Polycyclic aromatic hydrocarbons and birth outcomes in Mexico City

Summary

Principal Investigator: MARIE SYLVIA O'NEILL
Abstract: DESCRIPTION (provided by applicant): The size and weight of a baby at birth are important determinants of its survival and future health across the life course. Although multiple factors influence birth weight and size, air pollution exposure during pregnancy has been recently explored as a contributor. Millions of women are exposed to ambient air pollution, and levels can be especially high in developing countries. Reducing infant mortality is one of the Millennium Development Goals, so the public health importance of understanding and minimizing environmental contributors to poor birth outcomes is great. Most published epidemiology studies are based on population birth registries and lack the individual, clinical data and repeated measures needed to elucidate possible biological mechanisms mediating epidemiological associations between pollution and adverse birth outcomes. This proposed work presents a unique opportunity to study those mechanisms in a new cohort of 800 pregnant women residing in diverse regions of Mexico City, a mega-city with high air pollution levels. We will investigate how air pollution and the polycyclic aromatic hydrocarbon (PAH) component of particles can influence the outcome of pregnancy, and whether certain periods of gestation represent critical time windows and opportunities for preventive intervention. We will obtain biomarkers relevant to PAH exposure (DNA adducts) in blood samples provided by participants monthly during their pregnancies, and umbilical cord blood obtained at birth. We will also collect information on health history, clinical characteristics, tobacco smoke exposure, diet and time-activity patterns. Simultaneously, we will estimate spatial and temporal variability in air pollution exposure with data from the Mexico City Metropolitan Area (MCMA) air quality monitoring network (PM2.5, PM10, ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide), matched to the exact locations of participants'homes. DNA samples from mother and infant will be used to type genetic polymorphisms (CYP1A1, GSTM1, GSTT1, GSTP1, Xrcc1, XPD) relevant to the hypothesized mechanisms. We will evaluate whether ambient pollution and PAH adducts are associated with three outcomes: birth weight, head circumference and birth length, controlling for other risk factors, and which time windows are most relevant. We will examine effect modification by intake of antioxidant vitamins (E and C) and the genetic polymorphisms. Finally, we will complement this epidemiological study with a parallel toxicology in-vitro study which will involve collecting and characterizing air pollution particle samples (PM10 and PM2.5) on a monthly basis from five zones in MCMA and exposing a monocytic cell line (J774A.1) to evaluate PAH adducts. Any coherence between the human and in vitro evidence for a mechanistic association between pollution and these adducts will guide future studies. This multi-disciplinary, global health collaboration will evaluate potential environmental determinants of adverse birth outcomes, using a novel approach combining epidemiology and toxicology, with the goal of developing unique knowledge with far-reaching prevention implications. PUBLIC HEALTH RELEVANCE This research investigates how air pollution influences the risk of adverse birth outcomes, with a focus on understanding mechanisms and critical time windows of exposure. The goal is to develop knowledge to support 1) policy-makers who set and enforce health-protective air pollution standards;2) scientists involved in multi-disciplinary studies to understand environmental contributions to infant health, and 3) clinicians interested in prevention of adverse birth outcomes.
Funding Period: 2009-05-01 - 2015-01-31
more information: NIH RePORT

Top Publications

  1. pmc Do-not-resuscitate orders and predictive models after intracerebral hemorrhage
    D B Zahuranec
    University of Michigan Cardiovascular Center, 1500 East Medical Center Drive, SPC 5855, Ann Arbor, MI 48109 5855, USA
    Neurology 75:626-33. 2010
  2. pmc Statistical methods to study timing of vulnerability with sparsely sampled data on environmental toxicants
    Brisa Ney Sánchez
    Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, 48109, USA
    Environ Health Perspect 119:409-15. 2011
  3. pmc Preventing cold-related morbidity and mortality in a changing climate
    Kathryn C Conlon
    University of Michigan School of Public Health, Ann Arbor, MI 48109, USA
    Maturitas 69:197-202. 2011
  4. ncbi A latent variable approach to study gene-environment interactions in the presence of multiple correlated exposures
    Brisa N Sanchez
    Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA
    Biometrics 68:466-76. 2012
  5. ncbi Particulate matter promotes in vitro receptor-recognizable low-density lipoprotein oxidation and dysfunction of lipid receptors
    Natalia Manzano-León
    Instituto Nacional de Cancerologia, C P 14080 México, D F, Mexico
    J Biochem Mol Toxicol 27:69-76. 2013
  6. ncbi Variation in the composition and in vitro proinflammatory effect of urban particulate matter from different sites
    Natalia Manzano-León
    Instituto Nacional de Cancerologia, Av San Fernando 22, Col Seccion XVI, C P 14080, Mexico, D F, Mexico
    J Biochem Mol Toxicol 27:87-97. 2013
  7. pmc Environmental contaminant exposures and preterm birth: a comprehensive review
    Kelly K Ferguson
    Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan 48109 2029, USA
    J Toxicol Environ Health B Crit Rev 16:69-113. 2013
  8. pmc Outdoor air pollution, preterm birth, and low birth weight: analysis of the world health organization global survey on maternal and perinatal health
    Nancy L Fleischer
    University of South Carolina Arnold School of Public Health, Columbia, South Carolina, USA
    Environ Health Perspect 122:425-30. 2014

Research Grants

  1. EPIDEMIOLOGY OF ALCOHOL PROBLEMS
    Thomas K Greenfield; Fiscal Year: 2013
  2. Jules Stein Eye Institute Core Grant for Vision Research
    Wayne L Hubbell; Fiscal Year: 2013

Detail Information

Publications8

  1. pmc Do-not-resuscitate orders and predictive models after intracerebral hemorrhage
    D B Zahuranec
    University of Michigan Cardiovascular Center, 1500 East Medical Center Drive, SPC 5855, Ann Arbor, MI 48109 5855, USA
    Neurology 75:626-33. 2010
    ..To quantify the accuracy of commonly used intracerebral hemorrhage (ICH) predictive models in ICH patients with and without early do-not-resuscitate orders (DNR)...
  2. pmc Statistical methods to study timing of vulnerability with sparsely sampled data on environmental toxicants
    Brisa Ney Sánchez
    Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, 48109, USA
    Environ Health Perspect 119:409-15. 2011
    ..Identifying windows of vulnerability to environmental toxicants is an important area in children's health research...
  3. pmc Preventing cold-related morbidity and mortality in a changing climate
    Kathryn C Conlon
    University of Michigan School of Public Health, Ann Arbor, MI 48109, USA
    Maturitas 69:197-202. 2011
    ..We propose that future climate change adaptation research couple building energy and thermal comfort models with epidemiological data to evaluate and quantify the impacts of adaptation strategies...
  4. ncbi A latent variable approach to study gene-environment interactions in the presence of multiple correlated exposures
    Brisa N Sanchez
    Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA
    Biometrics 68:466-76. 2012
    ..We demonstrate the methods with an example from the Early Life Exposures in Mexico City to Neuro-Toxicants Study of lead exposure, iron metabolism genes, and birth weight...
  5. ncbi Particulate matter promotes in vitro receptor-recognizable low-density lipoprotein oxidation and dysfunction of lipid receptors
    Natalia Manzano-León
    Instituto Nacional de Cancerologia, C P 14080 México, D F, Mexico
    J Biochem Mol Toxicol 27:69-76. 2013
    ..Results indicate that particulate matter was capable of oxidizing low-density lipoproteins, favoring macrophage internalization, and also altered scavenger and low-density lipoproteins receptor function...
  6. ncbi Variation in the composition and in vitro proinflammatory effect of urban particulate matter from different sites
    Natalia Manzano-León
    Instituto Nacional de Cancerologia, Av San Fernando 22, Col Seccion XVI, C P 14080, Mexico, D F, Mexico
    J Biochem Mol Toxicol 27:87-97. 2013
    ..Cytokines produced by both cell lines only correlated with C(1) , suggesting that constituents associated with soil induced the inflammatory response and explain observed spatial differences...
  7. pmc Environmental contaminant exposures and preterm birth: a comprehensive review
    Kelly K Ferguson
    Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan 48109 2029, USA
    J Toxicol Environ Health B Crit Rev 16:69-113. 2013
    ..By identifying limitations and addressing the gaps that may have impeded the ability to identify true associations thus far, this review can guide future epidemiologic studies of environmental exposures and preterm birth...
  8. pmc Outdoor air pollution, preterm birth, and low birth weight: analysis of the world health organization global survey on maternal and perinatal health
    Nancy L Fleischer
    University of South Carolina Arnold School of Public Health, Columbia, South Carolina, USA
    Environ Health Perspect 122:425-30. 2014
    ..Inhaling fine particles (particulate matter with diameter ≤ 2.5 μm; PM2.5) can induce oxidative stress and inflammation, and may contribute to onset of preterm labor and other adverse perinatal outcomes...

Research Grants30

  1. EPIDEMIOLOGY OF ALCOHOL PROBLEMS
    Thomas K Greenfield; Fiscal Year: 2013
    ..We plan to build research capacity in the Center and other organizations, enhance careers of new investigators, and make key findings accessible to researchers, policy makers, practitioners, and the public. ..
  2. Jules Stein Eye Institute Core Grant for Vision Research
    Wayne L Hubbell; Fiscal Year: 2013
    ..Support in the form of the Core grant is requested to maintain these Modules through instrument service contracts, and to provide necessary personnel support to assist and train users and provide routine maintenance. ..