Background: Several single-exposure studies have documented possible effects of environmental factors on lung function, but none has relied on an exposome approach. We aimed to evaluate the association between a broad range of prenatal and postnatal lifestyle and environmental exposures and lung function in children. Methods: In this analysis, we used data from 1033 mother–child pairs from the European Human Early-Life Exposome (HELIX) cohort (consisting of six existing longitudinal birth cohorts in France, Greece, Lithuania, Norway, Spain, and the UK of children born between 2003 and 2009) for whom a valid spirometry test was recorded for the child. 85 prenatal and 125 postnatal exposures relating to outdoor, indoor, chemical, and lifestyle factors were assessed, and lung function was measured by spirometry in children at age 6–12 years. Two agnostic linear regression methods, a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering exposures independently, were applied to test the association with forced expiratory volume in 1 s percent predicted values (FEV1%). We tested for two-way interaction between exposures and corrected for confounding by co-exposures. Findings: In the 1033 children (median age 8·1 years, IQR 6·5–9·0), mean FEV1% was 98·8% (SD 13·2). In the ExWAS, prenatal perfluorononanoate (p=0·034) and perfluorooctanoate (p=0·030) exposures were associated with lower FEV1%, and inverse distance to nearest road during pregnancy (p=0·030) was associated with higher FEV1%. Nine postnatal exposures were associated with lower FEV1%: copper (p=0·041), ethyl-paraben (p=0·029), five phthalate metabolites (mono-2-ethyl 5-carboxypentyl phthalate [p=0·016], mono-2-ethyl-5-hydroxyhexyl phthalate [p=0·023], mono-2-ethyl-5-oxohexyl phthalate [p=0·0085], mono-4-methyl-7-oxooctyl phthalate [p=0·040], and the sum of di-ethylhexyl phthalate metabolites [p=0·014]), house crowding (p=0·015), and facility density around schools (p=0·027). However, no exposure passed the significance threshold when corrected for multiple testing in ExWAS, and none was selected with the DSA algorithm, including when testing for exposure interactions. Interpretation: Our systematic exposome approach identified several environmental exposures, mainly chemicals, that might be associated with lung function. Reducing exposure to these ubiquitous chemicals could help to prevent the development of chronic respiratory disease. Funding: European Community's Seventh Framework Programme (HELIX project).

The study has received funding from the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement number 308333—the HELIX project—for data collection and analyses. The HELIX program built on six existing cohorts that received previous funding, including the major cohorts listed here. MoBa (Norwegian Mother and Child Cohort Study) is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, and the US National Institutes of Health (NIH) National Institute of Environmental Health Sciences (NIEHS; contract number N01-ES-75558), and National Institute of Neurological Disorders and Stroke (grant number 1 UO1 NS 047537–01 and grant number 2 UO1 NS 047537–06A1). The RHEA project was financially supported by European Union projects (EU FP6–2003-Food-3-NewGeneris, EU FP6.STREP Hiwate, EU FP7 ENV.2007·1.2.2.2, Project No 211250 Escape, EU FP7–2008-ENV-1·2.1·4 Envirogenomarkers, EU FP7-HEALTH-2009-single stage CHICOS, EU FP7 ENV.2008.1.2.1.6, proposal number 226285 ENRIECO, EUFP7-HEALTH-2012 proposal number 308333 HELIX, FP7 European Union project, number 264357 MeDALL), and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, Heraklion district, Crete, Greece: 2011–14; “RHEA Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15). LC received additional funding from the Southern California Environmental Health Sciences Center (grant number P30ES007048) funded by NIEHS.