Analytic approach. Linear regression models were fitted to assess the relationship between continuous birth weight in full-term infants and air pollutant concentrations dur- ing the gestational windows of interest. We examined pollutants as linear terms in single- pollutant models. In the spatial capture area approach, separate linear regression models were fitted for each capture area, and effect estimates were pooled using inverse-variance weights to obtain a summary estimate and 95% confidence interval. All analyses were conducted using SAS version 9.2 (SAS Institute Inc., Cary, NC). Because ambient air pollution levels exhibit strong seasonal variation, and other risk factors for reduced birth weight may also vary by season (Darrow et al. 2009b), we smoothly controlled for seasonal trends using parametric cubic splines on the date of con- ception. We adjusted for long-term temporal trends in birth weight using a second cubic spline with one knot per year; a cubic term without knots was used in the distributed lag analyses. We also assessed potential confound- ing by mean temperature and mean dew point over the gestational window of interest. Although individual-level risk factors for reduced birth weight are unlikely to be con- founders of the air pollution and birth weight relationship in this temporal analysis, indi- vidual-level predictors of birth weight were included to improve precision. Covariates included maternal education (< 12 years, 12–15 years, or ≥ 16 years of education), parity (first born vs. second or higher), race/ ethnicity (Hispanic, non-Hispanic white, non-Hispanic black), marital status, reported tobacco use, infant sex, and maternal age (lin- ear spline with knots at 20 and 35 years). Finally, using interaction terms we exam- ined effect modification of air pollution by race and ethnicity (Hispanic, non-Hispanic white, non-Hispanic black) to investigate the hypothesis that certain racial or ethnic groups might have differing susceptibility to ambient air pollution. Results In the five-county cohort, the mean ± SD birth weight among full-term infants was 3,405 ± 477 g; for births within 4 miles of a monitor, the mean birth weight was 3,350 ± 475 g. Table 1 shows maternal and infant characteristics for these cohorts. Compared with the full five-county cohort, mothers residing within 4 miles of a monitor were younger, less educated, and more likely to be non-Hispanic black and unmarried. Table 2 presents descriptive statistics of the population-weighted pollutant averages for the two gestational windows of a priori interest. The interquartile ranges (IQRs) of the pollutant concentrations differed slightly Environmental Health Perspectives • volume 119 | number 5 | May 2011 between the exposure windows for some pollutants; we used the IQRs presented in Table 2 to scale the effect estimates presented in later tables. Correlations between the pol- lutants for each gestational window are pre- sented in Supplemental Material [Tables 1 and 2 (doi:10.1289/ehp.1002785)]. Five-county analysis. Table 3 shows the change in birth weight per IQR increase in pol- lutant concentration during the first month of pregnancy and the third trimester. Results for the first month of pregnancy exposure window were consistent with little or no association; we observed one association between PM2.5 nitrate concentration and increased birth weight (p < 0.05). Third-trimester concentra- tions of NO2, SO2, PM2.5 elemental carbon, and PM2.5 water-soluble metals were associated Air pollution and birth weight with small decreases in birth weight ranging from –3.9 to –16.5 g per IQR increase in pol- lutant concentration. The association between third-trimester CO concentrations and birth weight (–7.1 g per IQR) was borderline sig- nificant (p = 0.06). When we examined third- trimester exposures for infants stratified by gestational week (37–44), pollutant effect esti- mates were similar between longer and shorter gestations. Mean temperature and dew point were not predictive of birth weight in either gestational window and did not meaningfully change the effect estimates for pollution, so they were not included in the final models. Figure 1 shows results from the con- strained distributed lag models. Estimated month-specific effects reflect associations between pollutant concentrations and birth IQR 0.3 5 3 23 7 4 2.0 2.9 0.6 0.5 1.0 0.016 733 Table 2. Descriptive statistics of the assigned pollutant values in the five-county cohort. First month of gestation (4-week average) Third trimester Pollutant 1-hr maximum concentrationa CO (ppm) NO2 (ppb) SO2 (ppb) 8-hr maximum O3 (ppb)a 24-hr PM concentration (µg/m3) PM10a PM2.5a PM2.5–10b PM2.5 sulfateb PM2.5 nitrateb PM2.5 elemental carbonb PM2.5 organic carbonb PM2.5 water-soluble metalsb,c Mean ± SD 0.9 ± 0.2 23.6 ± 4.0 10.7 ± 3.4 44.8 ± 15.3 23.8 ± 6.3 16.5 ± 4.1 9.1 ± 2.5 4.9 ± 2.3 1.0 ± 0.5 1.6 ± 0.5 4.4 ± 1.0 0.030 ± 0.013 IQR 0.3 5 4 25 8 5 2.7 2.9 0.7 0.5 1.2 0.017 Mean ± SD 0.8 ± 0.2 23.8 ± 3.3 9.5 ± 2.0 44.2 ± 12.5 23.4 ± 4.2 16.4 ± 3.1 9.0 ± 1.7 5.1 ± 1.8 0.9 ± 0.4 1.6 ± 0.4 4.3 ± 0.6 0.031 ± 0.010 Pollutant monitoring methods: CO, infrared analyzer; NO2, chemiluminescence; SO2, fluorescence; O3, ultraviolet absorp- tion; PM10, federal reference method (eight sites) and tapered element oscillating microbalance (one site); PM2.5, federal reference method (eight sites) (U.S. EPA 1997) and tapered element oscillating microbalance (three sites); PM2.5–10, dichotomous sampler; PM2.5 components, particle composition monitor; sulfate and nitrate, ion chromatography; ele- mental and organic carbon, thermal optical reflectance; and water-soluble metals, x-ray fluorescence. For more details on air quality measurements and instrumentation see Hansen et al. (2006) and Ivy et al. (2008). aConcentrations reflect population-weighted ambient pollution values. bConcentrations reflect central monitor measure- ments. cWater-soluble metal index includes chromium, copper, iron, manganese, nickel, and vanadium. Table 3. Mean change in birth weight (Δg) and 95% confidence intervals (CI) for ambient air pollutant con- centrations in the first month of pregnancy and the third trimester for full-term births in five-county Atlanta. First month of gestation Third trimester (week 28 to birth) na Δg (95% CI) Pollutant 1-hr maximum concentration CO (ppm) NO2 (ppb) SO2 (ppb) 8-hr maximum O3 (ppb) 24-hr PM concentration (µg/m3) PM10 PM2.5 PM2.5–10 PM2.5 sulfate PM2.5 nitrate PM2.5 elemental carbon PM2.5 organic carbon PM2.5 water-soluble metals na 406,616 404,195 400,556 406,627 311,365 225,522 194,683 182,290 181,831 220,867 220,867 183,316 Δg (95% CI) –1.8 (–5.7 to 2.2) 0.4 (–1.8 to 2.6) 0.5 (–2.1 to 3.1) –1.2 (–7.5 to 5.2) 1.0 (–2.1 to 4.0) 0.0 (–3.7 to 3.7) –2.2 (–5.7 to 1.4) 0.8 (–4.5 to 6.1) 9.2 (3.0 to 15.4)* 0.7 (–2.4 to 3.8) –0.1 (–3.1 to 2.9) 2.5 (–3.5 to 8.5) 406,627 406,627 406,627 406,627 333,190 243,481 215,136 194,677 185,597 243,195 243,195 193,377 –7.1 (–14.5 to 0.2) –4.5 (–8.5 to –0.6)* –3.9 (–7.5 to –0.4)* –2.2 (–11.2 to 6.9) –2.3 (–7.4 to 2.8) –4.3 (–9.8 to 1.2) –3.1 (–7.6 to 1.4) –8.5 (–19.1 to 2.0) –5.5 (–15.4 to 4.5) –7.1 (–13.9 to –0.3)* –3.4 (–8.5 to 1.7) –16.5 (–28.4 to –4.7)* Change in birth weight and 95% CIs correspond to an IQR increase in pollutant value shown in Table 2. Models con- trolled for long-term trends, seasonal trends, gestational week, sex, and maternal marital status, education, age, race/ ethnicity, reported tobacco use, and parity. aNumber of infants with an assigned exposure. *p < 0.05.