Cerebrovascular disease at young age is related to mother's health during the pregnancy-The Northern Finland Birth Cohort 1966 study

Background and purpose For prevention of cerebrovascular diseases at younger age, it is important to understand the risk factors occurring early in life. We investigated the relationship between mothers' general health during pregnancy and the offspring's risk of cerebrovascular disease in age of 15 to 52 years. Methods Within the population-based prospective Northern Finland Birth Cohort 1966, 11,926 persons were followed from antenatal period to 52 years of age. Information on their mother's ill health conditions, i.e., hospitalizations, chronic diseases, medications, vitamin or iron supplement, fever, anemia, mood, and smoking was collected from 24th gestational week onwards. Ischemic and hemorrhagic cerebrovascular diseases of the offspring were identified from national registers in Finland. Cox proportional hazard models were used to estimate the association of mother's health conditions with incidence of cerebrovascular disease in the offspring, with adjustments for potential confounders. Results During 565,585 person-years of follow-up, 449 (2.8%) of the offspring had a cerebrovascular disease. Hospitalization during pregnancy was associated with an increased risk of cerebrovascular disease in the offspring (hazard ratio (HR) = 1.49; 95% confidence interval (CI) 1.06-2.08) after adjustment for confounders, as was having more than three ill health conditions (HR = 1.89; CI 1.14-3.11). Not using vitamin or iron supplement was associated with increased risk for cerebrovascular disease in the offspring (HR = 1.39; CI 1.01-1.89). Conclusions The results suggest that the risk of cerebrovascular disease may start as early as during the antenatal period, and the health characteristics of mothers during pregnancy may play a role in cerebrovascular disease risk of the offspring.Peer reviewe

Family's socioeconomic profile at birth and offspring mortality until midlife - The Northern Finland Birth Cohort 1966 study

Family's socioeconomic profile collected prenatally is known to predict offspring mortality during early life, but it remains unclear whether it has the potential to predict offspring mortality until later life. In this study, 12,063 individuals belonging to the Northern Finland Birth Cohort 1966 were followed up from mid-pregnancy for 52 years (570,000 person years). Five distinct socioeconomic profiles were identified by latent class analysis based on mother's marital status, education, and occupation; father's occupation; number of family members; location of residence, room count, and utilities; and family's wealth. The classes were highest status families (15.4% of the population), small families (22.1%), larger families (15.4%), average wealth families (23.4%), and rural families (23.3%). Their associations to offspring mortality, via linkage to national offspring death records, were analysed by Cox regression, stratified by sex and age groups (0-19, 20-38 and 40-52 years). In total, mortality was 9.2% among male and 5.0% among female offspring. Risk for midlife mortality was higher among male offspring from larger families (hazard ratio 2.19, 95% confidence interval 1.32-3.63), average wealth families (1.66, 1.02-2.73) and rural families (1.63, 1.00-2.68), relative to offspring from highest status families. It seems that family's socioeconomic profile constructed prenatally has predictive value for midlife mortality among male offspring. Premature mortality of men and women seem to be two distinct phenomena with differing underlying factors as socioeconomic profile was not associated with mortality among female offspring.Peer reviewe

Psychosocial factors and cancer incidence (PSY-CA):Protocol for individual participant data meta-analyses

OBJECTIVES: Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, prostate, colorectal, smoking-related, and alcohol-related); (2) to test the interaction between psychosocial factors and factors related to cancer risk (smoking, alcohol use, weight, physical activity, sedentary behavior, sleep, age, sex, education, hormone replacement therapy, and menopausal status) with regard to the incidence of cancer; and (3) to test the mediating role of health behaviors (smoking, alcohol use, weight, physical activity, sedentary behavior, and sleep) in the relationship between psychosocial factors and the incidence of cancer.METHODS: The psychosocial factors and cancer incidence (PSY-CA) consortium was established involving experts in the field of (psycho-)oncology, methodology, and epidemiology. Using data collected in 18 cohorts (N = 617,355), a preplanned two-stage individual participant data (IPD) meta-analysis is proposed. Standardized analyses will be conducted on harmonized datasets for each cohort (stage 1), and meta-analyses will be performed on the risk estimates (stage 2).CONCLUSION: PSY-CA aims to elucidate the relationship between psychosocial factors and cancer risk by addressing several shortcomings of prior meta-analyses.</p

Depression, anxiety, and the risk of cancer: An individual participant data meta-analysis

BACKGROUND: Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. METHODS: The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2). RESULTS: No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios [HRs], 1.06-1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04-1.23). CONCLUSIONS: Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers. PREREGISTRATION NUMBER: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=157677

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Nervous system medications and suicidal ideation and behaviour:the Northern Finland Birth Cohort 1966

Abstract The aim of this thesis was to explore the associations between the use of nervous system medications and suicidal ideation and behaviour in various different diagnostic groups in a large population-based cohort. Information on prescribed antipsychotic, antidepressant, benzodiazepine and antiepileptic medications within the Northern Finland Birth Cohort 1966 was collected from the register of the Social Insurance Institution of Finland and from a postal questionnaire sent to all cohort members in 1997. The presence of suicidal ideation and depression and anxiety symptoms was assessed via the Hopkins Symptom Checklist-25 questionnaire in 1997. Data on suicides were collected from the cause-of-death statistics and on suicide attempts from the Finnish Care Register for Health Care in a 15-year follow up. The use of antipsychotic, antidepressant, or benzodiazepine medication was associated with increased suicidal ideation, suicide attempts, and suicides. Antiepileptic medication was not associated with increased suicidality. The polypharmacy of nervous system medications was associated with increased suicidality. All nervous system medications were associated with increased severity of depression and anxiety symptoms. When depression and anxiety symptoms were taken into account, most of the associations between medication and suicidal ideation were statistically non-significant. Regarding specific groups, among those who did not have psychosis, high doses of antipsychotic medication correlated particularly with increased suicidal ideation even when other symptoms of depression and anxiety were taken into account. Among those with insomnia, the use of antidepressant medication associated with increased suicidal ideation also when other symptoms were taken into account. Although nervous system medication is associated with increased suicidal ideation, the association with other symptoms is also strong, and therefore it could not be stated that medication associates specifically with suicidal ideation. However, certain groups, i.e., non-psychotic subjects with high doses of antipsychotic medication, or subjects with insomnia and using antidepressant medication, should be closely monitored as they could be more vulnerable to suicidal ideation.Tiivistelmä Tämän väitöstutkimuksen tarkoituksena oli tutkia hermostoon vaikuttavien lääkkeiden, lähinnä psykoosilääkkeiden, masennuslääkkeiden, bentsodiatsepiinien sekä epilepsialääkkeiden, yhteyttä itsetuhoisiin ajatuksiin, itsemurhayrityksiin ja itsemurhiin. Aihetta tutkittiin eri diagnoosiluokissa suuressa väestöaineistossa, Pohjois-Suomen vuoden 1966 syntymäkohortissa. Tieto tutkimushenkilöiden lääkkeenkäytöstä vuodelta 1997 kerättiin Kelan lääkeostorekisteristä sekä postikyselyn avulla. Itsetuhoisten ajatusten ja muiden masennus- ja ahdistusoireiden vakavuutta mitattiin Hopkins Symptom Checklist-25 -kyselyn avulla vuonna 1997. Tieto itsemurhista kerättiin 15 vuoden seurannassa kuolinsyyrekisteristä ja tieto itsemurhayrityksistä hoitoilmoitusrekisteristä. Psykoosilääkkeiden, masennuslääkkeiden ja bentsodiatsepiinien käyttö oli yhteydessä lisääntyneisiin itsetuhoisiin ajatuksiin, itsemurhayrityksiin ja itsemurhiin. Epilepsialääkkeet eivät liittyneet itsetuhoisuuteen. Usean hermostoon vaikuttavan lääkkeen yhtäaikainen käyttö oli yhteydessä lisääntyneeseen itsetuhoisuuteen. Kaikki hermostoon vaikuttavat lääkkeet liittyivät lisääntyneisiin masennus- ja ahdistusoireisiin. Kun lääkityksen yhteys masennus- ja ahdistusoireisiin otettiin huomioon, lääkkeet eivät olleet erityisesti yhteydessä itsetuhoisiin ajatuksiin. Diagnostisten ryhmien välillä ei ollut eroa hermostoon vaikuttavien lääkkeiden ja itsemurhayritysten tai itsemurhien välisessä yhteydessä. Henkilöillä, joilla ei ole psykoosia, suuremmat psykoosilääkeannokset olivat yhteydessä itsetuhoisten ajatusten vakavuuteen kun muiden masennus- ja ahdistusoireiden vakavuus otettiin huomioon. Unettomuudesta kärsivillä henkilöillä masennuslääkkeen käyttö oli liittyi lisääntyneisiin itsetuhoisiin ajatuksiin kun muut oireet huomioitiin. Hermostoon vaikuttavat lääkkeet ovat yhteydessä lisääntyneisiin itsetuhoisiin ajatuksiin, mutta ne ovat myös vahvasti yhteydessä muihin masennus- ja ahdistusoireisiin. Tietyt henkilöt voivat kuitenkin olla erityisen herkkiä nimenomaan itsetuhoisille ajatuksille, ja heitä tulisi seurata erityisen tiiviisti. Tällaisia ovat henkilöt, joilla ei ole psykoosia, mutta jotka käyttävät suuria psykoosilääkeannoksia, sekä vakavasta unettomuudesta kärsivät henkilöt, jotka käyttävät masennuslääkettä

Adjusted productivity costs of stroke by human capital and friction cost methods:a Northern Finland Birth Cohort 1966 study

Abstract Background: Productivity costs result from loss of paid and unpaid work and replacements due to morbidity and mortality. They are usually assessed in health economic evaluations with human capital method (HCM) or friction cost method (FCM). The methodology for estimating lost productivity is an area of considerable debate. Objective: To compare traditional and adjusted HCM and FCM productivity cost estimates among young stroke patients. Methods: The Northern Finland Birth Cohort 1966 was followed until the age of 50 to identify all 339 stroke patients whose productivity costs were estimated with traditional, occupation-specific and adjusted HCM and FCM models by using detailed, national register-based data on care, disability, mortality, education, taxation and labour market. Results: Compared to traditional HCM, taking into account occupational class, national unemployment rate, disability-free life expectancy and decline in work ability, the productivity cost estimate decreased by a third, from €255,960 to €166,050. When traditional FCM was adjusted for occupational class and national unemployment rate, the estimate more than doubled from €3,040 to €7,020. HCM was more sensitive to adjustments for discount rate and wage growth rate than FCM. Conclusions: This study highlights the importance of adjustments of HCM and FCM. Routine register-based data can be used for accurate productivity cost estimates of health shocks

Lost individual income due to severe health events:life-course perspective in the Northern Finland Birth Cohort 1966

Abstract Background: Severe health events may lead to reduced income among survivors. Importantly, individuals’ risks for both severe health events and for lower income are shaped by early life course. Our aim was to consider early-life factors in determining lost individual income after stroke, heart attack and cancer between ages 18 and 50. Methods: A population-based Northern Finland Birth Cohort 1966 (N = 12 058) was used. Early-life factors were collected since mid-pregnancy until age 16 years and used to match all persons with stroke, heart attack, or cancer (n = 995) with four controls. Registered annual individual income development 15 years before and after the event was compared between cases and propensity score matched controls using time-to-event mixed models, stratified for sex. Results: Compared to controls, a new decreasing income trend emerged among women after stroke (logarithmic income per time −0.54; 95% CI −0.88 to −0.20), whereas men getting stroke showed declining earnings already by the time of the event, further declining after stroke (−1.00, −1.37 to −0.63). Getting heart attack was associated with a new declining trend both in women (−0.68; −1.28 to −0.09) and men (−0.69, −1.05 to −0.32). Income declined also among control men (−0.24, −0.34 to −0.14), who had higher income but were less educated than control women. Conclusions: Stroke and heart attack but not cancer have exogenous deleterious effects on individual economy, independently of early-life factors. The effects accelerate by time. Negative income trend in control men shows that severe health events do not explain all decrease in income

Maternal smoking trajectory during pregnancy predicts offspring’s smoking and substance use:the Northern Finland birth cohort 1966 study

Abstract The aim was to characterize the association of maternal smoking trajectory during pregnancy with offspring’s smoking, alcohol and substance use behavior. We used the prospective Northern Finland Birth Cohort 1966 study including 11,653 mothers and their offspring followed up from mothers’ mid-pregnancy to age of 46 years. Main exposure was number of smoked cigarettes per day at each month of pregnancy. Outcome measures were offspring’s smoking, alcohol and drug use at age 14, starting age of smoking, ever-smoking, and smoked pack-years until age 46. Four maternal smoking trajectories during pregnancy were identified with latent class trajectory modelling, namely “non-smokers” (86.0% of mothers), “early quitters” (2.0%), “late quitters” (2.1%), and “consistent smokers” (9.9%). In comparison to non-smokers, all maternal smoking was associated with offspring’s increased odds of lifetime smoking adjusted for sex of the child, father’s smoking, occupational status and place of residence of family, marital status and mood of mother, and desirability of pregnancy. The consistent smoker’s class was associated with offspring’s number of smoked pack years by midlife (median [interquartile range]: 8.3 [1.4–17.4] vs. 4.8 [0.0–13.0], p = 0.028), and alcohol use in young age (odds ratio 1.23 [95% confidence interval 1.05–1.43]). Overall, to prevent parent-offspring transmission of smoking, the cessation support should target women planning pregnancy. Negative effects of maternal continuous smoking during pregnancy include all substance use and reach up to offspring’s middle age