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LONDON — Maternal exposure to high levels of carbon monoxide (CO) or ozone is associated with increased cardiac defects in offspring, in the first study to show a link between air pollution and fetal damage. In January 1 American Journal of Epidemiology, Ritz et al. showed that cardiac birth defects increased in a dose-related manner with increasing maternal exposure to CO or ozone during the second month of pregnancy (Am J Epidemiol 2002, 155:17-25).The California-based study showed that women exposed to the highest levels of pollutants had nearly three times the risk of having an infant with a cardiac defect than did women living in areas with the least polluted air. As exposure during the second month of gestation increased, so did the risk of birth defects. The authors noted that the human heart begins to develop during the second month of gestation.These findings have implications for urban areas throughout the United States, as the levels of air pollution recorded in this study were relatively low compared to regulatory standards. "These are average levels around the country," said John Harris, a pediatrician, Chief of the California Birth Defects Monitoring Program, and coauthor of the study.The team examined the link between air pollution and birth defects — specifically, cardiac or orofacial cleft defects — using a population-based birth defects registry, the California Birth Defects Monitoring Program, and an air pollution monitoring network, the South Coast Air Quality Management District.Beate Ritz, Associate Professor in the Department of Epidemiology at the University of California, Los Angeles, School of Public Health, and lead author of the study, explained that she chose these two categories of birth defects because there is already a proposed link with smoking (which produces similar kinds of pollutants), as is the case for orofacial cleft defects, or they have been associated with other environmental agents, such the established link between water pollutants and heart defects.The researchers based their determination of a woman's exposure to air pollution on ambient air monitoring data for four pollutants: CO, nitrogen dioxide, ozone and particulate matter <10 ųm in diameter (PM10). They calculated the average values of these pollutants for each of the first three months of gestation for each woman, and for the second and third trimesters of each pregnancy.The merging of air quality and birth defects data led to the finding that carbon monoxide and ozone exposure during the second month of pregnancy correlated with an increased risk of cardiac anomalies in a dose-related manner. Specifically, the risk for ventricular septal defects increased with increasing second-month CO exposure. Similarly, rising ozone exposure during the second month corresponded to an increased risk for aortic artery and valve defects, pulmonary artery and valve anomalies, and conotruncal defects. Nitrogen dioxide and PM10 levels did not appear to increase the risk for cardiac anomalies in any significant or dose-related fashion. None of the four pollutants measured had a significant or dose-related effect on the risk of orofacial cleft defects.Harris described the observed dose-response pattern as a "very provocative finding," particularly given the importance of the second month of gestation in cardiac development. It is during this time period when air pollutants seemed to be most toxic to the heart. Ritz, too, was surprised by the strength of the dose-response effect, especially as cardiac birth defects are relatively uncommon.The study group included infants born and stillborn in Southern California — Los Angeles, Orange, San Bernardino, and Riverside counties — between 1987 and 1993 that belonged to mothers who resided within 10 miles of an air monitoring station. Study subjects comprising the 'control' group did not have a diagnosed birth defect before one year of age. The 'cases' group consisted of infants or fetuses that had a cardiac anomaly or orofacial cleft defect diagnosed in utero or within the first year of life. A broad spectrum of cardiac birth defects were included in the study criteria, including aortic, endocardial, mitral valve, conotruncal, and ventricular septal defects, as well as defects of the atrium and atrium septum, and of the pulmonary artery and valve. Orofacial cleft defects included cleft palate and cleft lip. Previous studies have established a relationship between ambient air pollution and adverse pregnancy outcomes, such as low birth weight and preterm birth, but these studies did not consider birth defects. But, the studies have demonstrated a link between potentially harmful environmental factors and birth defects, including use of pesticides in the home, proximity to toxic waste sites, and exposure to nitrates in water. This latest study draws attention to the risks associated with air pollutants released in tailpipe exhaust or formed as a result of motor vehicle emissions.This epidemiological study does not establish a cause-and-effect relationship between carbon monoxide and ozone exposure and cardiac birth defects. In fact, it may be that these pollutants do not cause the defects but are markers for toxins that were not measured by the air monitoring stations. But, whether the cause is CO, ozone, or some other pollutant, these findings have "applicability in virtually every urban area in the country," and they demonstrate the relatively low levels of air pollutants are "potentially quite toxic," said Harris. It is possible that regulatory standards for air pollutants might not be low enough to prevent their toxic effects on a developing fetus. Ritz speculated on a possible mechanism by which exposure to air pollutants could affect cardiac development in utero. Neural crest cells, which migrate and differentiate to form the parts of the heart in which defects were seen, are particularly sensitive to the oxidative effects of these pollutants. These cells lack an antioxidant defense system and are more likely to undergo programmed cell death (apoptosis) in the presence of strong oxidizing agents. Both Ritz and Harris emphasized the need to replicate and expand on these findings. The authors plan to repeat the study using data beginning in 1993 and, with the help of a new grant from the National Institute of Environmental Health, to perform more intensive studies that would include talking to the mothers to gain more detailed demographic, socioeconomic, and medical information.

First link between air pollutants and birth defects

Pregnant women exposed to high levels of air pollution have increased likelihood of neonatal cardiac defects.

Jan 9, 2002

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