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Prenatal Smoking Exposures and Epigenome-Wide Methylation in Newborn Blood.

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Title: Prenatal Smoking Exposures and Epigenome-Wide Methylation in Newborn Blood.
Authors: Hoang, Thanh T.1,2,3,4, Cosin-Tomas, Marta5,6,7, Yunsung Lee8, Monasso, Giulietta9,10, Zongli Xu11, Li, Sebastian Shaobo12, Xuehuo Zeng13, Starling, Anne P.14,15, Reimann, Brigitte16, Röder, Stefan17, Zillich, Lea18, Jima, Dereje D.19,20, Thio, Chris H. L.21, Pesce, Giancarlo22,23, Kersten, Elin T. G.24,25, Breeze, Charles E.26, Burkholder, Adam B.27, Lee, Mikyeong1, Ward, James M.28, BIOS Consortium
Source: Environmental Health Perspectives. Jul2026, Vol. 134 Issue 3, p289-302. 14p.
Subject Terms: Cotinine, Smoking cessation, Prenatal exposure delayed effects, Fatherhood, Research funding, Genome-wide association studies, Epigenomics, Parenting, Descriptive statistics, Meta-analysis, DNA methylation, Longitudinal method, Data analysis software, Passive smoking, Regression analysis, Children
Abstract: BACKGROUND: Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear. OBJECTIVE: To identify differential DNA methylation in newborns from maternal sustained smoking and less studied prenatal smoking exposures (i.e., maternal exposure to secondhand smoke [SHS] exposure during pregnancy, maternal quitting before pregnancy, paternal smoking around conception, and paternal quitting before pregnancy). METHODS: We conducted a large meta-analysis of prenatal tobacco smoking exposures and epigenome-wide newborn blood DNA methylation through the Pregnancy And Childhood Epigenetics Consortium (PACE). Across 19 cohorts, 11,175 parent-newborn pairs contributed information on at least one prenatal smoking exposure, mostly from questionnaires. Maternal blood or urine cotinine measurements, available in a few studies, provided objective data for maternal SHS and smoking during pregnancy. Primary analyses used Illumina450 K methylation data; secondary analyses in 5 cohorts examined CpGs unique to the EPIC array. RESULTS: Maternal sustained smoking associated with differential DNA methylation (false discovery rate [FDR] < 0.05) at 8,862 CpGs on the 450 K (푛 = 8,148) and did not differ by infant sex. We identified over 300 novel genes not previously identified in EWAS of smoking. No differential methylation was associated with maternal SHS, maternal former smoking, or paternal smoking around conception. However, cg24805739 (MED13L) was associated with former paternal former smoking. Forty-one novel genes were identified using maternal cotinine measurements compared to questionnaire. In EPIC unique analyses (푛 = 3,415), differential methylation was observed with maternal sustained smoking (211 CpGs), maternal SHS (5 CpGs), and paternal former smoking (4 CpGs). Smoking-associated CpGs in blood were strongly enriched for functional elements across multiple tissues. CONCLUSIONS: Maternal sustained smoking has the largest impact on newborn DNA methylation, suggesting a strong influence of the intrauterine environment. We observed minimal impacts for less studied exposures including SHS, maternal former smoking, and paternal smoking. [ABSTRACT FROM AUTHOR]
Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Prenatal Smoking Exposures and Epigenome-Wide Methylation in Newborn Blood.
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  Data: &lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Hoang%2C+Thanh+T%2E%22&quot;&gt;Hoang, Thanh T.&lt;/searchLink&gt;&lt;relatesTo&gt;1,2,3,4&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Cosin-Tomas%2C+Marta%22&quot;&gt;Cosin-Tomas, Marta&lt;/searchLink&gt;&lt;relatesTo&gt;5,6,7&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Yunsung+Lee%22&quot;&gt;Yunsung Lee&lt;/searchLink&gt;&lt;relatesTo&gt;8&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Monasso%2C+Giulietta%22&quot;&gt;Monasso, Giulietta&lt;/searchLink&gt;&lt;relatesTo&gt;9,10&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Zongli+Xu%22&quot;&gt;Zongli Xu&lt;/searchLink&gt;&lt;relatesTo&gt;11&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Li%2C+Sebastian+Shaobo%22&quot;&gt;Li, Sebastian Shaobo&lt;/searchLink&gt;&lt;relatesTo&gt;12&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Xuehuo+Zeng%22&quot;&gt;Xuehuo Zeng&lt;/searchLink&gt;&lt;relatesTo&gt;13&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Starling%2C+Anne+P%2E%22&quot;&gt;Starling, Anne P.&lt;/searchLink&gt;&lt;relatesTo&gt;14,15&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Reimann%2C+Brigitte%22&quot;&gt;Reimann, Brigitte&lt;/searchLink&gt;&lt;relatesTo&gt;16&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22R&#246;der%2C+Stefan%22&quot;&gt;R&#246;der, Stefan&lt;/searchLink&gt;&lt;relatesTo&gt;17&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Zillich%2C+Lea%22&quot;&gt;Zillich, Lea&lt;/searchLink&gt;&lt;relatesTo&gt;18&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Jima%2C+Dereje+D%2E%22&quot;&gt;Jima, Dereje D.&lt;/searchLink&gt;&lt;relatesTo&gt;19,20&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Thio%2C+Chris+H%2E+L%2E%22&quot;&gt;Thio, Chris H. L.&lt;/searchLink&gt;&lt;relatesTo&gt;21&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Pesce%2C+Giancarlo%22&quot;&gt;Pesce, Giancarlo&lt;/searchLink&gt;&lt;relatesTo&gt;22,23&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Kersten%2C+Elin+T%2E+G%2E%22&quot;&gt;Kersten, Elin T. G.&lt;/searchLink&gt;&lt;relatesTo&gt;24,25&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Breeze%2C+Charles+E%2E%22&quot;&gt;Breeze, Charles E.&lt;/searchLink&gt;&lt;relatesTo&gt;26&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Burkholder%2C+Adam+B%2E%22&quot;&gt;Burkholder, Adam B.&lt;/searchLink&gt;&lt;relatesTo&gt;27&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Lee%2C+Mikyeong%22&quot;&gt;Lee, Mikyeong&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Ward%2C+James+M%2E%22&quot;&gt;Ward, James M.&lt;/searchLink&gt;&lt;relatesTo&gt;28&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22BIOS+Consortium%22&quot;&gt;BIOS Consortium&lt;/searchLink&gt;
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22Environmental+Health+Perspectives%22&quot;&gt;Environmental Health Perspectives&lt;/searchLink&gt;. Jul2026, Vol. 134 Issue 3, p289-302. 14p.
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  Data: BACKGROUND: Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear. OBJECTIVE: To identify differential DNA methylation in newborns from maternal sustained smoking and less studied prenatal smoking exposures (i.e., maternal exposure to secondhand smoke [SHS] exposure during pregnancy, maternal quitting before pregnancy, paternal smoking around conception, and paternal quitting before pregnancy). METHODS: We conducted a large meta-analysis of prenatal tobacco smoking exposures and epigenome-wide newborn blood DNA methylation through the Pregnancy And Childhood Epigenetics Consortium (PACE). Across 19 cohorts, 11,175 parent-newborn pairs contributed information on at least one prenatal smoking exposure, mostly from questionnaires. Maternal blood or urine cotinine measurements, available in a few studies, provided objective data for maternal SHS and smoking during pregnancy. Primary analyses used Illumina450 K methylation data; secondary analyses in 5 cohorts examined CpGs unique to the EPIC array. RESULTS: Maternal sustained smoking associated with differential DNA methylation (false discovery rate [FDR] &lt; 0.05) at 8,862 CpGs on the 450 K (푛 = 8,148) and did not differ by infant sex. We identified over 300 novel genes not previously identified in EWAS of smoking. No differential methylation was associated with maternal SHS, maternal former smoking, or paternal smoking around conception. However, cg24805739 (MED13L) was associated with former paternal former smoking. Forty-one novel genes were identified using maternal cotinine measurements compared to questionnaire. In EPIC unique analyses (푛 = 3,415), differential methylation was observed with maternal sustained smoking (211 CpGs), maternal SHS (5 CpGs), and paternal former smoking (4 CpGs). Smoking-associated CpGs in blood were strongly enriched for functional elements across multiple tissues. CONCLUSIONS: Maternal sustained smoking has the largest impact on newborn DNA methylation, suggesting a strong influence of the intrauterine environment. We observed minimal impacts for less studied exposures including SHS, maternal former smoking, and paternal smoking. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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        Value: 10.1021/EHP.6c00142
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      – Code: eng
        Text: English
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      Pagination:
        PageCount: 14
        StartPage: 289
    Subjects:
      – SubjectFull: Cotinine
        Type: general
      – SubjectFull: Smoking cessation
        Type: general
      – SubjectFull: Prenatal exposure delayed effects
        Type: general
      – SubjectFull: Fatherhood
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      – SubjectFull: Research funding
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      – SubjectFull: Genome-wide association studies
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      – SubjectFull: Epigenomics
        Type: general
      – SubjectFull: Parenting
        Type: general
      – SubjectFull: Descriptive statistics
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      – SubjectFull: Meta-analysis
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      – SubjectFull: DNA methylation
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      – SubjectFull: Longitudinal method
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      – SubjectFull: Data analysis software
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      – SubjectFull: Passive smoking
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      – SubjectFull: Regression analysis
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      – SubjectFull: Children
        Type: general
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      – TitleFull: Prenatal Smoking Exposures and Epigenome-Wide Methylation in Newborn Blood.
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              Text: Jul2026
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