| Summary: | <p><strong>Objective</strong> To comprehensively examine the potential impacts of prenatal experience of the Chinese Great Famine on chronic disease risks in the middle age.</p>
<p><strong>Methods</strong> This study included 92 284 participants aged 39–51 years from China Kadoorie Biobank born around the famine period and without major chronic diseases at baseline. We categorised participants into non-famine births (born between 1 October 1956 and 30 September 1958, and 1 October 1962 and 30 September 1964) and famine births (born between 1 October 1959 and 30 September 1961). The outcomes were incident cardiovascular disease, cancer and respiratory system disease. Cox regression was used to estimate adjusted HR and 95% CI for famine exposure. Subgroup analyses were performed according to baseline characteristics.</p>
<p><strong>Results</strong> During a median 10.1 years of follow-up, we identified 4626 incident ischaemic heart disease (IHD) cases, 7332 cerebrovascular disease cases, 3111 cancer cases and 16 081 respiratory system disease cases. In the whole population, prenatal famine exposure was not statistically associated with the risks of developing any chronic diseases in adulthood. However, for urban participants, compared with non-famine births, famine births had a higher risk of cerebrovascular disease (HR 1.18; 95% CI 1.09 to 1.28); such association was not shown for rural participants (p for interaction <0.001). Also, we observed the associations of prenatal famine exposure with IHD (HR 1.15; 95% CI 1.05 to 1.26) and cerebrovascular disease (HR 1.13; 95% CI 1.05 to 1.21) in participants with lower physical activity level, but not in those with higher ones (all p for interaction=0.003).</p>
<p><strong>Conclusion</strong> Our findings indicate that prenatal exposure to the Chinese famine might be associated with an increased cardiovascular risk and such risk may be modified by adult lifestyle.</p>
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