Prenatal maternal smoke, DNA methylation, and multi-omics of tissues and child health

Purpose of review: Maternal tobacco smoking during pregnancy is of public health concern, and understanding the biological mechanisms can help to promote smoking cessation campaigns. This non-systematic review focuses on the effects of maternal smoking during pregnancy on offspring's epigenome, consistent in chemical modifications of the genome that regulate gene expression. Recent findings: Recent meta-analyses of epigenome-wide association studies have shown that maternal smoking during pregnancy is consistently associated with offspring's DNA methylation changes, both in the placenta and blood. These studies indicate that effects on blood DNA methylation can persist for years, and that the longer the duration of the exposure and the higher the dose, the larger the effects. Hence, DNA methylation scores have been developed to estimate past exposure to maternal smoking during pregnancy as biomarkers. There is robust evidence for DNA methylation alterations associated with maternal smoking during pregnancy; however, the role of sex, ethnicity, and genetic background needs further exploration. Moreover, there are no conclusive studies about exposure to low doses or during the preconception period. Similarly, studies on tissues other than the placenta and blood are scarce, and cell-type specificity within tissues needs further investigation. In addition, biological interpretation of DNA methylation findings requires multi-omics data, poorly available in epidemiological settings. Finally, although several mediation analyses link DNA methylation changes with health outcomes, they do not allow causal inference. For this, a combination of data from multiple study designs will be essential in the future to better address this topic.The study has received funding from the H2020-EU.3.1.2.—Preventing Disease Programme under grant agreement no 874583 (ATHLETE project). Marta Cosin-Tomas is funded by a Beatriu de Pinós Postdoctoral Contract awarded by Generalitat de Catalunya-AGAUR and European Commission- Horizon 2020 (2019 BP 00107). Ariadna Cilleros-Portet is funded by a grant from the Health Department of the Basque Government to Nora Fernandez-Jimenez (GVSAN-2019111085). Sofía Aguilar-Lacasaña is funded by a FI-AGAUR Predoctoral contract awarded by the Agència de Gestió d'Ajuts Universitaris i de Recerca (2022 FI_B 00797), Generalitat de Catalunya – Fons Social Europeu. We received support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program