HELSINKI, Finland — Results from a new multinational study suggests that exposure to maternal smoking during pregnancy or parental smoking during early childhood is associated with increased risk for multiple sclerosis (MS) later in life.
It is well-established that active smoking is a risk factor for MS and adds to a poor prognosis. But little was known about parental smoking and risk for future MS in children.
"Selective exposure to parental smoking at an early age may differentially increase MS risk in the general population and independently from the subject's past or current smoking habit," lead investigator Caterina Ferri, a neurologist and researcher at the University Hospital of Ferrara, Italy, said.
The findings were presented on June 30 at the Congress of the European Academy of Neurology 2024.
An Understudied Topic
The trial — Environmental Risk Factors In Multiple Sclerosis (EnvIMS) — is an ongoing population-based, multinational, case-control study investigating whether past environmental exposures affect MS risk in the general population.
"Early-life factors are crucial in determining the risk for MS, and this is an emerging field of research," Ferri said.
Data on the subject are limited and earlier studies yielded conflicting results, she added.
"If you compare two studies that have recently been published on maternal smoking during pregnancy...one says there is no association, while the other concludes that children of mothers who smoked had a higher risk of developing MS," Ferri said. "It is confusing."
Ferri and colleagues used data from Canadian, Italian, and Norwegian populations in EnvIMS and matched more than 4000 control subjects by sex, age, and geographical area to just over 2000 cases of MS diagnosed at age 18 years or older.
All participants completed the EnvIMS-Q questionnaire, which included questions about their parents' smoking history, including maternal smoking during pregnancy, maternal smoking during childhood independent of maternal smoking during pregnancy, and paternal smoking during childhood.
Results were adjusted for participants' age, smoking history, and history of infectious mononucleosis.
Age at MS onset varied from an average of 33.2 years of age in Italy to 37.6 in Norway, and disease duration was a mean of 5.6 years in Italy, 6.4 years in Canada, and 7.2 years in Norway.
As expected, ever-smokers were significantly more likely than nonsmokers to develop MS in Italy (P < .000001), Canada (P = .02), and Norway (P < .000001).
A history of infectious mononucleosis was also significantly associated with the risk of developing MS across all three populations studied.
Geographic Differences
Most of the association seen between parental smoking and MS was observed in the Norwegian population, Ferri reported.
Specifically, maternal smoking during pregnancy was significantly associated with MS in participants in Norway (odds ratio [OR], 1.38; P = .003). After adjustment for confounding factors, the association remained significant only among males (adjusted OR, 1.7; P = .017).
The association of maternal smoking during pregnancy with MS was not significant in Italy and Canada.
And although there was a tendency for paternal smoking to be associated with MS among Canadians (OR, 1.27; P = .024), this significance was lost after the statistical adjustment among both sexes.
There was no association between any parental smoking and MS in the Italian population. That study group was from Sardinia, which Ferri said is a region known to have a high familial risk for MS, which may have affected the findings there.
Asked by one of the chairs of the session if she could explain the regional discrepancies, Ferri noted that "MS is multifactorial. Each population has its own susceptibilities to the disease, and there are a lot of genetic and environmental risk factors that interact with each other."
Susceptibility is thought to be highest in the early stages of life because "the immune system is still developing in that phase," Ferri said. "The timing of exposure to environmental factors, for example breastfeeding or infections such as mononucleosis, is also important. During the early stages of life, an infection can be protection, but later in life it can be a risk factor."
In addition, there is "no definitive answer to whether the cause of the association is chemicals in tobacco smoke, or epigenetic modifications, or a complex interplay of both," Ferri said.
Asked for comment, Celia Oreja-Guevara, vice chair of neurology, Hospital Clínico San Carlos, Madrid, Spain, told Medscape Medical News that the results are not surprising.
"We know that when the mother or father is smoking at home, there is a risk for [smoking-related disease] in the children," Oreja-Guevara said.
The actual risk for future MS will probably "depend on the quantity of cigarettes smoked and what the parents smoke," she added, noting that nicotine content and that of other chemicals in cigarettes can vary widely between countries depending on the nationwide preference for certain brands.
"For example, people in Spain don't smoke the same cigarettes as people in the UK," she said.
EnvIMS is a large, multinational, case-control, population-based study resulting from the collaborative efforts of researchers in Italy, Norway, Canada, Serbia, and Sweden; it is funded by Italian and Canadian MS foundations and academic and health institutions in Italy, Norway, and Canada. Ferri and Oreja-Guevara report no relevant conflicts of interest.