Genetic, Biochemical, and Environmental Factors Associated with Pregnancy Outcomes in Newborns from the Czech Republic

Abstract

BackgroundOxidative damage to placental DNA can result in negative pregnancy outcomes, including intrauterine growth restriction (IUGR) and low birth weight (LBW).ObjectiveWe investigated associations between the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), a marker of oxidative DNA damage, in placental DNA, exposure to air pollutants during pregnancy, genetic polymorphisms in 94 selected genes, and pregnancy outcomes.MethodsWe studied 891 newborns who were IUGR- or LBW-affected or normal weight and were born between 1994 and 1999 in the Czech Republic in two districts with different levels of air pollution.ResultsWe found nonsignificantly elevated 8-oxodG levels in the IUGR-affected group compared with the non-IUGR group (p = 0.055). Similarly, slightly elevated 8-oxodG levels were found in the LBW-affected group compared with the non-LBW group (p < 0.050). In univariate analyses, we identified single nucleotide polymorphisms associated with 8-oxodG levels, IUGR, and LBW. Exposure to particulate matter < 2.5 μm was associated with increased 8-oxodG levels in placental DNA and LBW. However, multivariate-adjusted logistic regression revealed that above-median 8-oxodG levels were the only factor significantly associated with IUGR [OR = 1.56; 95% confidence interval (CI), 1.07–2.37; p = 0.022]. Above-median levels of 8-oxodG were associated with LBW (OR = 1.88; 95% CI, 1.15–3.06; p = 0.011). Other variables associated with LBW included sex and gestational age of the newborn, maternal smoking, and haplotypes in the promoter region of the gene encoding mannose-binding lectin 2 (MBL2). The role of air pollutants in the risk of adverse pregnancy outcomes seemed to be less important.ConclusionsLevels of 8-oxodG in placental DNA were associated with the risk of IUGR as well as LBW. Newborn’s sex, gestational age, maternal smoking, and genetic polymorphisms in the promoter region of the MBL2 gene were associated with LBW incidence.

Early life exposure to air pollution: How bad is it?

“…Any disruption in the efficiency of transplacental function in utero has the potential to negatively impact fetal growth and development, particularly during critical periods of organogenesis (Stevenson et al, 2003). Epidemiologic evidence suggests an association between PM 10 and PM 2.5 exposure during pregnancy and adverse birth outcomes, including increased infant mortality, LBW, IUGR, and preterm birth (Bell et al, 2010b; Rossner et al, 2011; Rudra et al, 2011). Similar studies have demonstrated no association between fetal air pollution exposure and LBW, suggesting that the correlation between exposure and effect is delicate and might be enhanced by external factors such as region, SES, and duration of exposure (Rossner et al, 2011).…”

“…Epidemiologic evidence suggests an association between PM 10 and PM 2.5 exposure during pregnancy and adverse birth outcomes, including increased infant mortality, LBW, IUGR, and preterm birth (Bell et al, 2010b; Rossner et al, 2011; Rudra et al, 2011). Similar studies have demonstrated no association between fetal air pollution exposure and LBW, suggesting that the correlation between exposure and effect is delicate and might be enhanced by external factors such as region, SES, and duration of exposure (Rossner et al, 2011). A growing body of literature investigating the link between PM exposure and adverse perinatal outcomes has emerged due to the increasing potential of exposure to PM during pregnancy.…”

“…Oxidative stress is a potential mechanism of the fetal insult resulting from pollutant exposure, but current research is severely limited. Studies have only been able to associate increased oxidative stress in utero in response to pollutant exposure (Damaceno-Rodrigues et al, 2009), or associate oxidative markers with an altered fetal measures (Rossner et al, 2011). Strong links between air pollution and oxidative stress, and how this causes adverse fetal outcomes needs to be examined before conclusions can be drawn.…”

Low level maternal smoking and infant birthweight reduction: genetic contributions of GSTT1 and GSTM1polymorphisms

“…Toxic chemicals could disturb foetal and placental cellular regulation via elevated DNA adducts and DNA damage [42]. Oxidative damage to placental DNA and increased levels of 8-oxodG in placental DNA can result in intrauterine growth restriction and low birthweight [43]. Maternal tobacco smoke exposure at an epigenome-wide level is associated with placental gene expression and DNA differential methylation and smoking-mediated birthweight reduction [44].…”

Impact of Air Pollution to Genome of Newborns

“…Ambient air exposure to PAHs poses a health risk due to their mutagenic, genotoxic and carcinogenic activity, which was detected only during the last two decades. PAHs are metabolized to form a wide range of products including highly reactive epoxides, which have capacity to bind to DNA, forming PAH-DNA adducts (4,5) and induce oxidative damage (6). Using acellular system Binkova et al (7) observed, that the genotoxicity of respirable particulate matter was related to the content of PAHs.…”