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Air pollution exposure during obstetric weeks 3\u20138 was assigned based on self\u2010reported residence. DNA was extracted from residual newborn blood spots, and DNA methylation levels were measured using the Illumina EPIC Array.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cases had higher exposure to both <jats:styled-content style=\"fixed-case\">PM<jats:sub>2<\/jats:sub><\/jats:styled-content><jats:sub>.5<\/jats:sub> and <jats:styled-content style=\"fixed-case\">O<jats:sub>3<\/jats:sub><\/jats:styled-content> compared to controls. No specific <jats:styled-content style=\"fixed-case\">CpG<\/jats:styled-content> loci were statistically significantly associated with <jats:styled-content style=\"fixed-case\">TOF<\/jats:styled-content> status or air pollution exposure; however, we observed associations between <jats:styled-content style=\"fixed-case\">TOF<\/jats:styled-content> case status and <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation at specific genomic regions with genes enriched for functions in metabolism. Additionally, there were significant regions that displayed differential <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation in relation to air pollution exposure within genes involved in apoptosis, necrosis, inflammation, and immune response pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Generally, air pollution exposure and TOF were associated with differential DNA methylation in distinct genes. These results highlight suggestive links between the environment, epigenome, and TOF to be further investigated in larger studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2473","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:55:49Z","timestamp":1745470549000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Using Residual Newborn Blood Spots to Investigate <scp>CpG<\/scp> Methylation in Relation to Air Pollution and Congenital Heart Defects"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7867-5126","authenticated-orcid":false,"given":"Thomas J.","family":"Luben","sequence":"first","affiliation":[{"name":"Center for Public Health and Environmental Assessment Office of Research and Development, US Environmental Protection Agency, RTP  North Carolina USA"},{"name":"Department of Epidemiology Gillings School of Global Public Health, University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle","family":"Roell","sequence":"additional","affiliation":[{"name":"Department of Environmental Sciences and Engineering Gillings School of Global Public Health, University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cailee E.","family":"Harrington","sequence":"additional","affiliation":[{"name":"Department of Environmental Sciences and Engineering Gillings School of Global Public Health, University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanette A.","family":"Stingone","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Columbia University  New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cavin K.","family":"Ward\u2010Caviness","sequence":"additional","affiliation":[{"name":"Center for Public Health and Environmental Assessment Office of Research and Development, US Environmental Protection Agency, RTP  North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania A.","family":"Desrosiers","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Gillings School of Global Public Health, University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca C.","family":"Fry","sequence":"additional","affiliation":[{"name":"Department of Environmental Sciences and Engineering Gillings School of Global Public Health, University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9115-5128","authenticated-orcid":false,"given":"Andrew F.","family":"Olshan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Gillings School of Global Public Health, University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.05.009"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu049"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.20292"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1420.003"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13253\u2010009\u20100004\u2010z"},{"key":"e_1_2_8_7_1","unstructured":"Blighe K. andJ.Lasky\u2010Su.2023.\u201cRegParallel: Standard Regression Functions in R Enabled for Parallel Processing Over Large Data\u2010Frames. 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