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Mother’s smoking during pregnancy is known to be associated with the offspring’s health outcomes, such as childhood behaviour and other health conditions later in life; some of these are related to mental health. However, the biological mechanisms that could be involved are not yet understood.
It has been suggested that epigenetics might play a role; epigenetics is the study of changes in DNA that do not alter the DNA sequence itself. These changes might influence gene activity and, consequently, gene functioning and development.

One of the most studied epigenetic mechanisms is DNA methylation – an addition of a methyl group to DNA – which has been suggested as a possible mechanism for the adverse health outcomes associated with maternal smoking during pregnancy.
It is already known that maternal smoking is associated with DNA methylation in newborns at more than 6000 DNA methylation sites. The aims of our study were to
• investigate if these associations persist throughout the offspring’s life-course
• examine if DNA methylation is the potential biological mechanism that links maternal smoking to various diseases – specifically mental health problems – in the offspring
We examined the exposure to maternal smoking and offspring DNA methylation in approximately 3000 mother-child pairs in five European studies. Information on mothers’ smoking habits during pregnancy was obtained from questionnaires. Offspring had blood samples taken at clinical examinations between the ages of 16 and 48 years, and DNA methylation was measured from these samples.
We found associations between exposure to maternal smoking and offspring DNA methylation in adolescents and adults at 69 DNA methylation sites. Results from our follow-up analyses were consistent with our hypothesis of DNA methylation being the potential mechanism in the association between maternal smoking and offspring mental health, specifically schizophrenia-related personality disorders.
Our results demonstrate that exposure to maternal smoking in utero is associated with persistent alterations in DNA methylation across the life-course until middle age. In addition, we found some evidence that DNA methylation is a potential biological mechanism through which maternal smoking is associated with schizophrenia in the offspring.




Get in Touch!


Prof. Christel Middeldorp, project coordinator

VU University Amsterdam
Dept. of Biological Psychology
email : c.m.middeldorp(at)

Natascha Stroo, project manager
VU University Amsterdam
Dept. of Biological Psychology
email : natascha.stroo(at)

Matteo Mauri, web & dissemination manager
University of Cagliari
email : matteo.mauri(at)

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