Ambient Air Pollution and Pregnancy Outcomes: A Review of the Literature

Radim J. Srám; Blanka Binková; Jan Dejmek; Martin Bobak

Disclosures

Environ Health Perspect. 2005;113(4):378-382. 

In This Article

Discussion

The studies reviewed above indicate that ambient air pollution is inversely associated with a number of birth outcomes. This is a relatively new area of environmental epidemiology; most reports have emerged over the last 10 years. A critical assessment of the evidence is therefore timely. Issues pertinent to different studies were considered separately above. Here, we consider questions common to all reproductive outcomes: publication bias, measurement of exposure, and the biologic plausibility of the effects on birth weight, IUGR, and preterm births.

Negative studies are less likely to be published, and studies published in non-English journals are less likely to be included in reviews. We included all studies we were able to identify. We cannot exclude the possibility that some negative studies, especially in the earlier period, remain unpublished. However, given the recent interest in this topic, it is likely that most studies over the last decade have been published or at least presented at conferences.

Most studies relied on routine monitoring of air pollution in large areas. Extrapolation from citywide or areawide measurements to individual exposures can be problematic. In this context, molecular epidemiologic studies are particularly valuable for the interpretation of the epidemiologic data. The molecular epidemiologic studies used biomarkers of exposure, mainly as the DNA adducts measured by 32P-postlabeling and PAH-DNA adducts assessed by enzyme-linked immunosorbent assays (Sˇrám and Binková 2000). Overall, these studies suggest that DNA adduct levels in maternal blood and placentas are higher in areas with higher pollution levels (Sˇrám et al. 1999; Whyatt et al. 1998), and significant district and seasonal differences in DNA adducts were found in subgroups with the GSTM1 null genotype (Topinka et al. 1997a, 1997b). The increase in the levels of DNA adducts related to pollution is similar to, but smaller in magnitude than, the differences between smoking and nonsmoking mothers. All this indicates that ambient air pollution levels do translate to higher individual exposures, even for unborn babies. This provides support for the validity of the epidemiologic studies reviewed above.

DNA adducts in placentas and the impact of PAHs on IUGR are consistent with findings of invitro studies that exposure to extracts of urban air PM increased DNA adducts and embryotoxicity (Binková et al. 1999, 2003). These findings indicate that particle-bound carcinogenic PAH concentrations may be taken as an index of the biologically active components in samples of particulates in air.

The molecular epidemiologic studies suggest biologic mechanisms for the effect of air pollution on birth outcomes. It has been shown that the levels of DNA adducts are positively related to risk of IUGR (Dejmek at al 2000; Sˇrám et al. 1999), birth weight, birth length, and head circumference (Perera et al. 1998, 1999), and hypoxanthine-guanine phosphoribosyltransferase ( HPRT ) locus mutation frequency in infants (Perera et al. 2002).

PAHs and/or their metabolites may bind to the aryl hydrocarbon receptor (AhR) and accumulate in the nucleus of cells, resulting in increased rates of mutagenesis. Because PAHs bind to the AhR, it may result in antiestrogenic activity through increased metabolism and the depletion of endogenous estrogens (Carpenter et al. 2002), thus disrupting the endocrine system by altering steroid function. Bui et al. (1986) hypothesized that benzo[ a ]pyrene exposure may interfere with uterine growth during pregnancy because of its antiestrogenic effects, thereby disrupting the endocrine system. Fetal toxicity may be further caused by DNA damage resulting in activation of apoptotic pathways (Nicol et al. 1995) or binding to receptors for placental growth factors resulting in decreased exchange of oxygen and nutrients (Dejmek et al. 2000).

The finding of higher DNA adduct levels in the infant compared with the mother suggests an increased susceptibility of the developing fetus to DNA damage (Perera et al. 1999). With respect to IUGR, it appears that the increased risk is principally due to exposure to carcinogenic PAHs. This finding is consistent with the idea of a primary role for carcinogenic PAHs in fetal growth modulation (Guyda 1991; MacKenzie and Angevine 1981; Rigdon and Rennels 1964; Zhang et al. 1995). Perera et al. (2003) labeled PAHs as significant independent determinants of birth outcomes. In addition, there appears to be an interaction between exposure to PAHs and genotypes that produce DNA adducts (Whyatt et al. 2001).

Although the specific steps of these pathways need to be further clarified, the molecular epidemiology studies and the similarity of effects of air pollution to those of smoking (Adriaanse et al. 1996; Windham et al. 1999) support the biologic plausibility of the effects.

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