Caesarean delivery, childhood asthma, and effect modification by sex: An observational study and meta-analysis

Background: Numerous studies indicate caesarean delivery is associated with childhood asthma. Sex-specific associations were reported in four of these studies, and in all four studies, the estimated association between caesarean delivery and asthma was of greater magnitude among girls, although most report a lack of evidence of multiplicative interaction. Methods: We assessed potential effect modification by sex, on the additive and multiplicative scales, of the association between caesarean delivery and asthma by ages 2 through 6 in up to 17 075 racially diverse children from a retrospective birth cohort, the Kaiser Air Pollution and Pediatric Asthma (KAPPA) Study. We also conducted a random-effects meta-analysis, combining our sex-stratified results (using the odds ratio for compatibility with previous studies) with previously published results. Results: Adjusted risk differences for caesarean delivery and asthma in the KAPPA cohort were higher among girls than boys at every follow-up age. By age 5, caesarean delivery was associated with an absolute 3.8% (95% confidence interval [CI] 0.4%, 7.3%) higher asthma risk among girls and a 1.9% (95% CI −1.7, 5.4) higher risk among boys. The summary odds ratio from the meta-analysis for caesarean delivery and asthma among girls was 1.26 (95% CI 1.14, 1.39) and 1.08 (95% CI 0.98, 1.20) among boys (P = 0.036). Conclusions: Higher, but imprecise, estimates for females across five studies should motivate investigators to estimate sex-specific associations for caesarean delivery and asthma and to explore biological mechanisms or sex-dependent biases that could explain this possible heterogeneity.