Is there a link between parental smoking, MS?

A study presented at EAN 2024 found that selective exposure to parental smoking at an early age may increase the risk of developing multiple sclerosis (MS) later in life.

“We wanted to study if parental smoking could be associated with MS status because knowledge in this field is scarce. If you compare studies on maternal smoking during pregnancy [MSDP], they say the opposite … It is confusing,” noted study lead author Dr Caterina Ferri from the S. Anna University Hospital of Ferrara in Italy, in the EAN press release.

“[In this study, we found that] parental smoking exposure may anticipate the clinical onset of MS,” Ferri said.

The team used data from the multinational case-control population-based EnvIMS* study. They evaluated the association between MS and smoking habits, MSDP, and maternal/paternal smoking from Canada (n=1,565), Italy (n=2,040), and Norway (n=2,674). The number of cases in these respective cohorts were 587, 707, and 957. Mean age at MS onset ranged between 33 and 37 years, and about 70 percent of the overall cohort were women. [EAN 2024, abstract OPR-039]

In the Norwegian subgroup, MS was significantly associated with MSDP (adjusted odds ratio [aOR], 1.3; p=0.021). When stratifying by sex, the association remained significant for men who had prior exposure to MSDP (aOR, 1.7; p=0.017).

Past exposure to maternal smoking during childhood was similarly associated with MS among Norwegians (aOR, 1.29; p=0.004), more so among men (aOR, 1.61; p=0.006).

In the Canadian cohort, MS was associated with paternal smoking (aOR, 1.21; p=0.096). This aligns with the theory asserting the role of paternal environment in a nongenetic inheritance of pre-conceptional exposures through the male germ line. [Bioessays 2018;doi:10.1002/bies.201700113]

The DOHaD theory

The early stages of life may render an individual susceptible to disease because the immune system is still developing during this period. Hence, endogenous factors may affect disease development, said Ferri.

Further investigation exploring MS risk factors are thus warranted, she noted. “The high variability in the association between MS and parental smoking among populations may be explained by other risk factors such as genetics, gut microbiota, or environmental exposures.”

Ferri pointed to the DOHaD** theory as a potential explanation for the findings. This theory suggests the existence of transgenerational transmission of risks from maternal and paternal lines to the offspring. [Physiol Rev 2014;94:1027-1076]

“[This theory stipulates that] during the prenatal phase, the risk is determined by the interplay between environmental exposures and genetic/epigenetic factors of the parents,” said Ferri. In the press release, she noted that “there are a lot of genetic and environmental risk factors that interact with each other in MS. It is a complex interplay.”

Ferri added that the timing of exposure to environmental factors (eg, breastfeeding, infections such as mononucleosis) is just as important. For instance, an infection may be protective during the early stages of life, but it can become a risk factor later in life.

“Prenatal and intrauterine exposures may be as important as early-life exposures,” she said. “It is a new concept that has never really been applied in MS, especially prenatal (intrauterine or preconception) exposure. It could be interesting to explore this field.”