Prenatal Exposure to Severe Stress and Risks of Ischemic Heart Disease and Stroke in Offspring.

Importance: Prenatal stress is associated with increased risks of several cardiovascular risk factors later in life. However, knowledge regarding the role of prenatal stress in the development of ischemic heart disease (IHD) and stroke is very limited. Objective: To examine prenatal stress, defined as maternal bereavement, and risks of IHD and stroke in the offspring. Design, Setting, and Participants: A cohort study was conducted using data from Danish and Swedish registries. Live singleton births during calendar years 1973-2016 in Denmark (followed up until December 31, 2016) and during calendar years 1973-2014 in Sweden (followed up until December 31, 2021) were included in the analysis. Exposure: Maternal loss of a close family member (partner, older children, parents, or siblings) the year before or during the pregnancy. Main Outcome and Measures: Diagnoses of IHD and stroke. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for IHD and stroke in the offspring according to maternal bereavement. Results: The study included 6 758 560 births (39.4% from Denmark; 51.4% boys). During the median follow-up of 24.6 (IQR, 13.9-35.1) years, 8664 offspring (0.1%) were diagnosed with IHD and 13 094 with stroke (0.2%). Overall, maternal bereavement the year before or during pregnancy was not associated with IHD (adjusted HR [AHR], 0.98; 95% CI, 0.85-1.13) or stroke (AHR, 1.04; 95% CI, 0.94-1.16) in offspring. Similarly, no associations were observed when exposure was classified by the mother's relationship to the deceased individual, ie, loss of older child or partner (HR, 0.85; 95% CI, 0.64-1.14 for IHD and 0.98; 95% CI, 0.77-1.25 for stroke) or loss of parent or sibling (HR, 1.03; 95% CI, 0.87-1.21 for IHD and 1.06; 95% CI, 0.94-1.19 for stroke). However, associations between loss in the third trimester and IHD (AHR, 1.50; 95% CI, 1.06-2.13), and loss due to cardiovascular disease and stroke (AHR, 1.22; 95% CI, 1.03-1.44) were identified when exposure was classified by time of loss or the relative's cause of death. Conclusions and Relevance: The findings of this study provide little support for the hypothesis that prenatal stress is associated with risks of IHD and stroke in the first 5 decades of life. However, the association observed between stress in the third trimester and IHD warrants further investigation.