Darrow et al. Materials and Methods Study population. We obtained vital record data for births to mothers residing in the five central counties of the Atlanta metropolitan area (Clayton, Cobb, DeKalb, Fulton, and Gwinnett counties) from the Office of Health Information and Policy, Georgia Division of Public Health. The study area included an area with a radius of 16 miles (25.7 km) at its narrowest and 32 miles (51.5 km) at its widest [see Supplemental Material, Figure 1 (doi:10.1289/ehp.1002785)]. We restricted analysis to full-term infants to separate the pathologies of reduced fetal growth from reduced pregnancy duration (i.e., preterm birth); results of our preterm birth analyses are reported separately (Darrow et al. 2009a). The cohort included singleton non-Hispanic African-American, non-Hispanic Caucasian, and Hispanic infants who reached at least 37 weeks of gestation and were born between 1 January 1994 and 31 December 2004 with- out major structural congenital birth defects (n = 417,280). Of these, 10,653 infants (2.5%) were excluded because of missing data. Gestational age was determined using the reported last menstrual period (LMP) date; if LMP date was missing, we substituted the clinical estimate (1.3% of records). After exclu- sions, 406,627 full-term births were eligible for analysis. Study protocols were approved by Emory University Institutional Review Board. Ambient air quality data. We obtained ambient air pollution levels from three sources: a) the U.S. EPA Air Quality System (U.S. EPA 2006), b) the Aerosol Research and Inhalation Epidemiology Study (ARIES) monitor located in downtown Atlanta (Hansen et al. 2006), and c) the Assessment of Spatial Aerosol Composition in Atlanta net- work (Butler et al. 2003). The daily air met- rics included 1-hr maximum CO, NO2, and SO2; 8-hr maximum O3; and 24-hr average Characteristic Term low birth weight (< 2,500 g) Female sex Maternal age group (years) < 20 20–34 ≥ 35 Maternal race/ethnicity Non-Hispanic white Non-Hispanic black Hispanic Maternal education (completed years) < 12 12–15 ≥ 16 Married First birth Reported tobacco use during pregnancy 732 Table 1. Maternal and infant characteristics [n (%)] for full-term births in five-county Atlanta and for births within 4 miles of a monitoring station, 1 January 1994 to 31 December 2004. Five-county Atlanta Births within 4 miles of a monitor PM10, PM2.5, PM2.5–10 (PM with aerody- namic diameter from 2.5 to 10 µm), PM2.5 sulfate, PM2.5 nitrate, PM2.5 organic carbon, PM2.5 elemental carbon, and a PM2.5 water- soluble metals index (sum of chromium, cop- per, iron, manganese, nickel, and vanadium). Gaseous pollutants were available for the entire study period. Daily PM10 monitoring began in January 1996 and daily PM2.5, PM2.5–10, and PM2.5 component monitoring began in August 1998. For CO, NO2, SO2, O3, PM10, and PM2.5, we calculated a population-weighted spatial average for each day in the study area using a method described in detail by Ivy et al. (2008). This approach incorporated all the monitoring data available for each pol- lutant on a given day in a spatial model that provided ambient pollutant levels at popu- lation census tracts, from which citywide population-weighted values were calculated robust to missing data at individual monitor- ing sites (Ivy et al. 2008). We used 5 CO mon- itors, 6 NO2 monitors, 5 SO2 monitors, 5 O3 monitors, 9 PM10 monitors, and 11 PM2.5 monitors to calculate the daily spatial averages. For the coarse PM measurements (PM2.5–10) and the PM2.5 component measurements, daily measurements from the centrally located ARIES monitor were used. We imputed O3 measurements for winters between 1994 and 1996 using a statistical model of tem- perature and week of year. In Bland–Altman plots, O3 values calculated using this predic- tion model showed strong agreement with the population-weighted spatial average O3 values in winters after 1996 when O3 was measured (mean difference, 0 ppb; limits of agreement, –6 to 6 ppb). Exposure assignment. Daily population- weighted pollutant values for five-county Atlanta were averaged over the time period corresponding to the gestational window of (n = 406,627) 10,615 (2.6) 200,748 (49.4) 42,420 (10.4) 303,755 (74.7) 60,452 (14.9) 183,946 (45.2) 164,731 (40.5) 57,950 (14.3) 78,926 (19.4) 189,818 (46.7) 137,883 (33.9) 262,769 (64.6) 176,592 (43.4) 19,236 (4.7) (n = 110,357) 3,601 (3.3) 54,590 (49.5) 15,282 (13.9) 80,113 (72.6) 14,962 (13.6) 29,962 (27.2) 63,712 (57.7) 16,683 (15.1) 28,761 (26.1) 50,709 (45.9) 30,887 (28.0) 55,574 (50.4) 48,763 (44.2) 4,603 (4.2) interest for each infant in the cohort. Using conventional obstetric notation, gestational age was calculated from the LMP date, and conception was estimated to occur on gestational day 14. For the first-month-of- pregnancy exposure window, pollutant con- centrations were averaged over the 28 days beginning on the estimated conception date (gestational days 14–41). For the third-tri- mester exposure window, pollutant concentra- tions were averaged over the period beginning on gestational day 196 (28 gestational weeks) and ending on the day of birth for each infant (mean length, 83 days; range, 64–119 days). In a sensitivity analysis, we assessed pollut- ant effects separately for infants born at each gestational week (37–44) so that infants were grouped by the length of their third trimester and results could be compared between longer and shorter gestations. For all pollutants and gestational windows presented, an exposure was assigned only when at least 85% of days in the averaging window had available pol- lution data; otherwise, the exposure was set to missing. To identify other potentially vulner- able gestational windows, we used constrained distributed lag models to assess associations for pollutant concentrations in each of the 9 months of pregnancy while controlling for pollutant concentrations in the other months of pregnancy. Although not previously applied in the context of air pollution and pregnancy outcomes (to our knowledge), distributed lag models have been used commonly in time- series air pollution studies to simultaneously assess the effects of pollution on multiple days (i.e., lags) before the health event (Schwartz 2000). Constraining the 9 month–specific effect estimates to follow the shape of a poly- nomial reduces the statistical noise due to the collinearity between exposures on neighbor- ing months of pregnancy. By imposing an underlying cubic structure, we assumed that the effects of air pollution across the 9 months of pregnancy follow a smooth cubic shape (as in our other analyses, the pollutant effect in any given month of pregnancy is assumed to be linear). For this analysis, months 1–8 of pregnancy were defined as consecutive 4-week periods beginning on the estimated concep- tion date; month 9 of pregnancy began on day 239 of gestation and ended on the day of birth (mean length of time, 40 days; range, 21–76 days). In a complementary approach to the five- county population-weighted spatial average exposure assignment described above, we cre- ated spatial capture areas around each moni- tor and conducted monitor-specific analyses for the cohorts of infants with residential geo- codes within 4 miles of each monitoring sta- tion. We limited these analyses to monitors that recorded daily pollutant concentrations. ovlume 119 | number 5 | May 2011 • Environmental Health Perspectives