The urban environment during pregnancy may influence child's respiratory health, but scarce evidence exists on systematic evaluation of multiple urban exposures (e.g., air pollution, natural spaces, noise, built environment) on children's lung function, wheezing, and asthma development. We aimed to examine the association of the urban environment during pregnancy with lung function, preschool wheezing, and school-age asthma. We included 5624 mother-child pairs participating in a population-based prospective birth cohort. We estimated 30 urban environmental exposures including air pollution, road traffic noise, traffic, green spaces, blue spaces, and built environment during pregnancy. At 10 years of age, lung function was measured by spirometry. Information on preschool wheezing and physician-diagnosed school-age asthma was obtained from multiple questionnaires. We described single-exposure associations with respiratory outcomes using an exposome-wide association study. We also identified patterns of urban exposures with hierarchical clustering on principal components analysis and examined their associations with respiratory outcomes using multivariate regression models. Single-exposure analyses showed associations of higher particulate matter (PM) with lower mid-expiratory flow (FEF25-75%) (e.g., for PM < 2.5 μm of diameter [PM2.5] z-score = -0.06 [-0.09, -0.03]) and higher forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) (e.g., for PM2.5 FEV1 0.05 [0.02, 0.08]) after correction for multiple-hypothesis testing. Cluster analysis described three patterns of urban exposures during pregnancy and showed that the cluster characterised by higher levels of air pollution, noise, walkability, street connectivity, and lower levels of natural spaces were associated with lower FEF25-75% (-0.08 [-0.17, 0.00]), and higher odds of preschool wheezing (1.21 [1.03, 1.43]). This study shows that the characteristics of the urban environment during pregnancy are of relevance to the offspring's respiratory health during childhood.
