Aguilera et al. pregnancy (Lee et al. 2003; Mannes et al. 2005), whereas others identified first trimester of exposure to NO2 as the only period influ- encing fetal growth, measured as continu- ous birth weight, LBW, or IUGR (Bell et al. 2007; Ha et al. 2001; Salam et al. 2005). Two studies found an association between NO2 and birth weight for the whole pregnancy but did not identify any specific harmful exposure period (Brauer et al. 2008; Liu et al. 2007). Finally, other studies did not observe any sig- nificant association between NO2 and fetal growth (Gouveia et al. 2004; Hansen et al. 2007; Liu et al. 2003; Slama et al. 2007). However, between-study comparisons are lim- ited by differences in study design, exposure assessment, and different outcome definitions (IUGR or birth weight treated as continuous or dichotomous variable). We found reductions in birth weight with increases in BTEX concentrations only among women who spent < 2 hr/day in nonresi- dential outdoor locations. This could poten- tially be due to less exposure misclassification (assumed nondifferential) in residence-based LUR estimates for this subset. Although rep- resenting a small portion of total daily activ- ity, time spent outdoors can signify direct exposure to traffic-related pollutants. Thus, women who spent a considerable amount of time (≥ 2 hr/day) in nonresidential out- door environments could have been exposed to a high variability of traffic-related NO2 and BTEX levels, very different than those reflected by the LUR estimates based on the residential address. This hypothesis is sup- ported by results obtained for a subset of 53 women of this cohort in their third trimester of pregnancy, selected to represent the geo- graphic distribution of the cohort addresses, and for which personal levels of NO2 were measured with passive samplers during 48 hr. In this subset, women who spent ≥ 2 hr/ day in nonresidential outdoor environments (reported for the 48-hr measurement period) showed higher personal levels of NO2 (β = 14.4 µg/m3; 95% confidence interval, 4.6– 24.3 µg/m3), compared with the reference group (< 2 hr/day) (Valero N, Aguilera I, Llop S, Esplugues A, de Nazelle A, Ballester F, et al., unpublished observations). A study con- ducted in Athens also found that time spent outdoors in the city center was a major con- tributor to personal exposure to toluene and xylenes (Alexopoulos et al. 2006). Nethery et al. (2008) found a better correlation (r = 0.72) between 48-hr personal exposure to nitric oxide and LUR-estimates based on home address in a subset of pregnant women who spent > 65% of sampling time at home, compared with those who spent ≤ 65% (r = 0.31). Although not statistically significant, effect estimates for BTEX in our cohort were also more pronounced among women who 1326 spent more time at home, compared with the whole cohort. Overall, results reinforce the need of considering time–activity patterns during pregnancy to better characterize the exposure (Ritz and Wilhelm 2008). The inclusion of LUR estimates based on work addresses also could improve exposure assessment among employed women (Nethery et al. 2008). In our study, we were unable to account for work-based LUR estimates for the whole subset of employed women because approximately 25% of them worked outside the area covered by our LUR models and 16% reported imprecise work addresses that we were unable to geocode. We did not con- duct a sensitivity analysis by working status because 37% (n = 160) of the 437 women who were employed at the beginning of the study changed their working status during the 12th- and 32nd-week interviews, making the trimester-specific classification of work- ing status in this subset prone to error, par- ticularly for the second trimester of pregnancy. Instead, we investigated differences in time– activity patterns by working status during the whole pregnancy and found that women who worked during the entire pregnancy spent less time in nonresidential outdoor environments. This suggests that this time–activity variable, although reported mainly as a walking activ- ity, is not an indicator of commuting but of a wider variety of transit activities. Several studies have reported seasonal pat- terns both in air pollution levels and in birth weight (Hazenkamp-von Arx et al. 2004; Murray et al. 2000). In Sabadell, daily mean levels of NO2, benzene, and toluene (measured at the fixed monitoring station) were higher in winter and lower in summer during the study period, probably due to seasonal differences in meteorologic conditions and traffic intensity. We also have found a seasonal pattern in birth weight, with lowest birth weights seen in infants conceived in winter. This effect is larger than that observed in other studies (Jedrychowski et al. 2004; Slama et al. 2007; Wilhelm and Ritz 2005) and independent from the air pollu- tion effects (p for interaction > 0.10), suggesting that seasonal effects on birth weight could be related to seasonal factors other than air pollu- tion, such as ambient temperature and sunlight (Murray et al. 2000; Tustin et al. 2004). LUR estimates of NO2 and BTEX lev- els were higher among women with higher educational level, compared with women with secondary or primary education. This could be explained by the higher percentage of women with university degree living in the city center, which is one of the districts with higher air pol- lution levels because of its higher road density and economic activity (Aguilera et al. 2008). O’Neill et al. (2003) found that people with lower SES tend to live in areas with higher levels of air pollution in North America. This evidence is more limited in Europe, with some studies suggesting that the inverse association may occur (Forastiere et al. 2007; Hoek et al. 2002). Differences between European and North American cities in their structure and social class distribution could explain these dis- crepancies. Within Europe, southern European cities have a more dense structure of roads and buildings, and thus higher traffic emissions, particularly in central districts (Muñoz 2003). Although preliminary, our results support the hypothesis that higher SES can be associated with living in more polluted areas in southern European cities. One of the strengths of our study is esti- mation of individual exposure to traffic-related air pollutants based on temporally adjusted LUR models applied to geocoded home addresses, whereas most studies assess expo- sure by using routinely measured air pollution levels and community-level residence (cen- sus data or postal codes). To date, only two studies have also applied temporally adjusted LUR models in Munich, Germany, and Vancouver, Canada (Brauer et al. 2008; Slama et al. 2007), although they did not take into account time–activity patterns as potential factors affecting exposure misclassification. In addition, we accounted for residential mobility during pregnancy when assigning exposures, and we were able to control for a considerable number of potential confounders not always available in studies relying on data from birth certificates, such as quantitative measures of maternal smoking, passive smoking, or mater- nal and paternal weight and height. Because we used ultrasound measurements to correct reported LMP dates that differed in ≥ 7 days from the ultrasound-based estimates, corrected gestational age could be biased if air pollution exposure shows an early effect on fetal growth (Slama et al. 2008b). However, analysis of gestational age (both corrected and noncorrected) by exposure categories during the first trimester indicated that the correc- tion of gestational age was not biased by air pollution effects. A limitation of this study was the relatively small sample size, which limited our ability to investigate other birth outcomes (i.e., PTB or IUGR) and evaluate interactions between air pollution exposure and potential effect modi- fiers such as maternal nutrition (Kannan et al. 2006). In addition, because we used daily mean levels of NO2 to temporally adjust the BTEX exposure model, identification of the second trimester as the most susceptible to BTEX exposure needs careful interpretation. Because NO2 and BTEX were highly correlated in space and time and both originate mainly from vehicle emissions in the study area, it remains unclear whether the more pronounced effect found for BTEX was independent of other traffic-related pollutants. Considering that ovlume 117 | number 8 | August 2009 • Environmental Health Perspectives