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http://jama.ama-assn.org/cgi/content/full/293/4/463
JAMA, 2005;293:463-469.

Vol. 293 No. 4, January 26, 2005
Exposure to Infant Siblings During Early Life and Risk of Multiple Sclerosis

Anne-Louise Ponsonby, PhD; Ingrid van der Mei, PhD; Terence Dwyer, MD; Leigh
Blizzard, PhD; Bruce Taylor, MD; Andrew Kemp, PhD; Rex Simmons, PhD; Trevor
Kilpatrick, PhD

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 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.






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