Maternal smoking around birth as a risk factor for offspring chronic obstructive pulmonary disease: Evidence from Mendelian randomization.

Introduction: Previous observational studies suggested that exposure of the fetus to maternal smoking during pregnancy may increase the likelihood of chronic obstructive pulmonary disease (COPD). Hence, following the STROBE-MR guidelines, we carried out a two-sample MR analysis to explore the association between maternal smoking around birth and offspring COPD.

Methods: We used independent single nucleotide polymorphisms (SNPs) related to maternal smoking around birth, obtained from genome-wide association study summary data, as instrumental variables (IVs). The dataset included 121634 controls and 276098 cases. The selected outcome was chronic obstructive pulmonary disease (COPD) in offspring, with 454945 controls and 13530 cases. We performed analyses using inverse variance weighting (IVW), weighted median, and MR-Egger regression methods. Multivariate MR included maternal illnesses (high blood pressure and heart disease) as covariates to address potential mediators. Sensitivity analysis was conducted using leave-one-out analysis, Cochran's Q test, and MR-Egger intercept test.

Results: In the univariate MR analysis, it was found that maternal smoking around birth significantly increased the likelihood of offspring COPD (IVW, OR=35.13; 95% CI: 10.18-121.20; p<0.001). Furthermore, after adjusting the variates for maternal illnesses, the relationship between maternal smoking around birth and offspring COPD remained statistically significant (adjusted odds ratio, AOR= 62.11; 95% CI: 16.60-232.46; p<0.001).

Conclusions: The study provides MR evidence of a potential association between maternal smoking around birth and increased COPD risk in offspring.