Search

Background: Mental stress is associated with higher mortality, but it remains controversial whether the association is causal or a consequence of a higher physical disease burden in those with a high mental stress load. Understanding causality is important when developing targeted interventions. We aimed to estimate the effect of mental stress on mortality by performing a 'natural' experiment using spousal bereavement as a disease-independent mental stressor., Methods: We followed a population-based matched cohort, including all individuals in Denmark bereaved in 1997-2014, for 17 years. Prospectively recorded register data were obtained for civil and vital status, 39 mental and physical diagnoses, and socioeconomic factors., Results: In total, 389 316 bereaved individuals were identified and 137 247 died during follow-up. Bereaved individuals had higher all-cause mortality than non-bereaved references in the entire study period. The relative mortality in the bereaved individuals was highest shortly after the loss (adjusted hazard ratio (aHR), first month: 2.50, 95% confidence interval (CI) 2.37-2.63; aHR, 6-12 months: 1.38, 95% CI 1.34-1.42). The excess mortality rate associated with bereavement rose with increasing number of physical diseases (1.33 v. 7.00 excess death per 1000 person-months for individuals with 0 v. ⩾3 physical conditions during the first month) and was exacerbated by the presence of mental illness. The excess mortality among bereaved individuals was primarily due to death from natural causes., Conclusions: Bereavement was associated with increased short-term and long-term mortality, even after adjustment for morbidities, which suggests that mental stress may play a causal role in excess mortality.

We aimed to examine whether early life bereavement, as indicator of severe stress, was associated with an increased risk of schizophrenia later in life.Based on population registers, we established a cohort of all children born in Denmark (N = 1 686 416) and Sweden (N = 2 563 659) from 1973 to 1997. Children were categorized as exposed if they lost a first-degree relative during the first 18 years of life. Outcome is the first diagnosis of schizophrenia as either inpatient or outpatient. Log-linear Poisson regression models were used to estimate incidence rate ratios (IRRs).A total of 188,850 children (4.6%) experienced death of a first-degree relative from birth to 18 years of age. Compared with unexposed children, those exposed had overall a 39% higher risk of schizophrenia (= 1.39, 95% CI [confidence interval]: 1.32-1.47). The IRR was particularly high if the family member committed suicide (aIRR = 2.11, 95% CI: 1.90-2.34) or died due to an injury or accident (aIRR = 1.44, 95% CI: 1.27-1.63). The IRR of schizophrenia decreased with increasing child's age at bereavement (P < 0.0001). Children who experienced >1 death during the first 18 years of life (aIRR = 1.79, 95% CI: 1.46-2.19) had a higher risk than those with a single death (aIRR = 1.37, 95% CI: 1.30-1.45).The study suggested that exposure to death of a first-degree relative before 18 years was associated with an increased risk of schizophrenia in later life. The complex mechanisms behind these associations remain to be elucidated., Competing Interests: The authors have no conflicts of interest to disclose.

Background: 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)., Methods: 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., Results: 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., Conclusions: 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., (© 2015 John Wiley & Sons Ltd.)

Objective: Recent studies have suggested that stress in a pregnant mother may affect the future health of the unborn child negatively. An excellent proxy for health problems is the use of healthcare resources. Using nationwide data, we examined whether persons born to mothers who lost a close relative during pregnancy have more contacts to general practice., Design: Population-based cohort study., Setting: Denmark., Participants: We included all children born in Denmark from 1973 to 2002 (N=2 032 528). Exposure of prenatal stress was defined as maternal bereavement by the death of a close relative during the antenatal period. The outcome of interest was contact with general practice between 2003 and 2009 when the participants were between 1 and 35 years of age. Poisson regression was used to assess the association between exposure and outcome., Outcome Measures: Contacts to general practitioner., Results: Overall, persons exposed to prenatal stress had 2% more GP contacts than those not exposed, primarily due to increased utilisation of healthcare services during late adolescence and early adulthood. The exposed persons born to mothers who had lost a spouse had a higher risk (relative risk (RR) 1.12, 95% CI 1.10 to 1.14) and so did those born to mothers who had lost a close relative due to unexpected death (RR 1.06, 95% CI 1.05 to 1.06). Exposed persons had more contacts to general practice in daytime and more psychometric tests, talk therapies and C reactive protein tests than unexposed persons., Conclusions: Prenatal stress following maternal bereavement was associated with a slightly increased utilisation of primary healthcare, mainly due to increased healthcare needs related to mental health and infections. Understanding how stress during pregnancy influences the future health of the child is an important aspect of prenatal care., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Maternal 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., Method: We 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., Results: A 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., Conclusions: Loss 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.

Introduction: Substance use disorder (SUD) is associated with major socioeconomic consequences but its etiology is only partly known. The disease predisposition may be established early in life and prenatal stress may play a role. We aimed to examine whether prenatal maternal bereavement, as the indicator of prenatal stress, was associated with an increased risk of SUD in offspring., Methods: This population-based cohort study included all children born in Denmark (N=1686416) and Sweden (N=2563659) from 1973 to 1997. The exposure was maternal bereavement by the death of a close relative 1 year before or during pregnancy. Children were followed from 10 years of age until their death, migration, onset of substance abuse, or December 31st, 2007. The main outcome is hospitalization due to substance use disorder (SUD)., Results: A total of 100363 children (2.45%) were born to mothers who had experienced bereavement 1 year before or during pregnancy. Overall, these exposed children had a similar risk of hospitalization due to SUD (IRR=1.02, 95% CI: 0.98-1.07), compared to unexposed children. Children born to mothers who lost a spouse during pregnancy had a two-fold risk (IRR=2.19, 95% CI: 1.74-2.76) and similar elevated risks were observed in children whose mothers lost a spouse during the first 10 years after child birth., Conclusions: Our data do not support a programming role of prenatal stress following maternal bereavement on SUD later in life. The increased risk in relation to spousal bereavement may mostly be explained by postpartum changes in familial environment., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: It has been suggested that maternal emotional stress during cardiogenesis may be a risk factor for congenital heart defects (CHD). We examined this association using bereavement around the time of conception as an indicator of maternal exposure to stress in a large registry-based study., Methods: We identified 1,770,878 singletons born in Denmark from January 1, 1978, to December 31, 2008. Of these, 44,820 children were born to mothers who had lost a first-degree relative during the time period from 1 year before their last menstrual period until delivery (6080 mothers lost a child or partner, and 38,740 mothers lost a parent or sibling). CHD diagnoses were identified from the Danish Registry of Congenital Heart Disease. We used logistic regression models to calculate prevalence odds ratios (ORs) of CHD for exposed children compared with unexposed children., Results: Exposed children had a slightly higher prevalence of CHD than unexposed children (0.94% vs 0.82%; adjusted OR = 1.11, 95% confidence interval 1.00-1.22). The association was most marked for children of mothers who had lost a child or partner (1.15% vs 0.82%; adjusted OR = 1.32, 1.04-1.67)., Conclusions: Prenatal exposure to severe emotional stress may slightly increase the prevalence of CHD in offspring.

Background: Prenatal stress may increase the susceptibility to childhood cancer by affecting immune responses and hormonal balance. We examined whether antenatal stress following maternal bereavement increased the risk of childhood cancer., Methods: All children born in Denmark from 1968 to 2007 (N=2 743 560) and in Sweden from 1973 to 2006 (N=3 400 212) were included in this study. We compared cancer risks in children born to women who lost a first-degree relative (a child, spouse, a parent, or a sibling) the year before pregnancy or during pregnancy with cancer risks in children of women who did not experience such bereavement., Results: A total of 9795 childhood cancer cases were observed during follow-up of 68 360 707 person years. Children born to women who lost a child or a spouse, but not those who lost other relatives, had an average 30% increased risk of any cancer (hazard ratio (HR) 1.30, 95% confidence interval (CI) 0.96-1.77). The HRs were the highest for non-Hodgkin disease (512 cases in total, HR 3.40, 95% CI 1.51-7.65), hepatic cancer (125 cases in total, HR 5.51, 95% CI 1.34-22.64), and testicular cancer (86 cases in total, HR 8.52, 95% CI 2.03-37.73)., Conclusion: Our data suggest that severe antenatal stress following maternal bereavement, especially due to loss of a child or a spouse, is associated with an increased risk of certain childhood cancers in the offspring, such as hepatic cancer and non-Hodgkin disease, but not with childhood cancer in general., (© 2012 Cancer Research UK)

Objective: The rise in the occurrence of childhood obesity during the last decades in many populations indicates an important role of environmental exposures, which may operate very early in life. We aimed to examine the association between bereavement during the first 6 years of life, as a stress indicator, and subsequent risk of overweight in school-aged children., Methods: We followed 46,401 singletons born in Denmark who underwent annual health examinations at 7-13 years of age in school of Copenhagen. A total of 492 children experienced bereavement by death of a parent during the first 6 years of life. We compared BMI levels, changes in BMI, and the prevalence of overweight at 7-13 years of age between bereaved and non-bereaved children., Results: Between bereaved children and non-bereaved children, there were no differences in average BMI levels at any age or changes in BMI at 7-13 years of age. Bereavement during the first 6 years of life was not associated with an increased risk of overweight at 7-13 years of age., Conclusion: This study did not support that stress induced by bereavement during the first 6 years of life has significant influence on overweight in later childhood., (Copyright © 2012 S. Karger GmbH, Freiburg.)

Background: The etiology of type-2 diabetes is only partly known, and a possible role of prenatal stress in programming offspring for insulin resistance has been suggested by animal models. Previously, we found an association between prenatal stress and type-1 diabetes. Here we examine the association between prenatal exposure to maternal bereavement during preconception and pregnancy and development of type-2 diabetes in the off-spring., Methods: We utilized data from the Danish Civil Registration System to identify singleton births in Denmark born January 1(st) 1979 through December 31(st) 2008 (N = 1,878,246), and linked them to their parents, grandparents, and siblings. We categorized children as exposed to bereavement during prenatal life if their mothers lost an elder child, husband or parent during the period from one year before conception to the child's birth. We identified 45,302 children exposed to maternal bereavement; the remaining children were included in the unexposed cohort. The outcome of interest was diagnosis of type-2 diabetes. We estimated incidence rate ratios (IRRs) from birth using log-linear poisson regression models and used person-years as the offset variable. All models were adjusted for maternal residence, income, education, marital status, sibling order, calendar year, sex, and parents' history of diabetes at the time of pregnancy., Results: We found children exposed to bereavement during their prenatal life were more likely to have a type-2 diabetes diagnosis later in life (aIRR: 1.31, 1.01-1.69). These findings were most pronounced when bereavement was caused by death of an elder child (aIRR: 1.51, 0.94-2.44). Results also indicated the second trimester of pregnancy to be the most sensitive period of bereavement exposure (aIRR:2.08, 1.15-3.76)., Conclusions: Our data suggests that fetal exposure to maternal bereavement during preconception and the prenatal period may increase the risk for developing type-2 diabetes in childhood and young adulthood.

Severe prenatal stress exposure has been found to increase the risk of neuropsychiatric conditions like schizophrenia. We examined the risk of attention-deficit/hyperactivity disorder (ADHD) in the offspring following prenatal maternal bereavement, as a potential source of stress exposure. We conducted a nationwide population-based cohort study including all 1,015,912 singletons born in Denmark from 1987 to 2001. A total of 29,094 children were born to women who lost a close relative during pregnancy or up to 1 year before pregnancy. These children were included in the exposed cohort and other children were in the unexposed cohort. We used Cox regression to estimate hazard ratios for ADHD, defined as the first-time ADHD hospitalization or first-time ADHD medication after 3 years of age. Boys born to mothers who were bereaved by unexpected death of a child or a spouse, had a 72% increased risk of ADHD [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.09-2.73]. Boys born to mothers who lost a child or a spouse during 0-6 months before pregnancy and during pregnancy had a HR of 1.47 (95% CI 1.00-2.16) and 2.10 (95% CI 1.16-3.80), respectively. Our findings suggest that prenatal maternal exposure to severe stress may increase the risk of ADHD in the offspring.

Objectives: Exposure to prenatal stress may affect neurodevelopment of the fetus, but whether this exposure increases the risk of cerebral palsy (CP) later in life is unknown. We aimed to examine the association between maternal bereavement during the prenatal time period and CP in childhood., Methods: We conducted a nationwide cohort study by linking information from nationwide registers. All 1,501,894 singletons born in Denmark from 1979 to 2004 were followed up from birth to the end of 2006. We identified 39,601 children whose mothers lost a close relative (child, spouse, parent, sibling) during pregnancy or up to 1 year before pregnancy and they were classified as the exposed group. The outcome of interest was the diagnosis of CP as registered in the National Hospital Register. We used Cox Regression to estimate the hazard ratios (HRs)., Results: Exposure to maternal bereavement after the loss of a child during the prenatal period was associated with an increased risk of CP among children born preterm without intrauterine growth retardation (HR 2.26, 95% CI, 1.09-3.79) and among children born at term with intrauterine growth retardation (HR 2.01, 95% CI, 1.04-3.89). Prenatal stress after maternal bereavement by loss of other relatives was not associated with an increased risk of CP., Conclusions: Our data suggest that extremely severe stress in prenatal life could increase the susceptibility for CP among children born preterm or with impaired fetal growth.

Objective: Prenatal stress has been linked to several adverse neurobehavioral outcomes, which may share a common pathophysiology with autism. We aimed to examine whether prenatal stress exposure after maternal bereavement is associated with an increased risk of autism later in life., Methods: We conducted a nationwide population-based cohort study of all 1492709 singletons in Denmark born from 1978 to 2003. A total of 37275 children were born to women who lost a close relative during pregnancy or up to 1 year before pregnancy. These children were included in the exposed group, and the remaining children were in the unexposed group. All children were followed up from birth until their death, migration, onset of autism, or the end of 2006. Information on autism was obtained from the Danish Psychiatric Central Register. We used Cox regression models to estimate hazard ratios in the exposed group compared with those in the unexposed group., Results: Maternal bereavement during the prenatal period was not associated with an increased risk of autism in the offspring. The hazard ratios did not differ by the nature of the exposure (maternal relationship to the deceased or cause of death). The hazard ratios were comparable between the 5 prenatal exposure periods under study (7-12 months before pregnancy, 0-6 months before pregnancy, first trimester, second trimester, and third trimester)., Conclusions: This is the first population-based cohort study to examine the effect of prenatal stress on autism in childhood. Our data do not support any strong association between prenatal stress after maternal bereavement and the risk of autism.

BackgroundThe loss of a close relative is one of the most stressful life events. In pregnancy, this experience has been associated with a higher risk of fetal death and under-five mortality, but little is known about potential effects on long-term mortality in offspring. We examined the association between prenatal maternal bereavement and mortality in a cohort of 5.3 million children followed until up to 37 years of age.MethodThe population-based cohort study included 5 253 508 live singleton births in Denmark (1973–2004) and Sweden (1973–2006). Children born to mothers who lost a child, spouse, sibling, or parent during or 1 year before pregnancy were categorized as exposed.ResultsPrenatal maternal bereavement was associated with a 10% increased all-cause mortality risk in offspring [mortality rate ratio (MRR) 1.10, 95% confidence interval (CI) 1.03–1.18]. The association was the most pronounced for children of mothers who lost a child/spouse (MRR 1.28, 95% CI 1.14–1.44) and was stronger during the first 10 years of life. Prenatal maternal bereavement may have stronger effects on natural causes of death in offspring, including infectious/parasitic disease (MRR 1.86, 95% CI 1.07–3.23), endocrine/nutritional/metabolic diseases (MRR 3.23, 95% CI 2.02–5.17), diseases of nervous system (MRR 3.36, 95% CI 2.47–4.58), and congenital malformations (MRR 1.39, 95% CI 1.08–1.80). No excess mortality risk in offspring was observed for unnatural causes of death.ConclusionPrenatal maternal bereavement was associated with an increased long-term mortality risk in offspring, particularly for selected natural causes of diseases and medical conditions. Our results support the fetal programming hypothesis that prenatal stress may contribute to ill health from physical diseases later in life. [ABSTRACT FROM AUTHOR]

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 (<32 and 32–36 weeks, respectively) and spontaneous and medically indicated 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. [ABSTRACT FROM PUBLISHER]