Risk of Alzheimer's Disease and Related Dementias in Persons with Glaucoma: A National Cohort Study.

PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks after glaucoma diagnosis in a large population-based cohort. DESIGN: National matched cohort study. PARTICIPANTS: A total of 324 730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3 247 300 age- and sex-matched population-based controls without prior dementia. METHODS: Cox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for sociodemographic factors and comorbidities. MAIN OUTCOME MEASURES: Alzheimer's disease, VaD, and all-cause dementia identified from nationwide inpatient and outpatient diagnoses through 2018. RESULTS: In 16 million person-years of follow-up, 32 339 persons (10%) with glaucoma and 226 896 controls (7%) were diagnosed with dementia. Persons with glaucoma had increased risks for AD (adjusted HR, 1.39; 95% confidence interval [CI], 1.35-1.43), VaD (1.66; 1.61-1.72), and all-cause dementia (1.57; 1.54-1.59). Among glaucoma subtypes, both primary open-angle and normal-tension glaucoma were associated with increased risk for AD (adjusted HR, 1.31; 95% CI, 1.27-1.36; and 1.28; 1.20-1.36, respectively) and VaD (1.61; 1.54-1.68; and 1.39; 1.28-1.50, respectively), whereas primary angle-closure glaucoma was associated with VaD (1.26; 1.02-1.56) but not AD (0.98; 0.82-1.18). These findings were similar in men and women. All risks were highest in persons diagnosed with glaucoma at ages ≥ 70 years and were not elevated for ages < 60 years. CONCLUSIONS: In this large national cohort, persons with glaucoma had increased risks for AD, VaD, and all-cause dementia, particularly those diagnosed with glaucoma at older ages. Persons with glaucoma may need increased monitoring for dementia to facilitate earlier detection and treatment. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Alcohol use disorder and risk of specific methods of suicide death in a national cohort.

INTRODUCTION: Alcohol use disorder (AUD) is among the strongest correlates of suicide death, but it is unclear whether AUD status is differentially associated with risk of suicide by particular methods. METHODS: The authors used competing risks models to evaluate the association between AUD status and risk of suicide by poisoning, suffocation, drowning, firearm, instruments, jumping, or other means in a large Swedish cohort born 1932-1995 (total N = 6,581,827; 48.8% female). Data were derived from Swedish national registers, including the Cause of Death Register and a range of medical registers. RESULTS: After adjusting for sociodemographic factors and familial liability to suicidal behavior, AUD was positively associated with risk of suicide for each method evaluated (cumulative incidence differences: 0.006-1.040 for females, 0.046-0.680 for males), except the association with firearm suicide in females. AUD was most strongly associated with risk of suicide by poisoning. Sex differences in the effects of AUD and family liability were observed for some, but not all, methods. Furthermore, high familial liability for suicidal behavior exacerbated AUD's impact on risk for suicide by poisoning (both sexes) and suffocation and jumping (males only), while the inverse interaction was observed for firearm suicide (males only). CONCLUSIONS: AUD increases risk of suicide by all methods examined and is particularly potent with respect to risk of suicide by poisoning. Differences in risk related to sex and familial liability to suicidal behavior underscore AUD's nuanced role in suicide risk. Future research should investigate targeted means restriction effectiveness among persons with AUD.

Sex ratio at birth across 100 years in Sweden and risk of cardiovascular disease and all-cause mortality - a national register study.

The human sex ratio at birth (SRB) undergoes temporary changes around a mean proportion of 0.51 male births. SRB has been well studied for historical, geographical, and secular trends, but until now not linked to health outcomes in the total population, e.g. for cardiovascular disease (CVD) or mortality during follow-up of birth cohorts. We used linkage analysis based on national registers in Sweden that cover all births from 1900 to 2016. SRB at birth was calculated by every 10-year birth cohort in all survivors living in 1997 for a follow-up analysis of risk of CVD and mortality with data from national registers. When the highest quartile of SRB was used as reference, a slightly increased risk of fatal CVD (HR 1.03 (95% confidence intervals, CI): 1.02-1.04), non-fatal CVD (HR 1.01; 95%CI: 1.01-1.02) and mortality (HR 1.02; 95%CI, 1.01-1.03) was found after full adjustments in men belonging to the lowest SRB quartile. A similar pattern was also found for fatal CHD in women. in the lowest SBR quartile compared to the highest, HR 1.03 (95%CI: 1.02-1.05). In conclusion, in birth cohorts with a relatively lower than expected number of males born, long-term adverse health effects were observed with slightly increased cardiovascular risk and total mortality at the population level. This could indicate that men belonging to so-called "culled cohorts" in a developed country during the 20th century are characterized by a slightly increased risk that could reflect negative early life influences and environmental exposures in pregnant women resulting in selective loss of male embryos or fetuses. In a public health perspective SRB could be of some importance to monitor as an aspect of birth statistics linked to relatively minor population health effects.

Preterm or early term birth and long-term risk of asthma into midadulthood: a national cohort and cosibling study.

BACKGROUND: Preterm birth is associated with pulmonary complications early in life; however, long-term risks of asthma into adulthood are unclear. OBJECTIVE: To determine asthma risks from childhood into adulthood associated with gestational age at birth in a large population-based cohort. METHODS: A national cohort study was conducted of all 4 079 878 singletons born in Sweden during 1973-2013, followed up for asthma identified from primary care, specialty outpatient and inpatient diagnoses in nationwide registries through 2018 (up to 46 years). Cox regression was used to adjust for potential confounders, and cosibling analyses assessed the influence of unmeasured shared familial (genetic and/or environmental) factors. RESULTS: In 91.9 million person-years of follow-up, 607 760 (14.9%) persons were diagnosed with asthma. Preterm birth was associated with increased risk of asthma at ages <10 years (adjusted HR 1.73; 95% CI 1.70 to 1.75), 10-17 years (1.29; 1.27 to 1.32) and 18-46 years (1.19; 1.17 to 1.22). Across all ages, adjusted HRs further stratified were 3.01 (95% CI 2.88 to 3.15) for extremely preterm (22-27 weeks), 1.76 (1.72 to 1.79) for very or moderately preterm (28-33 weeks), 1.31 (1.29 to 1.32) for late preterm (34-36 weeks) and 1.13 (1.12 to 1.14) for early term (37-38 weeks), compared with full-term (39-41 weeks) birth. These findings were not explained by shared familial factors. Asthma risks were elevated after spontaneous or medically indicated preterm birth and with or without perinatal respiratory complications. CONCLUSIONS: In this large national cohort, preterm and early term birth were associated with increased risks of asthma from childhood into midadulthood. Persons born prematurely need long-term follow-up into adulthood for timely detection and treatment of asthma.

Divorce and risk of suicide attempt: a Swedish national study.

BACKGROUND: Prior research has reported an association between divorce and suicide attempt. We aimed to clarify this complex relationship, considering sex differences, temporal factors, and underlying etiologic pathways. METHODS: We used Swedish longitudinal national registry data for a cohort born 1960-1990 that was registered as married between 1978 and 2018 (N = 1 601 075). We used Cox proportional hazards models to estimate the association between divorce and suicide attempt. To assess whether observed associations were attributable to familial confounders or potentially causal in nature, we conducted co-relative analyses. RESULTS: In the overall sample and in sex-stratified analyses, divorce was associated with increased risk of suicide attempt (adjusted hazard ratios [HRs] 1.66-1.77). Risk was highest in the year immediately following divorce (HRs 2.20-2.91) and declined thereafter, but remained elevated 5 or more years later (HRs 1.41-1.51). Divorcees from shorter marriages were at higher risk for suicide attempt than those from longer marriages (HRs 3.33-3.40 and 1.20-1.36, respectively). In general, HRs were higher for divorced females than for divorced males. Co-relative analyses suggested that familial confounders and a causal pathway contribute to the observed associations. CONCLUSIONS: The association between divorce and risk of suicide attempt is complex, varying as a function of sex and time-related variables. Given evidence that the observed association is due in part to a causal pathway from divorce to suicide attempt, intervention or prevention efforts, such as behavioral therapy, could be most effective early in the divorce process, and in particular among females and those whose marriages were of short duration.

Shared genetic and environmental etiology between substance use disorders and suicidal behavior.

BACKGROUND: Previous studies have demonstrated substantial associations between substance use disorders (SUD) and suicidal behavior. The current study empirically assesses the extent to which shared genetic and/or environmental factors contribute to associations between alcohol use disorders (AUD) or drug use disorders (DUD) and suicidal behavior, including attempts and death. METHODS: The authors used Swedish national registry data, including medical, pharmacy, criminal, and death registrations, for a large cohort of twins, full siblings, and half siblings (N = 1 314 990) born 1960-1980 and followed through 2017. They conducted twin-sibling modeling of suicide attempt (SA) or suicide death (SD) with AUD and DUD to estimate genetic and environmental correlations between outcomes. Analyses were stratified by sex. RESULTS: Genetic correlations between SA and SUD ranged from rA = 0.60-0.88; corresponding shared environmental correlations were rC = 0.42-0.89 but accounted for little overall variance; and unique environmental correlations were rE = 0.42-0.57. When replacing attempt with SD, genetic and shared environmental correlations with AUD and DUD were comparable (rA = 0.48-0.72, rC = 0.92-1.00), but were attenuated for unique environmental factors (rE = -0.01 to 0.31). CONCLUSIONS: These findings indicate that shared genetic and unique environmental factors contribute to comorbidity of suicidal behavior and SUD, in conjunction with previously reported causal associations. Thus, each outcome should be considered an indicator of risk for the others. Opportunities for joint prevention and intervention, while limited by the polygenic nature of these outcomes, may be feasible considering moderate environmental correlations between SA and SUD.

Adverse pregnancy outcomes and long-term risk of chronic kidney disease in women: national cohort and co-sibling study.

BACKGROUND: Women with adverse pregnancy outcomes may have higher subsequent risk of chronic kidney disease, but the long-term independent risks and potential causality are unclear. OBJECTIVE: This study aimed to determine long-term risks of chronic kidney disease associated with 5 major adverse pregnancy outcomes in a large population-based cohort, and to assess for familial confounding using co-sibling analyses. STUDY DESIGN: A national cohort study was conducted of all 2,201,279 women with a singleton delivery in Sweden from 1973 to 2015, followed up for chronic kidney disease identified from nationwide diagnoses through 2018. Cox regression was used to compute hazard ratios for chronic kidney disease associated with preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders, and gestational diabetes, adjusting for other adverse pregnancy outcomes and maternal factors. Co-sibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. RESULTS: In 56 million person-years of follow-up, 11,572 (0.5%) women were diagnosed with chronic kidney disease (median age, 61 years). All 5 adverse pregnancy outcomes were independently associated with increased chronic kidney disease risk. Within 10 years following delivery, adjusted hazard ratios associated with specific adverse pregnancy outcomes were: 7.12 for other hypertensive disorders (95% confidence interval, 5.88-8.62), 4.38 for preeclampsia (3.72-5.16), 3.50 for preterm delivery (2.95-4.15), 3.15 for gestational diabetes (2.53-3.92), and 1.22 for small for gestational age (1.02-1.44). All hazard ratios remained significantly elevated even 30 to 46 years after delivery (gestational diabetes, 3.32 [95% confidence interval, 2.96-3.72]; other hypertensive disorders, 2.44 [1.91-3.11]; preeclampsia, 2.03 [1.90-2.16]; preterm delivery, 1.56 [1.44-1.68]; and small for gestational age, 1.24 [1.16-1.31]). These findings were only partially (0%-45%) explained by shared familial factors. Women with multiple adverse pregnancy outcomes had further increases in risk. CONCLUSION: In this large national cohort, women who experienced any of 5 major adverse pregnancy outcomes had increased risk for chronic kidney disease up to 46 years later. Women with adverse pregnancy outcomes need early preventive actions and long-term monitoring to reduce risk of chronic kidney disease.

Diabetes risk during pregnancy among second-generation immigrants: A national cohort study in Sweden.

BACKGROUND AND AIMS: Gestational diabetes is more common in many first-generation immigrant women in Europe and other Western countries. Less is known about second-generation immigrant women; such knowledge is needed to understand generational influences on diabetes risk. We aimed to study second-generation immigrant women regarding the presence of all types of diabetes during pregnancy. METHODS AND RESULTS: A cohort study was conducted using the Swedish National Birth Register, the National Patient Register, and the Total Population Register. We used Cox regression analysis to compute hazard ratios (HRs) and 99% confidence intervals (99% CI) for any diabetes during pregnancy and specific subtypes (gestational diabetes, pre-existing diabetes type 1, pre-existing diabetes type 2) in second-generation immigrant women compared with Swedish-born women with two Swedish-born parents while adjusting for sociodemographic factors, family history of diabetes, body mass index, smoking habits, and comorbidities. The study population included a total of 989,986 deliveries and 17,938 diabetes cases. The fully adjusted HR (with 99% CI) for any type of diabetes during pregnancy among second-generation immigrant women was 1.11 (1.05-1.18). Higher risks were found in women with parents from Africa, Asia, or Eastern Europe, as well as Denmark. A lower risk for pre-existing type 1 diabetes was found overall and for women with parents from most geographic regions. CONCLUSION: In this national cohort study, the risk of all types of diabetes during pregnancy was increased in second-generation immigrant women. Diabetes prevention and treatment is especially important in these women both before and during pregnancy.

Preterm Delivery and Long-Term Risk of Stroke in Women: A National Cohort and Cosibling Study.

BACKGROUND: Stroke has a high burden of disease in women, and adverse pregnancy outcomes have been identified as important risk factors for stroke later in life. However, long-term risks of stroke associated with preterm delivery and whether such risks are attributable to familial confounding are unclear. Such knowledge is needed to improve long-term risk assessment and stroke prevention in women. METHODS: A national cohort study was conducted of all 2 188 043 women with a singleton delivery in Sweden in 1973 through 2015 who were followed up for stroke identified from nationwide diagnoses through 2015. Cox regression was used to compute adjusted hazard ratios (aHRs) for stroke associated with pregnancy duration, and cosibling analyses assessed for confounding by shared familial (genetic or environmental) factors. RESULTS: In 48.0 million person-years of follow-up, 36 372 (1.7%) women were diagnosed with stroke. In the 10 years after delivery, the aHR for stroke associated with preterm delivery (gestational age <37 weeks) was 1.61 (95% CI, 1.45-1.79) and further stratified was 2.81 (95% CI, 2.02-3.91) for extremely preterm (22-27 weeks), 2.07 (95% CI, 1.74-2.46) for very preterm (28-33 weeks), 1.38 (95% CI, 1.21-1.57) for late preterm (34-36 weeks), and 1.15 (95% CI, 1.06-1.24) for early term (37-38 weeks), compared with full-term (39-41 weeks) delivery. These risks remained similarly elevated at 10 to 19 years after delivery (preterm versus full-term: aHR, 1.61 [95% CI, 1.50-1.74]) and then declined but remained significantly elevated at 20 to 29 years (aHR, 1.35 [95% CI, 1.28-1.44]) and 30 to 43 years (aHR, 1.35 [95% CI, 1.27-1.42]). Preterm delivery was associated with both hemorrhagic (aHR, 1.31 [95% CI, 1.25-1.38]) and ischemic (aHR, 1.54 [95% CI, 1.47-1.61]) stroke across the entire follow-up period (up to 43 years). These findings were not explained by shared determinants of preterm delivery and stroke within families. Stroke risks were higher after either spontaneous or medically indicated preterm delivery, and recurrent preterm delivery was associated with further increases in risk. CONCLUSIONS: In this large national cohort, preterm delivery was associated with higher future risks of both hemorrhagic and ischemic stroke. These associations remained substantially elevated at least 40 years later, and were largely independent of covariates and shared familial factors. Preterm delivery should be recognized as a risk factor for stroke in women across the life course.

Drug use disorder and risk of incident and fatal prostate cancer among Swedish men: a nationwide epidemiological study.

PURPOSE: Prostate cancer is the second most common cancer in men and a leading cause of cancer mortality worldwide. Men with drug use disorders (DUD) may potentially be at high risk for prostate cancer mortality because of delayed diagnosis and/or undertreatment. In this study, we aimed to investigate prostate cancer incidence, mortality, and stage at time of diagnosis among men with DUD compared to the general male population in Sweden. METHODS: We performed a follow-up study based on Swedish national register data for the period January 1997-December 2016. The study was based on 1,361,532 men aged 50-75 years at inclusion, of whom 9,259 were registered with DUD. Cox regression analysis was used to compute adjusted hazard ratios (HRs) for incident and fatal prostate cancer, and cancer stage at time of diagnosis, associated with DUD. RESULTS: DUD was associated with a slightly increased risk of incident prostate cancer (HR: 1.07, 95% confidence interval [CI] 1.00-1.14, p = 0.048) and substantially higher risk of fatal prostate cancer (HR: 1.59, 95% CI 1.40-1.82, p < 0.001), adjusted for age, socioeconomic factors, and comorbidities related to tobacco smoking and alcohol use disorder. No association was found between DUD and prostate cancer stage at diagnosis. CONCLUSIONS: Men with DUD have an increased risk of fatal prostate cancer, possibly related to undertreatment in this patient population. Our findings should raise attention among medical staff and decision-makers towards a disadvantaged group of men in need of easily accessible prostate cancer evaluation and treatment.

The role of substance use disorders in the transition from suicide attempt to suicide death: a record linkage study of a Swedish cohort.

BACKGROUND: Suicidal behavior and substance use disorders (SUDs) are important public health concerns. Prior suicide attempts and SUDs are two of the most consistent predictors of suicide death, and clarifying the role of SUDs in the transition from suicide attempt to suicide death could inform prevention efforts. METHODS: We used national Swedish registry data to identify individuals born 1960-1985, with an index suicide attempt in 1997-2017 (N = 74 873; 46.7% female). We assessed risk of suicide death as a function of registration for a range of individual SUDs. We further examined whether the impact of SUDs varied as a function of (i) aggregate genetic liability to suicidal behavior, or (ii) age at index suicide attempt. RESULTS: In univariate models, risk of suicide death was higher among individuals with any SUD registration [hazard ratios (HRs) = 2.68-3.86]. In multivariate models, effects of specific SUDs were attenuated, but remained elevated for AUD (HR = 1.86 95% confidence intervals 1.68-2.05), opiates [HR = 1.58 (1.37-1.82)], sedatives [HR = 1.93 (1.70-2.18)], and multiple substances [HR = 2.09 (1.86-2.35)]. In secondary analyses, the effects of most, but not all, SUD were exacerbated by higher levels of genetic liability to suicide death, and among individuals who were younger at their index suicide attempt. CONCLUSIONS: In the presence of a strong predictor of suicide death - a prior attempt - substantial predictive power is still attributable to SUDs. Individuals with SUDs may warrant additional suicide screening and prevention efforts, particularly in the context of a family history of suicidal behavior or early onset of suicide attempt.

Oral contraceptive use and risk of suicidal behavior among young women.

BACKGROUND: Oral contraceptive use has been previously associated with an increased risk of suicidal behavior in some, but not all, samples. The use of large, representative, longitudinally-assessed samples may clarify the nature of this potential association. METHODS: We used Swedish national registries to identify women born between 1991 and 1995 (N = 216 702) and determine whether they retrieved prescriptions for oral contraceptives. We used Cox proportional hazards models to test the association between contraceptive use and first observed suicidal event (suicide attempt or death) from age 15 until the end of follow-up in 2014 (maximum age 22.4). We adjusted for covariates, including mental illness and parental history of suicide. RESULTS: In a crude model, use of combination or progestin-only oral contraceptives was positively associated with suicidal behavior, with hazard ratios (HRs) of 1.73-2.78 after 1 month of use, and 1.25-1.82 after 1 year of use. Accounting for sociodemographic, parental, and psychiatric variables attenuated these associations, and risks declined with increasing duration of use: adjusted HRs ranged from 1.56 to 2.13 1 month beyond the initiation of use, and from 1.19 to 1.48 1 year after initiation of use. HRs were higher among women who ceased use during the observation period. CONCLUSIONS: Young women using oral contraceptives may be at increased risk of suicidal behavior, but risk declines with increased duration of use. Analysis of former users suggests that women susceptible to depression/anxiety are more likely to cease hormonal contraceptive use. Additional studies are necessary to determine whether the observed association is attributable to a causal mechanism.

Pre-term delivery and long-term risk of heart failure in women: a national cohort and co-sibling study.

AIMS: Women who deliver pre-term have higher future risks of hypertension and ischaemic heart disease, but long-term risks of heart failure (HF) are unknown. We examined these risks in a large national cohort. METHODS AND RESULTS: All 2 201 284 women with a singleton delivery in Sweden during 1973-2015 were followed up for inpatient or outpatient HF diagnoses through 2015. Cox regression was used to compute hazard ratios (HRs) for HF associated with pregnancy duration, adjusting for other maternal factors. Co-sibling analyses assessed for confounding by shared familial (genetic and/or environmental) factors. In 48.2 million person-years of follow-up, 19 922 women were diagnosed with HF (median age: 60.7 years). Within 10 years after delivery, the adjusted HR was 2.96 [95% confidence interval (CI): 2.48-3.53] for HF associated with pre-term (gestational age: <37 weeks) compared with full-term (39-41 weeks) delivery. Stratified HRs were 4.27 (2.54-7.17) for extremely pre-term (22-27 weeks), 3.39 (2.57-4.48) for moderately pre-term (28-33 weeks), 2.70 (2.19-3.32) for late pre-term (34-36 weeks), and 1.70 (1.45-1.98) for early term (37-38 weeks). These HRs declined but remained elevated at 10-19 years (pre-term vs. full term: HR: 2.19; 95% CI: 1.94-2.46), 20-29 years (1.80; 1.67-1.95), and 30-43 years (1.56; 1.47-1.66) after delivery, and were not explained by shared familial factors. CONCLUSION: Pre-term and early term delivery were associated with markedly increased future hazards for HF, which persisted after adjusting for other maternal and familial factors and remained elevated 40 years later. Pre-term and early-term delivery should be recognized as risk factors for HF across the life course. KEY QUESTION: What are the long-term hazards for heart failure (HF) across the life course in women who deliver preterm? KEY FINDING: Preterm and early term delivery were associated with ∼3- and 1.7-fold adjusted hazards for HF in the next 10 years vs. full-term delivery. These hazards declined but remained elevated 40 years later, and were not explained by shared familial factors. TAKE HOME MESSAGE: Preterm and early term delivery were associated with increased future hazards for HF, which persisted for 40 years after adjusting for other maternal and familial factors. Preterm and early term delivery should be recognized as lifelong risk factors for HF.

Stroke Risks in Adult Survivors of Preterm Birth: National Cohort and Cosibling Study.

Background and Purpose: Clinicians will increasingly encounter adult patients who were born preterm and will need to understand their long-term sequelae. Adult survivors of preterm birth have been reported to have increased risks of hypertension and other stroke risk factors. However, their stroke risks have seldom been examined and the findings are discrepant, possibly due to small sample sizes, insufficient follow-up, or survivor bias. We examined whether preterm birth is associated with stroke in a large population-based cohort. Methods: A national cohort study was conducted of all 2 140 866 singletons born in Sweden from 1973 to 1994 who survived to age 18 years, who were followed up for first-time stroke through 2015 (maximum age 43 years). Cox regression was used to examine stroke risks associated with gestational age at birth, adjusting for other perinatal and parental factors. Cosibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. Results: In 28.0 million person-years of follow-up, 4861 (0.2%) people were diagnosed with stroke. At ages 18 to 43 years, the adjusted hazard ratio for stroke associated with preterm birth (<37 weeks) was 1.26 (95% CI, 1.12­1.43; P<0.001), and further stratified was 1.42 (1.11­1.81; P=0.005) for early preterm (22­33 weeks) and 1.22 (1.06­1.40; P=0.004) for late preterm (34­36 weeks), compared with full-term (39­41 weeks). Positive associations were found with both hemorrhagic stroke (early preterm: adjusted hazard ratio, 1.42 [95% CI, 1.04­1.94]; any preterm: 1.15 [0.97­1.35]) and ischemic stroke (early preterm: adjusted hazard ratio, 1.33 [95% CI, 0.87­2.03]; any preterm: 1.31 [1.07­1.60]). These findings were similar in men and women and only partially explained by shared determinants of preterm birth and stroke within families. Conclusions: In this large national cohort, preterm birth was associated with increased risks of both hemorrhagic and ischemic stroke in adulthood. Preterm birth survivors need early preventive evaluation and long-term clinical follow-up to reduce their lifetime risk of stroke.

Risk of hypertension into adulthood in persons born prematurely: a national cohort study.

AIMS: Preterm birth has been associated with elevated blood pressure early in life; however, hypertension risks from childhood into adulthood remain unclear. We conducted a large population-based study to examine gestational age at birth in relation to hypertension risks from childhood into adulthood. METHODS AND RESULTS: A national cohort study was conducted of all 4 193 069 singleton live births in Sweden during 1973-2014, who were followed up for hypertension identified from nationwide inpatient and outpatient (specialty and primary care) diagnoses from any health care encounters through 2015 (maximum age 43 years; median 22.5). Cox regression was used to examine gestational age at birth in relation to hypertension risk while adjusting for other perinatal and maternal factors, and co-sibling analyses assessed the potential influence of unmeasured shared familial (genetic and/or environmental) factors. In 86.8 million person-years of follow-up, 62 424 (1.5%) persons were identified with hypertension (median age 29.8 years at diagnosis). Adjusted hazard ratios for new-onset hypertension at ages 18-29 years associated with preterm (<37 weeks) and extremely preterm (22-27 weeks) birth were 1.28 [95% confidence interval (CI), 1.21-1.36] and 2.45 (1.82-3.31), respectively, and at ages 30-43 years were 1.25 (1.18-1.31) and 1.68 (1.12-2.53), respectively, compared with full-term birth (39-41 weeks). These associations affected males and females similarly and appeared substantially related to shared genetic or environmental factors in families. CONCLUSIONS: In this large national cohort, preterm birth was associated with increased risk of hypertension into early adulthood. Persons born prematurely may need early preventive evaluation and long-term monitoring for the development of hypertension.

Preterm birth and risk of type 1 and type 2 diabetes: a national cohort study.

AIMS/HYPOTHESIS: Preterm birth (gestational age <37 weeks) has been associated with insulin resistance early in life. However, no large population-based studies have examined risks of type 1 and type 2 diabetes and potential sex-specific differences from childhood into adulthood. Clinicians will increasingly encounter adults who were born prematurely and will need to understand their long-term risks. We hypothesised that preterm birth is associated with increased risks of type 1 and type 2 diabetes into adulthood. METHODS: A national cohort study was conducted of all 4,193,069 singletons born in Sweden during 1973-2014, who were followed up for type 1 and type 2 diabetes identified from nationwide diagnoses and pharmacy data to the end of 2015 (maximum age 43 years; median age at the end of follow-up 22.5 years). Cox regression was used to adjust for potential confounders, and co-sibling analyses assessed the influence of shared familial (genetic and/or environmental) factors. RESULTS: In 92.3 million person-years of follow-up, 27,512 (0.7%) and 5525 (0.1%) people were identified with type 1 and type 2 diabetes, respectively. Gestational age at birth was inversely associated with both type 1 and type 2 diabetes risk. Adjusted HRs for type 1 and type 2 diabetes at age <18 years associated with preterm birth were 1.21 (95% CI, 1.14, 1.28) and 1.26 (95% CI, 1.01, 1.58), respectively, and at age 18-43 years were 1.24 (95% CI, 1.13, 1.37) and 1.49 (95% CI, 1.31, 1.68), respectively, compared with full-term birth. The associations between preterm birth and type 2 (but not type 1) diabetes were stronger among females (e.g. at age 18-43 years, females: adjusted HR, 1.75; 95% CI, 1.47, 2.09; males: 1.28; 95% CI, 1.08, 1.53; p < 0.01 for additive and multiplicative interaction). These associations were only partially explained by shared genetic or environmental factors in families. CONCLUSIONS/INTERPRETATION: In this large national cohort, preterm birth was associated with increased risk of type 1 and type 2 diabetes from childhood into early to mid-adulthood. Preterm-born children and adults may need early preventive evaluation and long-term monitoring for diabetes.

Risk of being born preterm in offspring of survivors with childhood or adolescent central nervous system tumor in Sweden.

An increasing number of patients with central nervous system (CNS) tumor could survive to reproductive age. However, it is largely unknown whether the history of CNS tumor might affect pregnancy outcome. We aimed to explore the risk of being born preterm among children of CNS tumor survivors. By linking several nationwide registers in Sweden, we identified 1,369 children whose parents were childhood or adolescent CNS tumor survivors. Children whose parents did not have CNS tumor were matched randomly with a 5:1 ratio to generate the reference group. Conditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI). The prevalence of preterm birth (PTB) was 6.9% among children of survivors with CNS tumor and 5.2% among the matched controls. Children of survivors had an increased risk of PTB (adjusted OR = 1.29, 95%CI 1.01-1.65) compared to the matched controls. This risk was increased specifically among offspring of those diagnosed in childhood (adjusted OR = 1.53, 95%CI 1.14-2.06) but not adolescence (adjusted OR = 0.89, 95%CI 0.56-1.41). For families with more than one child, the risk was slightly lower among the second child as compared to the first child. The risk was negatively associated with time interval between parental diagnosis and childbirth. Parental medulloblastoma and ependymoma were most strongly associated with a higher risk of PTB. Children of survivors with CNS tumor experienced an elevated risk of PTB. However, the risk diminishes gradually after parental diagnosis of CNS tumor. Offspring of childhood CNS tumor survivors and medulloblastoma or ependymoma survivors may have the highest risk of PTB.

Healthcare utilisation prior to suicide in persons with alcohol use disorder: national cohort and nested case-control study.

BACKGROUND: Alcohol use disorder (AUD) is common and associated with increased risk of suicide. AIMS: To examine healthcare utilisation prior to suicide in persons with AUD in a large population-based cohort, which may reveal opportunities for prevention. METHOD: A national cohort study was conducted of 6 947 191 adults in Sweden in 2002, including 256 647 (3.7%) with AUD, with follow-up for suicide through 2015. A nested case-control design examined healthcare utilisation among people with AUD who died by suicide and 10:1 age- and gender-matched controls. RESULTS: In 86.7 million person-years of follow-up, 15 662 (0.2%) persons died by suicide, including 2601 (1.0%) with AUD. Unadjusted and adjusted relative risks for suicide associated with AUD were 8.15 (95% CI 7.86-8.46) and 2.22 (95% CI 2.11-2.34). Of the people with AUD who died by suicide, 39.7% and 75.6% had a healthcare encounter <2 weeks or <3 months before the index date respectively, compared with 6.3% and 25.4% of controls (adjusted prevalence ratio (PR) and difference (PD), <2 weeks: PR = 3.86, 95% CI 3.50-4.25, PD = 26.4, 95% CI 24.2-28.6; <3 months: PR = 2.03, 95% CI 1.94-2.12, PD = 34.9, 95% CI 32.6-37.1). AUD accounted for more healthcare encounters within 2 weeks of suicide among men than women (P = 0.01). Of last encounters, 48.1% were in primary care and 28.9% were in specialty out-patient clinics, mostly for non-psychiatric diagnoses. CONCLUSIONS: Suicide among persons with AUD is often shortly preceded by healthcare encounters in primary care or specialty out-patient clinics. Encounters in these settings are important opportunities to identify active suicidality and intervene accordingly in patients with AUD.

Association of preterm birth with lipid disorders in early adulthood: A Swedish cohort study.

BACKGROUND: Preterm birth has previously been linked with cardiovascular disease (CVD) in adulthood. However, associations with lipid disorders (e.g., high cholesterol or triglycerides), which are major risk factors for CVD, have seldom been examined and are conflicting. Clinicians will increasingly encounter adult survivors of preterm birth and will need to understand the long-term health sequelae. We conducted the first large population-based study to determine whether preterm birth is associated with an increased risk of lipid disorders. METHODS AND FINDINGS: A retrospective national cohort study was conducted of all 2,235,012 persons born as singletons in Sweden during 1973 to 1995 (48.6% women), who were followed up for lipid disorders identified from nationwide inpatient, outpatient, and pharmacy data through 2016 (maximum age 44 years). Cox regression was used to adjust for other perinatal and maternal factors, and co-sibling analyses assessed the potential influence of unmeasured shared familial (genetic and/or environmental) factors. A total of 25,050 (1.1%) persons were identified with lipid disorders in 30.3 million person-years of follow-up. Each additional 5 weeks of gestation were associated with a 14% reduction in risk of lipid disorders (adjusted hazard ratio [HR], 0.86; 95% CI, 0.83-0.89; P < 0.001). Relative to full-term birth (gestational age 39-41 weeks), the adjusted HR associated with preterm birth (<37 weeks) was 1.23 (95% CI, 1.16-1.29; P < 0.001), and further stratified was 2.00 (1.41-2.85; P < 0.001) for extremely preterm (22-27 weeks), 1.33 (1.19-1.49; P < 0.001) for very preterm (28-33 weeks), and 1.19 (1.12-1.26; P < 0.001) for late preterm (34-36 weeks). These findings were similar in men and women (e.g., preterm versus full-term, men: HR, 1.22; 95% CI, 1.14-1.31; P < 0.001; women: HR, 1.23; 1.12-1.32; P < 0.001). Co-sibling analyses suggested that they were substantially though not completely explained by shared genetic or environmental factors in families. The main study limitation was the unavailability of laboratory data to assess specific types or severity of lipid disorders. CONCLUSIONS: In this large national cohort, preterm birth was associated with an increased risk of lipid disorders in early- to midadulthood. Persons born prematurely may need early preventive evaluation and long-term monitoring for lipid disorders to reduce their future cardiovascular risks.

Pediatric Blood Lead Levels Within New York City Public Versus Private Housing, 2003-2017.

Objectives. To compare blood lead levels (BLLs) among children residing in public and private housing in New York City and examine the implications for lead identification and remediation policies. Methods. We examined electronic medical records for BLLs among 4693 children receiving care at a multisite Federally Qualified Health Center during 2003 to 2017. We plotted home addresses against city housing data to assess BLL differences between children living in public housing and private housing. Results. Only 0.25% of children residing in public housing had BLLs exceeding the upper reference limit of 5 micrograms per deciliter, as compared with 2.76% of children residing in private housing. After adjustment for age, gender, and race/ethnicity, public housing was associated with 92% lower odds of having a BLL of 5 micrograms per deciliter or above (odds ratio [OR] = 0.08; 95% confidence interval [CI] = 0.02, 0.33; P = .001). Decreases in BLLs were observed in both public and private housing over time. Conclusions. Children living in public housing in New York City were significantly less likely to have elevated BLLs than were children living in private housing. Decreases in BLLs over time were likely a result of lead reduction legislation.