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Introduction Human epidemiologic studies have shown a clear association of adverse prenatal and early postnatal development and increased risk of ischemic heart disease in adults (Barker et al. 1989). The [...], Epidemiological studies have demonstrated a relationship between the adverse influence of perinatal development and increased risk of ischemic heart disease in adults. From negative factors to which the fetus is subjected, the most important is hypoxia. The fetus may experience hypoxic stress under different conditions, including pregnancy at high altitude, pregnancy with anemia, placental insufficiency, and heart, lung, and kidney disease. One of the most common insults during the early stages of postnatal development is hypoxemia due to congenital cyanotic heart defects. Experimental studies have demonstrated a link between early hypoxia and increased risk of ischemia/reperfusion injury (I/R) in adults. Furthermore, it has been observed that late myocardial effects of chronic hypoxia, experienced in early life, may be sex-dependent. Unlike in males, perinatal hypoxia significantly increased cardiac tolerance to acute I/R injury in adult females, expressed as decreased infarct size and lower incidence of ischemic arrhythmias. It was suggested that early hypoxia may result in sex-dependent programming of specific genes in the offspring with the consequence of increased cardiac susceptibility to I/R injury in adult males. These results would have important clinical implications, since cardiac sensitivity to oxygen deprivation in adult patients may be significantly influenced by perinatal hypoxia in a sex-dependent manner. Key words: heart, perinatal hypoxia, ischemia/reperfusion injury, sex differences. Les etudes epidemiologiques ont montre un lien entre des influences defavorables du developpement perinatal et l'accroissement du risque de maladie cardiaque ischemique chez l'adulte. L'hypoxie est le plus important facteur negatif auquel le foetus puisse etre expose. Le foetus peut etre expose a un stress hypoxique dans differentes situations, comme la grossesse a une altitude elevee, la grossesse en anemie, l'insuffisance placentaire et des maladies du coeur, des poumons et des reins. L'une des agressions les plus frequentes que le foetus puisse subir au cours des stades precoces du developpement postnatal est l'hypoxie causee par des malformations cardiaques congenitales cyanotiques. Des etudes experimentales ont montre un lien entre l'hypoxie precoce et l'accroissement du risque de lesions d'ischemie/reperfusion (I/R) chez l'adulte. En outre, on a observe que des effets myocardiques tardifs de l'hypoxie chronique subie au debut de la vie pourraient varier en fonction du sexe. Contrairement a chez les males, l'hypoxie perinatale chez les femelles adultes entrainait une augmentation marquee de la tolerance du coeur aux lesions d'I/R aigues, avec une diminution de la taille de l'infarctus et de la frequence des arythmies ischemiques. On a laisse entendre que l'hypoxie precoce pourrait entrainer la programmation dependante du sexe de genes specifiques chez les rejetons et consequemment un accroissement de la susceptibilite du coeur aux lesions d'I/R chez les adultes males. Ces resultats pourraient avoir des repercussions cliniques importantes, puisque la sensibilite du coeur au manque d'oxygene chez des patients adultes pourrait etre influencee de facon notable par l'hypoxie perinatale, avec des effets variables selon le sexe. [Traduit par la Redaction] Mots-cles : coeur, hypoxie perinatale, lesions d'ischemie/reperfusion, differences entre les sexes.

Author(s): Dang Wei 1,*, Imre Janszky 1,2, Fang Fang 3, Hua Chen 1, Rickard Ljung 3,4, Jiangwei Sun 3, Jiong Li 5, Krisztina D. László 1 Introduction An increasing number [...], Background The death of a child is an extreme life event with potentially long-term health consequences. Knowledge about its association with ischemic heart diseases (IHDs) and acute myocardial infarction (AMI), however, is very limited. We investigated whether the death of an offspring is associated with the risk of IHD and AMI. Methods and findings We studied parents of live-born children recorded in the Danish (1973 to 2016) and the Swedish (1973 to 2014) Medical Birth Registers (n = 6,711,952; mean age at baseline 31 years, 53% women). We retrieved information on exposure, outcomes, and covariates by linking individual-level information from several nationwide registers. We analyzed the abovementioned associations using Poisson regression. A total of 126,522 (1.9%) parents lost at least 1 child during the study period. Bereaved parents had a higher risk of IHD and AMI than the nonbereaved [incidence rate ratios (IRRs) (95% confidence intervals (CIs)): 1.20 (1.18 to 1.23), P < 0.001 and 1.21 (1.17 to 1.25), P < 0.001, respectively]. The association was present not only in case of losses due to CVD or other natural causes, but also in case of unnatural deaths. The AMI risk was highest in the first week after the loss [IRR (95% CI): 3.67 (2.08 to 6.46), P < 0.001], but a 20% to 40% increased risk was observed throughout the whole follow-up period. Study limitations include the possibility of residual confounding by socioeconomic, lifestyle, or health-related factors and the potentially limited generalizability of our findings outside Scandinavia. Conclusions The death of an offspring was associated with an increased risk of IHD and AMI. The finding that the association was present also in case of losses due to unnatural causes, which are less likely to be confounded by cardiovascular risk factors clustering in families, suggests that stress-related mechanisms may also contribute to the observed associations.