Ambient air pollution during pregnancy and DNA methylation in umbilical cord blood, with potential mediation of associations with infant adiposity: The Healthy Start study

Anne P Starling; Cheyret Wood; Cuining Liu; Katerina Kechris; Ivana V Yang; Chloe Friedman; Deborah S K Thomas; Jennifer L Peel; John L Adgate; Sheryl Magzamen; Sheena E Martenies; William B Allshouse; Dana Dabelea

doi:10.1016/j.envres.2022.113881

Ambient air pollution during pregnancy and DNA methylation in umbilical cord blood, with potential mediation of associations with infant adiposity: The Healthy Start study

Environ Res. 2022 Nov;214(Pt 1):113881. doi: 10.1016/j.envres.2022.113881. Epub 2022 Jul 11.

Authors

Affiliations

¹ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: anne.starling@unc.edu.
² Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
³ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA; Center for Genes, Environment and Health, National Jewish Health, Denver, CO, USA.
⁴ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁵ Department of Geography and Earth Sciences, University of North Carolina Charlotte, NC, USA.
⁶ Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.
⁷ Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁸ Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA; Department of Epidemiology, Colorado School of Public Health, Colorado State University, Fort Collins, CO, USA.
⁹ Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA; Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
¹⁰ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Abstract

Background: Prenatal exposure to ambient air pollution has been associated with adverse offspring health outcomes. Childhood health effects of prenatal exposures may be mediated through changes to DNA methylation detectable at birth.

Methods: Among 429 non-smoking women in a cohort study of mother-infant pairs in Colorado, USA, we estimated associations between prenatal exposure to ambient fine particulate matter (PM_2.5) and ozone (O₃), and epigenome-wide DNA methylation of umbilical cord blood cells at delivery (2010-2014). We calculated average PM_2.5 and O₃ in each trimester of pregnancy and the full pregnancy using inverse-distance-weighted interpolation. We fit linear regression models adjusted for potential confounders and cell proportions to estimate associations between air pollutants and methylation at each of 432,943 CpGs. Differentially methylated regions (DMRs) were identified using comb-p. Previously in this cohort, we reported positive associations between 3rd trimester O₃ exposure and infant adiposity at 5 months of age. Here, we quantified the potential for mediation of that association by changes in DNA methylation in cord blood.

Results: We identified several DMRs for each pollutant and period of pregnancy. The greatest number of significant DMRs were associated with third trimester PM_2.5 (21 DMRs). No single CpGs were associated with air pollutants at a false discovery rate <0.05. We found that up to 8% of the effect of 3rd trimester O₃ on 5-month adiposity may be mediated by locus-specific methylation changes, but mediation estimates were not statistically significant.

Conclusions: Differentially methylated regions in cord blood were identified in association with maternal exposure to PM_2.5 and O₃. Genes annotated to the significant sites played roles in cardiometabolic disease, immune function and inflammation, and neurologic disorders. We found limited evidence of mediation by DNA methylation of associations between third trimester O₃ exposure and 5-month infant adiposity.

Keywords: Air pollution; Cord blood; DNA methylation; Epigenetics; Ozone; Particulate matter.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adiposity
Air Pollutants*
Air Pollution*
Child
Cohort Studies
DNA Methylation
Female
Fetal Blood
Humans
Infant
Infant, Newborn
Maternal Exposure
Obesity
Particulate Matter
Pregnancy
Prenatal Exposure Delayed Effects*

Substances

Air Pollutants
Particulate Matter

Abstract

Publication types

MeSH terms

Substances

Grants and funding