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There is emerging evidence that spouses of patients with cancer may have a higher prevalence of mental illness, but these studies have been limited by pre-post designs, focus on a single mental illness, and short follow-up periods.To assess the overall burden of psychiatric disorders among spouses of patients with cancer vs spouses of individuals without cancer and to describe possible changes in this burden over time.This population based cohort study included spouses of patients with cancer (diagnosed 1986-2016 in Denmark and 1973-2014 in Sweden; exposed group) and spouses of individuals without cancer (unexposed group). Members of the unexposed group were individually matched to individuals in the exposed group on the year of birth, sex, and country. Spouses with and without preexisting psychiatric morbidity were analyzed separately. Data analysis was performed between May 2021 and January 2022.Being spouse to a patient with cancer.The main outcome was a clinical diagnosis of psychiatric disorders through hospital-based inpatient or outpatient care. Flexible parametric models and Cox models were fitted to estimate hazard ratios (HRs) with 95% CIs, adjusted for sex, age and year at cohort entry, country, household income, and cancer history.Among 546 321 spouses in the exposed group and 2 731 574 in the unexposed group who had no preexisting psychiatry morbidity, 46.0% were male participants, with a median (IQR) age at cohort entry of 60 (51-68) years. During follow-up (median, 8.4 vs 7.6 years), the incidence rate of first-onset psychiatric disorders was 6.8 and 5.9 per 1000 person-years for the exposed and unexposed groups, respectively (37 830 spouses of patients with cancer [6.9%]; 153 607 of spouses of individuals without cancer [5.6%]). Risk of first-onset psychiatric disorders increased by 30% (adjusted HR, 1.30; 95% CI, 1.25-1.34) during the first year after cancer diagnosis, especially for depression (adjusted HR, 1.38; 95% CI, 1.30-1.47) and stress-related disorders (adjusted HR, 2.04; 95% CI, 1.88-2.22). Risk of first-onset psychiatric disorders increased by 14% (adjusted HR, 1.14; 95% CI, 1.13-1.16) during the entire follow-up, which was similar for substance abuse, depression, and stress-related disorders. The risk increase was more prominent among spouses of patients diagnosed with a cancer with poor prognosis (eg, pancreatic cancer: adjusted HR, 1.41; 95% CI, 1.32-1.51) or at an advanced stage (adjusted HR, 1.31; 95% CI, 1.26-1.36) and when the patient died during follow-up (adjusted HR, 1.29; 95% CI, 1.27-1.31). Among spouses with preexisting psychiatric morbidity, the risk of psychiatric disorders (first-onset or recurrent) increased by 23% during the entire follow-up (adjusted HR, 1.23; 95% CI, 1.20-1.25).In this cohort study of 2 populations in Denmark and Sweden, spouses of patients with cancer experienced increased risk of several psychiatric disorders that required hospital-based specialist care. Our results support the need for clinical awareness to prevent potential mental illness among the spouses of patients with cancer.

Background Adverse childhood life events are associated with increased risks of hypertension, ischemic heart disease, and stroke later in life. Limited evidence also suggests that stress in adulthood may increase the risk of atrial fibrillation (AF). Whether childhood adversity may lead to the development of AF is unknown. We investigated whether the loss of a parent or sibling in childhood is associated with an increased risk of AF and compared this effect to that of similar losses in young adulthood. Methods We studied 6,394,975 live-born individuals included in the Danish (1973–2018) and Swedish Medical Birth Registers (1973–2014). We linked data from several national registers to obtain information on the death of parents and siblings and on personal and familial sociodemographic and health-related factors. We analyzed the association between bereavement and AF using Poisson regression. Results Loss of a parent or sibling was associated with an increased AF risk both when the loss occurred in childhood and in adulthood; the adjusted incident rate ratios and 95% confidence intervals were 1.24 (1.14–1.35) and 1.24 (1.16–1.33), respectively. Bereavement in childhood was associated with AF only if losses were due to cardiovascular diseases or other natural causes, while loss in adulthood was associated with AF not only in case of natural deaths, but also unnatural deaths. The associations did not differ substantially according to age at loss and whether the deceased was a parent or a sibling. Conclusions Bereavement both in childhood and in adulthood was associated with an increased AF risk.

Increasing evidence suggests that parental death is associated with unhealthy behaviors and mental ill-health. Knowledge regarding the link between parental death and the risk of ischemic heart disease (IHD) and stroke remains limited.To investigate whether parental death is associated with an increased risk of IHD and stroke and whether these associations differ by the characteristics of the loss.This population-based cohort study, involving linkages between several nationwide registers, included 3 766 918 individuals born between 1973 and 1998 in Denmark and between 1973 and 1996 in Sweden. Participants were followed up until 2016 in Denmark and 2014 in Sweden. Data were analyzed from December 2019 to May 2021.Death of a parent.Diagnosis with or death due to IHD or stroke. Poisson regression was used to analyze the associations between parental death and IHD and stroke risk.Altogether, 48.8% of the participants were women, and 42.7% were from Denmark. A total of 523 496 individuals lost a parent during the study period (median age at loss, 25 years; IQR, 17-32 years). Parental death was associated with a 41% increased risk of IHD (incidence rate ratio [IRR], 1.41; 95% CI, 1.33-1.51) and a 30% increased risk of stroke [IRR, 1.30; 95% CI, 1.21-1.38). The associations were observed not only if the parent died because of cardiovascular or other natural causes but also in cases of unnatural deaths. The associations were stronger when both parents had died (IHD: IRR, 1.87; 95% CI, 1.59-2.21; stroke: IRR, 1.64; 95% CI, 1.35-1.98) than when 1 parent had died (IHD: IRR, 1.37; 95% CI, 1.28-1.47; stroke: IRR, 1.27; 95% CI, 1.19-1.36) but did not differ substantially by the offspring's age at loss or the deceased parents' sex. The risk of acute myocardial infarction was highest in the first 3 months after loss.In this cohort study, parental death in the first decades of life was associated with an increased risk of IHD and stroke. The associations were observed not only in cases of parental cardiovascular and other natural deaths but also in cases of unnatural deaths. Family members and health professionals may need to pay attention to the cardiovascular disease risk among parentally bereaved individuals.

Importance: Maternal immune activation during pregnancy is associated with increased risks of several mental disorders in offspring during childhood, but little is known about how maternal autoimmune diseases during pregnancy are associated with mental health in offspring during and after childhood. Objective: To investigate the association between maternal autoimmune diseases before childbirth and risk of mental disorders among offspring up to early adulthood. Design, Setting, and Participants: This population-based nationwide cohort study used data from Danish national registers on singletons born in Denmark from 1978 to 2015 with up to 38 years of follow-up. Data analyses were conducted from March 1, 2020, through September 30, 2021. Exposures: Maternal autoimmune disease diagnosed before or during pregnancy according to the Danish National Patient Register. Main Outcomes and Measures: The main outcome was mental disorders, defined by hospital diagnoses, in offspring. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for mental disorders. Results: Of the 2 254 234 singleton infants included in the study (median age, 16.7 years [IQR, 10.5-21.7 years]; 51.28% male), 2.26% were born to mothers with autoimmune diseases before childbirth. Exposed participants had an increased risk of overall mental disorders compared with their unexposed counterparts (HR, 1.16; 95% CI, 1.13-1.19; incidence, 9.38 vs 7.91 per 1000 person-years). Increased risks of overall mental disorders in offspring were seen in different age groups for type 1 diabetes (1-5 years: HR, 1.35 [95% CI, 1.17-1.57]; 6-18 years: HR, 1.24 [95% CI, 1.15-1.33]; >18 years: HR, 1.19 [95% CI, 1.09-1.30]) and rheumatoid arthritis (1-5 years: HR, 1.42 [95% CI, 1.16-1.74]; 6-18 years: HR, 1.19 [95% CI, 1.05-1.36]; >18 years: HR, 1.28 [95% CI, 1.02-1.60]). Regarding specific mental disorders, increased risk after exposure to any maternal autoimmune disorder was observed for organic disorders (HR, 1.54; 95% CI, 1.21-1.94), schizophrenia (HR, 1.35; 95% CI, 1.21-1.51), obsessive-compulsive disorder (HR, 1.42; 95% CI, 1.24-1.63), mood disorders (HR, 1.12; 95% CI, 1.04-1.21), and a series of neurodevelopmental disorders (eg, childhood autism [HR, 1.21; 95% CI, 1.08-1.36] and attention-deficit/hyperactivity disorder [HR, 1.19; 95% CI, 1.12-1.26]). Conclusions and Relevance: In this cohort study in Denmark, prenatal exposure to maternal autoimmune diseases was associated with increased risks of overall and type-specific mental disorders in offspring. Maternal type 1 diabetes and rheumatoid arthritis during pregnancy were associated with offspring's mental health up to early adulthood. Individuals prenatally exposed to autoimmune disease may benefit from long-term surveillance for mental disorders.

The role of stress in the prognosis of heart failure (HF) is unclear. This study investigated whether the death of a close family member, a severe source of stress, is associated with mortality in HF.This study assessed whether the death of a close family member is associated with mortality in HF.Patients from the Swedish Heart Failure Registry during 2000-2018 and/or in the Swedish Patient Register with a primary diagnosis of HF during 1987-2018 (N = 490,527) were included in this study. Information was obtained on death of family members (children, partner, grandchildren, siblings, and parents), mortality, sociodemographic variables, and health-related factors from several population-based registers. The association between bereavement and mortality was analyzed by using Poisson regression.Loss of a family member was associated with an increased risk of dying (adjusted relative risk: 1.29; 95% CI: 1.27-1.30). The association was present not only in case of the family member's cardiovascular deaths and other natural deaths but also in case of unnatural deaths. The risk was higher for 2 losses than for 1 loss and highest in the first week after the loss. The association between bereavement and an increased mortality risk was observed for the death of a child, spouse/partner, grandchild, and sibling but not of a parent.Death of a family member was associated with an increased risk of mortality among patients with HF. Further studies are needed to investigate whether less severe sources of stress can also contribute to poor prognosis in HF and to explore the mechanisms underlying this association.

ImportanceAn association between maternal preeclampsia and an increased risk of cardiovascular disease in the offspring is plausible, but evidence in this area is limited.ObjectiveTo investigate (1) the association between maternal preeclampsia and risks of ischemic heart disease (IHD) and stroke in the offspring, (2) whether the association varies by severity or timing of onset of preeclampsia, and (3) the role of preterm birth and small for gestational age (SGA) birth, both of which are related to preeclampsia and cardiovascular diseases, in this association.Design, Setting, and ParticipantsThis multinational population-based cohort study obtained data from Danish, Finnish, and Swedish national registries. Live singleton births from Denmark (1973-2016), Finland (1987-2014), and Sweden (1973-2014) were followed up until December 31, 2016, in Denmark and December 31, 2014, in Finland and Sweden. Data analyses were performed between September 2020 and September 2022.ExposuresPreeclampsia and its subtypes, including early onset (Main Outcomes and MeasuresDiagnoses of IHD and stroke were extracted from patient and cause-of-death registers. Cox proportional hazards regression models and flexible parametric survival models were used to analyze the associations. Sibling analyses were conducted to control for unmeasured familial factors.ResultsThe cohort included of 8 475 819 births (2 668 697 [31.5%] from Denmark, 1 636 116 [19.3%] from Finland, and 4 171 006 [49.2%] from Sweden, comprising 4 350 546 boys [51.3%]). Of these offspring, 188 670 (2.2%) were exposed to maternal preeclampsia, 7446 (0.1%) were diagnosed with IHD, and 10 918 (0.1%) were diagnosed with stroke during the median (IQR) follow-up of 19.3 (9.0-28.1) years. Offspring of individuals with preeclampsia had increased risks of IHD (adjusted hazard ratio [HR], 1.33; 95% CI, 1.12-1.58) and stroke (adjusted HR, 1.34; 95% CI, 1.17-1.52). These associations were largely independent of preterm or SGA birth. Severe forms of preeclampsia were associated with a higher stroke risk than less severe forms (severe vs mild or moderate: adjusted HR, 1.81 [95% CI, 1.41-2.32] vs 1.22 [95% CI, 1.05-1.42]; early vs late onset: adjusted HR, 2.55 [95% CI, 1.97-3.28] vs 1.18 [95% CI, 1.01-1.39]; with vs without SGA birth: adjusted HR, 1.84 [95% CI, 1.44-2.34] vs 1.25 [95% CI, 1.07-1.48]). Sibling analyses suggested that the associations were partially explained by unmeasured familial factors.Conclusions and RelevanceResults of this study suggest that offspring born to individuals with preeclampsia had increased IHD and stroke risk that were not fully explained by preterm or SGA birth, and that the associated risks for stroke were higher for severe forms of preeclampsia.

BACKGROUND Despite accumulating evidence suggesting that bereavement is associated with increased risks of cardiovascular morbidity and mortality, the association between bereavement and prognosis after acute myocardial infarction (AMI) has not been well documented. We investigated the association by using Swedish register data. METHODS AND RESULTS We studied 266 651 patients with a first AMI included in the SWEDEHEART (Swedish Web‐system for Enhancement and Development of Evidence‐based care in Heart disease Evaluated According to Recommended Therapies) quality register from 1991 to 2018. We obtained information on bereavement (ie, death of a partner, child, grandchild, sibling, or parent), on primary (nonfatal recurrent AMI and death attributed to ischemic heart disease) and secondary outcomes (total mortality, heart failure, and stroke) and on covariates from several national registers. The association was analyzed using Poisson regression. The bereaved patients had a slightly increased risk of the primary outcome; the corresponding risk ratio (RR) was 1.02 (95% CI, 1.00–1.04). An increased risk was noted any time bereavement occurred, except if the loss was in the year after the first AMI. The association was strongest for the loss of a partner, followed by the loss of a child, grandchild, sibling, or parent. We also observed increased risks for total mortality (RR, 1.14 [95% CI, 1.12–1.16]), heart failure (RR, 1.05 [95% CI, 1.02–1.08]), and stroke (RR, 1.09 [95% CI, 1.05–1.13]) following bereavement. CONCLUSIONS Bereavement was associated with an increased risk of poor prognosis after a first AMI. The association varied by the relationship to the deceased.

Pregnancy and childbirth entail increased risks of sickness absence (SA). Many women work in education and care, two branches characterised by high SA levels; it is not known if the link between childbirth and SA in these branches differs between private and public sectors. We examined SA and disability pension (DP) in relation to childbirth among women working in the education and care branches, and if these patterns differed between public and private sectors.We performed a Swedish register-based cohort study. Study participants were nulliparous women living in Sweden in December 2004 and employed in education or care (n = 120,013). We compared SA/DP in the three years before and after 2005 among women who had no childbirth during follow-up (B0), had one childbirth in 2005 and no more (B1), and had one childbirth in 2005 and at least one more during follow-up (B1+). Analyses were performed for all and by public or private sector.Of all studied women, 70% worked in the public sector. Women in B1 and B1+ had, except for the year before childbirth, comparable or lower mean combined SA/DP days than women in the B0 group; women in the B1+ group had, except for the year before childbirth, the lowest mean level of SA/DP. We observed no substantial differences in these patterns between public and private sectors.Patterns of SA/DP among nulliparous women who did or did not give birth did not differ substantially between public and private sectors among women in the educational and care branches.

Background and ObjectivesThe death of a child is an extreme life event with potentially long-term health consequences. Accumulating evidence suggests that parents who lost a child have increased risks of cardiovascular diseases, including ischemic heart disease and atrial fibrillation. Whether bereaved parents have an increased risk of stroke is unclear and was investigated in this study.MethodsWe conducted a population-based cohort study including parents who had a child born during 1973–2016 or 1973–2014 and recorded in the Danish and the Swedish Medical Birth Registers, respectively. We obtained information on child's death, parent's stroke, and socioeconomic and health-related characteristics through linkage between several population-based registers. We used Poisson regression to examine the association between the death of a child and the risk of stroke.ResultsOf the 6,711,955 study participants, 128,744 (1.9%) experienced the death of a child and 141,840 (2.1%) had a stroke during the follow-up. Bereaved parents had an increased risk of stroke; the corresponding incidence rate ratio (95% CI) was 1.23 (1.19–1.27). The association was present for all analyzed categories of causes of child death (cardiovascular, other natural, and unnatural death) and did not differ substantially according to the age of the deceased child, but was stronger if the parent had no or ≥3 than 1–2 live children at the time of the loss. The association was similar for ischemic and hemorrhagic stroke. The risk for hemorrhagic stroke was highest immediately after the death of a child and decreased afterwards. In contrast, there was no clear pattern over time in case of ischemic stroke.DiscussionThe death of a child was associated with a modestly increased risk of stroke. The finding that an association was observed in case of unnatural deaths is suggestive of the explanation that bereavement-related stress may contribute to the development of stroke. Although the death of a child often cannot be avoided, an understanding of its health-related consequences may highlight the need for improved support and attention from family members and health care professionals.

OBJECTIVE: We analyzed the associations between maternal bereavement the year before or during pregnancy and total and cause-specific infant mortality (IM). METHODS: We studied live singleton births from the Danish (1978-2008) and Swedish Medical Birth Registers (1973-2006; N = 5,114,246). Information on maternal sociodemographic, pregnancy-related, and health-related factors, and death of family members was obtained from nationwide registers. RESULTS: Among children of mothers with register links to family members and without the considered IM risk factors, 110,993 (2.76%) were exposed and 15,199 (0.4%) died in infancy. Death of an older child the year before or during pregnancy was associated with an increased IM risk (adjusted odds ratio [aOR; 95% confidence intervals {CIs}] = 2.05 [1.44-2.92]). Losing an older child the year before pregnancy or during pregnancy was associated with risks of prematurity-related IM (aOR [95% CI] = 2.61 [1.44-4.72] and 3.08 [1.70-5.57]) and with infant death in term-born children due to causes other than sudden infant death syndrome, congenital malformations, or asphyxia (aOR [95% CI] = 3.31 [1.58-6.96] and 5.10 [1.27-20.43]). Losing an older child during pregnancy was also associated with increased risks of sudden infant death syndrome (aOR [95% CI] = 5.41 [1.34-21.83]). Death of a partner during pregnancy was associated with IM (aOR [95% CI] = 1.83 [1.01-3.32]). The number of events was small and CIs were wide in some subanalyses, and caution is needed when interpreting our results. CONCLUSIONS: Severe prenatal stress may increase the risk of several types of IM. Whether less severe but more common maternal stressors shortly before or during pregnancy also increase IM risk warrants further investigation.

BackgroundMaternal stress during pregnancy may increase the risk of preterm delivery (PD), but the associations between stress and subtypes of PD are not clear. We investigated maternal loss of a close relative and risks of very and moderately PD (MethodWe studied 4 940 764 live singleton births in Denmark (1978–2008) and Sweden (1973–2006). We retrieved information on death of women's family members (children, partner, siblings, parents), birth outcomes and maternal characteristics from nationwide registries.ResultsOverall, the death of a close family member the year before pregnancy or in the first 36 weeks of pregnancy was associated with a 7% increased risk of PD [95% confidence interval (CI) 1.04–1.10]. The highest hazard ratios (HR) for PD were found for death of an older child [HR (95% CI) 1.20 (1.10–1.31)] and for death of a partner [HR (95% CI) 1.31 (1.03–1.66)]. These losses were associated with higher risks of very preterm [HR (95% CI) 1.61 (1.29–2.01) and 2.07 (1.15–3.74), respectively] than of moderately preterm [HR (95% CI) 1.14 (1.03–1.26) and 1.22 (0.94–1.58), respectively] delivery. There were no substantial differences in the association between death of a child or partner and the risk of spontaneous v. medically indicated PD.ConclusionsDeath of a close family member the year before or during pregnancy was associated with an increased risk of PD, especially very PD. Possible mechanisms include both spontaneous and medically indicated preterm birth.

We investigated whether bereavement of a close family member - a source of severe psychological stress exposure - the year before pregnancy is associated with gestational diabetes mellitus (GDM).We studied pregnant women with livebirths in Denmark during 1994-2008 and with births in Sweden during 1987-2006 (n = 2,569,446). We obtained data on death of women's parents, siblings, and older children, and on demographic and health- and pregnancy-related factors through linkage between nationwide registers.In multivariable models, death of a close relative the year before pregnancy was associated with a 14% increased odds of GDM [95% confidence intervals (CIs) 1.03, 1.26]. The odds ratios corresponding to the loss of a child, parent, and sibling were 1.51 (95% CI: 1.17, 1.95), 1.12 (95% CI: 1.00, 1.25), and 0.68 (95% CI: 0.40, 1.25), respectively. Deaths due to cardiovascular diseases or diabetes were more closely related to the risk of GDM than other types of deaths. We found no association between unnatural deaths and the risk of GDM.Death of a close relative the year before pregnancy was associated with a modestly increased GDM risk. Our findings according to the relative's cause of death suggest that differences in screening for GDM among exposure groups and residual confounding by familial factors related to metabolic and cardiovascular diseases may have contributed to this association. If there is a causal stress effect on GDM in this predominantly Nordic population, it is most likely small.

BACKGROUND: Prenatal stress has been associated to a number of neuropsychiatric diseases but its role on the development of eating disorders (ED) remains unknown. Infants and toddlers with feeding or eating disorders are also at an increased risk of such diseases in later childhood and adolescence. We aimed to examine whether prenatal stress following maternal bereavement is associated with ED in infants and toddlers.METHODS: This population-based cohort study included children born from 1977 to 2008 in Denmark (N = 2,127,126) and from 1977 to 2006 in Sweden (N = 2,974,908). Children were categorized as exposed if they were born to mothers who lost a close relative one year prior to or during pregnancy and were categorized as unexposed otherwise. They were followed until the age of 3 for a first diagnosis of ED. Poisson regression models were used to examine incidence rate ratio (IRR) between the exposed and the unexposed cohort.RESULTS: A total of 9,403 ED cases were identified and 179 of whom were in the exposed cohort. Offspring born to mothers bereaved by loss of a core family member (older child or spouse) within the six months before pregnancy had a higher risk of ED than the unexposed offspring (IRR: 1.63, 95 % confidence intervals (CI): 1.07-2.47). In stratified analyses, bereavement during the six months before pregnancy was associated with an increased risk of ED in boys (IRR: 2.21, 95 % CI: 1.28-3.82), but not in girls (IRR: 1.18, 95 % CI: 0.61-2.27).DISCUSSION: This is the first population-based study to explore the association between prenatal stress and the risk of ED in infants and toddlers within two Nordic countries. This study added new evidence of early life stress for etiology of ED while the potential mechanism still needs further studies.CONCLUSIONS: Prenatal stress following maternal bereavement by loss of a core family member is associated with an increased risk of ED among infants and toddlers. The six months before conception may be a susceptible time window, especially for boys.

BackgroundMaternal stress during pregnancy is associated with a modestly increased risk of fetal growth restriction and pre-eclampsia. Since placental abruption shares similar pathophysiological mechanisms and risk factors with fetal growth restriction and pre-eclampsia, we hypothesized that maternal stress may be implicated in abruption risk. We investigated the association between maternal bereavement during pregnancy and placental abruption.MethodWe studied singleton births in Denmark (1978–2008) and Sweden (1973–2006) (n = 5 103 272). In nationwide registries, we obtained data on death of women's close family members (older children, siblings, parents, and partners), abruption and potential confounders.ResultsA total of 30 312 (6/1000) pregnancies in the cohort were diagnosed with placental abruption. Among normotensive women, death of a child the year before or during pregnancy was associated with a 54% increased odds of abruption [95% confidence interval (CI) 1.30–1.82]; the increased odds were restricted to women who lost a child the year before or during the first trimester in pregnancy. In the group with chronic hypertension, death of a child the year before or in the first trimester of pregnancy was associated with eight-fold increased odds of abruption (odds ratio 8.17, 95% CI 3.17–21.10). Death of other relatives was not associated with abruption risk.ConclusionsLoss of a child the year before or in the first trimester of pregnancy was associated with an increased risk of abruption, especially among women with chronic hypertension. Studies are needed to investigate the effect of less severe, but more frequent, sources of stress on placental abruption risk.