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The link between air pollution exposure and adverse birth outcomes is of public health concern due to the relationship between poor pregnancy outcomes and the onset of childhood and adult diseases. As personal exposure measurements are difficult and expensive to obtain, proximate measures of air pollution exposure are traditionally used. We explored how different air pollution exposure metrics affect birthweight regression models. We examined the effect of maternal exposure to ambient levels of particulate matter <10, <2.5 μm in aerodynamic diameter (PM10, PM2.5) on birthweight among infants in North Carolina. We linked maternal residence to the closest monitor during pregnancy for 2000–2002 (n=350,754). County-level averages of air pollution concentrations were estimated for the entire pregnancy and each trimester. For a finer spatially resolved metric, we calculated exposure averages for women living within 20, 10, and 5 km of a monitor. Multiple linear regression was used to determine the association between exposure and birthweight, adjusting for standard covariates. In the county level model, an interquartile increase in PM10 and PM2.5 during the entire gestational period reduced birthweight by 5.3 g (95% CI: 3.3 – 7.4) and 4.6 g (95% CI: 2.3 – 6.8), respectively. This model also showed a reduction in birthweight for PM10 (7.1 g, 95% CI: 1.0–13.2) and PM2.5 (10.4 g, 95% CI: 6.4 – 14.4) during the third trimester. Proximity models for 20, 10, and 5 km distances showed similar results to the county level models. County level models assume that exposure is spatially homogeneous over a larger surface area than proximity models. Sensitivity analysis demonstrated that at varying spatial resolutions, there is still a stable and negative association between air pollution and birthweight, despite North Carolina’s consistent attainment of federal air quality standards.
Many epidemiological studies have been conducted to investigate the effect of maternal exposure to air pollution on adverse pregnancy outcomes (1–5). Results of these studies have shown that exposure to air pollution may elevate the risk of adverse birth outcomes, including low birthweight, preterm delivery, and small for gestational age (6–12).
Poor birth outcomes are significant predictors of neonatal mortality and morbidity (13). Evidence shows that children born low birthweight, preterm delivery, or small for gestational age are at an increased risk for both short-term neonatal morbidity and long-term health effects (14, 15). Such effects include mental retardation (16), severe vision loss (17), deafness (16), learning disabilities (18, 19), motor impairment (20), and cerebral palsy (21), as well as hypertension, cardiovascular disease, and type-2 diabetes in adulthood (22).
Although the biological mechanisms by which air pollutants may influence birthweight and fetal growth are as yet unknown, studies suggest that air pollution exposure during pregnancy may lead to placental inflammation, which impairs placental function, and chronic inflammation may in turn result in growth restriction (6). Data also suggest that fetuses may be more prone to genetic damage and process toxicants less efficiently than adults (23). Perera et al. (24) also propose that increased DNA adducts in the fetus relative to the mother could result in lower levels of detoxification enzymes and decreased DNA repair efficiency in the fetus.
Epidemiologists and policy makers are often interested in the effect of particulate air pollution on susceptible populations (25); thus pregnant women are of particular concern. Since the National Research Council (NRC) identified at risk subpopulations as a high priority research task, several studies have been conducted to better examine the effects of PM exposure and adverse pregnancy outcomes (1, 26, 27). In the last of four reports produced by the NRC in 2004, the group determined that more research needs to be done in order to clarify uncertainties about impacts of maternal exposure to PM on pregnancy and to understand how environmental factors can affect adverse pregnancy outcomes (28).
While much attention has been given to studying the relationship between adverse pregnancy outcomes and air pollution, many of these studies are limited to sparsely located monitoring station data (1, 2, 29). These studies use average measurements calculated from monitoring stations within city or county limits, or postal codes. Epidemiologists are aware that measurements obtained from ambient monitoring stations may not be representative of personal exposure for all subjects within a predetermined geographic area (30). Consequently, the use of personal exposure measures based on city or county levels may misclassify individual exposure.
Although many studies have found significant results, the traditional analyses may misclassify exposure because of the way the exposure is measured and modeled (31, 32). Using measurements based on residing either within a certain geographic area or proximity to a monitoring station as a proxy for personal exposure assumes that air pollution levels are spatially homogeneous across the defined geographic regions. While lacking precision, this method of estimating exposure for an individual or a population has been used in air pollution and health effects studies (33–35) as collection of accurate personal level exposures is often difficult and expensive to obtain. In the presence of potential measurement error, it is important to determine whether these various measurements affect the exposure-response relationship.
In this paper, we evaluate how robust the air pollution and birthweight relationship is to different air pollution measurements. For comparability to other studies (1, 3, 36), we use air pollution metrics based on county averages for the State of North Carolina. We then use buffering schemes associated with proximity models of 20, 10 and 5 km radii and compare how these different exposure metrics affect the birthweight model. Because previous studies have used distances ranging from 2 km to 50 km (37–39), we chose a range of distances for greater cross-study comparability. Our goal is to investigate how birthweight regression models change when different exposure metrics are used. Importantly, North Carolina communities are typically below the federal standards for both PM10 and PM2.5, so these analyses have direct relevance to the policy debate regarding setting regulatory standards to protect public health.
The North Carolina Detailed Birth Record (NCDBR) data were obtained from the North Carolina State Center for Health Statistics. The NCDBR data contain information on both birth outcomes and parental demographics for all registered births in North Carolina. We limited our analysis to the years 2000–2002 (n=350,754). The recorded birth information in the NCDBR used in this study included gestational age (weeks), infant sex, birthweight, congenital anomalies, and year of birth. The maternal characteristics recorded in the NCDBR included residential address, age, marital status, education, race and ethnicity, alcohol and tobacco use, plurality, birth order, and the trimester in which prenatal care began.
To link births from the NCDBR to the air pollution data, we used ArcGIS software to street geocode the residential addresses in the dataset at the individual record level. The total births successfully geocoded using the maternal residence at the time of delivery in North Carolina can be seen in Figure 1. Approximately 17% of the total births could not be geocoded due to unmatched address locations. To determine whether systematic differences exist between the full geocoded dataset and the subsets for which air pollution data were available, summary statistics (data not shown) were calculated using Census data from the zip code links and the DBR data. Differences were not significant enough to undermine the analytical work presented here.
We excluded multi-fetal births (3.3%), and infants characterized by congenital anomalies (0.9%). These exclusions were chosen as we sought to focus on those pregnancies that could reasonably be expected to go to term and deliver at a normal birthweight. We also excluded women < 15 and > 44 years (0.3%) with reported alcohol consumption (0.6%). Since 95% of the women in the dataset self-declared as non-Hispanic white, non-Hispanic black, or Hispanic, we excluded other races/ethnicities due to the small sample size for other minority groups. We excluded births with gestation <32 and >44 weeks (2.2%), birthweight <1000g and >5500g (1.0%), impossible birthweight and gestation combinations (0.1%) (Alexander et al., 1996), and mothers with any missing data on covariates (1.0%), leaving 259,962 cases. For the county level model, we focused on women who lived in a county with an active monitoring station while for the proximity models, we used only women within a 20, 10, and 5 km buffer of a monitoring station.
The air pollution datasets for PM10 and PM2.5 were obtained from the US EPA Air Quality System (AQS) for 1999–2002 (40). The analyses used births between the years of 2000–2002, and air pollution exposures from 1999–2002, since exposures for some 2000 births occurred in 1999. The AQS data contained the daily 24-hr average concentration (μg/m3) for PM10 and PM2.5. There were between 27 and 37 active PM10 monitors and between 37 and 41 active PM2.5 monitors in North Carolina during 1999–2002. The monitors recorded pollution measurements every day, every 3 days, or every six days with some monitors being added to or removed from operation during the years of the study. The difference in the frequency of recordings at certain monitoring stations is random and should not introduce any bias into the study. Locations of the PM10 and PM2.5 monitors in North Carolina can be seen in Figure 2.
To estimate air pollution exposure for the proximity models, each mother’s residence at the time of delivery was linked to the closest active monitor. The weeks of exposure were calculated based on the actual weeks of pregnancy as recorded in the NCDBR. Since birth date and gestational age were supplied as part of the NCDBR data, we calculated backwards the number of weeks of gestation from the delivery date to determine an estimated date of conception for each woman. Average maternal exposure was calculated for each pollutant by averaging the daily or weekly data of the closest monitoring station for each trimester. Trimesters were constructed based on the following categorization: 1–13 weeks of gestation, 14–26 weeks of gestations, and 27 weeks of gestation until birth. Exposure estimates averaged over the entire pregnancy were also calculated for each pollutant.
AQS data were not available for every day and week of the years 1999–2002. For each birth, the completeness of the exposure dataset was identified by taking the number of weeks of gestation and dividing it by the number of AQS concentration values for that birth. If the birth had more than 75% of the data and there was no more than one consecutive missing concentration value for that birth, then the average of the concentrations for the weeks before and after the missing value were used as a proxy for the exposure concentration during that week. If there was more than one consecutive missing value for a birth, then that birth was not included in the dataset because a sufficient proxy for the two weeks or more of missing air quality data was not available. After all exclusion criteria, exposure estimates were calculated for 195,141 mothers for at least one of the pollutants of interest.
Multiple linear regression modeling was used to determine the association between exposure to the pollutants of interest, PM10 and PM2.5, and birthweight. Using birthweight as a continuous outcome variable, we controlled for gestational age (32–34, 35–35, 37–38, 39–40, 41–42, 43–44 weeks), maternal race/ethnicity (non-Hispanic black, non-Hispanic white, or Hispanic), maternal education (< 9, 9–11, 12, 13–15, > 15 years), maternal age (15–19, 20–24, 25–29, 30–34, 35–39, 40–44 years), trimester prenatal care began, tobacco use during pregnancy (yes or no), marital status (married or unmarried), year of birth, firstborn (yes or no), and infant sex (male or female) for PM10 and PM2.5. The exposure estimates were considered as continuous variables. We then examined the exposure response relationship with county-wide estimates and estimates for mothers within 20, 10 and 5 km of a monitoring station.
A baseline model without the air pollution variables was constructed to examine which of the standard covariates mentioned above affect birthweight in our sample. We then constructed separate models for PM10 and PM2.5. For comparability to previous studies, we constructed models using all three trimester exposure estimates in the same model as well as models with a pregnancy-long estimate (41–43). All risk factors considered were observed as being associated with birthweight in recent literature (1, 2, 4, 44, 45).
Our analysis included estimating pollution exposures for sample populations at the county level, and within the 20, 10 and 5 km radial buffers surrounding monitors. At the county level, there were 195,141 observations with the restrictions described above and 167,851, 110,555, and 56,043 births at 20, 10 and 5 km, respectively. Table 1 shows the summary statistics for each of the four sample populations (county and 20, 10, and 5 km buffers). Among the 195,141 county-level births, the mean birthweight was 3,368 g and the prevalence of low birthweight was 5.4%. Approximately 11% reported smoking during pregnancy. Most of the mothers were non-Hispanic white (61%), married (68%), and with more than a high school education (52.8%). The mean PM10 and PM2.5 levels are higher than the median, a phenomenon driven by a few geographic areas with higher pollution levels (e.g., the greater Charlotte area).
The descriptive characteristics of the mothers living within 20 and 10 km of a monitoring station are similar to those in the county level dataset. Some maternal demographics change with proximity to the monitoring station, including maternal race/ethnicity, maternal education, and marital status. Moving from 20 km away to 5 km away from a monitoring station increases the non-Hispanic black population by approximately 14% and Hispanic population by 6.2%. There is also a decrease in the mothers with more than a high school education, as well as those who are married, as residence gets closer to a monitor. The incidence of LBW increases from 5.2% at 20 km to 6.3% at the 5 km buffer. The means ± standard deviations (SD) along with the interquartile range (IQR) and 25th, 50th and 75th percentiles of the average exposure of each pollutant are shown in Table 2 for the county and 20 km models. Summary statistics of the pollution averages for the 10 and 5 km models (not shown) were similar to the results at the 20 km level. For the 10 km buffer there were 75,111 and 86,573 observations for PM10 and PM2.5 respectively. At the 5 km level there were 35,212 and 42,782 observations for PM10 and PM2.5 respectively.
Average values of PM10 (PM2.5) concentration levels were approximately 22.7 (14.3) μg/m3. The PM2.5 average is below the National Ambient Air Quality Standard (NAAQS) annual mean of 15 μg/m3 and there is currently no annual PM10 standard. The correlations between PM10 and PM2.5 during each trimester remain relatively consistent with r2 ~0.7. The correlation between PM10 and PM2.5 exposure during the entire pregnancy was 0.63. Table 3 shows the correlation coefficients among trimester exposures for PM10 and PM2.5 at the county level model. Similar correlations were obtained at the 20, 10, and 5 km level.
In all of the baseline models with no air pollution estimates, the standard covariates carried the expected signs with positive correlation between birthweight and longer gestation (>40 weeks), male sex, more than a high school level education and higher parity; and negative correlation between birthweight and tobacco use during pregnancy, unmarried status, less than high school education, minority race groups, firstborns, mothers younger than 24 years and older than 40 years, and mothers who started prenatal care later in pregnancy. All covariates were statistically significant (p<.001) and were included in the models with pollution estimates. Table 4 shows the baseline models for PM10 at the county level and the 20 km level. Similar results (not shown) were obtained for both pollutants at the county level and the 20, 10, and 5 km buffer levels.
In the multiple regression models for the county level measure of air pollution exposure, PM10 and PM2.5 exposure in the third trimester and during the entire pregnancy were negatively associated with birthweight (Figure 3). An IQR increase in PM10 and PM2.5 during the entire gestational period reduced birthweight by 5.3 g [95% CI, 3.3 – 7.4] and 4.6 g (95% CI, 2.3 – 6.8) respectively. This model also showed a reduction in birthweight for PM10 (7.1 g, 95% CI=1.0–13.2) and PM2.5 (10.4 g, 95% CI= 6.4 – 14.4) during the third trimester.
Proximity models for 20, 10, and 5 km distances showed results similar to the county level models (Figure 3). During the entire gestational period, there were birthweight reductions between 7 and 8 g for PM10 and 7 and 10 g for PM2.5 per IQR increase in each pollutant. Exposure during the third trimester also showed significant results similar to the county level models for both pollutants. PM2.5 showed birthweight reductions at 20 and 10 km but not 5 km or the county level model. We also ran logistic models to see whether air pollution exposure predicted low birthweight or very low birthweight (results not shown here). The only statistically significant results were for pregnancy-long PM2.5 exposure and the odds ratios were very close to one.
County level models assume that air pollution exposure is spatially homogeneous over a larger surface area than city-wide or neighborhood level models. If air pollution concentrations are heterogeneous, with variability that increases as distance from the pollution source increases, then the associated measurement error may also be larger in exposure measurements based on large geographic regions. This misclassification in the pollution concentration could underestimate the true effects of air pollution exposure. For this reason, we explored the relationship between both county and neighborhood level averages of PM. This sensitivity analysis compared birthweight regression results using exposure metrics for PM10 and PM2.5 at various spatial resolutions from 2000–2002 in North Carolina. We observe some differences in both the magnitude of the coefficients and the significance of the estimates as well. The model for the entire gestational period showed both significant and negative associations for PM10 and PM2.5 with all the exposure metrics used.
Basu et al. (46) explore the use of different spatial measures of exposure in birthweight regression models and also found differences between the various metrics in a study in California in 2000. Basu et al. found that county level measures of PM2.5 produced a stronger reduction in birthweight than exposure measures within a 5-mile radius of a monitoring station. This California study limited analysis to non-Hispanic white and Hispanic mothers in California, where air pollution levels are relatively high compared to North Carolina. Although there are differences in the demographic composition and the air pollution levels, similar results were seen when comparing county-level models to proximity models.
In another study using data from Connecticut and Massachusetts, Bell et al. (1) saw reductions in birthweight at the county level during the entire pregnancy and the third trimester for both PM10 and PM2.5, which is consistent with the results in our study. This study had average PM levels similar to those in NC, with means of 22.3 and 11.9 μg/m3 for PM10 and PM2.5, respectively. Comparable results in the reduction of birthweight per IQR increase in PM10 and PM2.5 were seen in the North Carolina county level models and the models presented in the Bell et al. analysis.
Other studies have also found an inverse relationship between exposure to PM and reduction in birthweight, using both county level and neighborhood level exposure metrics. Dugandzic et al. (4), Gouveia et al. (47), and Yang et al. (37) all found a significant relationship in the first trimester for PM10 exposure and birthweight in a study in Taiwan, Canada and Brazil respectively. Salam et al. (43) in a California study found that exposure to PM10 during the 3rd trimester was negatively associated with birthweight. Mannes et al. (39) showed in a study in Australia that both PM10 and PM2.5 were associated with reduced birthweight during the second trimester as well as during the last month of pregnancy. In California, Parker et al. (48) found a negative effect of PM2.5 on birthweight for all three trimesters when comparing the highest and lowest levels of PM2.5. It is still unclear which exposure period is most affected and further analysis is certainly needed.
A limitation to this research is the quantity and placement of active PM monitoring sites each year. Monitoring sites are part of a long-term fixed network that was established for regulatory purposes, rather than for health effects research. In some geographic areas, such as those closer to major cities and roadways, there is a greater density of monitors. Monitoring data from these areas are more representative of ambient maternal exposures than in areas where the monitors were more distal from maternal residences. Thus, the exposures of women who lived in more urban areas were more accurately captured than those women who were at the far range of the 20 km buffer set for this study. Additionally, individual exposure measurements calculated using ambient concentrations readings from monitoring stations introduce misclassification errors into the study. Without using personal monitors, one cannot truly capture actual exposure.
We also make the assumption that pregnant women did not relocate during their pregnancy. Other relevant maternal information such as gestational weight gain, maternal nutrition, and indoor and occupational exposure estimates are factors that may affect birthweight but could not be examined. In addition, use of assisted reproductive technology, even among singleton pregnancies, is a known risk factor for PTB (49), but cannot be controlled for in our analyses (data not available).
This study examined only PM10 and PM2.5 which are highly correlated with each other and possibly with other pollutants. The PM10 monitors used in this study also measure ambient levels of PM2.5. Consequently, the lower birthweight associated with PM10 may in fact be indistinguishable from the birthweight effects attributable to PM2.5. To address this issue, the EPA’s Clean Air Scientific Advisory Committee has recommended that the Agency develop a new indicator for particles between 2.5 and 10 micrometers in diameter (PM2.5–10) because PM10 sampling is an imprecise measure of coarse particulate matter in this size range (50). At present, there is inadequate information on PM2.5–10 ambient levels, exposure, and health risks. In the October 2006 revision to the PM NAAQS, however, EPA retained PM10 as the indicator for coarse particles.
In North Carolina, the annual NAAQS for PM2.5 is 15.0 μg/m3 averaged over a three-year period for each monitor (51). In October 2006, the EPA rescinded the 50 μg/m3 annual standard for PM10, citing a lack of association between long-term exposure to current ambient levels of PM10 and adverse health effects. Consequently, there is currently no annual standard for PM10. Although average annual PM2.5 levels in North Carolina are less than the standard of 15 μg/m3, we still see robust relationships between PM2.5 exposure and birthweight. Similarly, PM10 levels are less than half of the previous NAAQS of 50 μg/m3, yet maternal exposure to PM10, both during the third trimester and during the entire pregnancy, is negatively associated with birthweight. While our results show a small reduction in birthweight for the entire pregnancy across both pollutants, average county levels of PM10 and PM2.5 (22.7, 14.3) were associated with a reduction in mean birthweight of 25.1 g (95% CI: 20.2 – 29.9) and 41.0 g (95% CI: 30.9 – 51.1), respectively. These reductions are meaningful in North Carolina, and potentially even more so in regions with air quality below the NAAQS.
Exposure to PM pollution during pregnancy is an important public health issue. In our study, the county level model produced consistent results with the proximity model for estimating reductions in birthweight during the entire pregnancy and in the third trimester for both PM10 and PM2.5. There were some differences in the first trimester for PM10 and the second trimester for PM2.5. In both cases, there was a reduction in birthweight at the 20 km and 10 km level but not at the county level or the 5 km level.
Our study provides comparability to previous studies by examining the relationship between birthweight and average county levels of PM10 and PM2.5. In addition, we go beyond the previous studies by constructing proximity models using 20, 10, and 5 km buffers around monitoring stations. These additional analyses indicate that the statistical significance and negative relationship between birthweight and air pollution is robust to the choice of air pollution metrics at substantially different geographic scales. Despite North Carolina’s consistent attainment of federal air quality standards, we still see a stable and negative association between both pollutants and birthweight in the third trimester and during the entire pregnancy at various spatial resolutions.
This research was supported by funding from the National Institutes of Health (1-P20-RR020782-01) and the Environmental Protection Agency (RD-83329301-0).
This work is supported by the Southern Center for Environmentally Driven Disparities and Birth Outcomes, EPA grant RD 83329301-0 and by the Center for Geospatial Medicine, NIH grant 1-P20-RR020782-01. We acknowledge important advice and guidance provided by Alan Gelfand, Martha Keating, and Kerry Williams.