Background Increasing evidence suggests that the death of a child is associated with increased risks of ischemic heart diseases and atrial fibrillation and the association is in part attributable to stress-related mechanisms. However, knowledge regarding the risk of heart failure (HF) after the death of a child is very limited. Purpose To study the association between the death of a child and the parents' risk of HF. Methods We conducted a population-based cohort study involving parents of live-born children recorded in the Danish and Swedish Medical Birth Registers during 1973–2016 and 1973–2014, respectively (n=6,717,531). We retrieved information on child death, HF diagnosis and parents' sociodemographic characteristics from several nationwide registries. We performed Poisson regression models to estimate incidence rate ratio (IRR) and 95% confidence intervals (CI) for HF. Results A total of 129,829 (1.9%) parents lost at least one child during the follow-up. Bereaved parents had a 35% higher risk of HF than non-bereaved parents [IRR (95% CI): 1.35 (1.29–1.41)]. The association was present not only if the child died due to cardiovascular or other natural causes [IRR (95% CI): 1.48 (1.25–1.75) and 1.35 (1.27–1.44), respectively], but also in case of unnatural deaths [IRR (95% CI): 1.32 (1.24–1.42)]. There was a trend toward a U-shaped association according to the deceased child's age at loss and the risk of HF. Bereaved parents who lost their only child or had three or more remaining live children at the time of loss had higher HF risk than those with one or two live children at the time of loss. We found no clear evidence for a difference in the association of interest over time. Conclusions The death of a child was associated with an increased risk of HF. The finding that not only cardiovascular and other natural deaths, but also unnatural deaths were associated with HF suggests that stress-related mechanisms may contribute to the development of HF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swedish Council for Working Life and Social Research and Karolinska Institutet's Research Foundation

Background A substantial body of evidence suggests that children exposed to maternal hypertensive disorders during pregnancy (HDP) have increased risks of preterm birth, fetal growth restriction and several cardiovascular risk factors (e.g., hypertension, obesity, diabetes) later in life. However, the direct evidence on the link between maternal HDP and the risk of severe cardiovascular diseases such as ischemic heart disease (IHD) and stroke in the offspring is very limited. Objective To investigate the associations between maternal HDP and the risk of IHD and stroke in the offspring. Methods We conducted a population-based cohort study by linking several national registers in Sweden and Finland. Live singleton births from the Swedish Medical Birth Register (1973–2014) and the Finnish Medical Birth Register (1987- 2014) were followed for IHD and stroke until 2014 by the national patient and cause of death registers. We performed Cox regression models to examine the association between maternal HDP and its subtypes, i.e., pre-existing chronic hypertension, gestational hypertension, and preeclampsia, and the risk of IHD, and stroke in the offspring while adjusting for relevant maternal and pregnancy-related confounders. We conducted sibling analyses to control for unmeasured shared familial (genetic and/or environmental) risk factors. Results Among the 5,807,122 singletons included in the study, 218,322 (3.76%) children were born to mothers with HDP. During the up to 41 years of follow-up, 2,340 (0.04%) offspring were diagnosed with IHD and 5,360 (0.09%) were diagnosed with stroke. Offspring exposed to maternal HDP had an increased risk of IHD (adjusted hazard ratio (aHR), 1.29; 95% confidence interval (CI), 1.01–1.63), and stroke (aHR,1.33; 95% CI, 1.14–1.56). Significantly increased rates of stroke were also observed in children exposed to the subtypes of maternal HDP: pre-existing chronic hypertension (aHR, 1.64; 95% CI, 1.03–2.60), gestational hypertension (HR, 1.38; 95% CI, 1.08–1.77), and preeclampsia (HR, 1.26; 95% CI, 1.02–1.55). The associations between maternal HDP and offspring's IHD and stroke were independent of preterm birth and small for gestational age at birth. Maternal HDP remained associated with stroke in the offspring (aHR, 1.94; 95% CI, 1.16–3.22), but not with IHD (aHR, 0.89; 95% CI, 0.47–1.67) in the sibling analyses. Conclusion Children to mothers with HDP have increased rates of IHD and stroke from childhood to young adulthood. While the link between maternal HDP and IHD in the offspring seemed to be attributed to confounding by familial factors, the relation between maternal HDP and stroke persisted even when considering such confounding. Persons born to mothers with HDP may benefit from early screening and prevention efforts to reduce the risk of IHD and stroke later in life. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swedish Heart and Lung Foundation