Birth order, sibship size and wheezing phenotypes: a systematic review and meta-analysis

Abstract

Background: Wheezing phenotypes, particularly characterized by temporal patterns of symptoms, have been extensively studied to identify patients with increased risk of developing asthma, but factors associated with specific phenotypes are yet to be fully elucidated. Here, we present findings from a larger systematic review, focusing on the relationship of birth order and sibship size with phenotypes of wheezing.

Method: We systematically searched 15 electronic databases with no restrictions on language or publication date. Screening, data extraction, and risk of bias assessment were performed independently by two reviewers. Comparable numerical data were synthesized using random-effects meta-analysis.

Results: Out of 17,466 de-duplicated studies, 69 were included. The meta-analysis indicated that having one or more siblings (OR 1.48, 95% CI 1.25-1.71) and being second or later child (OR 1.49, 95% CI 1.32-1.66) was associated with increased risk of any wheezing in infancy. Sibship size ≥2 was associated with an increased risk of recurrent wheezing (OR 1.60, 95% CI 1.11-2.09), but three of five studies investigating this association were on infants. No significant association was seen for any other examined phenotype (atopic, non-atopic, late-onset, or episodic (viral) wheezing).

Conclusion: Having siblings and being second or later child is associated with increased risk of wheezing in infancy. As no significant association was found with other phenotypes, it is probable that the observed role of siblings in wheezing stems from early cross-infections from older siblings.