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BACKGROUND: A recent meta-analysis suggested evidence for an effect of exposure to ambient air pollutants on risk of certain congenital heart defects. However, few studies have investigated the effects of traffic-related air pollutants with sufficient spatial accuracy. OBJECTIVES: We estimated associations between congenital anomalies and exposure to traffic-related air pollution in Barcelona, Spain. METHOD: Cases with nonchromosomal anomalies (n = 2,247) and controls (n = 2,991) were selected from the Barcelona congenital anomaly register during 1994-2006. Land use regression models from the European Study of Cohorts for Air Pollution Effects (ESCAPE), were applied to residential addresses at birth to estimate spatial exposure to nitrogen oxides and dioxide (NOx, NO2), particulate matter with diameter ≤ 10 μm (PM10), 10-2.5 μm (PMcoarse), ≤ 2.5 μm (PM2.5), and PM2.5 absorbance. Spatial estimates were adjusted for temporal trends using data from routine monitoring stations for weeks 3-8 of each pregnancy. Logistic regression models were used to calculate odds ratios (ORs) for 18 congenital anomaly groups associated with an interquartile-range (IQR) increase in exposure estimates. RESULTS: In spatial and spatiotemporal exposure models, we estimated statistically significant associations between an IQR increase in NO2 (12.2 μg/m3) and coarctation of the aorta (ORspatiotemporal = 1.15; 95% CI: 1.01, 1.31) and digestive system defects (ORspatiotemporal = 1.11; 95% CI: 1.00, 1.23), and between an IQR increase in PMcoarse (3.6 μg/m3) and abdominal wall defects (ORspatiotemporal = 1.93; 95% CI: 1.37, 2.73). Other statistically significant increased and decreased ORs were estimated based on the spatial model only or the spatiotemporal model only, but not both. CONCLUSIONS: Our results overall do not indicate an association between traffic-related air pollution and most groups of congenital anomalies. Findings for coarctation of the aorta are consistent with those of the previous meta-analysis. This work was jointly supported by the EUROCAT (European Surveillance of Congenital Anomalies) Joint Action, funded by the Public Health Programme 2008–2013 of the European Commission (grant agreement 20102204); the ARIBA (Air Pollution and Pregnancy in Barcelona) project, funded by a Fondo de Investigación Sanitaria (FIS) (grant agreement PI081109); and by the ESCAPE (European Study of Cohorts for Air Pollution Effects) project, funded under the European Union’s Seventh Framework Programme (grant agreement 211250). A.S. is funded by an Instituto de Salud Carlos III-FEDER fellowship (PFIS grant FI 10/00476). P.D. is funded by a Ramón y Cajal fellowship (RYC-2012-10995) awarded by the Spanish Ministry of Economy and Finance.