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|a The notion that a reduced exposure to microbial pathogens in early life increases the chances of the expression of atopic disease has come to be known as the hygiene hypothesis1. It has arisen from observations of the rapidly rising prevalence of atopic diseases in recent decades, the lower prevalence of atopy in lower socio-economic groups and the lower prevalence of atopy with rising birth order. Direct evidence for the hypothesis to date has been inconsistent. This case-control study involving 602 children aged one to four years in Norfolk, UK was designed to test the hypothesis with respect to atopic dermatitis (AD). Cases and matched controls were selected randomly from primary care databases and carefully defined using the UK Diagnostic Criteria for AD. Exposure to infection during infancy was measured with a range of direct and indirect methods including assays of salivary antibodies to Epstein Barr virus and Varicella Zostervirus, data extracted from primary care records and a questionnaire administered to parents. Odds ratios (OR) for the effect of these measures on AD were calculated using logistic regression with adjustment for possible biological and social confounding factors. Reduced odds of AD were associated with rising birth order (OR for one older sibling 0Æ59, 95% CI 0Æ42 to 0Æ84 and for two or more older siblings 0Æ49, 95% CI 0Æ31 to 0Æ77). None of the measures of exposure to infection reduced the odds of AD, either in the unadjusted or adjusted analyses. Some measures showed a weak association between exposure and greater odds of AD, in the opposite direction to that predicted by the hygiene hypothesis. These data confirm a significantly reduced risk of AD in second and subsequent siblings but this sibling effect of reduced odds with rising birth order does not appear to be explained by exposure to infection in early life. More generally, these data cast doubt on the hygiene hypothesis as a causal explanation for AD in young children.
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