title: Identifying sensitive windows for prenatal particulate air pollution exposure and mitochondrial DNA content in cord blood.
abstract: Changes in mitochondrial DNA (mtDNA) can serve as a marker of cumulative oxidative stress (OS) due to the mitochondria's unique genome and relative lack of repair systems. In utero particulate matter ≤2.5μm (PM2.5) exposure can enhance oxidative stress. Our objective was to identify sensitive windows to predict mtDNA damage experienced in the prenatal period due to PM2.5exposure using mtDNA content measured in cord blood.
  
  
  
  Women affiliated with the Mexican social security system were recruited during pregnancy in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study. Mothers with cord blood collected at delivery and complete covariate data were included (n=456). Mothers' prenatal daily exposure to PM2.5was estimated using a satellite-based spatio-temporally resolved prediction model and place of residence during pregnancy. DNA was extracted from umbilical cord leukocytes. Quantitative real-time polymerase chain reaction (qPCR) was used to determine mtDNA content. A distributive lag regression model (DLM) incorporating weekly averages of daily PM2.5predictions was constructed to plot the association between exposure and OS over the length of pregnancy.
  
  
  
  In models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, birth year, maternal education, and assay batch, we found significant associations between higher PM2.5exposure during late pregnancy (35-40weeks) and lower mtDNA content in cord blood.
  
  
  
  Increased PM2.5during a specific prenatal window in the third trimester was associated with decreased mtDNA content suggesting heightened sensitivity to PM-induced OS during this life stage.
authors.affiliation: Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: maria.rosa@mssm.edu.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Rosa
authors.affiliation: Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: allan.just@mssm.edu.
authors.forename: Allan C
authors.initials: AC
authors.lastname: Just
authors.affiliation: Department of Neurobiology, National Institute of Perinatology, Mexico City, Mexico. Electronic address: m.sanchezguerra@inper.gob.mx.
authors.forename: Marco Sánchez
authors.initials: MS
authors.lastname: Guerra
authors.affiliation: Department of Geography and Environmental Development, Ben-Gurion University of the Negev, P.O.B. 653, Beer Sheva, Israel. Electronic address: ikloog@bgu.ac.il.
authors.forename: Itai
authors.initials: I
authors.lastname: Kloog
authors.affiliation: Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: leon.hsu@mssm.edu.
authors.forename: Hsiao-Hsien Leon
authors.initials: HL
authors.lastname: Hsu
authors.affiliation: Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA. Electronic address: kb2891@cumc.columbia.edu.
authors.forename: Kasey J
authors.initials: KJ
authors.lastname: Brennan
authors.affiliation: Center for Nutrition and Health Research, National Institute of Public Health, Ministry of Health, Cuernavaca, Morelos, Mexico. Electronic address: adrianam@insp.mx.
authors.forename: Adriana Mercado
authors.initials: AM
authors.lastname: García
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: bcoull@hsph.harvard.edu.
authors.forename: Brent
authors.initials: B
authors.lastname: Coull
authors.affiliation: Kravis Children's Hospital, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: rosalind.wright@mssm.edu.
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Wright
authors.affiliation: Center for Nutrition and Health Research, National Institute of Public Health, Ministry of Health, Cuernavaca, Morelos, Mexico. Electronic address: mmtellez@insp.mx.
authors.forename: Martha María
authors.initials: MM
authors.lastname: Téllez Rojo
authors.affiliation: Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA. Electronic address: andrea.baccarelli@cumc.columbia.edu.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.affiliation: Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: robert.wright@mssm.edu.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
mesh_terms: D000328:Adult; D000397:Air Pollution / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000097:blood*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D006967:Hypersensitivity; D008297:Male; D018811:Maternal Exposure; D008800:Mexico; D009035:Mothers; D018384:Oxidative Stress; D052638:Particulate Matter / Q000008:administration & dosage* / Q000009:adverse effects*; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial; D052638:Particulate Matter
keywords: Distributive lag models; Mitochondrial DNA; Particulate matter; Prenatal exposure