Early-life exposure to tobacco smoke increase risk of frailty in adulthood: evidence from a large prospective cohort study

BACKGROUND: Early-life exposure to tobacco smoke has been associated with various adverse health outcomes and is considered as a critical public health concern now. However, its impact on frailty risk remains unclear. This study aimed to investigate the association between early-life exposure to tobacco smoke and frailty in adulthood, and to assess whether this association is independent of cumulative smoking exposure and mediated by systemic inflammation and telomere length. METHODS: Participants were recruited from the UK Biobank. Early-life exposure to tobacco smoke was assessed using two measurements: in utero tobacco smoke exposure (IUTSE) and age of smoking initiation (ASI). Frailty was evaluated by frailty index and physical frailty, respectively. Ordered logistic regression model and multiple linear regression model were used to analyze the association of IUTSE and ASI with frailty. RESULTS: Among participants included in the frailty index analysis, 96,934 (29.5%) had ITUSE and 18,498 (16.2%) with ASI in childhood (≤ 14 years). Compared with individuals without IUTSE, those with IUTSE had a significantly higher frailty index (β = 0.96, 95% CI 0.91-1.01) and increased risk of physical frailty (OR = 1.14, 95% CI 1.12-1.16). Compared to participants with ASI in adulthood (≥ 18 years), those in childhood had a significantly higher frailty index (β = 2.00, 95% CI 1.87-2.12) and increased risk of physical frailty (OR = 1.35, 95% CI 1.30-1.40). Similarly, participants with ASI in adolescence (15-17 years) had a moderately higher frailty index (β = 0.44, 95% CI 0.35-0.53) and slightly increased risk of physical frailty (OR = 1.05, 95% CI 1.02-1.08). The interaction effect between IUTSE and ASI on frailty index was marginally significant (P = 0.056). Pack-years of smoking partially mediated the association between early-life exposure to tobacco smoke and frailty index, with mediation proportion of only 9.13% for IUTSE, 29.03% for ASI in childhood, and 46.93% for ASI in adolescence. Inflammatory marker and telomere length were also identified as significant mediators. CONCLUSIONS: Early-life tobacco exposure could increase frailty risk and this association only partly explained by cumulative smoking exposure. Inflammatory marker and telomere length mediate this relationship. Our findings emphasize the importance of early-life preventive measures such as antenatal counseling and school-based interventions to reduce frailty risk in later life.