Organophosphate esters (OPEs) are widely used synthetic chemicals associated with increased plasma glucose in the general populations; however, evidence regarding their associations among pregnant women remains limited. In the Shanghai-Minhang Birth Cohort Study, urinary concentrations of eight OPE metabolites were measured at 12–16 weeks of gestation. Data on fasting plasma glucose (FPG) and 1 h-plasma glucose (1 h-PG) were obtained from medical records. Women were classified as having elevated glucose levels based on abnormal FPG, 1 h-PG, or a diagnosis of gestational diabetes mellitus (GDM). Multiple linear regression and Bayesian Kernel Machine Regression (BKMR) were employed to estimate associations between individual OPE metabolites or OPE mixtures and plasma glucose levels. Modified Poisson regression assessed the associations of OPE metabolites with the risk of elevated glucose levels. Compared with the lowest exposure group, the highest exposure to bis(1,3-dichloro-2-propyl) phosphate, dibutyl phosphate, and diphenyl phosphate was significantly associated with lower FPG levels. However, 1 h-PG levels tended to increase in the moderate exposure group, with ΣCl-OPEs showing a marginally significant association. Poisson regression results similarly indicated that pregnant women with moderate exposure had an increased risk of elevated glucose levels, though without statistical significance. The BKMR model produced similar findings, indicating that chlorinated-OPE primarily contributed to altered FPG and 1 h-PG, with bis(1,3-dichloro-2-propyl) phosphate and bis(1-chloro-2-propyl) phosphate being the major contributors, respectively. Additionally, associations between OPE exposure and decreased FPG levels were predominantly observed among pregnant women with daily fruit and vegetable intake. The present study observed different association patterns between OPE exposure and FPG or 1 h-PG levels, suggesting potential disruptive effects of OPEs on glucose homeostasis during pregnancy.

Importance:Bereavement is a known risk factor for cardiovascular disease (CVD), but it remains unclear whether the COVID-19 pandemic-which disrupted health care and increased social isolation-altered this association. Objective:To compare the association between bereavement and incident CVD before and during the pandemic. Design, Setting, and Participants:This cohort study of Swedish national health registries included individuals aged 30 years or older in Sweden during the pre-COVID-19 (2018-2019) and COVID-19 (2020-2021) periods. Analyses were performed between September 2024 and August 2025. Exposures:Bereavement exposure was defined as the loss of a partner, child, parent, or sibling. Main Outcomes and Measures:The first diagnosis of any CVD event, identified from an outpatient hospital visit or hospitalization via the Swedish Patient Register or death via the Swedish Cause of Death Register. Cox regression was used to estimate hazard ratios (HRs) of incident CVD after bereavement by study period, type of loss, and age. Results:Analysis included a total of 5 365 829 study participants (51.4% female; median [IQR] age, 51.6 [40.4-64.6] years) during the pre-COVID-19 period and 5 522 898 study participants (51.4% female; median [IQR] age, 49.8 [38.2-62.8] years) during the COVID-19 period. Overall, 372 477 (6.94%) and 368 902 (6.68%) incident CVD cases were identified during the pre-COVID-19 and COVID-19 periods, respectively. Bereavement was associated with increased CVD risk regardless of period or type of loss. However, the risk increment was greater during the COVID-19 period compared with the pre-COVID-19 period for loss of a partner (HR, 1.46 [95% CI, 1.41-1.51] vs 1.30 [95% CI, 1.26-1.35]; P for difference < .001) and sibling (HR, 1.23 [95% CI, 1.20-1.27] vs 1.16 [95% CI, 1.13-1.19]; P for difference = .003). No period difference was noted for the loss of a child or parent. The risk increment after loss of a partner or parent increased with age, while the risk after loss of a child or sibling decreased with age. Conclusions and Relevance:In this cohort study, bereavement was associated with increased CVD risk both before and during the COVID-19 pandemic; however, a stronger association for partner or sibling loss was noted during the pandemic. These findings suggest that bereavement may be a period of heightened cardiovascular vulnerability, underscoring the importance of targeted clinical monitoring and preventive care for bereaved individuals.

Abstract Objective To evaluate the associations between maternal history of psychiatric disorders and the risk cardiovascular disease (CVD) in offspring. Design Population based cohort study. Setting Nationwide health registers in Sweden. Participants All 4 171 005 liveborn singletons in Sweden from 1973 to 2014. Follow-up started at birth and ended until the first diagnosis of CVD, death, emigration, or December 31 st , 2023, whichever occurred first. Exposures for observational studies Maternal psychiatric disorders diagnosed before delivery (n=208,680, 5.0%). Main outcome measures The primary outcome was the first diagnosis of CVD in offspring, identified through hospital registers. Additional outcomes included specific CVD subtypes. To address potential familial confounding, a cousin comparison was performed, comparing the risk of CVD in offspring born to mothers who were biological sisters. Mediation analyses examined the roles of congenital heart disease, small for gestational age, and preterm birth. Results During up to 51 years of follow-up, 307 596 (7.4%) offspring had a diagnosis of CVD. Maternal history of psychiatric disorders was associated with a higher risk of overall CVD both in the full cohort (hazard ratio 1.19, 95% confidence interval 1.17 to 1.21) and the cousin-comparison cohort (n=1 577 113; 1.08, 1.03 to 1.13). In disease-specific analyses, a prominent association with heart failure was robustly observed in both the full cohort (1.59, 1.37 to 1.85) and the cousin comparison cohort (1.51, 1.06 to 2.17). Mediation analyses indicated that congenital heart disease mediated 9.5% of the association between maternal psychiatric disorders and offspring CVD risk. Preterm birth and small for gestational age contributed minimally (<3%) to the observed associations. Conclusions Maternal history of psychiatric disorders was associated with an increased risk of CVD up to early middle-age in offspring. Congenital heart disease partly mediated this association.

Early identification of individuals at risk of dementia is essential for effective prevention and timely intervention. Existing risk scores rely heavily on age, which limits their discriminative power at clinically relevant thresholds such as 65 years, when preventive strategies might be most impactful. We analysed 76 427 adults aged 65 years (52·1% women) from the UK and French THIN primary care databases. Using routinely collected diagnoses, prescriptions, and clinical characteristics, we developed and validated a transparent risk algorithm for incident Alzheimer’s disease and all-cause dementia. Logistic regression was compared with random forests, support vector machines, and neural networks to predict dementia risk at 2, 5, and 10 years. Model calibration was assessed using the Brier score. Key predictors included medication classes (eg, laxatives, urological drugs, antidepressants), sex, BMI, and number of comorbidities. At 65 years, calibration to a 5% false-positive rate identified 54·6%, 34·8%, and 23·6% of incident dementia cases at 2, 5, and 10 years, respectively. Conversely, calibration to a 50% detection rate yielded false-positive rates of 3·1%, 16·2%, and 20·8%. Precision among the top 1% of predicted risk ranged from 16·9% to 18·0%, representing a 10·7–46·2-fold enrichment of a hypothetical prevention randomised controlled trial over baseline prevalence. A simple, deployable algorithm based on prescriptions and clinical records, without laboratory data, can identify patients at high near-term risk of dementia at age 65. This approach is cost-effective, readily deployable in primary care, and offers substantial potential to enrich prevention trials and targeted screening programmes. Dementia is easier to prevent when people at risk are found early, but most existing tools rely mainly on age, so they work poorly when everyone is the same age. We wanted a way to spot higher-risk people at age 65, when prevention may help most. Using anonymous health records from more than 76,000 adults in the UK and France, we built a simple computer tool that looks only at routine information a family doctor already has, such as prescribed medicines and basic health details. The tool could pick out many of the people who later developed dementia. Because it is cheap and easy to use, it could help doctors and speed up research into ways to prevent dementia. Nedelec et al. developed a simple algorithm that uses routine primary care records, such as prescribed medicines, to identify people at higher risk of dementia at age 65. The tool detects some cases years in advance and could help enrich prevention trials and target screening.

Importance:The long-term risks of specific cardiovascular diseases (CVDs) among offspring exposed to various types of maternal diabetes in utero and the mechanisms underlying these risks remain unclear. Objective:To investigate the association between maternal diabetes during pregnancy and risks of overall CVD and specific CVD subtypes in offspring and whether adverse perinatal and early-life outcomes mediate associations. Design, Setting, and Participants:This nationwide population-based cohort study using linked national registers included individuals born in Sweden between January 1, 1973, and December 31, 2014, with follow-up through December 31, 2023. Exposures:Maternal diabetes during pregnancy, including gestational diabetes and pregestational diabetes (type 1 and type 2). Main Outcomes and Measures:The main outcomes were incident overall CVD and specific CVD subtypes in offspring, identified from national inpatient and outpatient registers. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Sibling analyses were conducted to account for shared familial factors. Mediation analyses assessed the contribution of congenital heart disease (CHD), preterm birth, and large for gestational age (LGA). Results:The study included 4 274 414 individuals (51.39% male; mean [SD] age, 27.4 [15.0] years at the end of follow-up), of whom 61 336 (1.46%) were exposed to maternal diabetes and 4 213 078 (98.56%) were not exposed. During a median 27.6 years (IQR, 17.2-37.4 years) of follow-up, 7.36% of total participants had a diagnosis of CVD. Any maternal diabetes was associated with an increased risk of overall CVD in offspring (HR, 1.16; 95% CI, 1.12-1.20); risk of CVD was higher for pregestational diabetes (HR, 1.29; 95% CI, 1.21-1.38) than for gestational diabetes (HR, 1.11; 95% CI, 1.05-1.17). These associations were also found in sibling analyses. Increased risks in offspring prenatally exposed to maternal diabetes were found for some CVD subtypes, including venous thromboembolism (HR, 1.20; 95% CI, 1.07-1.34), cerebrovascular diseases (HR, 1.31; 95% CI, 1.12-1.52), atrial fibrillation (HR, 1.27; 95% CI, 1.05-1.54), and heart failure (HR, 1.65; 95% CI, 1.37-2.00). In mediation analyses, CHD, preterm birth, and LGA directly and/or indirectly mediated 31.87%, 16.06%, and 14.18% of the association between any diabetes and offspring CVD risk, respectively. Conclusions and Relevance:This cohort study found that maternal diabetes during pregnancy was associated with increased long-term risks of overall CVD and some CVD subtypes in offspring, particularly following pregestational diabetes. These findings highlight the importance of associations of perinatal and early-life factors and offspring CVD risk later in life, especially in mothers with diabetes.

Bereavement is associated with an increased risk of mental illness. The COVID-19 pandemic caused excess mortality, and may have exacerbated the mental health impact of bereavement due to social restrictions and reduced healthcare access. Using Swedish national register data, this study aimed to compare the risk of mental illness following bereavement before (2018-2019) and during (2020-2021) the pandemic, exploring how the pandemic might have modified the psychological impact of bereavement and identifying high-risk groups.We conducted a nationwide matched cohort study including (1) 3,840,845 individuals (349,168 bereaved) before the pandemic, and (2) 5,132,988 individuals (466,636 bereaved) during the pandemic. Mental illness was defined as the first occurrence of any psychiatric diagnosis or suicidal behavior during each period. Multivariable Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We found that bereaved individuals had a significantly higher risk of mental illness compared to non-bereaved individuals in both periods (before pandemic: HR 1.42, 95%CI 1.34-1.49; during pandemic: HR 1.34, 95%CI 1.28-1.39). Bereaved individuals younger than 30 years had markedly higher risks of psychiatric disorders in the pre-pandemic period compared to the pandemic period. Higher risks of incident psychiatric disorders were observed for loss of a child or spouse, compared to loss of a sibling or parent, as well as for loss due to accident or suicide as compared to other causes. Furthermore, bereavement due to COVID-19 was associated with an increased risk of mental illness during the pandemic period (HR 1.38, 95% CI 1.21-1.59). In conclusion, bereavement was consistently associated with an increased risk of mental illness, before and during COVID-19 pandemic, although young individuals (<30 years) seemed more affected before the pandemic. However, further research in settings with a different pandemic burden and/or mitigation strategies is needed to assess the generalizability of our findings beyond Sweden.

BACKGROUND AND OBJECTIVES:The prevalence of Parkinson disease (PD), multiple sclerosis (MS), and motor neuron diseases (MNDs) is rising globally. However, it is unclear to what degree this is related to an increase in incidence or to improved survival after diagnosis. METHODS:We performed 2 nationwide, population-based, retrospective cohort studies, including all individuals living in Sweden between 2001 and 2016 and living in France between 2009 and 2022, respectively. Pooled mixed-effects regression models, with country as a random effect, were used to determine temporal trends in prevalence, crude and age-standardized and sex-standardized incidence, and age and life expectancy at diagnosis. RESULTS:Annualized prevalence of PD, MS, and MNDs increased significantly between 2003 and 2022 in the pooled model (PD: prevalence ratio [PR] per year = 1.014, p < 0.001; MS: PR = 1.029, p < 0.001; MND: PR = 1.028, p < 0.001). While the crude incidence of both PD and MS remained nearly stable over time (PD: incidence rate ratio [IRR] per year = 0.998, p < 0.001; MS: IRR = 0.992, p < 0.001), the standardized incidence showed a more marked decrease for PD (IRR = 0.986, p < 0.001) while remaining almost unchanged for MS (IRR = 0.995, p < 0.001). For MNDs, both the crude and standardized incidence increased over time (crude IRR = 1.018, p < 0.001; standardized IRR = 1.008, p < 0.001). Life expectancy at diagnosis of PD increased between 2003 and 2013 (+0.95 months per calendar year, p < 0.001) and then decreased between 2013 and 2022 (-1.20 months, p = 0.002), while it increased significantly over the entire study period for MS (+2.35 months, p < 0.001) and MNDs (+0.34 months, p = 0.01). DISCUSSION:These findings indicate that the rising MS prevalence is largely survival-driven and the rising MND prevalence reflects a true increase in incidence, whereas PD prevalence grows modestly, largely independent of incidence. Depending on the mechanism that drives prevalence, whether increased incidence reflecting changing risk factor exposures, improved survival due to therapeutic advances, or demographic aging of the population, inferences about underlying causes differ substantially between PD, MS, and MNDs, with direct implications for health care planning and etiologic research.

BACKGROUND:Accumulating evidence demonstrates associations between clonal hematopoiesis of indeterminate potential (CHIP) and increased risks of haematological and non-haematological health outcomes. Although adverse health consequences of CHIP have become well-documented, large knowledge gaps exist regarding the aetiology of CHIP. OBJECTIVE:To investigate risk factors for CHIP using large-scale phenotypic data and Mendelian randomisation analysis. METHODS:We utilised rich phenotypic and genomic data from the UK Biobank (UKB) to perform a cross-sectional study to systematically investigate risk factors of CHIP, including around 460,000 participants recruited from 2006 to 2010. We used Logistic regression to estimate odds ratios (ORs) of CHIP in relation to risk factors (sociodemographic factors, lifestyle factors, history of diseases, blood cell count, blood biochemistry parameters, proteomics biomarkers and metabolomics biomarkers). In addition, we conducted Mendelian Randomisation (MR) analyses to assess causality between the studied risk factors and CHIP, using publicly available summary statistics of genome-wide association studies (GWAS). RESULTS:We found that advanced age, smoking, history of several diseases (including breast cancer and leiomyoma of uterus), as well as several serum biomarkers (monocyte count, proteins LY75, SIGLEC6, SIRPB1 and CYB5R2) were associated with CHIP. CONCLUSION:Our findings expanded existing knowledge base by demonstrating novel risk factors of CHIP, especially history of several diseases and serum biomarkers. These findings advance understanding of the aetiology of CHIP.

Prenatal exposure to organophosphate esters (OPEs) and polybrominated diphenyl ethers (PBDEs) has been linked to disrupted fetal thyroid hormone (TH), though the underlying mechanisms remain unclear. Based on the S-MBCS cohort, we analyzed OPE metabolite concentrations in maternal urine during early pregnancy and PBDE levels in cord plasma. Methylation of five TH regulatory genes, namely deiodinase type 3 (DIO3), solute carrier family 16 member 2 (SLC16A2), solute carrier organic anion transporter family member 1C1 (SLCO1C1), thyrotropin-releasing hormone (TRH), and transthyretin (TTR), was quantified in the placenta. We investigated the associations between prenatal exposure to PBDEs and OPEs and DNA methylation of placental TH-related genes, using samples from 240 and 327 mother-newborn pairs, respectively. We further examined sex-specific differences in these associations and assessed whether the observed epigenetic alterations mediated the relationship between exposures and TH disruption. Mediation analyses were conducted in a subset of mother-newborn pairs with available TH measurements in cord plasma. BDE-47 and ΣPBDE showed sex-specific relationships with DIO3 and SLC16A2 methylation, with a significant positive association in females and a non-significant inverse association in males. Both BDE-47 and ΣPBDEs were linked to SLCO1C1 hypermethylation. OPE metabolites were positively associated with DIO3 and TTR methylation, predominantly in females. Mediation analyses suggested that SLCO1C1 hypermethylation mediated 6.5-7.0 % of the association between ΣPBDE exposure and reduced free triiodothyronine. These findings highlight sex-specific epigenetic changes in placental TH-related genes in relation to PBDE and OPE exposure, providing novel insights into fetal thyroid disruption pathways.

BACKGROUND:Pairwise associations among fine particulate matter (PM2.5), gut microbiota, and cardiovascular disease (CVD) have been established. However, the mediating role of gut microbiota in the relationship between PM2.5 and its components and CVD remains unclear. METHODS:We included 1459 participants from the China Multi-Ethnic Cohort between May 2018 and September 2019. CVD was identified using ICD-10 codes based on hospital surveillance system. PM2.5 and its components were sourced from the ChinaHighAirPollutants dataset. Gut microbiota was obtained from 16S rRNA sequencing of stool samples, and five α-indexes along with 1088 gut compositions were used as mediators. Cox proportional hazards and multiple linear regression were used to explore the associations among PM2.5 and its components, gut microbiota, and CVD. Causal mediation analysis was conducted to evaluate the potential mediating role of gut microbiota between PM2.5 and its components and CVD. RESULTS:Among all the participants, 204 (14.0 %) had developed CVD during a 5501 person-year follow-up (median, 3.8 years). The ACE, Chao1, and Obs indexes positively mediated the associations of PM2.5 and its components with both CVD and stroke, with mediation proportions ranging from 7.9 % to 8.9 % for CVD and 10.0 %-12.1 % for stroke. The ACE index had the highest mediation proportion (12.1 %) in the relationship between sulfate and stroke. The genus Pasteurella also demonstrated a mediating role, accounting for 2.6 %-3.2 % for CVD, and 2.5 %-3.6 % for stroke, exhibiting the highest mediation proportion (3.6 %) on the association between black carbon or nitrate and stroke. CONCLUSION:Three α-indexes (ACE, Chao1, and Obs) and the Pasteurella positively mediated the association between PM2.5 and its components and CVD risk. Enhancing the richness of gut microbiota could potentially reduce the risk of CVD induced by PM2.5 and its components.

Although past screening cohorts have suggested a decline in the risk of dementia, it is important to monitor the population-level incidence and survival of diagnosed dementia, to inform care utilization and public health policies. This study provides nationwide analyses on time trends in the incidence of dementia diagnosis in Sweden between 2007 and 2022, as well as 5-year survival after a dementia diagnosis. Data from the total Swedish population aged ≥ 61 years during the period 2007–2022 were used. Incident dementia diagnoses were identified from specialist care and dispensed anti-dementia drugs. The annual incidence rate of dementia diagnosis was calculated for the period 2007–2022. The proportion of individuals that survived 5 years after dementia diagnosis was compared across years of diagnosis. Health status at dementia diagnosis was assessed by calculating Charlson Comorbidity Index and Hospital Frailty Risk Score. Annual incidence rate of dementia diagnosis decreased from early 2010s and onwards, particularly among older age groups of 80–89 and ≥ 90 years. Mean age at dementia diagnosis remained constant, i.e., 82.2 years during 2007–2009 and 82.2 years during 2019–2022. The proportion of individuals with frailty at diagnosis increased from 74.3

BACKGROUND:Many studies have investigated early predictors for Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, evidence is sparse regarding specific and common predictors for these diseases. We aimed to identify medication use, health conditions, and blood biomarkers that might be associated with the risk of AD, PD, and ALS ten years later. METHODS:We conducted population-based nested case-control studies of AD, PD, and ALS using electronic medical records in Europe (France, the UK, and Sweden) and Australia. We retrieved data on medication use, diagnosed health conditions, and measured blood biomarkers from electronic medical records or biomedical cohorts. Conditional logistic regression models and meta-analysis were applied to assess the associations between these factors and the risk of receiving a diagnosis of AD, PD, or ALS. FINDINGS:We included a total of 149,642 AD cases (mean age: 79.1-81.2 years), 252,696 PD cases (73.2-75.9 years), and 27,533 ALS cases (64.4-69.6 years). The prescription of psychoanaleptics and nasal preparations was consistently associated with an increased risk of AD, PD, and ALS 5-10 years later. Constipation and use of related medications were associated with an increased risk of AD and PD, while diabetes and use of antidiabetics were associated with a reduced risk of ALS. A higher level of triglycerides was associated with a lower risk of AD, whereas a higher level of Apolipoprotein B was associated with a lower risk of PD, 5-10 years later. INTERPRETATION:Psychoanaleptics and nasal preparations may serve as common predictors for diagnosis of AD, PD, and ALS 5-10 years later. Conversely, the increased prevalence of constipation is specific to AD and PD, while the decreased prevalence of diabetes and use of antidiabetics is specific to ALS. FUNDING:EU Joint Programme-Neurodegenerative Disease Research.

Accumulating evidence indicates that elevated maternal glucose concentrations during pregnancy are associated with adverse birth outcomes, but the mechanistic underpinnings remain unclear. This study aimed to evaluate the associations between maternal glucose concentrations and DNA methylation levels in genes related to the peroxisome proliferator-activated receptor (PPAR) signaling pathway in the human placenta and explore the potential mediating role of placental DNA methylation in the relationship between maternal glucose concentrations and neonatal anthropometric measures. Maternal glucose concentrations were obtained from medical records, and neonatal anthropometric parameters were measured in 335 mother–infant pairs. DNA methylation levels of 14 genes related to the PPAR signaling pathway were analyzed in placental samples. Multiple linear regression models and mediation analyses were used to examine the associations and potential mediation effects. Higher maternal fasting plasma glucose (FPG) concentrations were generally associated with hypomethylation of genes related to the PPAR signaling pathway, with stronger effects in male neonates. Maternal 1-h plasma glucose concentrations after the glucose challenge test exhibited weaker but consistent patterns. Mediation analyses indicated that hypomethylation of ACAA1 mediated 29.00

Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) has been reported to be linked to a series of adverse health outcomes in mothers and their children. As the gut microbiota is a sensitive biomarker for assessing the toxicity of environmental contaminants, this study attempted to investigate whether prenatal PFASs exposure was associated with the gut microbiota of infants. Based on the Shanghai-Minhang Birth Cohort Study, this prospective cohort study included 69 mother-infant pairs. Fasting blood samples were collected from pregnant women for the PFASs assay. We collected fecal samples of infants at 1 year of age and analyzed the V3-V4 hypervariable region of the bacterial 16 S rRNA gene by high-throughput sequencing. Among the detected 11 PFASs, the concentration of perfluorooctanoic acid (22.19 ng/mL) was the highest, followed by perfluorooctane sulfonic acid (12.08 ng/mL). Compared with infants whose mothers’ total PFASs concentrations during pregnancy were at the 40th percentile or lower (reference group), the species richness and diversity of microbiota were lower in infants prenatally exposed to a high level of PFASs (the sum of PFASs concentrations above the 60th percentile). Prenatal exposure to PFASs was associated with a higher proportion of Acidaminococcaceae, Acidaminococcus, Megamonas, Megasphaera micronuciformis and Megamonas funiformis in infants. The changes of the species have been suggested to be associated with immune and metabolic dysfunction in humans. Functional alterations of gut microbiota due to PFASs exposure were dominated by an enrichment of butanoate metabolism. Our preliminary findings may shed light on the potential role of the microbiota underlying the well-known impact of prenatal PFASs exposure on health outcomes of humans in later life.

BackgroundThe 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 findingsWe 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.ConclusionsIn 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.

AbstractChildren born to mothers with polycystic ovary syndrome have a higher prevalence of cardiovascular risk factors and of subclinical cardiovascular disease, but the association between maternal polycystic ovary syndrome and cardiovascular disease in offspring is unclear. We conduct a register-based cohort study of 6 839 703 live singleton births from Denmark (1973–2016) and Sweden (1973–2014) and follow them for up to 48 years. Using Cox regression models, we find that offspring of mothers with polycystic ovary syndrome have a higher risk of overall cardiovascular diseases and of its specific subtypes, independently of comorbidities related to polycystic ovary syndrome. Cousin analyzes suggest that familial confounding does not explain our results. If our findings are replicated by future studies, children of women with polycystic ovary syndrome may benefit from early cardiovascular prevention efforts.