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

Abstract

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. Video Abstract.

Keywords: Asthma; Hygiene hypothesis; Respiratory sounds; Siblings; Systematic review.

Fig. 1

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram. http://www.prisma-statement.org/

Fig. 2

Domain ratings and overall rating of the included studies. Red: “weak”, yellow: “moderate”, green: “strong” rating

Fig. 3

Map of the countries of participants in the included studies. The two letter code indicates the country name and the number indicates how many reports there are from said country. AR Argentina, AT Austria, AU Australia, BB Barbados, BD Bangladesh, BE Belgium, BO Bolivia (Plurinational State of), BR Brazil, BY Belarus, CA Canada, CH Switzerland, CI Côte d'Ivoire, CL Chile, CM Cameroon, CN China, CO Colombia, CU Cuba, DE Germany, DK Denmark, DO Dominican Republic, EC Ecuador, EE Estonia, ES Spain, ET Ethiopia, FI Finland, FJ Fiji, FR France, GA Gabon, GB United Kingdom of Great Britain and Northern Ireland, GH Ghana, GR Greece, HK Hong Kong, HU Hungary, ID Indonesia, IE Ireland, IL Israel, IM Isle of Man, IN India, IR Iran (Islamic Republic of), IS Iceland, IT Italy, JM Jamaica, JP Japan, KG Kyrgyzstan, KR Korea, Republic of, KW Kuwait, LT Lithuania, MA Morocco, MG Madagascar, MK North Macedonia, MT Malta, MX Mexico, MY Malaysia, NC New Caledonia, NG Nigeria, NL Netherlands, NO Norway, NZ New Zealand, OM Oman, PA Panama, PE Peru, PF French Polynesia, PH Philippines, PL Poland, PT Portugal, SA Saudi Arabia, SD Sudan, SE Sweden, SG Singapore, SY Syrian Arab Republic, TH Thailand, TK Tokelau, TR Turkey, TW Taiwan, Province of China, US United States of America, UY Uruguay, VE Venezuela (Bolivarian Republic of), WS Samoa, ZA South Africa

Fig. 4

Number of reports published by year among included reports (a) and overall rating of the included reports by year (b)

Fig. 5

Forest plot for birth order ≥ 2 vs. 1 (a) and sibship size ≥ 2 vs 1 (b) in relation to any wheezing (≥ 1 episode in last ≤ 1.5 years). df Satterwhite degrees of freedom, K number of studies, N number of subjects (if not available, the number of subjects for the most similar exposure-outcome pair or for the whole study is stated), No. number, RR risk ratio

Fig. 6

Forest plot for birth order ≥ 2 vs. 1 (a) and sibship size ≥ 2 vs. 1 (b) in relation to current asthma (in last year). df Satterwhite degrees of freedom, K number of studies, N number of subjects (if not available, the number of subjects for the most similar exposure-outcome pair or for the whole study is stated), No. number, RR risk ratio

Fig. 7

Forest plot for birth order ≥ 2 vs. 1 (a) and sibship size ≥ 2 vs. 1 (b) in relation to ever asthma. df Satterwhite degrees of freedom, K number of studies, N number of subjects (if not available, the number of subjects for the most similar exposure-outcome pair or for the whole study is stated), No. number, RR risk ratio