Maternal benzene exposure and low birth weight risk in the United States: A natural experiment in gasoline reformulation Sammy Zahran a,b,n , Stephan Weiler c , Howard W. Mielke d,e , Anita Alves Pena c a Department of Economics, Center for Disaster and Risk Analysis, Colorado State University, C312A Clark Building, Fort Collins, CO, 80523-1771, USA b Department of Epidemiology, Colorado School of Public Health, Colorado State University, C312A Clark Building, Fort Collins, CO, 80523-1771, USA c Department of Economics, Colorado State University, Fort Collins, CO 80523-1771, USA d Center for Bioenvironmental Research, Tulane University, 1430 Tulane Ave SL-3, New Orleans, LA 70112, USA e Department of Chemistry, Tulane University, New Orleans, LA 70118, USA article info Article history: Received 2 March 2011 Received in revised form 17 November 2011 Accepted 17 November 2011 Available online 15 December 2011 Keywords: Benzene emissions Benzene ambient concentration Birth weight Low birth weight abstract We investigate the relationship between maternal exposure to benzene and birth weight outcomes for resident births in the United States in 1996 and 1999, taking advantage of a natural experiment afforded by the regulation of benzene content of gasoline in various American cities. Regression results show that a unit increase (mg/m 3 ) in maternal exposure to benzene reduces birth weight by 16.5 g (95% CI, 17.6 to 15.4). A unit increase in benzene exposure increases the odds of a low birth weight event by 7%. Similarly, a 1 mg/m 3 increase in benzene concentration increases the odds of very low birth weight event by a multiplicative factor of 1.23 (95% CI, 1.19 to 1.28). Difference-in-differences analyses show that birth weight increased by 13.7 g (95% CI, 10.7 to 16.8) and the risk of low birth weight decreased by a factor of .95 (95% CI, .93 to .98) in counties experiencing a 25% decline in benzene concentrations from 1996 to 1999. Public health policy and economic implications of results are discussed. & 2011 Elsevier Inc. All rights reserved. 1. Introduction Low birth weight is a significant predictor of neonatal mortal- ity and post-natal morbidity (Hack et al., 1995). The known risk factors for low birth weight include demographic variables like maternal age, maternal education, marital status, and infant sex (Kramer, 1987; Lin et al., 2007; Alexander et al., 2003; Khoshnood et al., 2005; Kleinman and Madans, 1985; Valero de Bernabe et al., 2004), gestation and obstetric variables like adequacy of prenatal care and history of prior preterm or small-for-gestational age infants (Shi et al., 2004), and toxic exposure and behavioral variables like maternal cigarette, alcohol use, and maternal weight gain and nutrition (Kramer, 1987; Seidman et al., 1989). Researchers also note that maternal exposure to criteria air pollutants like carbon monoxide and particulate matter signifi- cantly decrease infant birth weight (Parker et al., 2005; Bell et al., 2007a,b; Woodruff et al., 2003). Preliminary research indicates that other, non-criteria air pollutants like benzene may cause fetal harm (S ˇ ra ´m et al., 2005; Agency for Toxic Substances and Disease Registry (ATSDR), 1997, 2007; National Center for Environmental Assessment (NCEA), 1998, 2002; Duarte-Davidson et al., 2001). Animal studies, for example, find that maternal benzene exposure is fetotoxic, resulting in lower birth weight, delayed bone formation, and stunted bone marrow growth (ATSDR, 2007; Laskin et al., 1995; Snyder and Hedli, 1996). Pregnant women exposed to benzene and other aromatic organic solvents in petrochemical work settings are known to have lower birth weight infants (Chen et al., 2000). Maternal residential proximity to hazardous waste landfills containing benzene and volatile organic compounds is associated with low birth weight risk (Berry and Bove, 1997). A prospective study of non-smoking pregnant women reports significant negative associations between benzene exposure, fetal head circumference, and birth weight (Slama et al., 2009). The biological mechanisms by which benzene affects birth weight are not precisely understood. Intrauterine growth retarda- tion seems the most plausible pathway. Benzene is known to produce several toxic metabolites that cause oxidative damage in cells and suppress cell growth (ATSDR, 2007; Laskin et al., 1995; Rao and Snyder, 2006). Exposed to low levels of benzene, both petrochemical industry workers and service station attendants present with significantly higher urine biomarkers t,t-muconic Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/envres Environmental Research 0013-9351/$ - see front matter & 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.envres.2011.11.008 n Corresponding author at: Department of Economics, Colorado School of Public Health, Center for Disaster and Risk Analysis, School of Global Environmental Sustainability, Colorado State University, C312A Clark Building, Fort Collins, CO 80523-1771, USA. Fax: þ1 970 491 2925. E-mail addresses: szahran@colostate.edu (S. Zahran), Stephan.Weiler@colostate.edu (S. Weiler), hmielke@tulane.edu (H.W. Mielke), anita.pena@colostate.edu (A.A. Pena). Environmental Research 112 (2012) 139–146