Smoking during pregnancy causes chemical changes to a baby’s DNA that affect its risk of smoking-related conditions in adulthood, a study has found.

The research, led by scientists at Imperial College London and the University of Oulu in Finland, analysed data from more than 18,000 people in several countries, including the UK, US and Australia, to study the impacts of maternal smoking on cardiovascular health.

Their findings are published in the Lancet’s journal EBioMedicine and are the first to uncover a mechanism for exactly how smoking during pregnancy may have an impact on the development of disease over the life-course – by affecting the DNA without changing the genetic ‘code’ itself.

Instead, smoking can add or remove chemical groups attached to the outside of the DNA – called ‘epigenetic’ tags, from the Greek word ‘epi’ meaning on or above the DNA.

According to the team, these epigenetic changes found in people whose mothers smoked while they were in the womb, or in current smokers, are strongly linked to smoking-related disease risk factors, including adult obesity.

“Our study shows compelling evidence that changes in epigenetic markers may persist over the lifetime of an individual,” said Professor Marjo-Riitta Jarvelin, from Imperial’s School of Public Health, and who led the research group.

Harming health

Smoking during pregnancy can lead to premature birth and low birth weight, as well as predisposing the child to higher risk for cardio-metabolic risk factors in later life, but the exact mechanisms underlying these longer-term effects were unclear. Yet despite the known risks, it is estimated that worldwide more than half of women (53%) who smoke daily continue to smoke during pregnancy.

Professor Jarvelin added: “These findings are important for health policy makers to further draw attention towards increasing awareness on smoking cessation programs and for better prevention strategies in maternity clinics and health centres.”

Our study shows compelling evidence that changes in epigenetic markers may persist over the lifetime of an individual Professor Marjo-Riitta Jarvelin Study author

Inside our cells, the DNA can be regulated by adding or removing markers to the DNA, like chemical sticky notes, through a process called DNA methylation. These epigenetic changes can alter how certain regions of DNA are read and copied, so affect the activity of key genes.

In the latest study, researchers focused on methylation of a gene called GFI1, known to be linked with smoking.

Using data from 22 population-based studies from Europe, the US and Australia, the team looked at the link between maternal smoking and epigenetic changes in a number of regions of the gene.

They identified lower DNA methylation of GFI1 in those who smoked or whose mother smoked while they were pregnant.

Altering DNA

According to the researchers, these epigenetic changes are associated with increased body mass index (BMI), blood pressure and blood lipids levels in adulthood, meaning exposure to cigarette smoking in the womb ultimately increases a person’s risk for a range of health conditions in adulthood, including diabetes, heart disease and stroke.

Priyanka Parmar from the University of Oulu, said: “Such epigenetic loci might serve as objective biomarkers of past environmental exposures that could be used for preventive health measures. This discovery provides a strong foundation for further work to unravel emerging smoking epigenetic markers with downstream detrimental health outcomes.”

Cigarette smoking accounts for an estimated six million deaths each year and even former smokers are at long-term risk of cardiovascular diseases, lung cancer and stroke.

The researchers add that while their work highlights an underlying epigenetic component for maternal smoking exposure and disease risk, the size of the effect and exactly how much it increases a person’s risk is unclear. The team now hopes to explore more genetic regions linked with maternal smoking exposure and disease risk, highlighting that their work focused on just six genetic markers out of a potential 6000.

This study develops from a large international collaboration between 17 research academic organisations, organised under the Global MethQTL and DynaHEALTH consortia, linking data from Europe, US and Australia.

The research was supported by the Medical Research Council, Wellcome Trust, the European Union Seventh Framework Program and Horizon 2020 programme.

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‘Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults’ by Priyanka Parmar et al. is published in the journal EBioMedicine. DOI: 10.1016/j.ebiom.2018.10.066