Studies of air pollutant associations with preterm birth have been reviewed in several recent publications. Criteria air pollutants, including ozone, particulate matter (of sizes ≤2.5 and ≤10 microns in aerodynamic diameter, PM2.5
, respectively), carbon monoxide (CO), oxides of nitrogen (NOx
), and sulfur dioxide (SO2
) received the most attention (Glinianaia et al. 2004
; Shah and Balkhair 2011
; Sram et al. 2005
). While conclusions from individual reviews have been conflicting, the most recent assessment of the evidence asserted that a relationship exists between SO2
exposures and preterm birth (Shah and Balkhair 2011
). Associations with other criteria air pollutants are less definitive (Stillerman et al. 2008
Environmental tobacco smoke (ETS) exposure in relation to preterm birth has been examined extensively and reviewed recently as well. A meta-analysis that improved upon previous reviews by clearly excluding mothers who were active smokers observed an elevated odds of preterm delivery in relation to ETS exposure in models of crude data (OR=1.2, 95% CI=0.99 to 1.46) which was attenuated in an adjusted analysis (RR=1.07, 95%CI=0.93 to 1.22) (Salmasi et al. 2010
). However, other assessments, including one by the US Department of Health and Human Services (2006)
, have concluded that ETS exposure decreases gestational duration (Stillerman et al. 2008
; Wigle et al. 2008
Other air contaminants, particularly polycyclic aromatic hydrocarbons (PAH) and volatile organic compounds (VOC), received less attention in previous reviews, and hence the literature on the relationships between these exposures and preterm birth was examined here (, ).
PAH are released in the combustion of coal, oil and gas, and other organic matter, and humans are exposed through inhalation of contaminated air (ATSDR 1995
). Major contributors are inhalation of ETS and PAH bound to particulate matter, which complicates estimation of PAH-specific effects. Additionally, exposure can occur via dietary sources of PAH, for example via consumption of charbroiled foods. Exposure assessment is most commonly performed via air monitoring, but more recently has moved toward biomonitoring with urine measures of hydroxylated PAH metabolites or blood measures of parent compounds or DNA-adducts.
Three studies have used air measurements to assess the relationship between PAH and preterm birth. Vassilev and colleagues (2001)
used ambient air monitoring data in New Jersey between 1990 and 1991 to create estimates of average exposure to polycyclic organic matter (including PAHs, arenes, and polyhalo compounds) within each census tract (n=
214,493). Significantly elevated odds of preterm birth in mothers residing in medium and high PAH-exposure areas compared to mothers residing in low exposure areas (OR for medium compared to low=1.09, 95%CI=1.04 to 1.14; OR for high compared to low=1.25, 95%CI=1.19 to 1.31) were noted in adjusted models. Since maternal tobacco use appeared equally distributed across air pollution categories, no adjustments were made for this factor in the analysis.
In a more recent study in Los Angeles County, where exposures to PAH and other air pollutants are particularly high, Wilhelm et al. (2011)
similarly found increased odds of preterm birth in association with an interquartile range increase in ambient total PAH levels averaged across the duration of pregnancy after adjustments for maternal age, race/ethnicity, education, and parity (OR=1.3, 95%CI=1.15 to 1.47; n=
112,915). Significantly elevated OR were observed for individual PAH (benzo[a]pyrene, benzo[g,h,i]perylene, and naphthalene) as well. Due to the use of birth certificates in the study, they were unable to adjust for maternal smoking or exposure to ETS during pregnancy. A third study that employed the use of personal air monitoring data, collected among non-smoking women during the third trimester of pregnancy, found that African American mothers, but not Dominican mothers, had nearly a 5-fold rise in odds of preterm birth in association with an ln-unit increase in PAH exposure in New York City (OR=4.68, 95%CI=1.84 to 11.9; n=
224) (Choi et al. 2008
). These ORs were reported from models adjusted for maternal pre-pregnancy body mass index, infant sex and parity, season of delivery, and months of gestational ETS exposure.
Studies using various biomonitoring methods have similarly observed a positive association between PAH exposure and preterm birth. Singh and colleagues (2008)
performed a small case-control study of non-smoking women in Lucknow, India, between 2005 and 2006, measuring PAH concentrations in placental tissue. Significantly higher levels of two individual PAH (fluoranthene and benzo(b
)fluoranthene) in preterm cases (n=
29) compared to controls (n=
31) were found, although no adjustments were made for potential confounders. Also, in the aforementioned study of Guiyu, China, where e-waste recycling lead to high levels of environmental pollution, Guo and colleages (2012)
measured 7 carcinogenic PAH in umbilical cord blood in deliveries from Guiyu and from Chaonan, an uncontaminated area, for comparison (n
=183, adverse birth outcomes=18). They observed generally higher values of the PAH measured in cord blood from adverse compared to normal births (adverse birth outcomes included infants born preterm, low birth weight, and with congenital malformations, as well as stillbirths). Furthermore, 2 individual PAH (chrysene and benzo[a]anthracene) were inversely associated with gestational age (Guo et al. 2012
). Again, however, no adjustments were made for covariates, namely maternal smoking or ETS exposure.
Volatile organic compounds (VOC) are a large class of compounds that move readily from the liquid phase to air. These include some of the previously described drinking water contaminants, such as TCE and PCE, as well as many others such as acetone, benzene, and formaldehyde. Benzene is one VOC that has received significant attention because of its carcinogenic potential. It is released in many industrial processes into the air, and also from automobile emissions and tobacco smoke. Two studies examined the relationship between maternal benzene exposure and preterm birth. In the previously described study by Wilhelm et al. (2011)
, significantly increased odds of preterm birth were found in association with an interquartile range increase in benzene (adjusted OR=1.09, 95%CI=1.06 to 1.13). Further, a study in Valencia, Spain, examined benzene exposure measured via ambient air monitors and found elevated odds of preterm birth in individuals exposed to greater than 2.7 μg/m3
across the duration of pregnancy (OR for 1 μg/m3
increase in benzene exposure level = 6.46, 95%CI=1.58 to 26.4; n=
785) (Llop et al. 2010
). Formaldehyde exposure was examined in relation to preterm birth in one publication with no significant results (Maroziene and Grazuleviciene 2002
), but otherwise no studies examined associations between other VOC exposures and preterm birth.
Limitations and recommendations
In summary, previous reviews strongly suggest associations between preterm birth and environmental exposures to (1) SO2
, (2) PM2.5
, and (3) ETS. Studies of PAH exposure and preterm birth indicate a relationship, although additional studies that address the importance of PAH compared to other components of the complex mixture, such as PM and ETS, would be useful. Studies on air pollutant exposures and preterm birth suffer from several limitations recently identified by Slama et al. (2008)
at the International Workshop on Air Pollution and Human Reproduction. Moving forward, the workshop report called for (1) More prospective studies, (2) Attention to important confounders such as seasonality of exposure/delivery as well as maternal nutrition status (3) Advancement in exposure assessment methods, such as using biomarkers of exposure, and identifying key exposure windows (e.g., first trimester of pregnancy), and (4) Exploration of potential toxicologic mechanisms to explain exposure-outcome relationships (Slama et al. 2008
). Addressing these issues may help to better explore some of the associations observed to date between ambient air pollution exposures and preterm birth.