Perinatal exposure to maternal smoking and adulthood smoking behaviors in predicting cardiovascular diseases: A prospective cohort study

Abstract

Background and aims: Little is known about the associations between perinatal exposure to maternal smoking and cardiovascular disease (CVD) incidence in offspring, and whether such associations are modified by adulthood and genetically determined smoking behaviors.

Methods: A total of 414,588 participants without CVD at baseline were included from the UK Biobank in 2006-2010 and followed up through 2018. Cox-proportional hazard models were used to examine the association of perinatal maternal smoking with CVD, and both multiplicative and additive interaction analyses were performed to investigate the modification effects of own smoking behaviors.

Results: During a median follow-up of 8.93 years, we observed 10,860 incident CVD events, including 7006 myocardial infarction (MI) and 4147 stroke. We found that perinatal exposure to maternal smoking was associated with increased risks of CVD (HR: 1.10; 95% CI: 1.05-1.14), MI (1.10; 1.05-1.16) and stroke (1.10; 1.03-1.18). In addition, we observed significant interactions between perinatal exposure to maternal smoking and adulthood exposure to own smoking on CVD and MI on both the multiplicative and additive scales (all p < 0.05). The attributable proportions due to additive interaction between perinatal and adulthood exposure to smoking were 14% (9%-19%) for CVD and 16% (10%-22%) for MI, respectively. Perinatal exposure to maternal smoking also showed an interaction with genetically determined smoking on MI (p < 0.05), but no interactions were found on the total CVD and stroke.

Conclusions: Our results indicate that perinatal exposure to maternal smoking is associated with increased risks of CVD events, and such relations are modified by adulthood smoking behaviors.

Keywords: Adulthood smoking; Cardiovascular diseases; Interaction; Maternal smoking.

Figure 1.

Association between perinatal exposure to maternal smoking and risks of cardiovascular diseases stratified by adulthood smoking behaviors. Multivariate adjusted hazard ratio and 95% CI of cardiovascular diseases were estimated from Cox proportional hazards models; adjusted for sex, age, race, assessment center, Townsend deprivation index, average total annual household income, cancer, diabetes, hypertension, angina, high cholesterol, antihypertensive drugs, and lipid treatment, aspirin use, birth weight, part of a multiple birth, body mass index, alcohol drinking status, sedentary time, physical activity, healthy diet score. CVD, cardiovascular disease; MI, myocardial infarction. ^a Composite of MI and stroke.

Figure 2.

Hazard ratios of risks of cardiovascular diseases according to joint classification of perinatal maternal smoking and PRS-SMK (in tertiles). Multivariate adjusted hazard ratio of cardiovascular diseases were estimated from Cox proportional hazards models; adjusted for sex, age, ethnicity (British, Irish, any other white background), assessment center, batch effects (106 batches), the first 10 genetic principal components, Townsend deprivation index, average total annual household income, cancer, diabetes, hypertension, angina, high cholesterol, antihypertensive drugs, and lipid treatment, aspirin use, birth weight, part of a multiple birth, body mass index, smoking status, alcohol drinking status, sedentary time, physical activity, healthy diet score. CVD, cardiovascular disease; HR, hazard ratio; MI, myocardial infarction; PRS-SMK, polygenic risk scores of smoking. ^a Composite of MI and stroke.