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.

Perinatal depression and risk of maternal cardiovascular disease: a Swedish nationwide study.

BACKGROUND AND AIMS: Increasing evidence suggests that some reproductive factors/hazards are associated with a future risk of cardiovascular disease (CVD) in women. While major (non-perinatal) depression has consistently been associated with CVD, the long-term risk of CVD after perinatal depression (PND) is largely unknown. METHODS: A nationwide population-based matched cohort study involving 55 539 women diagnosed with PND during 2001-14 in Sweden and 545 567 unaffected women individually matched on age and year of conception/delivery was conducted. All women were followed up to 2020. Perinatal depression and CVD were identified from Swedish national health registers. Using multivariable Cox models, hazard ratios (HR) of any and type-specific CVD according to PND were estimated. RESULTS: The mean age at the PND diagnosis was 30.8 [standard deviation (SD) 5.6] years. During the follow-up of up to 20 years (mean 10.4, SD 3.6), 3533 (6.4%) women with PND (expected number 2077) and 20 202 (3.7%) unaffected women developed CVD. Compared with matched unaffected women, women with PND had a 36% higher risk of developing CVD [adjusted HR = 1.36, 95% confidence interval (CI): 1.31-1.42], while compared with their sisters, women with PND had a 20% higher risk of CVD (adjusted HR = 1.20, 95% CI 1.07-1.34). The results were most pronounced in women without a history of psychiatric disorder (P for interaction < .001). The association was observed for all CVD subtypes, with the highest HR in the case of hypertensive disease (HR = 1.50, 95% CI: 1.41-1.60), ischaemic heart disease (HR = 1.37, 95% CI: 1.13-1.65), and heart failure (HR 1.36, 95% CI: 1.06-1.74). CONCLUSIONS: Women with PND are at higher risk of CVD in middle adulthood. Reproductive history, including PND, should be considered in CVD risk assessments of women.

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.

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.

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.

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.

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.

Death of a child and the risk of atrial fibrillation: a nationwide cohort study in Sweden.

AIMS: The role of psychological stress in the aetiology of atrial fibrillation (AF) is unclear. The death of a child is one of the most severe sources of stress. We aimed to investigate whether the death of a child is associated with an increased risk of AF. METHODS AND RESULTS: We studied parents with children born during 1973-2014 included the Swedish Medical Birth Register (n = 3 924 237). Information on death of a child, AF and socioeconomic, lifestyle and health-related covariates was obtained through linkage to nationwide population and health registers. We examined the link between death of a child and AF risk using Poisson regression. Parents who lost a child had a 15% higher risk of AF than unexposed parents [incidence rate ratio (IRR) and 95% confidence intervals (CI): 1.15 (1.10-1.20)]. An increased risk of AF was observed not only if the child died due to cardiovascular causes [IRR (95% CI): 1.35 (1.17-1.56)], but also in case of deaths due to other natural [IRR (95% CI): 1.15 (1.09-1.21)] or unnatural [IRR (95% CI): 1.10 (1.02-1.19)] causes. The risk of AF was highest in the 1st week after the loss [IRR (95% CI): 2.87 (1.44-5.75)] and remained 10-40% elevated on the long term. CONCLUSIONS: Death of a child was associated with a modestly increased risk of AF. Our finding that an increased risk was observed also after loss of a child due to unnatural deaths suggests that stress-related mechanisms may also be implicated in the development of AF.

Death of an offspring and parental risk of ischemic heart diseases: A population-based cohort study.

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

Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study.

BACKGROUND: The prevalence of cardiovascular disease (CVD) has been increasing in children, adolescents, and young adults in recent decades. Exposure to adverse intrauterine environment in fetal life may contribute to the elevated risk of early-onset CVD. Many studies have shown that maternal hypertensive disorders of pregnancy (HDP) are associated with increased risks of congenital heart disease, high blood pressure, increased BMI, and systemic vascular dysfunction in offspring. However, empirical evidence on the association between prenatal exposure to maternal HDP and early-onset CVD in childhood and adolescence remains limited. METHODS AND FINDINGS: We conducted a population-based cohort study using Danish national health registers, including 2,491,340 individuals born in Denmark from 1977 to 2018. Follow-up started at birth and ended at the first diagnosis of CVD, emigration, death, or 31 December 2018, whichever came first. Exposure of maternal HDP was categorized as preeclampsia or eclampsia (n = 68,387), gestational hypertension (n = 18,603), and pregestational hypertension (n = 15,062). Outcome was the diagnosis of early-onset CVD from birth to young adulthood (up to 40 years old). We performed Cox proportional hazards regression to evaluate the associations and whether the association differed by maternal history of CVD or diabetes before childbirth. We further assessed the association by timing of onset and severity of preeclampsia. The median follow-up time was 18.37 years, and 51.3% of the participants were males. A total of 4,532 offspring in the exposed group (2.47 per 1,000 person-years) and 94,457 in the unexposed group (2.03 per 1,000 person-years) were diagnosed with CVD. We found that exposure to maternal HDP was associated with an increased risk of early-onset CVD (hazard ratio [HR]: 1.23; 95% CI = 1.19 to 1.26; P < 0.001). The HRs for preeclampsia or eclampsia, gestational hypertension, and pregestational hypertension were 1.22 (95% CI, 1.18 to 1.26; P < 0.001), 1.25 (95% CI, 1.17 to 1.34; P < 0.001), and 1.28 (95% CI, 1.15 to 1.42; P < 0.001), respectively. We also observed increased risks for type-specific CVDs, in particular for hypertensive disease (HR, 2.11; 95% CI, 1.96 to 2.27; P < 0.001) and myocardial infarction (HR, 1.49; 95% CI, 1.12 to 1.98; P = 0.007). Strong associations were found among offspring of mothers with CVD history (HR, 1.67; 95% CI, 1.41 to 1.98; P < 0.001) or comorbid diabetes (HR, 1.56; 95% CI, 1.34 to 1.83; P < 0.001). When considering timing of onset and severity of preeclampsia on offspring CVD, the strongest association was observed for early-onset and severe preeclampsia (HR, 1.48, 95% CI, 1.30 to 1.67; P < 0.001). Study limitations include the lack of information on certain potential confounders (including smoking, physical activity, and alcohol consumption) and limited generalizability in other countries with varying disparities in healthcare. CONCLUSIONS: Offspring born to mothers with HDP, especially mothers with CVD or diabetes history, were at increased risks of overall and certain type-specific early-onset CVDs in their first decades of life. Further research is warranted to better understand the mechanisms underlying the relationship between maternal HDP and early-onset CVD in offspring.

Prenatal Maternal Bereavement and Its Association With Intellectual Disability in the Offspring.

OBJECTIVE: This study aimed to examine the association of a mother's loss of a close relative before or during pregnancy with intellectual disability (ID) in the offspring. METHODS: We performed a nationwide population-based cohort study based on Danish national registries. All live-born singletons born in Denmark during the 1978-2016 period (n = 2,216,601) were followed up starting from birth to 38 years of age. Log-linear Poisson regression was used to estimate the association between maternal bereavement (the death of an older child, a partner, or a parent 1 year before or during pregnancy) and the risk of ID in the offspring. RESULTS: Maternal bereavement during or before pregnancy was associated with an increased risk of ID (incidence rate ratio [IRR] = 1.15; 95% confidence interval [CI] = 1.04-1.28). The risk of ID was increased by 27% when maternal bereavement occurred during pregnancy (IRR = 1.27; 95% CI = 1.08-1.49). When stratifying on the child's sex, we also observed an increased risk of ID associated with maternal bereavement during pregnancy both for male (IRR = 1.25; 95% CI = 1.02-1.53) and for female (IRR = 1.31; 95% CI = 1.02-1.69), respectively. The IRRs for unnatural death of a relative were also elevated (IRR = 1.22; 95% CI = 0.91-1.64) in general, although the difference was not statistically significant. CONCLUSIONS: Our findings suggest that prenatal stress due to maternal loss of a close relative may increase the risk of offspring's ID of both sexes, in particular when the loss happened during pregnancy.

Maternal hypertensive disorders and neurodevelopmental disorders in offspring: a population-based cohort in two Nordic countries.

Maternal hypertensive disorders during pregnancy (HDP) have been associated with neuropsychiatric problems in offspring. We aim to investigate the associations between specific types of maternal HDP and offspring neurodevelopmental disorders and further examine whether the timing of onset and severity of HDP would affect these associations. The study population consisted of 4,489,044 live-born singletons in Denmark during 1978-2012 and Sweden during 1987-2010. Maternal HDP was categorized into chronic hypertension, gestational hypertension, and pre-eclampsia; pre-eclampsia was further stratified according to timing (early-onset, late-onset), or severity (moderate, severe) of the disease. Neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID), were defined by ICD-coded register diagnosis. Cox regression was used to calculate hazard ratios (HR) while adjusting for potential confounders, and sibling analyses assessed the influence of unmeasured shared familial factors. Maternal HDP was associated with increased risks of ADHD (HR, 1.24; 95% confidence interval [CI], 1.20-1.28), ASD (1.29 [1.24-1.34]), and ID (1.58 [1.50-1.66]) in offspring, respectively, which was mostly driven by pre-eclampsia. The strongest associations were observed for early-onset and severe pre-eclampsia, and the corresponding HRs for ADHD, ASD and ID were 1.93 [1.73-2.16], 1.86 [1.61-2.15], and 3.99 [3.42-4.65], respectively. The results were similar in the sibling analyses. The associations between maternal HDP and offspring neurodevelopmental disorders were consistent across the subgroups of sex, preterm status, parity, maternal age and psychiatric disorders. Maternal HDP, especially early-onset pre-eclampsia, are associated with increased risks of ADHD, ASD, and ID in particular, independent of shared familial factors.

Death of a Parent During Childhood and the Risk of Ischemic Heart Disease and Stroke in Adult Men.

OBJECTIVE: The death of a parent during childhood is a severe life event with potentially long-term consequences. Earlier studies have shown an increased risk of cardiovascular diseases (CVD) after the death of a spouse, child, or sibling. Whether parental death during childhood is associated with an increased risk of incident CVD is unknown and was investigated in this study. METHODS: We studied 48,992 men born 1949 to 1951 and enlisted for military conscription in 1969 to 1970. We obtained information on death of a parent during childhood, CVD up to 2008, and covariates by linking the questionnaire and the clinical examination data from conscription with nationwide socioeconomic and health registers. RESULTS: Men who lost a parent during childhood had an increased risk of ischemic heart disease (IHD; adjusted hazard ratio (HR) and 95% confidence interval [CI] = 1.30 [1.13-1.49]) but not of stroke during the 39-year follow-up (adjusted HR [95% CI] = 0.87 [0.66-1.15]). Maternal death was associated with IHD both when the loss was due to cardiovascular (adjusted HR [95% CI] = 2.04 [1.02-4.08]) and unnatural causes (adjusted HR [95% CI] = 2.50 [1.42-4.42]); in case of paternal death, an increased IHD risk was observed only when the loss was due to cardiovascular causes (adjusted HR [95% CI] = 1.82 [1.37-2.42]). There were no substantial differences in CVD according to the child's age at the loss. CONCLUSIONS: Parental death during childhood was associated with an increased risk of IHD in men. If these associations are confirmed in future studies, the long-term effects of childhood bereavement may warrant attention.

Maternal Bereavement the Year Before or During Pregnancy and Total and Cause-Specific Infant Mortality: A Cohort Study From Denmark and Sweden.

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.

Sickness absence and disability pension in relation to first childbirth and in nulliparous women according to occupational groups: a cohort study of 492,504 women in Sweden.

BACKGROUND: Childbirth has been suggested to increase sickness absence (SA) and disability pension (DP). This may vary by occupation; however, knowledge in this field remains limited. We explored SA and DP in the years before and after childbirth among women in four occupational groups and those without occupation. METHODS: We studied nulliparous women aged 18-39 years, living in Sweden on December 31, 2004 (n = 492,504). Women were categorized into five skill-level based occupational groups and three childbirth groups; no childbirths within 3 years (B0), first childbirth in 2005 with no childbirth within 3 years (B1), and first childbirth in 2005 with at least one more birth within 3 years (B1+). We compared crude and standardized annual mean SA (in spells> 14 days) and DP net days in the 3 years before and 3 years after first childbirth date. RESULTS: Women in the highest skill level occupations and managers, had less mean SA/DP days during most study years than women in the lowest skill level occupations group. In B1 and B1+, absolute differences in mean SA/DP, particularly in SA, among occupational groups were highest during the year before childbirth. DP was most common in B0, regardless of group and year. CONCLUSIONS: We found that women's mean SA/DP days before and after first childbirth was higher with decreasing skill-level of the occupational group and these differences were most pronounced in the year before childbirth. DP was most common among women not giving birth, regardless of occupational group.

School climate and mental health among Swedish adolescents: a multilevel longitudinal study.

BACKGROUND: School is one of the most formative institutions for adolescents' development, but whether school environment affects mental health is uncertain. We investigated the association between the school's pedagogical and social climate and individual-level mental health in adolescence. METHODS: We studied 3416 adolescents from 94 schools involved in KUPOL, a longitudinal study conducted in eight regions in Sweden. School climate was reported by the school's teaching personnel and by the final year students using the teacher and the student versions of the Pedagogical and Social Climate Questionnaire, respectively. Index persons' mental health was assessed with the Center for Epidemiological Studies Depression Scale for Children and the Strengths and Difficulties Questionnaire. We performed multilevel logistic regression models adjusted for individual, familial and school-level confounders measured in grade 7 and exposure and outcome measured in grades 8 and 9. RESULTS: The adjusted odds ratios and 95% confidence intervals comparing the middle and the high to the lowest tertile of the total teacher school climate score were 1.47 (1.10-1.97) and 1.52 (1.11-2.09) for depressive symptoms and 1.50 (1.08-2.08) and 1.64 (1.16-2.33) for the total strengths and difficulties score. In contrast, there was no association between total student school climate score and mental health. CONCLUSIONS: We found that teacher-, but not student-rated school climate was associated with an increased risk of poor mental health at the student level; the association was most pronounced for internalizing problems. Given schools' importance for adolescents' development, further studies are needed to clarify the mechanisms underlying the observed association.

Association between adolescents' academic aspirations and expectations and mental health: a one-year follow-up study.

Background: Mental health problems among youth have increased in Sweden in recent decades, as has competition in higher education and the labour market. It is unknown whether the increasing emphasis put on educational achievement might negatively affect adolescents' mental health. We aimed to investigate the relationship between adolescents' academic aspirations and expectations and the risk of mental health problems. Methods: We studied 3343 Swedish 7th grade adolescents (age 13), who participated in the first two waves of the KUPOL longitudinal study; participants answered a questionnaire encompassing the five-item Future Aspirations and Goals (FG) subscale of the Student Engagement Instrument, two questions about their own academic aspirations and expectations and two mental health instruments: the Center for Epidemiological studies for Children (CES-DC) (α=.90) and the Strengths and Difficulties Questionnaire (SDQ) (α=.78). The association between aspirations and expectations at baseline and mental health at follow-up was analysed using logistic regression models adjusting for baseline mental health, socio-demographic and family factors. Results: The FG subscale was inversely and linearly associated with the odds of high CES-DC score [adjusted OR (odds ratio) 0.71, 95% CI (confidence interval): 0.59-0.86], total Strengths and Difficulties Questionnaire score (OR 0.59, 95% CI 0.49-0.71), and its internalizing (OR 0.70, 95% CI 0.59-0.84) and externalizing problems scores (OR 0.58, 95% CI 0.48-0.71). Conclusions: Adolescents with high individual academic aspirations have less mental health problems at 1-year follow-up. Future studies should investigate whether interventions aimed at increasing aspirations and engagement in school may prevent mental health problems in adolescence.

The Risk of Gestational Diabetes Mellitus Following Bereavement: A Cohort Study from Denmark and Sweden.

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.

Prenatal maternal bereavement and risk of eating disorders in infants and toddlers: a population-based cohort study.

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.