Exposure to infant siblings during early life and risk of multiple sclerosis

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 imaging-confirmed 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]: <1 infant-year, 1.00 [reference]; 1 to <3 infant-years, 0.57 [95% confidence interval {CI}, 0.33-0.98]; 3 to <5 infant-years, 0.40 [95% CI, 0.19-0.92]; ≥5 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.