The association of maternal smoking around birth with chronic respiratory diseases in adult offspring: A Mendelian randomization study.

ABSTRACT

INTRODUCTION: Maternal smoking during pregnancy disturbs fetal lung development, and induces in their offspring childhood respiratory diseases. Whether it has a continued impact on offspring adult lung health and exerts a casual effect of chronic respiratory diseases (CRDs), remains uncertain. We seek to determine the causal relationships between maternal smoking around birth and offspring adult CRDs, using summary data from previously described cohorts. METHODS: Mendelian randomization (MR) study was used to analyze the genome-wide associations of maternal smoking around birth and offspring adult CRDs, including respiratory insufficiency, chronic obstructive pulmonary disease (COPD), related respiratory insufficiency, emphysema, COPD, COPD hospital admissions, early onset of COPD, later onset of COPD, asthma, idiopathic pulmonary fibrosis (IPF), lung cancer (LC), small cell lung carcinoma (SCLC), and lung squamous cell carcinoma (LUSC). RESULTS: After removing single-nucleotide polymorphisms (SNPs) associated with smoking by the offspring, maternal smoking around birth was associated with increased risk of offspring adult respiratory diseases (OR=1.14; 95% CI 1.013-1.284; p=0.030), respiratory insufficiency (OR=2.413; 95% CI 1.039-5.603; p=0.040), COPD (OR=1.14; 95% CI 1.013-1.284; p=0.003), and asthma (OR=1.336; 95% CI 1.161-1.538; p<0.001). Besides, maternal smoking during pregnancy was associated with a greater risk of LUSC (OR=1.229; 95% CI 0.992-1.523; p=0.059) than the risk of IPF (OR=1.001; 95% CI 0.999-1.003; p=0.224), LC (OR=1.203; 95% CI 0.964-1.501; p=0.103), or SCLC (OR=1.11; 95% CI 0.77-1.601; p=0.577). CONCLUSIONS: In this MR analysis, maternal smoking around birth caused a strong risk factor for the offspring to develop lung problems and CRDs in adulthood. The policy related to smoking cessation for mothers during pregnancy should be encouraged.