Exposure to Infant Siblings During Early Life and Risk of Multiple Sclerosis

Abstract

Context The "hygiene hypothesis" has implicated sibship as a marker of infection load during early life and suggests that exposure or reexposure to infections can influence the developing immune system. Viral infection has also been implicated in the pathogenesis of multiple sclerosis (MS). Objectives To evaluate whether exposure to infant siblings in early life is associated with the risk of MS, and to explore the possible mechanism for any apparent protective effect, including altered Epstein-Barr virus (EBV) infection patterns. Design, Setting, and Patients Population-based case-control study in Tasmania, Australia, from 1999 to 2001 based on 136 cases of magnetic resonance imagingconfirmed MS and 272 community controls, matched on sex and year of birth. Main Outcome Measure Risk of MS by duration of contact with younger siblings aged less than 2 years in the first 6 years of life. Results Increasing duration of contact with a younger sibling aged less than 2 years in the first 6 years of life was associated with reduced MS risk (adjusted odds ratios [AORs]: Ͻ1 infant-year, 1.00 [reference]; 1 to Ͻ3 infant-years, 0.57 [95% confidence interval {CI}, 0.33-0.98]; 3 to Ͻ5 infant-years, 0.40 [95% CI, 0.19-0.92]; Ն5 infant-years, 0.12 [95% CI, 0.02-0.88]; test for trend, P=.002). A history of exposure to infant siblings was associated with a reduced IgG response to EBV among controls. Controls with at least 1 infant-year contact had a reduced risk of infectious mononucleosis and a reduced risk of very high composite EBV IgG titers (AOR, 0.33; 95% CI, 0.11-0.98) compared with other controls. The inverse association between higher infant contact and MS was independent of EBV IgG titer. Conclusion Higher infant sibling exposure in the first 6 years of life was associated with a reduced risk of MS, possibly by altering childhood infection patterns and related immune responses.

Number of Siblings and the Risk of Lymphoma, Leukemia, and Myeloma by Histopathology

“…Our null results on NHL with number of siblings, based on >7,000 cases, are in broad agreement with a case-control study from Italy that reported no association of family characteristics with NHL (16). It has been suggested that a high number of younger siblings may be associated with a higher probability of EBV infection, independent of number of older siblings (30,60). In our Database, the number of younger siblings showed no significant effect.…”

Dual role of infections as risk factors for coronary heart disease

“…According to our study "the hygiene hypothesis" [18,20] might also be relevant for explaining development of CHD. Improved hygiene in the early childhood might partially explain the rise of the greatest epidemic of the 20 th century, the coronary heart disease.…”

“…A high contact exposure within the first 6 years of life with younger siblings less than two years of age in the same household was recently shown to be associated with a reduced risk and delayed onset of multiple sclerosis [20]. The number of siblings was used as a marker of infection load during early life.…”

Combined effects of smoking, anti-EBNA antibodies, and HLA-DRB1*1501 on multiple sclerosis risk

“…10 In the Tasmanian study, total anti-EBNA IgG titers were measured using an ELISA assay (Panbio, Brisbane, Australia). 9 Notably, 2 studies measured anti-EBNA-1, while the third measured total anti-EBNA. To address the appropriateness of combining these data, we examined the relationship in the NHS cohorts, where information is available on both EBNA-1 and total EBNA.…”

“…This is a population-based study using prevalent cases. 8,9 Cases were identified through a variety of population-based strategies, including information sessions at MS societies and invitation letters from neurologists to patients. Two community controls were selected from a voter registration for compulsory political elections and matched to each case by sex and birth year (response rate ϭ 76%).…”