Birth weight of offspring and subsequent cardiovascular mortality of the parents

Background: Restricted fetal growth has been associated with increased blood pressure, insulin resistance, and cardiovascular disease in later life. These associations may be due to processes during fetal development with long-term consequences for metabolic and cardiovascular function (the fetal origins hypothesis). However, it has also been hypothesized that common genetic factors could underlie both restricted fetal development and disease risk (the fetal insulin hypothesis). Methods: We have investigated associations between offspring size at birth and parental mortality in a record linkage study including all 783,814 children born in Sweden between 1973 and 1980. The deaths of 10,368 mothers and 22,807 fathers had been recorded by date and causes of death. Data were analyzed using Cox proportional hazards regression models, with parents' age as the time axis. Results: Offspring birth weight (adjusted for gestational age) was inversely associated with all-cause mortality and cardiovascular mortality in the parents, with weaker associations for fathers than for mothers. The inverse association between birth weight and cardiovascular disease mortality was greatest for parents who died at younger ages. Cancer and alcohol-related causes of death were also related to offspring birth weight. A sensitivity analysis suggests that confounding by smoking is unlikely to entirely explain the associations. Conclusion: Associations between offspring birth characteristics and parents' mortality could, at least in part, reflect genetic factors that influence both birth weight and cardiovascular disease risk.