Smoking during pregnancy tied to raised MS risk in mothers, offspring

Women who smoked during pregnancy, and their offspring, showed a significantly higher risk of developing multiple sclerosis (MS) in a recent Danish study.

“Our observations add further to the evidence implicating smoking in the development of MS and suggest that intra-uterine exposure to tobacco smoke may increase MS risk,” the researchers wrote in “Smoking during pregnancy and risk of multiple sclerosis in offspring and mother: A Danish nationwide register-based cohort study,” which was published in the Multiple Sclerosis Journal.

While the exact cause of MS isn’t known, the neurodegenerative autoimmune disease is thought to arise through a combination of genetic and environmental factors, one being smoking. People with a history of smoking have about a 50% higher risk of developing the disease than those who never smoked. Passive smoking, or exposure to secondhand smoke, is also linked to a higher risk of the disease.

Smoking during pregnancy is known to affect fetal development, including the brain and immune system. Women who smoke during pregnancy increase the risk of immune diseases in their children, but the exact relationship with the risk of MS hasn’t been established.

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A 42% higher risk

“Results vary considerably between the previous investigations, ranging from no association to a threefold increased MS risk in offspring born to women who smoked during pregnancy,” said researchers who examined data from Danish health registries to explore a link between smoking in pregnancy and MS risk for both mother and child. Smoking habits were self-reported.

The analysis included 789,299 Danish women who were pregnant in Denmark between 1991-2018. Among them, 198,014 (25%) reported smoking during pregnancy, and 3,591 women (4.5%) later developed MS.

Women who were registered as smokers during their pregnancy were found to be at about a 42% higher risk of MS than those who didn’t, a finding generally consistent with studies that link smoking to MS risk in non-pregnant populations.

A total of 879,135 singleton, or non-twin, babies were born to these women between 1991-2008. Among them, 293 were diagnosed with MS later in life, 110 of whom (38%) had been exposed to maternal smoking during pregnancy. This amounted to about a 38% higher risk of MS with prenatal exposure to smoking after adjusting for age, sex, and birth weight, among other factors. There was no difference in MS risk between male and female offspring.

Fetal exposure to nicotine during pregnancy leads to changes in gene activity related to myelin, the substance surrounding nerve cells that’s attacked in MS, previous preclinical research has indicated.

“A similar mechanism might contribute to an increased susceptibility to MS among offspring exposed to maternal smoking,” the scientists wrote.

How does secondhand smoking factor in?

It’s also possible that exposure to secondhand smoke throughout childhood has an effect. Smoking by parents is associated with a higher risk that a child will eventually smoke themselves, which could contribute to MS risk.

“Our study is limited by the lack of information on the offspring’s possible exposure to passive smoking during childhood and on their personal smoking habits,” said the researchers, who noted most children born during the analysis period would still be young at the study’s follow-up and wouldn’t have reached the age when MS usually arises.

The researchers said their study “supports the notion that individuals whose mothers smoked during pregnancy are at an elevated risk of MS compared with individuals of mothers who did not smoke during pregnancy.”

The mechanisms linking smoking and MS are not fully understood, but it’s believed tobacco might affect the immune system, and that smoking and the Epstein-Barr Virus (EBV), recognized as a leading cause of MS, may combine to raise the risk of the disease.

“Other mechanisms entertained in explaining the increased MS risk in smokers include triggering of pro-inflammatory cascades through airway irritation and disruption of the blood–brain barrier,” the researchers said.