parameter. Our study aimed to identify a childhood general health score and assess its association with a wide range of pre- and post-natal environmental exposures. Methods The analysis is based on 870 children (6–12 years) from six European birth cohorts participating in the Human Early-Life Exposome project. A total of 53 prenatal and 105 childhood environmental factors were considered, including lifestyle, social, urban and chemical exposures. We built a general health score by averaging three sub-scores (cardiometabolic, respiratory/allergy and mental) built from 15 health parameters. By construct, a child with a low score has a low general health status. Penalized multivariable regression through Least Absolute Shrinkage and Selection Operator (LASSO) was fitted in order to identify exposures associated with the general health score. Findings: The results of LASSO show that a lower general health score was associated with maternal passive and active smoking during pregnancy and postnatal exposure to methylparaben, copper, indoor air pollutants, high intake of caffeinated drinks and few contacts with friends and family. Higher child’s general health score was associated with prenatal exposure to a bluespace near residency and postnatal exposures to pets, cobalt, high intakes of vegetables and more physical activity. Against our hypotheses, postnatal exposure to organochlorine compounds, perfluorooctanoate and childhood medium intake of sodas and bakery products were associated with a higher child’s general health score. Conclusion By using a general health score summarizing the child cardiometabolic, respiratory/allergy and mental health, this study reinforced previously suspected environmental factors associated with various child health parameters (e.g. tobacco, air pollutants) and identified new factors (e.g. pets, bluespace) warranting further investigations.

Background Studies looking at associations between environmental chemicals and child behaviour usually consider only one exposure or family of exposures. Objective This study explores associations between prenatal exposure to a wide range of environmental chemicals and child behaviour. Methods We studied 708 mother-child pairs from five European cohorts recruited in 2003–2009. We assessed 47 exposure biomarkers from eight chemical exposure families in maternal blood or urine collected during pregnancy. We used the Strengths and Difficulties Questionnaire (SDQ) to evaluate child behaviour between three and seven years of age. We assessed associations of SDQ scores with exposures using an adjusted least absolute shrinkage and selection operator (LASSO) considering all exposures simultaneously and an adjusted exposome-wide association study (ExWAS) considering each exposure independently. Results LASSO selected only copper (Cu) as associated with externalizing behaviour. In the ExWAS, bisphenol A [BPA, incidence rate ratio (IRR): 1.06, 95% confidence interval (95%CI): 1.01;1.12] and mono-n-butyl phthalate (MnBP, IRR: 1.06, 95%CI: 1.00;1.13) were associated with greater risk of externalizing behaviour problems. Cu (IRR: 0.90, 95%CI: 0.82;0.98), perfluoroundecanoate (PFUnDA, IRR: 0.92, 95%CI: 0.84;0.99) and organochlorine compounds (OCs) were associated with lower risk of externalizing behaviour problems, however the associations with OCs were mainly seen among women with insufficient weight gain during pregnancy. Internalizing score worsen in association with exposure to diethyl thiophosphate (DETP, IRR: 1.11, 95%CI: 1.00;1.24) but the effect was driven by the smallest cohort. Internalizing score improved with increased concentration of perfluorooctane sulfonate (PFOS, IRR: 0.92, 95%CI: 0.85;1.00), however the association was driven by the two smallest cohorts with the lowest PFOS concentrations. Discussion This study added evidence on deleterious effects of prenatal exposure to BPA and MnBP on child behaviour. Other associations should be interpreted cautiously since they were not consistent with previous studies or they have not been studied extensively., Graphical abstract Unlabelled Image, Highlights • We studied simultaneous effect of prenatal exposure to several compounds on child behaviour. • 47 exposure biomarkers from 8 chemical exposure families were studied in 5 European cohorts. • Bisphenol A and mono-n-butyl phthalate were associated with increased behavioural problems in children. • Copper was associated with decreased behavioural problems.

Supported by the Spanish Institute of Health Carlos III (Co-funded by European Regional Development Fund “A way to make Europe”) (CP14/00108, PI16/00261, MS14/00108 [to J.J.]), the Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya - Fons Social Europeu (2017 FI_B 00636 [to N.V-T.]), the Spanish Ministry of Science and Innovation (RYC-2012-10995 [to P.D.] and RYC-2011-08796 [to D.R.]), Obra Social Cajastur/Fundación Liberbank, Universidad de Oviedo, CIBERESP, Department of Health of the Basque Government, the Provincial Government of Gipuzkoa, the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain), Generalitat Valenciana, Generalitat de Catalunya, Fundació La marató de TV3, and the EU Commission. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya., López-Vicente, M., Ribas Fitó, N., Vilor-Tejedor, N., Garcia-Esteban, R., Fernández-Barrés, S., Dadvand, P., Murcia, M., Rebagliato, M., Ibarluzea, J., Lertxundi, A., Fernández-Somoano, A., Tardón, A., López-Sabater, M.C., Romaguera, D., Vrijheid, M., Sunyer, J., Julvez, J.