ABSTRACT
Approximately 3.3% of U.S. live-born children have a major birth defect (Centers for Disease Control and Prevention 2013; Parker et al. 2010); these defects account for 20% of infant deaths as well as 2.3% of premature death and disability (McKenna et al. 2005). Oral clefts, neural tube defects (NTDs), and congenital heart defects (CHD) are the most common classes of birth defects (Parker et al. 2010). These defects are thought to originate in the first trimester as a result of polygenic inherited disease or gene-environment interactions (Brent 2004). Suspected nongenetic risk factors for these birth defects include folate deficiency (Wald and Sneddon 1991), maternal smoking (Honein et al. 2006), alcohol abuse and solvent use (Romitti et al. 2007), and exposure to benzene (Lupo et al. 2010b; Wennborg et al. 2005), toluene (Bowen et al. 2009), polycyclic aromatic hydrocar-
bons (PAHs) (Ren et al. 2011), and petroleum-based solvents, including aromatic hydrocarbons (Chevrier et al. 1996). Associations between air pollution [volatile organic compounds (VOCs), particulate matter (PM), and nitrogen dioxide (NO2)] and low birth weight and preterm birth have been reported (Ballester et al. 2010; Brauer et al. 2008; Dadvand et al. 2013; Ghosh et al. 2012; Llop et al. 2010). Many of these air pollutants are emitted during development and production of natural gas (referred to herein as NGD), and concerns have been raised that they may increase risk of adverse birth outcomes and other health effects (Colborn et al. 2011; McKenzie et al. 2012). Increased prevalence of low birth weight and small for gestational age and reduced APGAR scores were reported in infants born to mothers living near NGD in Pennylvania (Hill 2013).
