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Background: The ''hygiene hypothesis'' postulates that infections during infancy may protect against asthma and atopy. There is also some evidence that antibiotic and/or paracetamol use may increase the risk of asthma. Methods: The study measured the association between infections, and medication use early in life and the risk of asthma at age 6-7 years. It involved 1584 children who had been notified to public health services with serious infections at age 0-4 years, and 2539 children sampled from the general population. For both groups, postal questionnaires were completed by parents. Results: There was little difference in the prevalence of current wheezing between the childhood infections group (prevalence = 23.5%) and the general population group (prevalence = 24.3%). There was also little difference whether the major site of infection was gastrointestinal (prevalence = 24.1%), invasive (prevalence = 24.6%) or respiratory (prevalence = 21.1%). However, in both groups, there were associations with antibiotic (OR = 1.78, 95% CI 1.49 to 2.14) or paracetamol (OR = 1.38, 95% CI 1.04 to 1.83) use in the first year of life or recent paracetamol use (OR = 2.10, 95% CI 1.78 to 2.49) and current wheezing. There was a weak protective effect of childhood infections in children who had not used antibiotics in the first year of life (OR = 0.78, 95% CI 0.55 to 1.10). Conclusions: These findings are consistent with other evidence that antibiotic use early in life may increase the risk of asthma. They are also consistent with some preliminary evidence associating paracetamol use with an increased risk of asthma. Any protective effect of notifiable childhood infections was weak.

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BackgroundAssociations of larger families with lower prevalences of hay fever, eczema and objective markers of allergic sensitization have been found fairly consistently in affluent countries, but little is known about these relationships in less affluent countries.MethodsQuestionnaire data for 210 200 children aged 6–7 years from 31 countries, and 337 226 children aged 13–14 years from 52 countries, were collected by Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC). Associations of disease symptoms and labels of asthma, rhinoconjunctivitis and eczema were analysed by numbers of total, older and younger siblings, using mixed (multi-level) logistic regression models to adjust for individual covariates and at the centre level for region, language and national affluence.ResultsIn both age groups, inverse trends (P < 0.0001) were observed for reported ‘hay fever ever’ and ‘eczema ever’ with increasing numbers of total siblings, and more specifically older siblings. These inverse associations were significantly (P < 0.005) stronger in more affluent countries. In contrast, symptoms of severe asthma and severe eczema were positively associated (P < 0.0001) with total sibship size in both age groups. These associations with disease severity were largely independent of position within the sibship and national GNI per capita.ConclusionsThese global findings on sibship size and childhood asthma, rhinoconjunctivitis and eczema suggest at least two distinct trends. Inverse associations with older siblings (observations which prompted the ‘hygiene hypothesis’ for allergic disease) are mainly a phenomenon of more affluent countries, whereas greater severity of symptoms in larger families is globally more widespread.