The risk of stillbirth increased with prenatal exposure to several types of ambient air pollution, especially if exposure occurred during the third trimester, a small meta-analysis found.
Random effects models found that increases in maternal exposure to a variety of air pollutants resulted in small, but substantial increased risk of stillbirth throughout pregnancy, reported Nazeeba Siddika, MD, of University of Oulu in Finland, and colleagues.
They examined 13 studies total, but due to study design, only two to three met criteria for meta-analysis. In those studies, there was a range from a 1.4% increased risk of stillbirth for exposure to particulate matter (EE 1.014, 95% CI 0.948-1.085) to a 6.6% increased risk of stillbirth for exposure to nitrous oxide (EE 1.066, 95% CI 0.965-1.178). While there were trends in the increase of stillbirth rates associated with air pollution, none reached significance, they wrote in Occupational and Environmental Medicine.
Leonardo Trasande, MD, of NYU School of Medicine in New York City has done research into the health effects and potential healthcare costs associated with air pollution, which has included preterm birth and endocrine disorders. In an email to MedPage Today, he said that this study adds to concerns about the preventable disease burden and costs of air pollution.
"Stillbirth is a relatively rare outcome, and yet it is striking to see concordant and near-significant associations with air pollution," said Trasande, who was not involved with the current study. "Further research is needed, but, given that placental inflammation contributes substantially to stillbirths and that air pollution can cause that inflammation, these findings speak to the need for proactive prevention."
Siddika and colleagues acknowledged that the biological mechanisms associated with air pollutants that lead to fetal death are not clear, writing that one study suggested "the direct crossing of air pollutants across the placenta [causes] irreversible damage to the dividing cells of the growing fetus and [triggers] hypoxic damage or immune-mediated injury during critical periods of development."
Three studies examined air pollutant exposure by trimester. Risks of stillbirth were highest in the third trimester for increased prenatal exposure to sulfur dioxide, carbon dioxide, particulate matter, and ozone. Notably, exposure to carbon dioxide in the third trimester was linked to a 5.2% increase in the risk of stillbirth (EE 1.052, 95% CI 0.973-1.138).
Of all the examined air pollutants, Siddika's group noted that only the toxic effects of carbon dioxide are well-established. A prior study said that it crosses the placental barrier, and compromises delivery of oxygen to fetal tissues. The two studies examining carbon dioxide exposure found an overall 2.5% increased risk of stillbirth associated with increased exposure to the pollutant (EE 1.025, 95% CI 0.984-1.066). However, these associations did not reach significance.
Limitations to the meta-analysis included the fact that most studies used centralized air monitoring data, which does not take variabilities in exposure into account, as well as the potential for residual confounding. Also, studies used different definitions for stillbirth (early and late fetal death versus late fetal death only).
In an accompanying editorial, Marie Pedersen, PhD, of University of Copenhagen in Denmark, characterized stillbirth as "one of the most neglected tragedies in global health today" and said that the existing evidence deserves additional investigation.
"Although the reported summary effect estimates were relatively small, the ubiquitous nature of ambient air pollution exposure suggests that exposure to ambient air pollution may have a large population-attributable risk for stillbirth," she wrote. "If the evidence of an association between ambient air pollution and stillbirth is confirmed in future studies, it would be of major public health importance."
Siddika and colleagues agreed, stating that future research should use more personal monitoring methods to track air pollution, as well as take into account such factors as the mothers' activity, change in residence, occupation, and outdoor activities.
Siddika and colleagues disclosed no relevant relationships with industry.
Pedersen disclosed support from a grant from the Danish Council for Independent Research.
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