Is sibship composition a risk factor for childhood asthma? Systematic review and meta-analysis

Background Following the "hygiene hypothesis", the role of sibship composition in asthma and wheezing has been extensively studied, but the findings are inconsistent. For the first time, this systematic review and meta-analysis synthesized evidences from studies investigating the association of sibship size and birth order with risk of asthma and wheezing.Methods Fifteen databases were searched to identify eligible studies. Study selection and data extraction were performed independently by pairs of reviewers. Meta-analysis with robust variance estimation (RVE) was used to produce pooled risk ratio (RR) effect estimates from comparable numerical data.Results From 17,466 identified records, 158 reports of 134 studies (> 3 million subjects) were included. Any wheezing in the last = 1.5 years occurred more frequently in infants with = 1 sibling [pooled RR 1.10, 95% confidence interval (CI) 1.02-1.19] and = 1 older sibling (pooled RR 1.16, 95% CI 1.04-1.29). The pooled effect sizes for asthma were overall statistically nonsignificant, although having = 1 older sibling was marginally protective for subjects aged = 6 years (pooled RR 0.93, 95% CI 0.88-0.99). The effect estimates weakened in studies published after 2000 compared with earlier studies.Conclusions Being second-born or later and having at least one sibling is associated with a slightly increased risk of temporary wheezing in infancy. In contrast, being second-born or later is associated with marginal protection against asthma. These associations appear to have weakened since the turn of the millennium, possibly due to lifestyle changes and socioeconomic development.