Prenatal Exposure to Severe Stress and the Risk of Heart Failure Up to Middle-Age.

Background: Prenatal stress is a potential risk factor for cardiovascular disease, but its association with heart failure (HF) is unknown.

Objectives: The purpose of this study was to investigate whether prenatal stress, defined as maternal bereavement, was associated with HF risk up to middle-age.

Methods: This cohort study included 6,758,560 live singleton births from the Danish (1973-2016) and the Swedish (1973-2014) Medical Birth Registers. The authors retrieved information on death of the mothers' close family members (partner, older children, parents, and siblings) and offspring's HF (up to 2016 in Denmark and 2020 in Sweden) from nationwide registers. They estimated HRs and 95% CIs for HF in the offspring according to maternal bereavement.

Results: During up to 48 years of follow-up, 4,812 offspring (0.07%) had a diagnosis of HF. Maternal loss of any close family member was not associated with HF in the offspring (adjusted HR: 1.04; 95% CI: 0.88-1.23). However, the most severe forms of bereavement, ie, death of a partner or an older child (adjusted HR: 1.47; 95% CI: 1.06-2.04) and unnatural death of a relative (adjusted HR: 2.77; 95% CI: 1.49-5.17), were associated with increased risks of HF. Congenital heart disease and preterm birth contributed substantially to the association of maternal loss of a partner or older child with HF risk in the offspring.

Conclusions: Maternal loss of a partner or older child and loss of a close relative caused by unnatural causes the year before or during pregnancy were associated with increased risk of HF in offspring.