Research | Children’s Health Association between GIS-Based Exposure to Urban Air Pollution during Pregnancy and Birth Weight in the INMA Sabadell Cohort Inmaculada Aguilera,1,2,3,4 Mònica Guxens,1,2,3 Raquel Garcia-Esteban,1,2,3 Teresa Corbella,5 Mark J. Nieuwenhuijsen,1,2,3 Carles M. Foradada,6 and Jordi Sunyer1,2,3,4 1Centre for Research in Environmental Epidemiology, Barcelona, Spain; 2Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain; 3Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Barcelona, Spain; 4Pompeu Fabra University, Barcelona, Spain; 5Servei de Salut, Ajuntament de Sabadell, Sabadell, Spain; 6Servei de Ginecologia i Obstetrícia, Hospital de Sabadell, Sabadell, Spain Background : There is growing evidence that traffic-related air pollution reduces birth weight. Improving exposure assessment is a key issue to advance in this research area. o Bjectiv : We investigated the effect of prenatal exposure to traffic-related air pollution via geographic information system (GIS) models on birth weight in 570 newborns from the INMA (Environment and Childhood) Sabadell cohort. Methods : We estimated pregnancy and trimester-specific exposures to nitrogen dioxide and aro- matic hydrocarbons [benzene, toluene, ethylbenzene, m/p-xylene, and o-xylene (BTEX)] by using temporally adjusted land-use regression (LUR) models. We built models for NO2 and BTEX using four and three 1-week measurement campaigns, respectively, at 57 locations. We assessed the rela- tionship between prenatal air pollution exposure and birth weight with linear regression models. We performed sensitivity analyses considering time spent at home and time spent in nonresidential outdoor environments during pregnancy. r esult : In the overall cohort, neither NO2 nor BTEX exposure was significantly associated with birth weight in any of the exposure periods. When considering only women who spent < 2 hr/day in nonresidential outdoor environments, the estimated reductions in birth weight associated with an interquartile range increase in BTEX exposure levels were 77 g [95% confidence interval (CI), 7–146 g] and 102 g (95% CI, 28–176 g) for exposures during the whole pregnancy and the second trimester, respectively. The effects of NO2 exposure were less clear in this subset. c onclusi : The association of BTEX with reduced birth weight underscores the negative role of vehicle exhaust pollutants in reproductive health. Time–activity patterns during pregnancy comple- ment GIS-based models in exposure assessment. k ey words : air pollution, aromatic hydrocarbons, birth weight, cohort study, exposure assessment, geographic information system, INMA study, nitrogen dioxide, pregnancy. Environ Health Perspect 117:1322–1327 (2009). doi:10.1289/ehp.0800256 available via http://dx.doi.org/ [Online 13 April 2009] air pollution during pregnancy and birth weight in an urban cohort from the Spanish INMA (Environment and Childhood) Study. We also examined the influence of time– activity patterns during pregnancy in the asso- ciation between air pollution and birth weight. Methods Cohort. The study area is Sabadell, a city of nearly 200,000 inhabitants situated in the metropolitan area of Barcelona, Spain. Women who visited the public health center of Sabadell in the 12th week of pregnancy and fulfilled the inclusion criteria were eli- gible to participate in the study (Ribas-Fitó et al. 2006). Main exclusion criteria were being < 16 years of age, nonsingleton preg- nancy, not planning to deliver at the Hospital of Sabadell, and having followed an assisted reproduction program. Women were inter- viewed in the 12th and 32nd weeks of preg- nancy and answered several questionnaires on sociodemographic characteristics, health status, use of drugs, occupational data, envi- ronmental exposures, time–activity pat- terns, and a food-frequency questionnaire. The protocol of the INMA study, including a detailed description of data collection and assessment of determinants and outcomes, has been published elsewhere (Ribas-Fitó et al. 2006). The study was approved by the Ethical Committees of the Municipal Institute of Medical Research and the Hospital of Sabadell, and all subjects gave written informed consent before participating. Address correspondence to I. Aguilera, Centre for Research in Environmental Epidemiology, Barcelona Biomedical Research Park, Doctor Aiguader 88, 08003 Barcelona, Spain. Telephone: 34-93-2147300. Fax: 34-93-2147301. E-mail: iaguilera@creal.cat We thank K. Meliefste (Institute for Risk Assessment Sciences, Utrecht University, the Netherlands) and R. Fernández-Patier, A. Aguirre, T. Bomboi, and D. Herce (National Centre for Environmental Health, Madrid, Spain) for the labo- ratory analysis of passive samplers. The INMA (Environment and Childhood) study has the financial support of the “Carlos III Health Institute, Spanish Ministry of Health” (G03/176), Red de Centros de Investigación en Epidemiología y Salud Pública (C03/09), and Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública. The authors declare they have no competing financial interests. Received 6 October 2008; accepted 13 April 2009. ovlume 117 | number 8 | August 2009 • Environmental Health Perspectives Fetal growth is an important indicator of the health of newborns and infants that may influence the health status in the adulthood (Sinclair et al. 2007). In recent years, a grow- ing body of research has associated prena- tal exposure to air pollution with adverse pregnancy outcomes, including intrauterine growth restriction (IUGR), low birth weight (LBW), preterm birth (PTB), and intrauter- ine mortality. Detailed reviews of these stud- ies have concluded that the strength of the evidence differs among air pollutants, birth outcomes, and exposure periods, although differences in study design, exposure assess- ment, and definition of outcomes make com- parability of results difficult (Glinianaia et al. 2004; Lacasaña et al. 2005; Šrám et al. 2005; Wang and Pinkerton 2007). To advance in this emerging and fast- growing field, some key methodologic issues have been highlighted (Gilliland et al. 2005; Ritz and Wilhelm 2008; Slama et al. 2008a). Because most studies have linked birth out- comes and covariates from birth certificate records with routinely measured air pollut- ants, one priority is to develop prospective 1322 cohort studies that are able to obtain high- quality individual data on outcomes, cova- riates, and exposure estimates. Because pregnancy is a well-defined and relatively nar- row period of exposure, identification of win- dows of greater susceptibility to air pollution is also a key issue, but is difficult because of the lack of biological knowledge and the cor- relations among trimester- or month-specific exposures. Furthermore, exposure assessment can be improved by using approaches based on geographic information systems (GIS) that take into account small-area variations in vehicle exhaust pollutants, such as land- use regression (LUR). Because LUR models have mainly been used for estimating annual average exposures, being able to accurately incorporate temporal variability in the LUR models is key for studies of birth outcomes, where shorter-term exposures are of interest. Improving exposure assessment also requires consideration of women’s residential mobility (Fell et al. 2004) and time–activity patterns during pregnancy (Nethery et al. 2009). In this study we assessed the relationship between GIS-based exposure to traffic-related