Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1289/EHP16303
Licence creative commons licence
Title (Primary) Prenatal smoking exposures and epigenome-wide methylation in newborn blood
Author Hoang, T.T.; Cosin-Tomas, M.; Lee, Y.; Monasso, G.; Xu, Z.; Shaobo Li, S.; Zeng, X.; Starling, A.P.; Reimann, B.; Röder, S. ORCID logo ; Zillich, L.; Jima, D.D.; Thio, C.H.L.; Pesce, G.; Kersten, E.T.G.; Breeze, C.E.; Burkholder, A.B.; Lee, M.; Ward, J.M.; BIOS Consortium, ; Alfano, R.; Deuschle, M.; Duijts, L.; Ghassabian, A.; Gómez Herrera, L.-C.; Jaddoe, V.W.V.; Motsinger-Reif, A.A.; Lie, R.T.; Nawrot, T.S.; Page, C.M.; Send, T.S.; Sharp, G.; Stein, D.J.; Streit, F.; Sunyer, J.; Wilcox, A.J.; Zar, H.J.; Koppelmann, G.H.; Annesi-Maesano, I.; Corpeleijn, E.; Snieder, H.; Hoyo, C.; Hüls, A.; Sirignano, L.; Witt, S.H.; Herberth, G. ORCID logo ; Plusquin, M.; Dabelea, D.; Yeung, E.; Wiemels, J.L.; Richmond, R.C.; Taylor, J.A.; Felix, J.F.; Håberg, S.E.; Bustamante, M.; London, S.J.
Source Titel Environmental Health Perspectives
Year 2025
Department IMMU
Supplements https://ehp.niehs.nih.gov/doi/suppl/10.1289/EHP16303/suppl_file/ehp16303.smcontents.508.pdf
https://ehp.niehs.nih.gov/doi/suppl/10.1289/EHP16303/suppl_file/ehp16303.s001.acco.pdf
https://ehp.niehs.nih.gov/doi/suppl/10.1289/EHP16303/suppl_file/ehp16303.s002.codeanddata.acco.zip
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, 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 on maternal SHS and smoking during pregnancy. Primary analyses used Illumina450K 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 450K (n=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 paternal former smoking. Forty-one novel genes were identified using maternal cotinine measurements compared to questionnaire. In EPIC unique analyses (n=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.




Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=31306
Hoang, T.T., Cosin-Tomas, M., Lee, Y., Monasso, G., Xu, Z., Shaobo Li, S., Zeng, X., Starling, A.P., Reimann, B., Röder, S., Zillich, L., Jima, D.D., Thio, C.H.L., Pesce, G., Kersten, E.T.G., Breeze, C.E., Burkholder, A.B., Lee, M., Ward, J.M., BIOS Consortium, , Alfano, R., Deuschle, M., Duijts, L., Ghassabian, A., Gómez Herrera, L.-C., Jaddoe, V.W.V., Motsinger-Reif, A.A., Lie, R.T., Nawrot, T.S., Page, C.M., Send, T.S., Sharp, G., Stein, D.J., Streit, F., Sunyer, J., Wilcox, A.J., Zar, H.J., Koppelmann, G.H., Annesi-Maesano, I., Corpeleijn, E., Snieder, H., Hoyo, C., Hüls, A., Sirignano, L., Witt, S.H., Herberth, G., Plusquin, M., Dabelea, D., Yeung, E., Wiemels, J.L., Richmond, R.C., Taylor, J.A., Felix, J.F., Håberg, S.E., Bustamante, M., London, S.J. (2025):
Prenatal smoking exposures and epigenome-wide methylation in newborn blood
Environ. Health Perspect. 10.1289/EHP16303