Severe Prenatal Grief May Increase Child’s Heart Failure Risk

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For mothers, experiencing the loss of a partner or child shortly before or during pregnancy could elevate the risk of heart failure (HF) in the child well into middle age, according to new study results.

Published in JACC Heart Failure, the study came to these findings based on follow-up of more than 6.7 million live single births from the 1973-2016 Danish and 1973-2014 Swedish Medical Birth Registers. The researchers theorized that maternal stress experienced shortly before or during pregnancy could create an unfavorable environment within the womb, potentially leading to negative outcomes during pregnancy and impacting the cardiovascular health of the offspring later in life. The death of a close relative—seen as a significant stressor—was examined in this study as a form of prenatal stress. By focusing on maternal bereavement, the study aimed to explore the influence of severe prenatal stress on the risk of developing HF in offspring by middle age.

Of the study cohort, a total of 167,192 participants experienced prenatal stress as a result of maternal bereavement in the year preceding or during pregnancy. Mothers within the exposed group tended to be older, married, and smokers and possess a family history of cardiovascular disease compared with those in the unexposed group. During the follow-up period of up to 48 years, 4812 offspring (0.07%) received an HF diagnosis.

The study found that maternal loss of any close family member did not show a clear association with HF in the offspring (adjusted HR [aHR], 1.04; 95% CI, 0.88-1.23). However, the most severe forms of bereavement, such as the death of a partner or an older child (aHR, 1.47; 95% CI, 1.06-2.04) and the unnatural death of a relative (aHR, 2.77; 95% CI, 1.49-5.17), were both linked to increased risks of HF in the child. The study also noted that congenital heart disease and preterm birth significantly contributed to the association between maternal loss of a partner or older child and HF risk in the offspring.

“According to several classification systems of severity of sources of stress, death in the nuclear family, i.e., of a partner or of a child, is likely to be perceived as more stressful and to require a greater life adjustment than deaths in the extended family,” the study authors said. “Similarly, sudden, unnatural deaths are considered to be more stressful than natural deaths. The fact that an association between maternal bereavement and HF in offspring was confined to the most severe forms of stress, i.e., loss of a partner or older child or unexpected loss, is suggestive of a dose-response effect.”

The reasons for the slightly stronger association between the loss of a partner or older child and the risk of HF during childhood compared to young adulthood are not fully understood, but the authors offered 2 plausible explanations to consider. First, pediatric HF is mainly attributed to congenital heart disease (CHD), with an increased risk reported after maternal bereavement. This suggests that CHD plays a significant role, especially in childhood HF cases. Additionally, children born subsequent to the loss of an older sibling may have received heightened attention from the health care system, potentially leading to earlier detection of HF during childhood.

The study's limitations include potential oversight of milder cases of HF from primary care settings, despite high positive predictive values in patient registers. Residual confounding may exist due to unmeasured genetic, familial, lifestyle, and health-related factors, and there was a lack of data on maternal participation in psychotherapy or interventions for bereaved individuals. According to the study authors, future research should look into whether there is a link between more frequent but less severe sources of prenatal stress and the development of early-onset HF.

Reference

Yang F, Janszky I, Roos N, Li J, László KD. Prenatal exposure to severe stress and the risk of heart failure up to middle-age. JACC Heart Fail. Published online February 21, 2024. doi:10.1016/j.jchf.2024.01.009