Early contact with infant siblings reduces risk of multiple sclerosis

BMJ 2005; 330 doi: (Published 27 January 2005) Cite this as: BMJ 2005;330:216
  1. Susan Mayor
  1. London

People who had more exposure to infant siblings during the first six years of life have a lower risk of developing multiple sclerosis than people with less exposure, potentially because of increased childhood infection and related immune responses, says a study published this week.

The study looked at 136 adults (average age 43.5 years) with multiple sclerosis confirmed by magnetic resonance imaging and 272 controls (average age 43.6 years) matched by sex and year of birth. The participants, all residents of Tasmania, were interviewed between March 1999 and June 2001.

The aim was to assess whether a range of factors, including exposure to infant siblings in early life, was associated with the risk of developing the disease (JAMA 2005;293: 463-9).

The results showed that a longer duration of contact with a younger sibling aged less than two years in the first six years of life was associated with a lower risk of developing multiple sclerosis and a delayed age of onset of the disease. The risk of developing multiple sclerosis was 43% lower (adjusted odds ratio 0.57 (95% confidence interval 0.33 to 0.98)) in patients who had between one and three years of contact with a younger infant sibling than in patients who had contact of less than a year (the reference group). Three to five years of contact gave a 60% lower risk (0.4 (0.19 to 0.92), and five years or more gave an 88% lower risk (0.12 (0.02 to 0.88) (P for trend 0.002).

The study than explored possible mechanisms for the protective effect of exposure to an infant sibling. Previous studies have shown that multiple sclerosis is associated with a later onset of childhood infections. A particularly strong association was found for later infection with Epstein-Barr virus (EBV), a common type of herpes virus (BMJ 2003;326: 731). Infection results in a higher level in adulthood of IgG antibodies directed against the virus, which has also been shown to be associated with multiple sclerosis.

The new study showed that in the control group a history of exposure to infant siblings was associated with a lower IgG response to EBV, indicating that this might be a protective factor against multiple sclerosis. Control participants with at least one year of contact with an infant sibling had a lower risk of glandular fever (infectious mononucleosis) and a lower risk of very high composite EBV IgG titres than other participants in the control group (adjusted odds ratio 0.33 (0.11 to 0.98)).

Anne-Louise Ponsonby, of the National Centre for Epidemiology and Population Health at the Australian National University, Canberra, and lead researcher of the study, said: “The finding that higher infant contact in early life was associated with reduced EBV antibody titres and a reduced likelihood of infectious mononucleosis among healthy controls strengthens the inference that infant contact in early life may alter childhood infection patterns and related immune responses and reduce the risk of MS [multiple sclerosis].”

Dr Ponsonby said that the findings might be explained by the “hygiene hypothesis,” which proposes that contracting infections in early life lessens the risk of developing allergic and autoimmune disorders by influencing the development of the immune system. Having siblings may increase the number of early life infections. A protective role for early life infection in the development of multiple sclerosis is consistent with several features of the disease, she said, including the apparent recent increase in incidence that has accompanied a decline in rates of childhood infection.

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