Rossner et al. association between exposures to PM2.5 and B[a]P and pregnancy outcomes. We do not have any definite explanation for the conflict- ing results we obtained. We speculate that the reduced sample size in our study when compared with the original project may be one of the reasons. In addition, the samples in studies by Dejmek et al. were collected earlier in the 1990s, when the concentrations of air pollutants, particularly in the Teplice region, were higher than at the end of the decade. Finally, Dejmek et al. split the concentrations of PM2.5 into tertiles. IUGR was associated only with the highest concentrations of PM2.5 (the third tertile; Dejmek et al. 1999). In con- trast, we used the median in our calculations and therefore did not test separately the effect of PM2.5 levels in the third tertile on the inci- dence of IUGR or LBW. Genetic polymorphisms may modulate the response of the organism to various fac- tors and affect its ability to cope with adverse conditions. Given the sample size that we ana- lyzed, we were able to use a moderately high- throughput method of SNP detection that allowed us to assess 574 SNPs in 95 genes and 2 gene deletions. Although we did not detect any SNP asso- ciated with either oxidative DNA damage or IUGR, in univariate analysis we found four genes (MBL2, CCL7, CCL11, and CCL18) modifying the incidence of LBW. After adjust- ing for other variables, only MBL2 remained a significant factor affecting LBW. The MBL2 gene encodes MBL, a protein that plays an important role in innate immunity. The pro- tein has diverse functions that include com- plement activation, opsonophagocytosis, the modulation of inflammation, and the clearance of apoptotic cells (Dommett et al. 2006). It provides the first-line defense against microor- ganisms. Polymorphisms in exon 1 that affect the levels of MBL in serum have been described (Garred 2008). The MBL2 promoter 1 has been shown to be highly polymorphic. In particular, the variant alleles in three SNPs (rs11003125, rs7096206, and rs7095891) cause lower activity of the promoter (Garred 2008), thus decreasing the concentrations of MBL in serum. These SNPs were associated with shorter gestational age (van de Geijn et al. 2008) as well as with LBW (Thevenon et al. 2009). In our study, we identified 10 SNPs in the promoter region of MBL2 that were associated with LBW. These SNPs form three haplotypes. The homozygous combination of the most frequent haplotype was inversely asso- ciated with LBW. Although the SNPs affecting LBW differed from those identified previously (Thevenon et al. 2009), they are also in the pro- moter region, and thus our results support the data of Thevenon et al. (2009). These authors also analyzed MBL concentrations in serum and found that lower levels are associated with 270 polymorphisms that increased the LBW risk. This is in contrast with van de Geijn et al. (2008), who reported that shorter gestational age was associated with higher serum levels of MBL. Because we did not measure serum lev- els of MBL, we can only speculate that lower frequency haplotypes modify the activity of the promoter, thus changing the serum levels of MBL. This may negatively affect immune responses or induce inflammation, ultimately resulting in LBW. Whereas univariate analyses indicate that only IUGR is associated with 8-oxodG lev- els in placental DNA, multivariate-adjusted analyses identified both IUGR and LBW as adverse pregnancy outcomes where oxidative DNA damage appears to play a significant role. No other variable significantly affecting IUGR was found. Thus, it seems that oxidative DNA damage resulting from various sources is a key event leading to the IUGR syndrome. On the other hand, LBW was affected by sev- eral variables. We saw the strongest association with gestational age, sex, and the haplotype in the promoter region of MBL2. Based on these findings, we cannot confirm our hypoth- esis that 8-oxodG is an intermediate in the air pollution-adverse pregnancy outcome pathway [Supplemental Material, Figure 1 (doi:10.1289/ehp.1002470)]. It seems rather more probable that oxidative damage is one of the independent factors (a key factor in the case of IUGR) that collectively contribute to adverse pregnancy outcomes. Conclusions Our results suggest that levels of 8-oxodG in placental DNA play a significant role in both IUGR- and LBW-affected pregnancies. IUGR is associated mostly with 8-oxodG, whereas LBW is further affected by the sex and gesta- tional age of the child, maternal smoking, and genetic polymorphisms in the MBL2 gene, the protein product of which is an important factor in innate immunity. The role of air pol- lution in the risk for both adverse pregnancy outcomes in this particular data set seems to be less important. Ref Rencs Avogbe PH, Ayi-Fanou L, Autrup H, Loft S, Fayomi B, Sanni A, et al. 2005. Ultrafine particulate matter and high-level benzene urban air pollution in relation to oxidative DNA damage. Carcinogenesis 26(3):613–620. Bamberg C, Kalache KD. 2004. Prenatal diagnosis of fetal growth restriction. Semin Fetal Neonatal Med 9(5):387–394. Barker DJ. 1995. Fetal origins of coronary heart disease. BMJ 311(6998):171–174. Biri A, Bozkurt N, Turp A, Kavutcu M, Himmetoglu O, Durak I. 2007. Role of oxidative stress in intrauterine growth restriction. Gynecol Obstet Invest 64(4):187–192. Bobak M. 2000. Outdoor air pollution, low birth weight, and pre- maturity. Environ Health Perspect 108:173–176. Brauer M, Lencar C, Tamburic L, Koehoorn M, Demers P, Karr C. 2008. A cohort study of traffic-related air pollu- tion impacts on birth outcomes. Environ Health Perspect 116:680–686. Dejmek J, Solansky I, Benes I, Lenícek J, Sram RJ. 2000. The impact of polycyclic aromatic hydrocarbons and fine par- ticles on pregnancy outcome. Environ Health Perspect 108:1159–1164. Dejmek J, Selevan SG, Benes I, Solansky I, Sram RJ. 1999. Fetal growth and maternal exposure to particulate matter during pregnancy. Environ Health Perspect 107:475–480. Dommett RM, Klein N, Turner MW. 2006. Mannose-binding lectin in innate immunity: past, present and future. Tissue Antigens 68(3):193–209. Garred P. 2008. Mannose-binding lectin genetics: from A to Z. Biochem Soc Trans 36(Pt 6):1461–1466. Gluckman PD, Hanson MA. 2006. The consequences of being born small—an adaptive perspective. Horm Res 65(suppl 3):5–14. Institute of Health Information and Statistics of the Czech Republic. 2008. Mother and newborn 2008 [in Czech]. Available: http://www.uzis.cz/download_file.php?file=3662 [accessed 16 July 2010]. Kannan S, Misra DP, Dvonch JT, Krishnakumar A. 2006. Exposures to airborne particulate matter and adverse perinatal outcomes: a biologically plausible mechanistic framework for exploring potential effect modification by nutrition. Environ Health Perspect 114:1636–1642. Kelly FJ. 2003. Oxidative stress: its role in air pollution and adverse health effects. Occup Environ Med 60(8):612–616. Lewtas J. 2007. Air pollution combustion emissions: character- ization of causative agents and mechanisms associated with cancer, reproductive, and cardiovascular effects. Mutat Res 636(1–3):95–133. Li M, Huang SJ. 2009. Innate immunity, coagulation and pla- centa-related adverse pregnancy outcomes. Thromb Res 124(6):656–662. Loft S, Hogh Danielsen P, Mikkelsen L, Risom L, Forchhammer L, Moller P. 2008. Biomarkers of oxidative damage to DNA and repair. Biochem Soc Trans 36(pt 5):1071–1076. Maisonet M, Correa A, Misra D, Jaakkola JJ. 2004. A review of the literature on the effects of ambient air pollution on fetal growth. Environ Res 95(1):106–115. McIntire DD, Bloom SL, Casey BM, Leveno KJ. 1999. Birth weight in relation to morbidity and mortality among new- born infants. N Engl J Med 340(16):1234–1238. Moller P, Folkmann JK, Forchhammer L, Brauner EV, Danielsen PH, Risom L, et al. 2008. Air pollution, oxida- tive damage to DNA, and carcinogenesis. Cancer Lett 266(1):84–97. Myatt L, Cui X. 2004. Oxidative stress in the placenta. Histochem Cell Biol 122(4):369–382. Orhan H, Onderoglu L, Yucel A, Sahin G. 2003. Circulating bio- markers of oxidative stress in complicated pregnancies. Arch Gynecol Obstet 267(4):189–195. Peter Stein T, Scholl TO, Schluter MD, Leskiw MJ, Chen X, Spur BW, et al. 2008. Oxidative stress early in pregnancy and pregnancy outcome. Free Radic Res 42(10):841–848. Pinto JP, Stevens RK, Willis RD, Kellogg R, Mamane Y, Novak J, et al. 1998. Czech Air Quality Monitoring and Receptor Modeling Study. Environ Sci Technol 32(7):843–854. Pope CA III, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, et al. 2002. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 287(9):1132–1141. Poston L, Raijmakers MT. 2004. Trophoblast oxidative stress, antioxidants and pregnancy outcome—a review. Placenta 25(suppl A):S72–S78. Potdar N, Singh R, Mistry V, Evans MD, Farmer PB, Konje JC, et al. 2009. First-trimester increase in oxidative stress and risk of small-for-gestational-age fetus. BJOG 116(5):637–642. Risom L, Moller P, Loft S. 2005. Oxidative stress-induced DNA damage by particulate air pollution. Mutat Res 592(1– 2):119–137. Rossner P Jr, Svecova V, Milcova A, Lnenickova Z, Solansky I, Santella RM, et al. 2007. Oxidative and nitrosative stress markers in bus drivers. Mutat Res 617:23–32. Rossner P Jr, Milcova A, Libalova H, Novakova Z, Topinka J, Balascak I, et al. 2009. Biomarkers of exposure to envi- ronmental pollutants in mothers and their transplacental transfer to the foetus. Part II: oxidative damage. Mutat Res 669(1–2):20–26. Rossner P Jr, Svecova V, Milcova A, Lnenickova Z, Solansky I, Sram RJ. 2008a. Seasonal variability of oxidative stress markers in city bus drivers. Part I: oxidative damage to DNA. Mutat Res 642:14–20. Rossner P Jr, Svecova V, Milcova A, Lnenickova Z, Solansky I, Sram RJ. 2008b. Seasonal variability of oxidative stress ovlume 119 | number 2 | February 2011 • Environmental Health Perspectives