The impact of in utero tobacco exposure on smoking behaviors, cardiovascular disease risk and all-cause mortality in adulthood: A UK Biobank study

Abstract

The knowledge regarding the negative impacts of in utero tobacco exposure (IUTE) on cardiovascular disease (CVD) was incomplete. This study aims to assess the association between IUTE and the risks of CVD incidence and all-cause mortality, discuss the inter-group difference based on genetic susceptibility and smoking behaviors after birth, and explore the potential mediating factors. Utilizing a total of 375,024 participants from the UK Biobank, the outcomes include myocardial infarction, stroke, chronic ischemic heart disease, nonrheumatic aortic valve disorders, cardiomyopathy, heart failure, atherosclerosis, aortic aneurysm and dissection, and all-cause mortality. During a median follow-up period of 14.6 years, 50,434 cases of CVD were recorded. IUTE was significantly associated with increased CVD incidence (HR 1.10, 95 % CI 1.08-1.12) and all-cause mortality (HR 1.11, 95 % CI 1.09-1.14). Interaction effects between IUTE, smoking behaviors after birth, and genetic risk scores for CVD were observed significant (P for interaction < 0.005). The results of the cross-sectional study revealed a significant positive association between IUTE and smoking behaviors after birth (OR 1.08, 95 % CI 1.06-1.09). Mediation analysis indicated that smoking behaviors (Proportion = 12.40 %, P < 0.001) and HDL-c levels (Proportion = 14.20 %, P < 0.001) partially mediated the IUTE-CVD relationship. This study demonstrated that individuals with IUTE have a higher risk of developing CVD, and smoking behaviors after birth have multifaceted influence on this correlation. These findings underscore the importance of mothers avoiding smoking during pregnancy to mitigate adverse effects on their offspring.

Keywords: All-cause mortality; Cardiovascular disease; Genetic susceptibility; In utero tobacco exposure; Smoking behaviors.

Graphical abstract

Fig. 1

Flowchart of participants enrollment.

Fig. 2

Overall incidence of CVD in groups with and without IUTE. The solid lines represent the estimated survival curves for different groups. The shaded area around these curves represents the 95% confidence intervals.

Fig. 3

Overall incidence of all-cause mortality in groups with and without IUTE. The solid lines represent the estimated survival curves for different groups. The shaded area around these curves represents the 95% confidence intervals.

Fig. 4

Mediation effects of smoking behaviors and HDL-c on IUTE to CVD. (A) The mediation role of HDL-c on IUTE to CVD; (B) The mediation role of smoking behaviors on IUTE to CVD.

Fig. 5

Mediation effects of smoking behaviors on IUTE to six clinically prevalent CVDs. (A) The mediation role of smoking behaviors on IUTE to myocardial infarction; (B) The mediation role of smoking behaviors on IUTE to stroke; (C) The mediation role of smoking behaviors on IUTE to atherosclerosis; (D) The mediation role of smoking behaviors on IUTE to chronic ischaemic heart disease; (E) The mediation role of smoking behaviors on IUTE to heart failure; (F) The mediation role of smoking behaviors on IUTE to aortic aneurysm and dissection.

Fig. 6

Mediation effects of HDL-c on IUTE to six clinically prevalent CVDs. (A) The mediation role of HDL-c on IUTE to myocardial infarction; (B) The mediation role of HDL-c on IUTE to stroke; (C) The mediation role of HDL-c on IUTE to atherosclerosis; (D) The mediation role of HDL-c on IUTE to chronic ischaemic heart disease; (E) The mediation role of HDL-c on IUTE to heart failure; (F) The mediation role of HDL-c on IUTE to aortic aneurysm and dissection.