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.

Bidirectional association between autoimmune disease and perinatal depression: a nationwide study with sibling comparison.

Although major depression, characterized by a pro-inflammatory profile, genetically overlap with autoimmune disease (AD) and the perinatal period involve immune system adaptations and AD symptom alterations, the bidirectional link between perinatal depression (PND) and AD is largely unexplored. Hence, the objective of this study was to investigate the bidirectional association between PND and AD. Using nationwide Swedish population and health registers, we conducted a nested case-control study and a matched cohort study. From 1,347,901 pregnancies during 2001-2013, we included 55,299 incident PND, their unaffected full sisters, and 10 unaffected matched women per PND case. We identified 41 subtypes of AD diagnoses recorded in the registers and compared PND with unaffected population-matched women and full sisters, using multivariable regressions. Women with an AD had a 30% higher risk of subsequent PND (95% CI 1.2-1.5) and women exposed to PND had a 30% higher risk of a subsequent AD (95% CI 1.3-1.4). Comparable associations were found when comparing exposed women with their unaffected sisters (nested case-control OR: 1.3, 95% CI 1.2-1.5, matched cohort HR: 1.3, 95% CI 1.1-1.6), and when studying antepartum and postpartum depression. The bidirectional association was more pronounced among women without psychiatric comorbidities (nested case-control OR: 1.5, 95% CI 1.4-1.6, matched cohort HR: 1.4, 95% CI 1.4-1.5) and strongest for multiple sclerosis (nested case-control OR: 2.0, 95% CI 1.6-2.3, matched cohort HR: 1.8, 95% CI 1.0-3.1). These findings demonstrate a bidirectional association between AD and PND independent of psychiatric comorbidities, suggesting possibly shared biological mechanisms. If future translational science confirms the underlying mechanisms, healthcare providers need to be aware of the increased risk of PND among women with ADs and vice versa.

Suicide attempt and death by suicide among parents of young individuals with cancer: A population-based study in Denmark and Sweden.

BACKGROUND: The psychological toll on parents of a child receiving a cancer diagnosis is known to be high, but there is a knowledge gap regarding suicidal behavior among these parents. The aim of this study was to investigate the risk of suicide attempt and death by suicide in relation to having a child with cancer. METHODS AND FINDINGS: We performed a binational population-based and sibling-controlled cohort study, including all parents with a child diagnosed with cancer in Denmark (1978 to 2016) or Sweden (1973 to 2014), 10 matched unexposed parents per exposed parent (population comparison), and unaffected full siblings of the exposed parents (sibling comparison). Suicide attempt was identified through the Patient Register and the Psychiatric Central Register in Denmark and the Patient Register in Sweden, whereas death by suicide was identified through the Danish Causes of Death Register and the Swedish Causes of Death Register. In population comparison, we used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of suicide attempt and death by suicide associated with cancer diagnosis of a child, adjusting for sex, age, country of residence, calendar year, marital status, highest attained educational level, household income, history of cancer, history of psychiatric disorder, and family history of psychiatric disorder. The sibling comparison was performed to assess the role of familial confounding in the studied associations. The population comparison consisted of 106,005 exposed parents and 1,060,050 matched unexposed parents, with a median age of 56 at cohort entry and 46.9% male. During the median follow-up of 7.3 and 7.2 years, we observed 613 (incidence rate [IR], 58.8 per 100,000 person-years) and 5,888 (IR, 57.1 per 100,000 person-years) cases of first-onset suicide attempt among the exposed and unexposed parents, respectively. There was an increased risk of parental suicide attempt during the first years after a child's cancer diagnosis (HR, 1.15; 95% CI, [1.03, 1.28]; p = 0.01), particularly when the child was 18 or younger at diagnosis (HR, 1.25; 95% CI, [1.08, 1.46]; p = 0.004), when the child was diagnosed with a highly aggressive cancer (HR, 1.60; 95% CI, [1.05, 2.43]; p = 0.03), or when the child died due to cancer (HR, 1.63; 95% CI, [1.29, 2.06]; p < 0.001). The increased risk did not, however, maintain thereafter (HR, 0.86; 95% CI: [0.75, 0.98]; p = 0.03), and there was no altered risk of parental death by suicide any time after the child's cancer diagnosis. Sibling comparison corroborated these findings. The main limitation of the study is the potential residual confounding by factors not shared between full siblings. CONCLUSIONS: In this study, we observed an increased risk of parental suicide attempt during the first years after a child's cancer diagnosis, especially when the child was diagnosed during childhood, or with an aggressive or fatal form of cancer. There was, however, no altered risk of parental death by suicide at any time after a child's cancer diagnosis. Our findings suggest extended clinical awareness of suicide attempt among parents of children with cancer, especially during the first few years after cancer diagnosis.

Prenatal Exposure to Severe Stress and Risks of Ischemic Heart Disease and Stroke in Offspring.

Importance: Prenatal stress is associated with increased risks of several cardiovascular risk factors later in life. However, knowledge regarding the role of prenatal stress in the development of ischemic heart disease (IHD) and stroke is very limited. Objective: To examine prenatal stress, defined as maternal bereavement, and risks of IHD and stroke in the offspring. Design, Setting, and Participants: A cohort study was conducted using data from Danish and Swedish registries. Live singleton births during calendar years 1973-2016 in Denmark (followed up until December 31, 2016) and during calendar years 1973-2014 in Sweden (followed up until December 31, 2021) were included in the analysis. Exposure: Maternal loss of a close family member (partner, older children, parents, or siblings) the year before or during the pregnancy. Main Outcome and Measures: Diagnoses of IHD and stroke. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for IHD and stroke in the offspring according to maternal bereavement. Results: The study included 6 758 560 births (39.4% from Denmark; 51.4% boys). During the median follow-up of 24.6 (IQR, 13.9-35.1) years, 8664 offspring (0.1%) were diagnosed with IHD and 13 094 with stroke (0.2%). Overall, maternal bereavement the year before or during pregnancy was not associated with IHD (adjusted HR [AHR], 0.98; 95% CI, 0.85-1.13) or stroke (AHR, 1.04; 95% CI, 0.94-1.16) in offspring. Similarly, no associations were observed when exposure was classified by the mother's relationship to the deceased individual, ie, loss of older child or partner (HR, 0.85; 95% CI, 0.64-1.14 for IHD and 0.98; 95% CI, 0.77-1.25 for stroke) or loss of parent or sibling (HR, 1.03; 95% CI, 0.87-1.21 for IHD and 1.06; 95% CI, 0.94-1.19 for stroke). However, associations between loss in the third trimester and IHD (AHR, 1.50; 95% CI, 1.06-2.13), and loss due to cardiovascular disease and stroke (AHR, 1.22; 95% CI, 1.03-1.44) were identified when exposure was classified by time of loss or the relative's cause of death. Conclusions and Relevance: The findings of this study provide little support for the hypothesis that prenatal stress is associated with risks of IHD and stroke in the first 5 decades of life. However, the association observed between stress in the third trimester and IHD warrants further investigation.

Preterm Birth, Small for Gestational Age, and Large for Gestational Age and the Risk of Atrial Fibrillation Up to Middle Age.

Importance: Adverse birth outcomes, including preterm birth, small for gestational age (SGA), and large for gestational age (LGA) are associated with increased risks of hypertension, ischemic heart disease, stroke, and heart failure, but knowledge regarding their associations with atrial fibrillation (AF) is limited and inconsistent. Objective: To investigate whether preterm birth, SGA, or LGA are associated with increased risks of AF later in life. Design, Setting, and Participants: This multinational cohort study included Danish, Swedish, and Finnish national health registries. Live singleton births in Denmark from 1978 through 2016, in Sweden from 1973 through 2014, and in Finland from 1987 through 2014, who were followed up until December 31, 2016, in Denmark, December 31, 2021, in Sweden, and December 31, 2014, in Finland were included. Data analyses were performed between January 2021 and August 2022. Exposures: Preterm birth (less than 37 gestational weeks), SGA (less than 10th percentile birth weight for gestational age), and LGA (more than 90th percentile birth weight for gestational age) identified from medical birth registers. Main Outcomes and Measures: Diagnosis of AF obtained from nationwide inpatient and outpatient registers. The study team ran multivariable Cox proportional hazard models and flexible parametric survival models to estimate hazard ratios (HRs) and 95% CIs for AF according to preterm birth, SGA, and LGA. Sibling analyses were conducted to control for unmeasured familial factors. Results: The cohort included 8 012 433 study participants (maximum age, 49 years; median age, 21 years; male, 51.3%). In 174.4 million person-years of follow-up, 11 464 participants had a diagnosis of AF (0.14%; median age, 29.3 years). Preterm birth and LGA were associated with increased AF risk in both the full population cohort and in the sibling analyses; the multivariate HRs from the cohort analyses were 1.30 (95% CI, 1.18-1.42) and 1.55 (95% CI, 1.46-1.63), respectively. Preterm birth was more strongly associated with AF in childhood than in adulthood. Children born SGA had an increased risk of AF in the first 18 years of life but not afterwards. Conclusions and Relevance: Preterm births and LGA births were associated with increased risks of AF up to middle age independently of familial confounding factors. Individuals born SGA had an increased AF risk only during childhood.

Rheumatoid arthritis and the risk of postpartum psychiatric disorders: a Nordic population-based cohort study.

BACKGROUND: Postpartum psychiatric disorders (PPD) are common complications of childbirth. A common explanation for their development is that the psychological, hormonal, and immune changes associated with pregnancy and parturition may trigger psychiatric symptoms postpartum. Rheumatoid arthritis (RA) is characterized by abnormalities in the activity of the hypothalamic-pituitary-adrenal axis and of the immune system, but its association with PPD is unknown. We analyzed whether women with RA before childbirth have an increased risk of PPD. METHODS: We conducted a large population-based cohort study including mothers of singleton births in the Danish (1995-2015), Finnish (1997-2013), and Swedish Medical Birth Registers (2001-2013) (N = 3,516,849). We linked data from the Medical Birth Registers with data from several national socioeconomic and health registers. Exposure was defined as having a diagnosis of RA before childbirth, while the main outcome was a clinical diagnosis of psychiatric disorders 90 days postpartum. We analyzed the association between RA and PPD using Cox proportional hazard models, stratified by a personal history of psychiatric disorders. RESULTS: Among women without a history of psychiatric disorders, the PPD incidence rate was 32.2 in the exposed and 19.5 per 1000 person-years in the unexposed group; women with RA had a higher risk of overall PPD than their unexposed counterparts [adjusted hazard ratio (HR) = 1.52, 95% confidence intervals (CI) 1.17 to 1.98]. Similar associations were also observed for postpartum depression (HR = 1.65, 95% CI 1.09 to 2.48) and other PPD (HR = 1.59, 95% CI 1.13 to 2.24). Among women with a history of psychiatric disorders, the incidence rate of overall PPD was 339.6 in the exposed and 346.6 per 1000 person-years in the unexposed group; RA was not associated with PPD. We observed similar associations between preclinical RA (RA diagnosed after childbirth) and PPD to those corresponding to clinical RA. CONCLUSIONS: Rheumatoid arthritis was associated with an increased PPD risk in women without, but not in those with a psychiatric history. If our findings are confirmed in future studies, new mothers with RA may benefit from increased surveillance for new-onset psychiatric disorders postpartum.

Loss of a child and the risk of atrial fibrillation: a Danish population-based prospective cohort study.

BACKGROUND: Several studies suggest that bereavement is associated with increased risks of ischaemic heart disease, heart failure, stroke and cardiovascular mortality. Knowledge regarding the link between bereavement and the risk of atrial fibrillation (AF) is limited. We investigated whether the death of a child, one of the most severe forms of bereavement, is associated with AF. METHODS: We conducted a population-based cohort study involving parents of live-born children during 1973-2016 from the Danish Medical Birth Register (n=2 804 244). Information on children's death, parental AF and sociodemographic and other health-related characteristics was obtained by individual-level linkage between several Danish population-based registers. We analysed the association between loss of a child and AF using Poisson regression. RESULTS: During the up to 39 years follow-up, 64 216 (2.3%) parents lost a child and 74 705 (2.7%) had an AF. Bereaved parents had a higher risk of AF than the non-bereaved; the corresponding incidence rate ratio (IRR) and 95% CI were 1.12 (1.08 to 1.17). The association was present both when the child died of cardiovascular diseases (IRR (95% CI): 1.42 (1.20 to 1.69)), and of other causes (IRR (95% CI): 1.11 (1.06 to 1.16)), tended to be U-shaped according to the deceased child's age at loss, but did not differ substantially according to the number of remaining live children at loss, the number of deceased children or the time since the loss. CONCLUSIONS: The death of a child was associated with a modestly increased risk of AF. Bereaved parents may benefit from increased support from family members and health professionals.

Evaluation of Maternal Infection During Pregnancy and Childhood Leukemia Among Offspring in Denmark.

Importance: Maternal infection is common during pregnancy and is an important potential cause of fetal genetic and immunological abnormalities. Maternal infection has been reported to be associated with childhood leukemia in previous case-control or small cohort studies. Objective: To evaluate the association of maternal infection during pregnancy with childhood leukemia among offspring in a large study. Design, Setting, and Participants: This population-based cohort study used data from 7 Danish national registries (including the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Cancer Registry, and others) for all live births in Denmark between 1978 and 2015. Swedish registry data for all live births between 1988 and 2014 were used to validate the findings for the Danish cohort. Data were analyzed from December 2019 to December 2021. Exposures: Maternal infection during pregnancy categorized by anatomic locations identified from the Danish National Patient Registry. Main Outcomes and Measures: The primary outcome was any leukemia; secondary outcomes were acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML). Offspring childhood leukemia was identified in the Danish National Cancer Registry. Associations were first assessed in the whole cohort using Cox proportional hazards regression models, adjusted for potential confounders. A sibling analysis was performed to account for unmeasured familial confounding. Results: This study included 2 222 797 children, 51.3% of whom were boys. During the approximately 27 million person-years of follow-up (mean [SD], 12.0 [4.6] years per person), 1307 children were diagnosed with leukemia (ALL, 1050; AML, 165; or other, 92). Children born to mothers with infection during pregnancy had a 35% increased risk of leukemia (adjusted hazard ratio [HR], 1.35 [95% CI, 1.04-1.77]) compared with offspring of mothers without infection. Maternal genital and urinary tract infections were associated with a 142% and 65% increased risk of childhood leukemia, with HRs of 2.42 (95% CI, 1.50-3.92) and 1.65 (95% CI, 1.15-2.36), respectively. No association was observed for respiratory tract, digestive, or other infections. The sibling analysis showed comparable estimates to the whole-cohort analysis. The association patterns for ALL and AML were similar to that for any leukemia. No association was observed for maternal infection and brain tumors, lymphoma, or other childhood cancers. Conclusions and Relevance: In this cohort study of approximately 2.2 million children, maternal genitourinary tract infection during pregnancy was associated with childhood leukemia among offspring. If confirmed in future studies, our findings may have implications for understanding the etiology and developing preventive measures for childhood leukemia.

The joint effect between fetal growth and health behaviors on the risk of cardiovascular diseases in young adulthood.

PURPOSE: To investigate the individual and the joint effect of impaired fetal growth and adult health behaviors on the risk of cardiovascular diseases (CVDs). METHODS: A total of 15,618 individuals were included from three sub-cohorts of the Stockholm Public Health Cohort. Data on participants' birthweight and gestational age were retrieved from the Medical Birth Register. Data on the diagnoses of CVDs were extracted from the Swedish National Patient Register and the Cause of Death Register. Data on health behaviors were identified from self-reported questionnaires, and health behavioral profile was defined based on the recommendations of the American Health Association. The associations of fetal growth and health behaviors with the risk of CVDs were analyzed using Cox proportional hazard model. RESULTS: Individuals born small for gestational age (SGA) had a higher risk of CVDs than those born appropriate for gestational age (AGA), and the adjusted hazard ratio (HR) and 95% confidence interval (CI) was 1.88 (1.44, 2.47). Participants born SGA and having poor health behavioral profile in adulthood had a higher risk of CVDs than those born AGA and having ideal health behaviors with adjusted HR (95% CI) being 3.58 (1.95, 6.56). CONCLUSIONS: Impaired fetal growth was associated with an increased risk of CVDs in adulthood, and the risk was highest in individuals with both impaired fetal growth and poor health behaviors in adulthood.

Bereavement in childhood and young adulthood and the risk of atrial fibrillation: a population-based cohort study from Denmark and Sweden.

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.

Birth Weight, Gestational Age, and Risk of Cardiovascular Disease in Early Adulthood: Influence of Familial Factors.

The association between intrauterine growth restriction and cardiovascular disease (CVD) later in life might be confounded by familial factors. We conducted a binational register-based cohort study to assess associations of birth weight for gestational age (GA), a proxy for intrauterine growth restriction, and GA with CVD risk in early adulthood, before and after addressing familial factors via sibling comparison. We included 3,410,334 live nonmalformed singleton births from Sweden (1973-1996) and Denmark (1978-1998). During a median follow-up period of 10 years from age 18 years onwards, 29,742 individuals developed incident CVD (hypertension, ischemic heart disease, or cerebrovascular disease). Compared with individuals born with appropriate birth weight for GA (AGA; 10th-90th percentiles) or full term (39-40 gestational weeks), individuals born severely small for GA (SGA; ≤3rd percentile) or preterm (22-36 weeks) were at increased risk of CVD (hazard ratio (HR) = 1.38 (95% confidence interval (CI): 1.32, 1.45) and HR = 1.31 (95% CI: 1.25, 1.38), respectively). The association was attenuated when comparing individuals born SGA with their AGA siblings (HR = 1.11, 95% CI: 0.99, 1.25) but remained robust when comparing individuals born preterm with their term siblings (HR = 1.21, 95% CI: 1.07, 1.37). Our findings suggest that both SGA and preterm birth are associated with CVD risk in early adulthood, with greater familial confounding noted for SGA birth.

Risk of Psychiatric Disorders Among Spouses of Patients With Cancer in Denmark and Sweden.

Importance: 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. Objectives: 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. Design, Setting, and Participants: 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. Exposures: Being spouse to a patient with cancer. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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.

Association of Maternal Preeclampsia With Offspring Risks of Ischemic Heart Disease and Stroke in Nordic Countries.

Importance: An association between maternal preeclampsia and an increased risk of cardiovascular disease in the offspring is plausible, but evidence in this area is limited. Objective: To 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 Participants: This 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. Exposures: Preeclampsia and its subtypes, including early onset (<34 gestational weeks) and late onset (≥34 gestational weeks), severe and mild or moderate, and with and without SGA birth. Main Outcomes and Measures: Diagnoses 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. Results: The 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 Relevance: Results 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.

Sickness absence and disability pension three years before and seven years after first childbirth: A Swedish population-based cohort study.

AIMS: There is a widely held belief, in Sweden and internationally, that women with children are more likely to be on sickness absence (SA) than their nulliparous counterparts. However, empirical findings in the field are limited and inconsistent. We aimed to explore initially nulliparous women's patterns of SA and disability pension (DP) three years before and seven years after 2009, by later parity. METHODS: We conducted a longitudinal cohort study of nulliparous women in Sweden on 31 December 2009 (N=426,918). We compared crude and standardized numbers of SA/DP net days in the three years before (Y-3 to Y-1) and the seven years (Y+1 to Y+7) after the date of the first birth in 2010 or 2 July 2010 in the following three groups: (1) women with no childbirth during the seven-year follow-up and an additional nine months (i.e. 7.8 years), (2) women with a first childbirth in 2010 and no additional childbirth during the next 7.8 years, and (3) women with their first childbirth in 2010 and minimum one more during the next 7.8 years. RESULTS: Women remaining nulliparous had consistently more standardized mean SA/DP days than women giving birth. Compared with women with one birth, women with several births had similar mean numbers of standardized SA/DP days during Y-3 and Y-2, more during Y+1 to Y+3 and fewer during Y+4 to Y+7. CONCLUSIONS: In contrast to the widely held societal belief, we found that in all years women who gave birth had fewer SA/DP days than those remaining nulliparous.

Bereavement and Prognosis After a First Acute Myocardial Infarction: A Swedish Register-Based Cohort Study.

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.

Sickness absence in relation to first childbirth in nulliparous women, employed in the education and care branches in the public or private sectors: A Swedish longitudinal cohort study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Bereavement and Prognosis in Heart Failure: A Swedish Cohort Study.

BACKGROUND: 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. OBJECTIVES: This study assessed whether the death of a close family member is associated with mortality in HF. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Death of a Parent and the Risk of Ischemic Heart Disease and Stroke in Denmark and Sweden.

Importance: 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. Objectives: 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. Design, Setting, and Participants: 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. Exposures: Death of a parent. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.