Research | Children’s Health Ambient Air Pollution and Birth Weight in Full-Term Infants in Atlanta, 1994–2004 Lyndsey A. Darrow,1 Mitchel Klein,1 Matthew J. Strickland,1 James A. Mulholland,2 and Paige E. Tolbert 1 1Department of Environmental Health, Emory University, Atlanta, Georgia, USA; 2Department of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA Background : An emerging body of evidence suggests that ambient levels of air pollution during pregnancy are associated with fetal growth. o Bjectivs : We examined relationships between birth weight and temporal variation in ambient levels of carbon monoxide, nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone, particulate matter ≤ 10 µm in diameter (PM10), ≤ 2.5 µm (PM2.5), 2.5 to 10 µm (PM2.5–10), and PM2.5 chemical com- ponent measurements for 406,627 full-term births occurring between 1994 and 2004 in five central counties of metropolitan Atlanta. Methods : We assessed relationships between birth weight and pollutant concentrations during each infant’s first month of gestation and third trimester, as well as in each month of pregnancy using distributed lag models. We also conducted capture-area analyses limited to mothers residing within 4 miles (6.4 km) of each air quality monitoring station. r esult : In the five-county analysis, ambient levels of NO2, SO2, PM2.5 elemental carbon, and PM2.5 water-soluble metals during the third trimester were significantly associated with small reductions in birth weight (–4 to –16 g per interquartile range increase in pollutant concentrations). Third-trimester estimates were generally higher in Hispanic and non-Hispanic black infants relative to non-Hispanic white infants. Distributed lag models were also suggestive of associations between air pollutant concentrations in late pregnancy and reduced birth weight. The capture-area analyses provided little support for the associations observed in the five-county analysis. c onclusi : Results provide some support for an effect of ambient air pollution in late pregnancy on birth weight in full-term infants. k ey words : air pollution, air pollution epidemiology, birth weight, particulate matter, pregnancy outcomes. Environ Health Perspect 119:731–737 (2011). doi:10.1289/ehp.1002785 [Online 14 December 2010] Birth weight has long been recognized as a strong predictor of infant morbidity and mor- tality. Over the last 10 years, epidemiologic studies have reported relationships between ambient air pollution and measures of reduced fetal growth (Glinianaia et al. 2004; Šrám et al. 2005). To separate effects on fetal growth from effects on length of gestation, investigators have examined low birth weight (< 2,500 g) in full-term infants, birth weight adjusted for gestational age, and small for gestational age (commonly defined as birth weight below the 10th percentile for gesta- tional age). Many studies suggest an asso- ciation between fetal growth and ambient particulate matter (PM), although the gesta- tional window of effect has not been consis- tent across studies. Associations with PM have been reported most commonly for early preg- nancy exposures (e.g., first month, first tri- mester) (Gouveia et al. 2004; Liu et al. 2003; Rich et al. 2009) and late pregnancy expo- sures (e.g., third trimester) (Bell et al. 2007; Rich et al. 2009; Wilhelm and Ritz 2005), although other investigators have observed associations only in midpregnancy or not at all (Hansen et al. 2007; Lee et al. 2003; Mannes et al. 2005). Gaseous air pollutants have also been investigated in relation to measures of fetal growth and show similar inconsisten- cies. Literature reviews and meeting reports conclude that further research is warranted to clarify the gestational windows of susceptibil- ity and to identify specific pollutants or pollut- ant constituents associated with fetal growth (Slama et al. 2008; Woodruff et al. 2009). There is increasing interest in traffic-related air pollutants such as carbon monoxide (CO), nitrogen oxides (NOx), and primary exhaust particles (e.g., elemental carbon) because of reports implicating proximity to traffic sources in reduced fetal growth (Rocha et al. 2008; Wilhelm and Ritz 2003). Air pollution could act through several biological mechanisms to inhibit fetal growth. Pulmonary and placental inflammation, increased blood coagulation and viscosity, and altered endothelial and vascular function could compromise uteroplacental blood flow and inhibit the placental transfer of oxygen and nutrients from mother to fetus. Some of these mechanisms are thought to be involved in the well-documented relationship between maternal active and passive smoking and fetal growth restriction (Gabbe 2002; U.S. Department of Health and Human Services 2001, 2006). Studies of maternal smoking suggest that the third trimester is a particu- larly vulnerable exposure window (Lieberman et al. 1994; U.S. Department of Health and Human Services 2001). Furthermore, the third trimester corresponds to the period of Environmental Health Perspectives • volume 119 | number 5 | May 2011 most rapid fetal growth and fat accumulation (Gabbe 2002). Early pregnancy may also be a period of vulnerability, with abnormal reac- tion between trophoblast and uterine tissue around the time of implantation leading to chronic placental insufficiency throughout pregnancy (Torry et al. 2004). Evidence sup- porting early pregnancy effects comes from a toxicologic study that found early pregnancy exposures among mice to be the most harmful (Rocha et al. 2008). We investigated relationships between ambient levels of air pollution during pregnancy and birth weight in a cohort of 406,627 full-term births occurring between 1994 and 2004 in the five central counties of metropolitan Atlanta, Georgia. Pollutants examined included CO, nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), particulate matter ≤ 10 µm in diameter (PM10), PM2.5 (< 2.5 µm), and PM2.5 chemi- cal component measurements that are rarely available on a daily basis and have not been previously assessed in relation to measures of fetal growth. We focused on two gestational windows of a priori interest based on previ- ous air pollution studies, studies of maternal active and passive smoking, and toxicologic evidence: the first month of gestation and the third trimester. In a novel use of distributed lag models, we used a data-based approach to explore associations in each of the 9 months of gestation to identify other potentially vul- nerable gestational windows. Address correspondence to L. Darrow, Rollins School of Public Health, Emory University, Department of Environmental Health, 1518 Clifton Rd., Atlanta, GA 30322 USA. Telephone: (404) 727-4595. Fax: (404) 727-8744. E-mail: ldarrow@sph.emory.edu Supplemental Material is available online (doi:10.1289/ehp.1002785 via http://dx.doi.org/). We are grateful to the Georgia Division of Public Health, Office of Health Information and Policy, for providing the vital record data. We also thank the Electric Power Research Institute (EP-P4353/C2124) for providing the Aerosol Research and Inhalation Epidemiology Study air quality measurements. This work was supported by the National Institute of Environmental Health Sciences (NIEHS; R01- ES-012967-02S2A1) and the U.S. Environmental Protection Agency (EPA) Science to Achieve Results (STAR) fellowship program (FP-91655101-0). The content is solely the responsibility of the authors and does not represent the official views of the U.S. EPA or NIEHS. The authors declare they have no actual or potential competing financial interests. Received 27 July 2010; accepted 14 December 2010. 731