Abstract
OBJECTIVE: The influence of maternal smoking around birth (MSAB) on offspring allergic diseases, specifically childhood asthma (CA), allergic rhinitis (AR), allergic conjunctivitis (AC), and atopic dermatitis (AD) remains incompletely understood. We performed a rigorous mendelian randomization (MR) study to obtain the unconfounded association between MSAB and allergic diseases in offspring with and without adjustment for the effect of breastfeeding. METHODS: Utilizing publicly available information of MSAB, breastfeeding, CA, AR, AC, and AD from large-scale genome-wide association studies (GWAS), we performed a two-sample mendelian randomization (TSMR) analysis to assess the respective causal relationship of MSAB and breastfeeding to allergic diseases in offspring. To get a reliable conclusion, MR Egger regression, weighted median, and inverse variance weighted (IVW) were employed to estimate the causality, with IVW as the primary analysis. Multivariate MR (MVMR) analysis was used to assess the effect of MSAB on allergic diseases after adjusting for breastfeeding's impact. Sensitivity analysis was conducted using the Cochran Q test, MR-Egger, and leave-one-out approaches to ensure the reliability and stability of results. RESULTS: The TSMR analysis demonstrated MSAB increased the risks of CA (P(IVW) = 0.013, OR: 1.018, 95%CI: 1.004 to 1.033) and AD (P(IVW) = 0.006, OR: 8.293, 95%CI: 1.815 to 37.884) in offspring. Conversely, breastfeeding decreased the risk of CA (P(IVW) <0.001, OR: 0.946, 95%CI: 0.918 to 0.974). MSAB still increased the risks of CA (P = 0.0497, OR: 1.013, 95%CI: 1.000017 to 1.026) and AD (P = 0.003, OR: 13.800, 95%CI: 2.490 to 269.246) after adjusting for breastfeeding. We observed no strong indication of a negative causality between MSAB and AC and AR. CONCLUSION: Our findings provided robust evidence of the adverse effects of MSAB on offspring. We emphasized the urgency of smoking cessation around birth and the importance of breastfeeding even in smoking mothers.