Air Pollution and Adverse Pregnancy Outcomes: Response
Liu, Shiliang, Krewski, Daniel, Shi, Yuanli, Chen, Yue, Burnett, Richard T., Environmental Health Perspectives
We thank Bukowski for his critical comments on our article (Liu et al. 2003), in which we reported associations between ambient air pollution and adverse pregnancy outcomes in Vancouver, Canada. In recent years, air pollution has come to be recognized as an important risk factor for a number of adverse health outcomes, particularly cardiorespiratory morbidity (Burnett et al. 1997, 2001; Lin et al. 2002, 2003; Yang et al. 2003) and mortality (Burnett et al. 1997; Dockery et al. 1993; Pope et al. 1995; Villeneuve et al. 2003).
The adverse effects of air pollution on pregnancy outcomes, such as low birth weight (LBW), preterm birth, intrauterine growth retardation (IUGR), and developmental anomalies are of increasing concern. Before our study, there were reports of associations between particulate (total suspended particulate) and gaseous (carbon monoxide, sulfur dioxide, and nitrogen dioxide) air pollutants and adverse pregnancy outcomes from southern California (Ritz et al. 2000, 2002), China (Wang et al. 1997; Xu et al. 1995), and the Czech Republic (Bobak 2000; Dejmek et al. 1999). Replication of these findings in different populations under different conditions of exposure is an important aspect of epidemiologic research, with consistency of results strengthening the weight of evidence for a true association between exposure and outcome.
Data on important predictors of adverse pregnancy outcomes were not available to us for use in our study (Liu et al. 2003). Although numerous risk factors have been identified (including maternal age, parity, infant sex, and season of birth, as well as gestational age and birth weight, in the case of LBW and preterm birth, respectively, which we were able to take into account), our understanding of the etiology of adverse pregnancy outcomes remains far from sufficient (Kramer 2003). The omission of known or unknown risk factors for birth anomalies may lead to uncontrolled or residual confounding of the association between air pollution and adverse pregnancy outcomes, as Bukowski suggests. However, the extent to which residual confounding might occur in our data is unclear. Schwartz and Morris (1995) have argued that the estimated effects of air pollution are unlikely to be confounded by these factors because they are unlikely to be correlated with daily air pollution levels.
Exposure assessment is always a critical factor in environmental epidemiology (Rothman 1993). Like most other studies of air pollution and population health, our study (Liu et al. 2003) relied on ecologic rather than personal indicators of exposure, with average ambient air pollution concentrations determined using one or more fixed site monitors within census areas in Vancouver. Janssen et al. (1998, 1999) have suggested that air pollution levels from outdoor monitoring stations can provide useful surrogates for personal exposure. Exposure misclassification due to the use of fixed site ambient monitors rather than personal dosimeters is likely to underestimate rather than overestimate the effect of air pollution on birth outcomes (Mallick et al. 2002; Zeger et al. 2000).
The weight of evidence that air pollution is causally related to adverse pregnancy outcomes would be considerably increased through understanding of biological mechanisms by which such effects could occur.
Burkowski notes that we (Liu et al. 2003) included a number of statistical tests of the strength of association between air pollution and adverse pregnancy outcomes, and observes that multiple testing raises the risk of false positives. Our a priori strategy for hypothesis testing focused on predetermined stages of pregnancy (month or trimester), which are thought to represent periods of differential susceptibility to exogenous exposures. Findings from both epidemiologic and toxicologic studies suggest that the fetus is most susceptible to the effects of air pollution during the first trimester (Generoso et al. …