Michelle Wilhelm

Local Variations in CO and Particulate Air Pollution and Adverse Birth Outcomes in Los Angeles County, California, USA

We extended our previous analyses of term low birth weight (LBW) and preterm birth to 1994–2000, a period of declining air pollution levels in the South Coast Air Basin. We speculated that the effects we observed previously for carbon monoxide, particulate matter < 10 μm in aero-dynamic diameter (PM10), and traffic density were attributable to toxins sorbed to primary exhaust particles. Focusing on CO, PM10, and particulate matter < 2.5 μm in aerodynamic diameter (PM2.5), we examined whether varying residential distances from monitoring stations affected risk estimates, because effect attenuation may result from local pollutant heterogeneity inadequately captured by ambient stations. We geocoded home locations, calculated the distance to the nearest air monitors, estimated exposure levels by pregnancy period, and performed logistic regression analyses for subjects living within 1–4 mi of a station. For women residing within a 1-mi distance, we observed a 27% increase in risk for high (≥ 75th percentile) first-trimester CO exposures and preterm birth and a 36% increase for high third-trimester pregnancy CO exposures and term LBW. For particles, we observed similar size effects during early and late pregnancy for both term LBW and preterm birth. In contrast, smaller or no effects were observed beyond a 1-mi distance of a residence from a station. Associations between CO and PM10 averaged over the whole pregnancy and term LBW were generally smaller than effects for early and late pregnancy. These new results for 1994–2000 generally confirm our previous observations for the period 1989–1993, again linking CO and particle exposures to term LBW and preterm birth. In addition, they confirm our suspicions about having to address local heterogeneity for these pollutants in Los Angeles.

Meeting Report: Atmospheric Pollution and Human Reproduction

Background There is a growing body of epidemiologic literature reporting associations between atmospheric pollutants and reproductive outcomes, particularly birth weight and gestational duration. Objectives The objectives of our international workshop were to discuss the current evidence, to identify the strengths and weaknesses of published epidemiologic studies, and to suggest future directions for research. Discussion Participants identified promising exposure assessment tools, including exposure models with fine spatial and temporal resolution that take into account time–activity patterns. More knowledge on factors correlated with exposure to air pollution, such as other environmental pollutants with similar temporal variations, and assessment of nutritional factors possibly influencing birth outcomes would help evaluate importance of residual confounding. Participants proposed a list of points to report in future publications on this topic to facilitate research syntheses. Nested case–control studies analyzed using two-phase statistical techniques and development of cohorts with extensive information on pregnancy behaviors and biological samples are promising study designs. Issues related to the identification of critical exposure windows and potential biological mechanisms through which air pollutants may lead to intrauterine growth restriction and premature birth were reviewed. Conclusions To make progress, this research field needs input from toxicology, exposure assessment, and clinical research, especially to aid in the identification and exposure assessment of feto-toxic agents in ambient air, in the development of early markers of adverse reproductive outcomes, and of relevant biological pathways. In particular, additional research using animal models would help better delineate the biological mechanisms underpinning the associations reported in human studies.

Association between Local Traffic-Generated Air Pollution and Preeclampsia and Preterm Delivery in the South Coast Air Basin of California

Background Preeclampsia is a major complication of pregnancy that can lead to substantial maternal and perinatal morbidity, mortality, and preterm birth. Increasing evidence suggests that air pollution adversely affects pregnancy outcomes. Yet few studies have examined how local traffic-generated emissions affect preeclampsia in addition to preterm birth. Objectives We examined effects of residential exposure to local traffic-generated air pollution on preeclampsia and preterm delivery (PTD). Methods We identified 81,186 singleton birth records from four hospitals (1997–2006) in Los Angeles and Orange Counties, California (USA). We used a line-source dispersion model (CALINE4) to estimate individual exposure to local traffic-generated nitrogen oxides (NOx) and particulate matter < 2.5 μm in aerodynamic diameter (PM2.5) across the entire pregnancy. We used logistic regression to estimate effects of air pollution exposures on preeclampsia, PTD (gestational age < 37 weeks), moderate PTD (MPTD; gestational age < 35 weeks), and very PTD (VPTD; gestational age < 30 weeks). Results We observed elevated risks for preeclampsia and preterm birth from maternal exposure to local traffic-generated NOx and PM2.5. The risk of preeclampsia increased 33% [odds ratio (OR) = 1.33; 95% confidence interval (CI), 1.18–1.49] and 42% (OR = 1.42; 95% CI, 1.26–1.59) for the highest NOx and PM2.5 exposure quartiles, respectively. The risk of VPTD increased 128% (OR = 2.28; 95% CI, 2.15–2.42) and 81% (OR = 1.81; 95% CI, 1.71–1.92) for women in the highest NOx and PM2.5 exposure quartiles, respectively. Conclusion Exposure to local traffic-generated air pollution during pregnancy increases the risk of preeclampsia and preterm birth in Southern California women. These results provide further evidence that air pollution is associated with adverse reproductive outcomes.

Ambient Air Pollution and Autism in Los Angeles County, California

Background: The prevalence of autistic disorder (AD), a serious developmental condition, has risen dramatically over the past two decades, but high-quality population-based research addressing etiology is limited. Objectives: We studied the influence of exposures to traffic-related air pollution during pregnancy on the development of autism using data from air monitoring stations and a land use regression (LUR) model to estimate exposures. Methods: Children of mothers who gave birth in Los Angeles, California, who were diagnosed with a primary AD diagnosis at 3–5 years of age during 1998–2009 were identified through the California Department of Developmental Services and linked to 1995–2006 California birth certificates. For 7,603 children with autism and 10 controls per case matched by sex, birth year, and minimum gestational age, birth addresses were mapped and linked to the nearest air monitoring station and a LUR model. We used conditional logistic regression, adjusting for maternal and perinatal characteristics including indicators of SES. Results: Per interquartile range (IQR) increase, we estimated a 12–15% relative increase in odds of autism for ozone [odds ratio (OR) = 1.12, 95% CI: 1.06, 1.19; per 11.54-ppb increase] and particulate matter ≤ 2.5 µm (OR = 1.15; 95% CI: 1.06, 1.24; per 4.68-μg/m3 increase) when mutually adjusting for both pollutants. Furthermore, we estimated 3–9% relative increases in odds per IQR increase for LUR-based nitric oxide and nitrogen dioxide exposure estimates. LUR-based associations were strongest for children of mothers with less than a high school education. Conclusion: Measured and estimated exposures from ambient pollutant monitors and LUR model suggest associations between autism and prenatal air pollution exposure, mostly related to traffic sources.

Methodological issues in studies of air pollution and reproductive health

In the past decade there have been an increasing number of scientific studies describing possible effects of air pollution on perinatal health. These papers have mostly focused on commonly monitored air pollutants, primarily ozone (O(3)), particulate matter (PM), sulfur dioxide (SO(2)), carbon monoxide (CO), and nitrogen dioxide (NO(2)), and various indices of perinatal health, including fetal growth, pregnancy duration, and infant mortality. While most published studies have found some marker of air pollution related to some types of perinatal outcomes, variability exists in the nature of the pollutants and outcomes associated. Synthesis of the findings has been difficult for various reasons, including differences in study design and analysis. A workshop was held in September 2007 to discuss methodological differences in the published studies as a basis for understanding differences in study findings and to identify priorities for future research, including novel approaches for existing data. Four broad topic areas were considered: confounding and effect modification, spatial and temporal exposure variations, vulnerable windows of exposure, and multiple pollutants. Here we present a synopsis of the methodological issues and challenges in each area and make recommendations for future study. Two key recommendations include: (1) parallel analyses of existing data sets using a standardized methodological approach to disentangle true differences in associations from methodological differences among studies; and (2) identification of animal studies to inform important mechanistic research gaps. This work is of critical public health importance because of widespread exposure and because perinatal outcomes are important markers of future child and adult health.

Comparing exposure assessment methods for traffic-related air pollution in an adverse pregnancy outcome study.

BACKGROUND Previous studies reported adverse impacts of traffic-related air pollution exposure on pregnancy outcomes. Yet, little information exists on how effect estimates are impacted by the different exposure assessment methods employed in these studies. OBJECTIVES To compare effect estimates for traffic-related air pollution exposure and preeclampsia, preterm birth (gestational age less than 37 weeks), and very preterm birth (gestational age less than 30 weeks) based on four commonly used exposure assessment methods. METHODS We identified 81,186 singleton births during 1997-2006 at four hospitals in Los Angeles and Orange Counties, California. Exposures were assigned to individual subjects based on residential address at delivery using the nearest ambient monitoring station data [carbon monoxide (CO), nitrogen dioxide (NO(2)), nitric oxide (NO), nitrogen oxides (NO(x)), ozone (O(3)), and particulate matter less than 2.5 (PM(2.5)) or less than 10 (PM(10))μm in aerodynamic diameter], both unadjusted and temporally adjusted land-use regression (LUR) model estimates (NO, NO(2), and NO(x)), CALINE4 line-source air dispersion model estimates (NO(x) and PM(2.5)), and a simple traffic-density measure. We employed unconditional logistic regression to analyze preeclampsia in our birth cohort, while for gestational age-matched risk sets with preterm and very preterm birth we employed conditional logistic regression. RESULTS We observed elevated risks for preeclampsia, preterm birth, and very preterm birth from maternal exposures to traffic air pollutants measured at ambient stations (CO, NO, NO(2), and NO(x)) and modeled through CALINE4 (NO(x) and PM(2.5)) and LUR (NO(2) and NO(x)). Increased risk of preterm birth and very preterm birth were also positively associated with PM(10) and PM(2.5) air pollution measured at ambient stations. For LUR-modeled NO(2) and NO(x) exposures, elevated risks for all the outcomes were observed in Los Angeles only--the region for which the LUR models were initially developed. Unadjusted LUR models often produced odds ratios somewhat larger in size than temporally adjusted models. The size of effect estimates was smaller for exposures based on simpler traffic density measures than the other exposure assessment methods. CONCLUSION We generally confirmed that traffic-related air pollution was associated with adverse reproductive outcomes regardless of the exposure assessment method employed, yet the size of the estimated effect depended on how both temporal and spatial variations were incorporated into exposure assessment. The LUR model was not transferable even between two contiguous areas within the same large metropolitan area in Southern California.

Air Pollution and Infant Death in Southern California, 1989–2000

OBJECTIVE. We evaluated the influence of outdoor air pollution on infant death in the South Coast Air Basin of California, an area characterized by some of the worst air quality in the United States. METHODS. Linking birth and death certificates for infants who died between 1989 and 2000, we identified all infant deaths, matched 10 living control subjects to each case subject, and assigned the nearest air monitoring station to each birth address. For all subjects, we calculated average carbon monoxide, nitrogen dioxide, ozone, and particulate matter <10 μm in aerodynamic diameter exposures experienced during the 2-week, 1-month, 2-month, and 6-month periods before a case subjects death. RESULTS. The risk of respiratory death increased from 20% to 36% per 1-ppm increase in average carbon monoxide levels 2 weeks before death in early infancy (age: 28 days to 3 months). We also estimated 7% to 12% risk increases for respiratory deaths per 10-μg/m3 increase in particulate matter <10 μm in aerodynamic diameter exposure experienced 2 weeks before death for infants 4 to 12 months of age. Risk of respiratory death more than doubled for infants 7 to 12 months of age who were exposed to high average levels of particulates in the previous 6 months. Furthermore, the risk of dying as a result of sudden infant death syndrome increased 15% to 19% per 1-part per hundred million increase in average nitrogen dioxide levels 2 months before death. Low birth weight and preterm infants seemed to be more susceptible to air pollution-related death resulting from these causes; however, we lacked statistical power to confirm this heterogeneity with formal testing. CONCLUSIONS. Our results add to the growing body of literature implicating air pollution in infant death from respiratory causes and sudden infant death syndrome and provide additional information for future risk assessment.

Traffic-Related Air Toxics and Term Low Birth Weight in Los Angeles County, California

Background: Numerous studies have linked criteria air pollutants with adverse birth outcomes, but there is less information on the importance of specific emission sources, such as traffic, and air toxics. Objectives: We used three exposure data sources to examine odds of term low birth weight (LBW) in Los Angeles, California, women when exposed to high levels of traffic-related air pollutants during pregnancy. Methods: We identified term births during 1 June 2004 to 30 March 2006 to women residing within 5 miles of a South Coast Air Quality Management District (SCAQMD) Multiple Air Toxics Exposure Study (MATES III) monitoring station. Pregnancy period average exposures were estimated for air toxics, including polycyclic aromatic hydrocarbons (PAHs), source-specific particulate matter < 2.5 μm in aerodynamic diameter (PM2.5) based on a chemical mass balance model, criteria air pollutants from government monitoring data, and land use regression (LUR) model estimates of nitric oxide (NO), nitrogen dioxide (NO2) and nitrogen oxides (NOx). Associations between these metrics and odds of term LBW (< 2,500 g) were examined using logistic regression. Results: Odds of term LBW increased approximately 5% per interquartile range increase in entire pregnancy exposures to several correlated traffic pollutants: LUR measures of NO, NO2, and NOx, elemental carbon, and PM2.5 from diesel and gasoline combustion and paved road dust (geological PM2.5). Conclusions: These analyses provide additional evidence of the potential impact of traffic-related air pollution on fetal growth. Particles from traffic sources should be a focus of future studies.

Paternal support and preterm birth, and the moderation of effects of chronic stress: a study in Los Angeles County mothers

Maternal psychosocial stress is an important risk factor for preterm birth, but support interventions have largely been unsuccessful. The objective of this study is to assess how support during pregnancy influences preterm birth risk and possibly ameliorates the effects of chronic stress, life event stress, or pregnancy anxiety in pregnant women. We examined 1,027 singleton preterm births and 1,282 full-term normal weight controls from a population-based retrospective case–control study of Los Angeles County, California women giving birth in 2003, a mostly Latina population (both US-born and immigrant). We used logistic regression to assess whether support from the baby’s father during pregnancy influences birth outcomes and effects of chronic stress, pregnancy anxiety, and life event stress. Adjusted odds of preterm birth decreased with better support (OR 0.73 [95%CI 0.52, 1.01]). Chronic stress (OR 1.46 [95%CI 1.11, 1.92]), low confidence of a normal birth (OR 1.57 [95% CI 1.17, 2.12]), and fearing for the baby’s health (OR 1.67 [95%CI 1.30, 2.14]) increased preterm birth risk, but life events showed no association. Our data also suggested that paternal support may modify the effect of chronic stress on the risk of preterm birth, such that among mothers lacking support, those with moderate-to-high stress were at increased odds of delivering preterm (OR 2.15 [95%CI 0.92, 5.03]), but women with greater support had no increased risk with moderate-to-high chronic stress (OR 1.13 [95%CI 0.94, 1.35]). Paternal support may moderate the effects of chronic stress on the risk of preterm delivery.

Traffic-related air toxics and preterm birth: a population-based case-control study in Los Angeles county, California

BackgroundNumerous studies have associated air pollutant exposures with adverse birth outcomes, but there is still relatively little information to attribute effects to specific emission sources or air toxics. We used three exposure data sources to examine risks of preterm birth in Los Angeles women when exposed to high levels of traffic-related air pollutants - including specific toxics - during pregnancy.MethodsWe identified births during 6/1/04-3/31/06 to women residing within five miles of a Southern California Air Quality Management District (SCAQMD) Multiple Air Toxics Exposure Study (MATES III) monitoring station. We identified preterm cases and, using a risk set approach, matched cases to controls based on gestational age at birth. Pregnancy period exposure averages were estimated for a number of air toxics including polycyclic aromatic hydrocarbons (PAHs), source-specific PM2.5 (fine particulates with aerodynamic diameter less than 2.5 μm) based on a Chemical Mass Balance model, criteria air pollutants based on government monitoring data, and land use regression (LUR) estimates of nitric oxide (NO), nitrogen dioxide (NO2) and nitrogen oxides (NOx). Associations between these metrics and odds of preterm birth were estimated using conditional logistic regression.ResultsOdds of preterm birth increased 6-21% per inter-quartile range increase in entire pregnancy exposures to organic carbon (OC), elemental carbon (EC), benzene, and diesel, biomass burning and ammonium nitrate PM2.5, and 30% per inter-quartile increase in PAHs; these pollutants were positively correlated and clustered together in a factor analysis. Associations with LUR exposure metrics were weaker (3-4% per inter-quartile range increase).ConclusionsThese latest analyses provide additional evidence of traffic-related air pollutions impact on preterm birth for women living in Southern California and indicate PAHs as a pollutant of concern that should be a focus of future studies. Other PAH sources besides traffic were also associated with higher odds of preterm birth, as was ammonium nitrate PM2.5, the latter suggesting potential importance of secondary pollutants. Future studies should focus on accurate modeling of both local and regional spatial and temporal distributions, and incorporation of source information.