Ambient Air Pollution During Pregnancy and DNA Methylation in Umbilical Cord Blood, with Potential Mediation of Associations with Infant Adiposity: The Healthy Start Study

Overview

Journal Environ Res

Publisher Elsevier

Specialty Environmental Health

Date 2022 Jul 14

PMID 35835166

Authors

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

Affiliations

Soon will be listed here.

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) and ozone (O), and epigenome-wide DNA methylation of umbilical cord blood cells at delivery (2010-2014). We calculated average PM and O 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 O 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 (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 O 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 and O. 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 O exposure and 5-month infant adiposity.

Citing Articles

Newborn adiposity is associated with cord blood DNA methylation at IGF1R and KLF7.

Josefson J, Kuang A, Allard C, Bianco M, Lowe Jr W, Scholtens D Obesity (Silver Spring). 2024; 32(10):1923-1933.

PMID: 39165088 PMC: 11421971. DOI: 10.1002/oby.24109.

Exposure to air pollution is associated with DNA methylation changes in sperm.

Schrott R, Feinberg J, Newschaffer C, Hertz-Picciotto I, Croen L, Daniele Fallin M Environ Epigenet. 2024; 10(1):dvae003.

PMID: 38559770 PMC: 10980975. DOI: 10.1093/eep/dvae003.

Early-life exposure to residential black carbon and childhood cardiometabolic health.

Friedman C, Dabelea D, Glueck D, Allshouse W, Adgate J, Keller K Environ Res. 2023; 239(Pt 2):117285.

PMID: 37832765 PMC: 10842121. DOI: 10.1016/j.envres.2023.117285.

References

Symanski E, McHugh M, Zhang X, Craft E, Lai D . Evaluating narrow windows of maternal exposure to ozone and preterm birth in a large urban area in Southeast Texas. J Expo Sci Environ Epidemiol. 2015; 26(2):167-72. PMC: 11519844. DOI: 10.1038/jes.2015.32. View

Crume T, Ogden L, Daniels S, Hamman R, Norris J, Dabelea D . The impact of in utero exposure to diabetes on childhood body mass index growth trajectories: the EPOCH study. J Pediatr. 2011; 158(6):941-6. PMC: 3090715. DOI: 10.1016/j.jpeds.2010.12.007. View

Lee J, Kalia V, Perera F, Herbstman J, Li T, Nie J . Prenatal airborne polycyclic aromatic hydrocarbon exposure, LINE1 methylation and child development in a Chinese cohort. Environ Int. 2016; 99:315-320. PMC: 5810919. DOI: 10.1016/j.envint.2016.12.009. View

Furlong C, Suzuki S, Stevens R, Marsillach J, Richter R, Jarvik G . Human PON1, a biomarker of risk of disease and exposure. Chem Biol Interact. 2010; 187(1-3):355-61. PMC: 3035622. DOI: 10.1016/j.cbi.2010.03.033. View

Nwanaji-Enwerem J, Colicino E, Trevisi L, Kloog I, Just A, Shen J . Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study. Environ Epigenet. 2016; 2(2). PMC: 4957520. DOI: 10.1093/eep/dvw006. View

Leek J, Johnson W, Parker H, Jaffe A, Storey J . The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012; 28(6):882-3. PMC: 3307112. DOI: 10.1093/bioinformatics/bts034. View

Nobles C, Williams A, Ouidir M, Sherman S, Mendola P . Differential Effect of Ambient Air Pollution Exposure on Risk of Gestational Hypertension and Preeclampsia. Hypertension. 2019; 74(2):384-390. PMC: 6620155. DOI: 10.1161/HYPERTENSIONAHA.119.12731. View

Durinck S, Spellman P, Birney E, Huber W . Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat Protoc. 2009; 4(8):1184-91. PMC: 3159387. DOI: 10.1038/nprot.2009.97. View

Yang R, Luo D, Zhang Y, Hu K, Qian Z, Hu L . Adverse Effects of Exposure to Fine Particulate Matters and Ozone on Gestational Hypertension. Curr Med Sci. 2019; 39(6):1019-1028. DOI: 10.1007/s11596-019-2137-9. View

10.

Stieb D, Chen L, Eshoul M, Judek S . Ambient air pollution, birth weight and preterm birth: a systematic review and meta-analysis. Environ Res. 2012; 117:100-11. DOI: 10.1016/j.envres.2012.05.007. View

11.

Renauer P, Coit P, Jeffries M, Merrill J, McCune W, Maksimowicz-McKinnon K . DNA methylation patterns in naïve CD4+ T cells identify epigenetic susceptibility loci for malar rash and discoid rash in systemic lupus erythematosus. Lupus Sci Med. 2015; 2(1):e000101. PMC: 4577980. DOI: 10.1136/lupus-2015-000101. View

12.

Yao M, Liu Y, Jin D, Yin W, Ma S, Tao R . Relationship betweentemporal distribution of air pollution exposure and glucose homeostasis during pregnancy. Environ Res. 2020; 185:109456. DOI: 10.1016/j.envres.2020.109456. View

13.

Yuan L, Zhang Y, Gao Y, Tian Y . Maternal fine particulate matter (PM) exposure and adverse birth outcomes: an updated systematic review based on cohort studies. Environ Sci Pollut Res Int. 2019; 26(14):13963-13983. DOI: 10.1007/s11356-019-04644-x. View

14.

Guo P, Chen Y, Wu H, Zeng J, Zeng Z, Li W . Ambient air pollution and markers of fetal growth: A retrospective population-based cohort study of 2.57 million term singleton births in China. Environ Int. 2019; 135:105410. DOI: 10.1016/j.envint.2019.105410. View

15.

Ritz B, Wilhelm M . Ambient air pollution and adverse birth outcomes: methodologic issues in an emerging field. Basic Clin Pharmacol Toxicol. 2008; 102(2):182-90. PMC: 3656653. DOI: 10.1111/j.1742-7843.2007.00161.x. View

16.

Plusquin M, Chadeau-Hyam M, Ghantous A, Alfano R, Bustamante M, Chatzi L . DNA Methylome Marks of Exposure to Particulate Matter at Three Time Points in Early Life. Environ Sci Technol. 2018; 52(9):5427-5437. DOI: 10.1021/acs.est.7b06447. View

17.

Tang X, Zhou J, Luo F, Han Y, Heianza Y, Cardoso M . Air pollution and gestational diabetes mellitus: evidence from cohort studies. BMJ Open Diabetes Res Care. 2020; 8(1). PMC: 7103802. DOI: 10.1136/bmjdrc-2019-000937. View

18.

Cao W, Dong M, Sun X, Liu X, Xiao J, Feng B . Associations of maternal ozone exposures during pregnancy with maternal blood pressure and risk of hypertensive disorders of pregnancy: A birth cohort study in Guangzhou, China. Environ Res. 2020; 183:109207. DOI: 10.1016/j.envres.2020.109207. View

19.

De Prins S, Koppen G, Jacobs G, Dons E, Van de Mieroop E, Nelen V . Influence of ambient air pollution on global DNA methylation in healthy adults: a seasonal follow-up. Environ Int. 2013; 59:418-24. DOI: 10.1016/j.envint.2013.07.007. View

20.

Reese S, Xu C, den Dekker H, Lee M, Sikdar S, Ruiz-Arenas C . Epigenome-wide meta-analysis of DNA methylation and childhood asthma. J Allergy Clin Immunol. 2018; 143(6):2062-2074. PMC: 6556405. DOI: 10.1016/j.jaci.2018.11.043. View