Prenatal exposure to maternal stress following bereavement and cardiovascular disease: A nationwide population-based and sibling-matched cohort study

Aims Cardiovascular disease (CVD) is among the leading determinants of mortality and morbidity, and causation may begin in the early intrauterine environment. Prenatal exposures to glucocorticoids or stress are potential risk factors of CVD later in life, but empirical evidence from large population studies is lacking. We explored the association between prenatal stress due to maternal bereavement following the death of a relative and CVD in the exposed offspring. Methods and results This population-based study included 2,607,851 children born in Denmark (1970-2008). Of these participants, 73,708 (2.8%) had a CVD event during follow-up (up to 40 years). A total of 50,940 (2.0%) subjects born to mothers who lost a relative during pregnancy or the year before were categorized as exposed. Cox Proportional Hazards models were used to analyse the data. The overall hazard ratio (HR) (95% confidence interval) of having a CVD was 1.13 (1.06-1.20); the estimate was 1.24 (1.11-1.38) for heart disease and 1.27 (1.01-1.60) for hypertension. Additional sibling-matched analyses showed an overall attenuated association (1.08 (0.94-1.24)). Conclusion Our results suggested a modest association between prenatal stress and CVD, both in childhood and early adulthood, which could be of importance, especially at an older age when the individuals are followed over a long period.