A Study On The Causal Inference Between Early-life Exposure To Famine And Stroke Risk In Mid-to Late Life In China Based On The Marginal Structure Model

Objective:Limited research has examined the specific role that famine exposure at different life stages plays in adulthood stroke risk,and the existing studies are inconsistent,leaving the mechanism unclear.To explore the causal implications of early exposure to the Great Chinese Famine on stroke risk in mid-to late life and determine whether these associations were mediated by cognitive function,and depression.Methods:This study was based on the China Health and Retirement Longitudinal Study(CHARLS).According to the date of birth,the respondents divided them into fetally exposed,childhood-exposed.adolescence/adulthood-exposed and unexposed groups.T-test one-way ANOVA and chi-square test were used to analyze and compare the population characteristics at baseline.Based on a counterfactual framework,marginal structural models were used to estimate the natural direct effect of early-life exposure to Chinese famine and the natural indirect effects through cognitive function and depression for causal inference.The dose-response relationship was analyzed based on the joint categories of famine and severity of famine.Further,stratified analysis was conducted according to the famine severity,gender,type of residence,and education level.Finally,the robust results were obtained through sensitivity analysis.Results:This study sampled 12,681 individuals,the analysis results showed that famine exposure at different life stages can increase the risk of stroke in middle-aged and elderly people.Cognitive function and depressive symptoms partially mediated the relationship between exposure to famine in childhood and adolescence/adulthood and the risk of stroke in middle-aged and elderly adults,with 36.25%and 27.55%,respectively.Evidence suggested a dose-response relationship between stroke risk and famine severity.The risk of stroke was observed in the adolescent/adulthoodexposed group in areas with severe famine(OR=3.79,95%CI:1.69-8.53)than in areas with less severe famine(OR=3.65,95%CI:1.90-7.02).Conclusion:Early stages of life exposed to the Chinese Famine were associated with higher risk of stroke in mid-to late life.Therefore,to the extent that strengthening cognitive intervention and psychological support can reduce the risk of stroke in elderly people exposed to famine in early life.