Vrijheid et al. et al. (2009) based their groupings of car- diac anomalies and orofacial clefts on the ana- tomic classification used in the first study by Ritz et al. (2002); inclusion and exclusion of chromosomal, syndromic, and multiple anomalies still differed among these studies. The Georgia study (Strickland et al. 2009) used a more detailed system of diagnostic codes for cardiac anomalies. The U.K. stud- ies (Dadvand et al. 2011a, 2011b; Dolk et al. 2010; Rankin et al. 2009) all used coding and grouping system based on the International Classification of Diseases, 9th Revision (World Health Organization 1975) and the minor anomaly exclusion criteria proposed by the European Surveillance of Congenital Anomalies (EUROCAT 2009). In all but one study (Dadvand et al. 2011a), exposure assessments were based on the routine measurements of air pollutant concentrations at fixed-site air pollution mon- itoring stations. Most commonly, exposures were assigned using the monitoring station nearest to the maternal residence at the time of the birth. Distances of residence from the monitors varied and in some studies inclu- sion of study subjects was limited by their distance to the monitor [e.g., 16 km in the Ritz et al. (2002) study, 10 km in the Rankin et al. (2009) study]. Number and density of monitors also varied, as did the maximum distance of subjects from the nearest monitor (Table 1). Dadvand et al. (2011a) developed a spatiotemporal model in which black smoke and SO2 concentrations at the maternal resi- dence were predicted using concentrations measured at 56 monitors and data on traffic, meteorology, and land cover. The Georgia study (Strickland et al. 2009) differed from others in that temporal data from one central monitoring station in the county were related to the vulnerable window of each pregnancy in a time-series analysis. Nearly all other stud- ies defined windows of pregnancy suscep- tible to the development of the congenital anomalies under study (usually weeks 3–8 of gestation) and averaged exposure over those windows. The Dolk et al. (2010) study assigned mean pollutant concentrations meas- ured in one year (1996) to the census ward level of residence and was not able to estimate exposure in pregnancy time windows. Most studies focused on the most com- monly monitored air pollutants: PM10 (nine studies), SO2 (eight studies), NO2 (seven studies), CO (seven studies), and O3 (seven studies). Less frequently studied pollutants Table 1. Studies on air pollution and risk of congenital anomalies. Setting Design Case and control definition Exposure assessment California (USA), Case–control 3,121 cases with cardiac Average of 24-hr Reference Ritz et al. 2002 Gilboa et al. 2005 Kim et al. 2007 Rankin et al. 2009 Strickland et al. 2009 600 four counties, 1987–1993; 754,030 births Texas (USA), seven counties, 1997–2000; 607,500 births Seoul (South Korea), 2001–2004; 1,514 births Northern region (UK), 1985–1990; 242,268 births Georgia (USA), five counties, 1986–2003; 715,500 births Exposure range in second month of gestation p25–p75: CO, 1.14–2.39 ppm O3, 1.07–2.86 pphm p25–p75: CO, 0.4–0.7 ppm NO2, 1.3–2.1 pphm O3, 1.8–3.1 pphm PM10, 19.5–29 μg/m3 SO2, 1.3–2.7 ppb Mean: PM10, 89.7 μg/m3 NOx, 16.0–23.9 ppb O3, 24.4–30.1 pphm PM10, 44.8–64.5 μg/m3 SO2, 2.4–5.0 ppb p25–p75: SO2, 2.7–4.5 μg/m3 Black smoke, 1.1–2.8 μg/m3 IQR: CO, 0.3 ppm NO2, 5.7 ppb O3, 3.0 pphm PM10, 14.2 μg/m3 SO2, 4.0 ppb Gestational period Months 1, 2, and 3; trimesters 2 and 3; 3 months preconception Adjustment variables Maternal age, race, education, prenatal care, infant sex, decade of birth, parity, birth type, season of conception, and other air pollutants Weeks 3–8 Maternal age, education, race/ ethnicity, marital status, illness, tobacco use, season of conception, plurality, parity, infant sex, prenatal care, and gravidity Trimesters 1, 2, Infant sex, birth and 3 order, season of birth, maternal age, education, alcohol, and body mass index Months 1, 2, Maternal age, plurality, and 3 gestational age, population density, and season of conception First trimester Birth weight, sex, and material deprivation Weeks 3–7 Week of year, and cubic spline for day of follow-up continued next page ovlume 119 | number 5 | May 2011 • Environmental Health Perspectives Case–control 1,719 cases with cardiac Birth cohort 14 cases with structural or oral facial cleft defects; live births and fetal deaths > 20 weeks gestations; 9,357 controls, randomly selected from all births and fetal deaths defects or oral clefts; live births and fetal deaths > 20 weeks gestation; 3,667 controls, live births, and fetal deaths, frequency matched by vital status, year of birth, and county defects in cohort of 1,514 births with or without cleft palate diagnosed at birth; 6,530 controls randomly selected from all live births congenital anomaly; live births and fetal deaths ≥ 20 weeks gestation; 15,000 controls randomly selected from all live and stillbirths 3,338 cases with an indication of cardiovascular malformation; all live births, stillbirths, and fetal deaths > 20 weeks measurements of CO, NO2, O3, and PM10 at nearest monitoring station (within 16 km) Average hourly or daily concentrations of CO, NO2, O3, PM10, and SO2, measured at the nearest, or next nearest, monitor in the county (median distance to monitor, 8.6–14.2 km; maximum, 36–54 km) Average PM10 concentration from nearest of 27 monitoring stations of CO, NOx, O3, PM10, and SO2, measured at 72 monitoring stations in Taiwan; inverse distance-weighted average assigned to each residence Average of daily black smoke and SO2 from all monitoring stations within 10 km of maternal residence Average of daily measurements of CO, NO2, O3, PM10, and SO2 from one central monitoring station; daily time-series analysis using conception dates Hwang and Taiwan, Case–control 653 cases with cleft lip Jaakkola 2008 2001–2003; 721,289 births Monthly average of p25–p75: continuous concentration CO, 0.48–0.76 ppm Case–control 2,779 cases with Time series