title: Maternal residential proximity to major roadways, birth weight, and placental DNA methylation.
abstract: Exposure to traffic pollution during fetal development has been associated with reduced fetal growth, and there is evidence to suggest that epigenetic mechanisms in the placenta in the form of variant DNA methylation may be a potential mechanism underlying this effect.
  
  
  
  To examine the association between residential proximity to nearest major roadway, as a marker of traffic-related pollution, fetal growth and placental DNA methylation.
  
  
  
  We obtained residential addresses, placenta samples, and demographic data from 471 women following delivery of term infants. Using generalized linear models we evaluated the association between living close to a major roadway (defined as living ≤150m from a primary highway or primary road or ≤50m from a secondary road) and fetal growth and DNA methylation of repetitive elements (LINE-1 and AluYb8). We evaluated epigenome-wide methylation in a subset of 215 women to further investigate specific variation in DNA methylation associated with proximity to major roadways.
  
  
  
  Living close to a major roadway was associated with a 175.9g (95% CI: -319.4, -32.5; p=0.016) lower birth weight, 1.8 (95% CI: 0.9, 3.8; p=0.09) times the odds of being small for gestational age, and 0.82 percentage points (95% CI: -1.57, -0.07; p=0.03) lower mean placental LINE-1 methylation levels in fully adjusted models. In epigenome-wide analyses, 7 CpG sites were significantly associated with residential proximity to major roadways. Additional adjustment for placental methylation did not attenuate the association between roadway proximity and birth weight.
  
  
  
  Living close to major roadways was associated with both lower fetal growth and significant placental epigenetic changes. However, the observed epigenetic changes appear insufficient to explain the observed association between roadway proximity and fetal growth.
authors.affiliation: Department of Epidemiology, Brown University School of Public Health, Providence, RI, United States.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Kingsley
authors.affiliation: Department of Epidemiology, Brown University School of Public Health, Providence, RI, United States.
authors.forename: Melissa N
authors.initials: MN
authors.lastname: Eliot
authors.affiliation: Department of Epidemiology, University of North Carolina Gillings School of Public Health and School of Medicine, Chapel Hill, NC, United States; Department of Medicine, University of North Carolina Gillings School of Public Health and School of Medicine, Chapel Hill, NC, United States.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Whitsel
authors.affiliation: Department of Epidemiology, Brown University School of Public Health, Providence, RI, United States.
authors.forename: Yen-Tsung
authors.initials: YT
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, Brown University School of Public Health, Providence, RI, United States; Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, United States.
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
authors.affiliation: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.affiliation: Department of Epidemiology, Brown University School of Public Health, Providence, RI, United States. Electronic address: Gregory_Wellenius@brown.edu.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Wellenius
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000032:analysis* / Q000633:toxicity; D015415:Biomarkers; D001724:Birth Weight; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D006798:Housing / Q000592:standards*; D006801:Humans; D007223:Infant; D016014:Linear Models; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D001335:Vehicle Emissions / Q000032:analysis* / Q000633:toxicity
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D001335:Vehicle Emissions
keywords: Birth weight; Epigenetics; Placenta; Pollution; Traffic