Elena Isaevska1, Chiara Moccia2, Federica Asta3, Fabio Cibella4, Luigi Gagliardi5, Luca Ronfani6, Franca Rusconi7, Maria Antonietta Stazi8, Lorenzo Richiardi9. 1. Department of Medical Sciences, University of Turin, CPO Piemonte, Turin, Italy. Electronic address: elena.isaevska@unito.it. 2. Department of Medical Sciences, University of Turin, CPO Piemonte, Turin, Italy. Electronic address: chiara.moccia@unito.it. 3. Department of Epidemiology, Lazio Regional Health Service, ASL Roma 1, Rome, Italy. Electronic address: f.asta@deplazio.it. 4. Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), Palermo, Italy. Electronic address: fabio.cibella@ibim.cnr.it. 5. Division of Neonatology and Pediatrics, Ospedale Versilia, Viareggio, AUSL Toscana Nord Ovest, Pisa, Italy. Electronic address: luigi.gagliardi@uslnordovest.toscana.it. 6. Clinical Epidemiology and Public Health Research Unit, Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy. Electronic address: luca.ronfani@burlo.trieste.it. 7. Unit of Epidemiology, Meyer Children's University Hospital, Florence, Italy. Electronic address: franca.rusconi@meyer.it. 8. Center "Behavioral Sciences and Mental Health", Istituto Superiore di Sanità, Rome, Italy. Electronic address: antonia.stazi@iss.it. 9. Department of Medical Sciences, University of Turin, CPO Piemonte, Turin, Italy. Electronic address: lorenzo.richiardi@unito.it.
Abstract
BACKGROUND: Exposure to air pollution during the first 1000 days of life (from conception to the 2nd year of life) might be of particular relevance for long-term child health. Changes in molecular markers such as DNA methylation and telomere length could underlie the association between air pollution exposure and pollution-related diseases as well as serve as biomarkers for past exposure. The objective of this systematic review was to assess the association between air pollution exposure during pregnancy and the first two years of life and changes in DNA methylation or telomere length in children. METHODS: PubMed was searched in October 2020 by using terms relative to ambient air pollution exposure, DNA methylation, telomere length and the population of interest: mother/child dyads and children. Screening and selection of the articles was completed independently by two reviewers. Thirty-two articles matched our criteria. The majority of the articles focused on gestational air pollution exposure and measured DNA methylation/telomere length in newborn cord blood or placental tissue, to study global, candidate-gene or epigenome-wide methylation patterns and/or telomere length. The number of studies in children was limited. RESULTS: Ambient air pollution exposure during pregnancy was associated with global loss of methylation in newborn cord blood and placenta, indicating the beginning of the pregnancy as a potential period of susceptibility. Candidate gene and epigenome-wide association studies provided evidence that gestational exposure to air pollutants can lead to locus-specific changes in methylation, in newborn cord blood and placenta, particularly in genes involved in cellular responses to oxidative stress, mitochondrial function, inflammation, growth and early life development. Telomere length shortening in newborns and children was seen in relation to gestational pollutant exposure. CONCLUSIONS: Ambient air pollution during pregnancy is associated with changes in both global and locus-specific DNA methylation and with telomere length shortening. Future studies need to test the robustness of the association across different populations, to explore potential windows of vulnerability and assess the role of the methylation and telomere length as mediators in the association between early exposure to ambient air pollutants and specific childhood health outcomes.
BACKGROUND: Exposure to air pollution during the first 1000 days of life (from conception to the 2nd year of life) might be of particular relevance for long-term child health. Changes in molecular markers such as DNA methylation and telomere length could underlie the association between air pollution exposure and pollution-related diseases as well as serve as biomarkers for past exposure. The objective of this systematic review was to assess the association between air pollution exposure during pregnancy and the first two years of life and changes in DNA methylation or telomere length in children. METHODS: PubMed was searched in October 2020 by using terms relative to ambient air pollution exposure, DNA methylation, telomere length and the population of interest: mother/child dyads and children. Screening and selection of the articles was completed independently by two reviewers. Thirty-two articles matched our criteria. The majority of the articles focused on gestational air pollution exposure and measured DNA methylation/telomere length in newborn cord blood or placental tissue, to study global, candidate-gene or epigenome-wide methylation patterns and/or telomere length. The number of studies in children was limited. RESULTS: Ambient air pollution exposure during pregnancy was associated with global loss of methylation in newborn cord blood and placenta, indicating the beginning of the pregnancy as a potential period of susceptibility. Candidate gene and epigenome-wide association studies provided evidence that gestational exposure to air pollutants can lead to locus-specific changes in methylation, in newborn cord blood and placenta, particularly in genes involved in cellular responses to oxidative stress, mitochondrial function, inflammation, growth and early life development. Telomere length shortening in newborns and children was seen in relation to gestational pollutant exposure. CONCLUSIONS: Ambient air pollution during pregnancy is associated with changes in both global and locus-specific DNA methylation and with telomere length shortening. Future studies need to test the robustness of the association across different populations, to explore potential windows of vulnerability and assess the role of the methylation and telomere length as mediators in the association between early exposure to ambient air pollutants and specific childhood health outcomes.
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