Authors
Thanh T Hoang, Marta Cosin-Tomas, Yunsung Lee, Giulietta Monasso, Zongli Xu, Sebastian Shaobo Li, Xuehuo Zeng, Anne P Starling, Brigitte Reimann, Stefan Röder, Lea Zillich, Dereje D Jima, Chris H L Thio, Giancarlo Pesce, Elin T G Kersten, Charles E Breeze, Adam B Burkholder, Mikyeong Lee, James M Ward, BIOS Consortium, Rossella Alfano, Michael Deuschle, Liesbeth Duijts, Akhgar Ghassabian, Laura-Concepció Gómez Herrera, Vincent Wv Jaddoe, Alison A Motsinger-Reif, Rolv T Lie, Tim S Nawrot, Christian M Page, Tabea S Send, Gemma Sharp, Dan J Stein, Fabian Streit, Jordi Sunyer, Allen J Wilcox, Heather J Zar, Gerard H Koppelman, Isabella Annesi-Maesano, Eva Corpeleijn, Harold Snieder, Cathrine Hoyo, Anke Hüls, Lea Sirignano, Stephanie H Witt, Gunda Herberth, Michelle Plusquin, Dana Dabelea, Edwina Yeung, Joseph L Wiemels, Rebecca C Richmond, Jack A Taylor, Janine F Felix, Siri E Håberg, Mariona Bustamante, Stephanie J London
Published in
Environmental health perspectives. Volume 134. Issue 3. Pages 289-302. Jul 07, 2026. Epub Apr 16, 2026.
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 (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 former 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.
PMID:
42428256
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.
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