European Journal Of Epidemiology[JOURNAL]
Sun
200 papers
Evaluating the physical and psychosocial impact of serious physical combat injuries in UK armed forces personnel-the ADVANCE cohort study.
Dyball D, Schofield S, Burdett H … +6 more , Boos CJ, Bull AMJ, Cullinan P, Fear NT, Bennett AN, ADVANCE Study
Eur J Epidemiol · 2025 Oct · PMID 40991147 · Full text
The ADVANCE cohort study is a prospective cohort study investigating the impact of sustaining a serious physical combat injury whilst on deployment to Afghanistan on long-term health outcomes. The cohort will provide ess...
The ADVANCE cohort study is a prospective cohort study investigating the impact of sustaining a serious physical combat injury whilst on deployment to Afghanistan on long-term health outcomes. The cohort will provide essential data on medical/psychosocial risk factors and outcomes associated with combat injury and establish injury-specific mechanisms of disease. Participants include UK Armed Forces personnel who sustained serious physical combat injuries and a frequency-matched comparison group who sustained no such injuries (uninjured group). The cohort consists of 1145 participants, with a baseline response rate of 59.6% for the injured group (n = 579) and 56.3% for the uninjured group (n = 566). The first follow up of this cohort retained 92% of the sample (n = 1053/1145). This cohort profile describes the baseline and first follow up demographics for ADVANCE, as well as details on published research projects spanning military epidemiology, physical health, including cardiovascular, respiratory, musculoskeletal and neurological, mental health and health-related behaviours. These projects comprise identification of early risk factors for disease and observed differences in health-characteristics between groups. Since baseline assessment of the cohort, ADVANCE has expanded investigations across physical and mental health domains, utilising advice from participant engagement and an international scientific advisory group. Researchers working on the ADVANCE cohort continue to engage with policy makers, clinicians and participants to ensure a wide-ranging impact from work conducted.Registration: The ADVANCE Study is registered at ISRCTN ID: ISRCTN57285353.
Ultra-processed food intake and risk of type 2 diabetes: a pooled analysis of three prospective cohorts of Korean adults and an updated meta-analysis.
Kim Y, Cho Y, Koo B … +3 more , Chen Z, Sun Q, Oh H
Eur J Epidemiol · 2025 Nov · PMID 40956553 · Publisher ↗
Studies suggest a positive association between ultra-processed food (UPF) intake and type 2 diabetes risk. However, studies were primarily conducted in Western populations with diets and disease profiles different from p...
Studies suggest a positive association between ultra-processed food (UPF) intake and type 2 diabetes risk. However, studies were primarily conducted in Western populations with diets and disease profiles different from populations living elsewhere. In addition, the dose-response relationship needs to be further elucidated. We conducted an individual-level pooled analysis of three Korean prospective cohorts (n = 72,776). UPF intake (in the percentage of g/d as the main UPF unit) was assessed using validated food frequency questionnaires and categorized according to Nova classification. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We subsequently conducted a meta-analysis of prospective studies, including recent studies from both Western and non-Western populations, to assess the dose-response relationship. In a pooled analysis of Korean cohorts (up to 18 years of follow-up), the highest (vs. lowest) quartile of UPF intake was associated with an increased type 2 diabetes risk (pooled HR [95% CI] = 1.11 [1.02, 1.21] , p-trend = 0.03). The positive association persisted after additional adjustment for BMI, nutritional factors (fiber, sodium, and carbohydrate intakes), or diet quality score. Among individual UPF subgroups, processed meats, ready-to-eat/heat mixed dishes, and ice cream were positively associated with diabetes risk. In a meta-analysis of 17 prospective cohorts, every 10% (of g/d) increment in UPF intake was associated with a 10% (summary RR [95% CI] = 1.10 [1.08, 1.12] ) higher risk in a dose-response fashion. Our meta-evidence supports that higher UPF intake may monotonically increase type 2 diabetes risk.
Generalized additive mixed models to discern data-driven theoretically informed strategies for public brain, cognitive and mental health.
Lammer L, Beyer F, Riedel-Heller S … +4 more , Sacher J, Glaesmer H, Villringer A, Witte AV
Eur J Epidemiol · 2025 Nov · PMID 40947435 · Full text
Social isolation is recognized as a public health emergency. However, major guidelines provide vastly different recommendations on how to target it, and no strategy has been substantiated on firm theoretical or empirical...
Social isolation is recognized as a public health emergency. However, major guidelines provide vastly different recommendations on how to target it, and no strategy has been substantiated on firm theoretical or empirical grounds, yet. Rose's seminal The Strategy of Preventive Medicine provided a theoretical framework for such arbitrations between approaches. Therein, determining the shape of the relationship between risk factor and outcome is of paramount importance. However, quantitative approaches immediately applying this theory to evidence are still lacking. Thus, in this pre-registered analysis, we pursued a novel approach and employed generalized additive mixed models to model the shape of social isolation's Links to brain, cognitive and mental health outcomes in a well-characterised population-based sample. We derived brain measures from 3T MRIs, assessed cognitive functions with extensive neuropsychological testing and measured social isolation and mental health outcomes using established questionnaires. Overall, we studied over 10,000 (mean age 58a, 53% women) participants at baseline and over 5500 (mean age 64a, 53% women) at follow-up after ~ 6 years. The relationship of social contact with almost all outcomes was firmly linear and did not differ above and below the standard threshold for social isolation. Only for processing speed did we detect a steeper slope amongst socially isolated individuals. Hence, most of the health effects of social contact were observed in individuals that would not be categorised as socially isolated. Applying advanced statistical methods to a large and well-characterised dataset we provide evidence in support of a shift in focus away from individual-level and towards population-level preventive approaches.
Elucidating some common biases in randomized controlled trials using directed acyclic graphs.
Gabriel EE, Ocampo A, Sjölander A
Eur J Epidemiol · 2025 Sep · PMID 40932610 · Publisher ↗
Although the ideal randomized clinical trial is the gold standard for causal inference, real randomized trials often suffer from imperfections that may hamper causal effect estimation. Stating the estimand of interest ca...
Although the ideal randomized clinical trial is the gold standard for causal inference, real randomized trials often suffer from imperfections that may hamper causal effect estimation. Stating the estimand of interest can help reduce confusion about what is being estimated, but it is often difficult to determine what is and is not identifiable given a trial's specific imperfections. We demonstrate how directed acyclic graphs can be used to elucidate the consequences of common imperfections, such as noncompliance, unblinding, and drop-out, for the identification of the intention-to-treat effect, the total treatment effect and the physiological treatment effect. We assert that the physiological treatment effect is not identifiable outside a trial with perfect compliance and no dropout, where blinding is perfectly maintained.
Caveats of assessing incidence trends using publicly available registry data.
Arndt V, Kim-Wanner SZ, Holleczek B … +3 more , Nennecke A, Peters F, Waldmann A
Eur J Epidemiol · 2025 Oct · PMID 40906028 · Full text
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Plasma metabolites, metabolic risk score and colorectal cancer risk: a prospective cohort study.
Deng Y, Yang M, Peng P … +17 more , Lin Y, Lin J, Huang J, Wu K, Hu X, Ni Z, Hu D, Zhang M, He B, Chen Y, Tian L, Cheng C, Luo Q, Qin P, Chen X, Yang J, Hu F
Eur J Epidemiol · 2025 Dec · PMID 40906027 · Publisher ↗
The associations of colorectal cancer (CRC) risk with metabolites, lifestyle factors and their joint effects have not been fully elucidated. Therefore, we conducted a prospective cohort study to estimate the associations...
The associations of colorectal cancer (CRC) risk with metabolites, lifestyle factors and their joint effects have not been fully elucidated. Therefore, we conducted a prospective cohort study to estimate the associations of CRC risk with metabolites, metabolic risk score (MRS) and its joint associations with lifestyle factors. This study included 82,514 participants with plasma metabolites data in the UK Biobank. LASSO-COX and Random Forest was used to select metabolites. Cox regression was utilized to construct MRS and estimate the associations of CRC risk with metabolites, MRS and its joint associations with lifestyle factors. Single-cell RNA sequencing data were analyzed to identify metabolism-related genes and metabolic pathways during CRC progression. During a median follow-up of 13.28 years, 1151 incident CRC cases were identified. MRS, constructed using 6 metabolites, was significantly associated with increased CRC risk (HR = 1.39, 95% CI 1.22-1.56 for high vs. low MRS), with the strongest association for proximal colon cancer (HR = 1.51, 95% CI 1.24-1.84), followed by distal colon cancer and rectal cancer (HR = 1.35, 95% CI 1.05-1.72; HR = 1.37, 95% CI 1.11-1.69). Joint associations were identified between MRS and lifestyle factors with CRC risk. Individuals with healthy sleep, never smoking, healthy diet, and healthy lifestyle but high MRS also exhibited elevated CRC risk. Linoleic acid, histidine and tyrosine metabolism pathways played important roles during normal intestinal mucosa to CRC progression. Pre-diagnostic metabolites and MRS were significantly associated with increased CRC risk, especially proximal colon cancer. Individuals should maintain normal metabolite levels and healthy lifestyles for CRC prevention.
An instrumental variable analysis of body mass index and risk of long-term sick leave: the HUNT Study, Norway.
Moe K, Skarpsno ES, Nilsen TIL … +5 more , Kaspersen SL, Ose SO, Carslake D, Mork PJ, Aasdahl L
Eur J Epidemiol · 2025 Oct · PMID 40906026 · Full text
A more comprehensive understanding of the causal relationships between body mass index (BMI) and sick leave is needed. We aimed to examine the effect of BMI on the risk of cause-specific and all-cause long-term sick leav...
A more comprehensive understanding of the causal relationships between body mass index (BMI) and sick leave is needed. We aimed to examine the effect of BMI on the risk of cause-specific and all-cause long-term sick leave using an instrumental variable approach. The study included 21,918 adults participating in the two latest surveys of the population-based HUNT Study (HUNT3, 2006-2008 and HUNT4, 2017-2019) linked with registry data on cause-specific sick leave, including musculoskeletal and mental disorders. We used Cox regression to estimate risk of long-term sick leave per standard deviation (SD) increase in z-score of BMI, applying both conventional analysis of own BMI and instrumental variable analysis based on offspring BMI. In the conventional analyses, hazard ratios per SD increase in z-score of BMI ranged from 1.04 (95% confidence interval (CI) 0.99-1.08) for mental health disorders in women to 1.17 (95% CI 1.13-1.22) for musculoskeletal disorders in men. The instrumental variable approach supported that higher BMI increased the risk of long-term sick leave, except for sick leave due to mental health disorders in men. The analyses suggested that offspring BMI as an instrument is not independent of shared confounding. The results from both the conventional and instrumental variable analyses show that higher BMI increases the risk of long-term sick leave, except for sick leave due to mental health disorders in men. The instrumental variable method is likely to remove bias due to reverse causation, but residual bias due to shared confounding factors cannot be ruled out.
Associations of serum iron and its status change with mortality risk: prospective findings from the MJ cohort.
Liu Y, Wen CP, Pan J … +8 more , Cui J, Lu W, Sun T, Ning X, Lee JH, Li W, Tu H, Wu X
Eur J Epidemiol · 2025 Dec · PMID 40888985 · Publisher ↗
Previous studies on serum iron levels and mortality risk have yielded inconsistent findings based on single-point measurements. How serum iron levels and their longitudinal changes influence all-cause and cause-specific...
Previous studies on serum iron levels and mortality risk have yielded inconsistent findings based on single-point measurements. How serum iron levels and their longitudinal changes influence all-cause and cause-specific mortality remains unknown. This study investigated associations between baseline serum iron levels, their longitudinal changes, and all-cause and cause-specific mortality in a prospective cohort. Participants were recruited from the Taiwan MJ cohort (1997-2007) and followed until December 31, 2022. Baseline serum iron was categorized as low, normal, or high. Based on changes at a second visit, participants were further classified as persistent normal, progression to abnormal, reversion to normal, or persistent abnormal. Cox proportional hazard models were used for analysis. Over a median follow-up of 19.0 years, 33,005 deaths occurred. Fully adjusted models demonstrated J-shaped associations between serum iron and all-cause and cause-specific mortality (all P < 0.001), with higher all-cause mortality risks in low (HR 1.27, 95% CI [1.23, 1.31]) and high iron groups (HR 1.37, 95% CI [1.30, 1.44]). Compared to persistent normal levels, those with progression to abnormal, reversion to normal, or persistent abnormal serum iron exhibited elevated mortality risks (HRs: 1.22 [1.15, 1.30], 1.16 [1.09, 1.24], 1.49 [1.36, 1.63], respectively). Moreover, maintaining normal serum iron status alongside a healthy lifestyle exhibited the lowest mortality risks. Long term abnormal serum iron status was linked to increased mortality, which could be mitigated through lifestyle modifications, suggesting significance of serum iron monitoring and potential intervention.
Women in Healthy Transition (KISO) Survey: a cohort of 153,800 women aged 45-59 years living in Denmark.
Biener SN, Jørgensen TSH, Hybholt M
Eur J Epidemiol · 2025 Oct · PMID 40864411 · Full text
The nationwide Women in Healthy Transition (KISO) Survey Cohort is a population-based longitudinal prospective cohort study established to explore the significant data gap on women's symptoms through different stages of...
The nationwide Women in Healthy Transition (KISO) Survey Cohort is a population-based longitudinal prospective cohort study established to explore the significant data gap on women's symptoms through different stages of menopause in a Northern European context. The KISO Survey Cohort was set up to represent women aged 45-59 years living in Denmark. In total 575,863 women were invited to participate in the study at baseline. Data were collected through digital questionnaires from June to December 2024 and included self-reported information on stages of menopause, menopausal symptoms, quality of life, physical activity, and work productivity loss using validated scales as well as information on various health, social and lifestyle factors. The follow-up of the KISO Survey Cohort will be conducted through digital questionnaires every three years over a 15-year period, inviting baseline respondents and eligible women aged 45-59 at follow-up. A total of 153,800 women completed the baseline questionnaire, yielding a 27% response rate. Among the participants, 8% were in premenopause, 24% in perimenopause, and 45% in postmenopause. Moreover, 13% had induced menopause and 10% were undergoing menopausal hormone therapy. The KISO Survey Cohort is the first large-scale longitudinal study on menopausal symptoms among women in Denmark. Data are coupled with the personal identification numbers (CPR) enabling opportunities to link data to national administrative registers. This ongoing study, thus, offers unique and extensive data, enabling future research to advance our understanding of menopause, how it affects women, and its long-term effects on women.
Associations of potentially inappropriate medications in older adults with mortality and hospitalizations: methodological challenges in pharmacoepidemiology.
Degen M, Schöttker B
Eur J Epidemiol · 2025 Sep · PMID 40847213 · Full text
Previous studies on the association of potentially inappropriate medication (PIM) use with hospitalization risk and all-cause mortality among older adults were prone to confounding and biases. Using data from 217,111 par...
Previous studies on the association of potentially inappropriate medication (PIM) use with hospitalization risk and all-cause mortality among older adults were prone to confounding and biases. Using data from 217,111 participants of the population-based United Kingdom Biobank, aged 60-69 years, including 95,187 participants with primary care data linkage, the main analysis was a prospective new user design with 1:1 propensity-score stratified by indication matching of new PIM users and new appropriate medication (AM) users (assessed with the EURO-FORTA list). Results were compared to previous approaches with a prevalent user design and a new user design without propensity score matching. 43,307 (19.9%) participants used at least one PIM at baseline. Among 11,812 propensity score matched individuals with new PIM or new AM prescription within 2 years after baseline, new PIM use was associated with non-significantly 20% increased 1-month hospitalization (hazard ratio (HR) [95% confidence interval (95% CI)]: 1.20 [0.76-1.90]) and 23% increased 1-year mortality (1.23 [0.80-1.89]). Null-results were obtained with the prevalent user design (HRs [95% CIs]: 1-month hospitalization: 1.04 [0.83-1.31]; 1-year mortality: 1.01 [0.82-1.23]) and slightly stronger associations in new user design without propensity score matching stratified by indication (1-month hospitalization (1.24 [0.95-1.61]); 1-year mortality (HR [95% CI] 1.57 [1.24-2.00]). This first study with an appropriate methodology showed that previous pharmacoepidemiologic studies on the risk of PIM for hospitalization and mortality have either under- or overestimated the risk. Effect sizes of about 20% appear biologically plausible and larger studies are needed to detect such weak associations with statistical significance.
The impact of modifiable risk factor reduction on future dementia burden: a microsimulation modeling study.
Brück CC, de Nijs K, Ikram MA … +2 more , Wolters FJ, de Kok IMCM
Eur J Epidemiol · 2025 Sep · PMID 40847212 · Full text
Approximately 30%-50% of dementia cases are attributable to modifiable risk factors, but the impact of risk reduction strategies on dementia incidence at a population level is uncertain. Reliable estimates of interventio...
Approximately 30%-50% of dementia cases are attributable to modifiable risk factors, but the impact of risk reduction strategies on dementia incidence at a population level is uncertain. Reliable estimates of intervention effects require accounting for changes in life expectancy when intervening on risk factors, and model realistic reduction scenarios that consider co-occurrence of risk factors. Using the microsimulation model MISCAN-Dementia, we assessed the effect of interventions on mid-life hypertension and late-life smoking on dementia and mortality risk. We modeled risk factor reductions, from small reductions to complete elimination, and evaluated effects on dementia incidence and prevalence, number of cases, and life years with and without dementia. All risk factor reductions resulted in lower dementia incidence and prevalence, fewer dementia cases, and more dementia-free life years. Eliminating smoking resulted in 1.4% fewer dementia cases for women and 2.5% for men over their lifetime. Eliminating hypertension reduced dementia cases by 1.1% for women and 3.3% for men. The number of dementia cases and life years with dementia decreased until around age 90, after which a slight increase was observed due to prolonged life expectancy with the reductions. Reducing smoking and hypertension will result in additional life years without dementia and a modest reduction in overall dementia cases, with some additional dementia cases in the oldest old. These findings emphasize the potential of dementia risk reduction strategies and the importance of considering concurrent changes in mortality when evaluating risk factor reductions.
Risk of primary sclerosing cholangitis among patients with gastritis: a nationwide cohort study.
Älgå LL, Ekheden I, Thuresson M … +1 more , Ludvigsson JF
Eur J Epidemiol · 2025 Oct · PMID 40847211 · Full text
The pathogenesis of primary sclerosing cholangitis (PSC), a severe autoimmune liver disease, remains largely unknown. Infection with Helicobacter pylori (H. pylori) and subsequent gastritis could act as a triggering even...
The pathogenesis of primary sclerosing cholangitis (PSC), a severe autoimmune liver disease, remains largely unknown. Infection with Helicobacter pylori (H. pylori) and subsequent gastritis could act as a triggering event of PSC, as H. pylori seems to be more prevalent in chronic liver disease. However, the risk of PSC among patients with gastritis and its precursor, H. pylori infection, is undetermined. In this nationwide cohort study, we included Swedish individuals undergoing a gastroscopy with biopsy during 1990-2017 showing gastritis (n = 306 588) or H. pylori (n = 11 890). Three control groups were used (1) matched controls from the Swedish general population (n = 1 544 667), (2) individuals with a gastric biopsy indicating normal mucosa (n = 318 754) and (3) sibling controls (n = 231 879). We calculated the hazard ratios (HRs) for PSC development, adjusting for age, sex, calendar year, county, comorbidities, alcohol-related disorders, education, and country of birth. Patients with a histological diagnosis of gastritis or H. pylori were more likely to be diagnosed with PSC during follow up. Compared to the general Swedish population, the fully adjusted HR for PSC among patients with gastritis was 3.35 (95% CI 2.67-4.20). However, compared to secondary controls with a normal gastric mucosa, the PSC risk was not increased among patients with gastritis. Patients with a gastroscopy biopsy showing gastritis have a moderately increased risk for PSC later in life but not compared to other individuals undergoing gastrointestinal work up ("normal mucosa)". The association with PSC may be non-specific and apply to several gastrointestinal disorders.
Chronic high consumption of energy drinks and cardiovascular risk in adolescents-results of the EDKAR-study.
Menzel J, Spinka F, Pie MJ … +6 more , Deichl A, Knüppel S, Ehlers A, Nagl B, Edelmann F, Weikert C
Eur J Epidemiol · 2025 Nov · PMID 40847210 · Full text
In recent years, acute cardiovascular effects of high energy drink (ED) consumption have been described, but no data are available on chronic high consumption of EDs and cardiovascular risk in adolescents. As a first stu...
In recent years, acute cardiovascular effects of high energy drink (ED) consumption have been described, but no data are available on chronic high consumption of EDs and cardiovascular risk in adolescents. As a first study, the present study investigated differences in a variety of cardiological parameters in adolescents (aged 15-18 years) with a chronic high consumption of EDs (ED consumption: ≥ four days/week for ≥ last 12 months, > 3 mg caffeine from EDs/kg bodyweight/day) compared to a control group. In study phase 1 of the cross-sectional EDKAR-study, data from 5100 pupils in Berlin (Germany) on their ED consumption and lifestyle factors were assessed using an online questionnaire. Based on these, adolescents with a chronic high ED consumption (n = 97) and a control group (n = 160) were cardiologically examined at Charité - Universitätsmedizin Berlin. Blood pressure, heart rate, electrocardiographic and echocardiographic parameters were assessed. Cardiological risk factors like educational background, smoking, alcohol consumption and sleep duration were investigated. The study noticed no significant and/or clinically relevant differences in any of the cardiological parameters e.g., heart rate (Chronic high ED consumption: Geometric mean (95%-CI): 74.8 BPM (68.5-81.8) vs. control group: 71.9 BPM (65.2-79.2), p = 0.23). However, half of the high consumers reported having experienced adverse effects after consuming EDs. Furthermore, adolescents with chronic high ED consumption reported a considerably higher intake of alcohol, higher smoking rates and shorter sleep duration in comparison to the control group. Accordingly, chronic high ED consumption is associated with lifestyle factors with a potential negative impact on the cardiovascular system.
Cohort profile: the West-China hospital alliance longitudinal epidemiology wellness (WHALE) study.
Lin Y, Yang Y, Li Z … +13 more , Du L, Shi R, Shi Q, Xu X, Yin G, Zhang F, Huang W, Huang Y, Liao G, Liu Q, Li W, Song H, Huang J
Eur J Epidemiol · 2025 Sep · PMID 40847209 · Full text
The West-China Hospital Alliance Longitudinal Epidemiology Wellness (WHALE) Study establishes a robust, multidimensional database to provide comprehensive insights into health-to-disease transitions, advancing proactive...
The West-China Hospital Alliance Longitudinal Epidemiology Wellness (WHALE) Study establishes a robust, multidimensional database to provide comprehensive insights into health-to-disease transitions, advancing proactive healthcare and enhancing understanding of the interplay among genetic, behavioral, and environmental factors in disease. The WHALE Study includes a database and a cohort. The WHALE Database, established in 2010, integrates health check-up data from 11 hospitals, covering sociodemographic, lifestyle, medical history, and clinical data. The WHALE Health Trajectory Cohort, launched in November 2024, recruits adults with at least three health check-ups, featuring biennial active follow-ups and passive linkage with regional healthcare databases. As of January 2025, the WHALE Database includes over 3.4 million health records from 1,526,686 participants, with a mean age of 40.3 years and a balanced gender distribution. Notably, 23.88% of participants had at least three health check-ups, and 3.31% had more than ten, highlighting a significant proportion with repeated measurements. The study provides key insights into health trajectories by examining the associations of biomarker data and their trajectory patterns with aging, pre-disease conditions, and disease diagnoses. The strengths of the WHALE Study include its large sample size, longitudinal design, diverse representation, comprehensive data, and robust quality control. Limitations include potential selection bias, data variability across centers, and reliance on self-reported data for some variables.
Clinical and epidemiological characteristics of the 2024-2025 measles outbreak in Sarajevo Canton.
Jogunčić A, Baljić R, Tekin A … +7 more , Salčinović A, Dizdarević I, Sejtarija Memišević A, Gazibera B, Muratspahić A, Lal A, Sporišević L
Eur J Epidemiol · 2025 Sep · PMID 40801991 · Publisher ↗
Abstract loading — click title to view on PubMed.
Associations between multiple perinatal exposures and risk of childhood hospitalisation with infection: a registry-based study in two countries.
Todd IMF, Pedersen LH, Magnus MC … +3 more , Nassar N, Miller JE, Burgner DP
Eur J Epidemiol · 2025 Oct · PMID 40801990 · Full text
Several perinatal exposures impact severe infection risk in offspring. However, most studies consider exposures in isolation rather than the impact of multiple co-occurring perinatal exposures. Here, we investigated the...
Several perinatal exposures impact severe infection risk in offspring. However, most studies consider exposures in isolation rather than the impact of multiple co-occurring perinatal exposures. Here, we investigated the risk of hospitalised childhood infections associated with combinations of multiple perinatal exposures. We studied liveborn, singleton births in Denmark between 1997 and 2019 (n = 1,113,708) and Norway between 2008 and 2018 (n = 470,270) through national registry linkage. Seven perinatal exposures were evaluated including maternal antibiotic use during pregnancy, maternal smoking, maternal diabetes, hypertensive disorders of pregnancy, caesarean section birth, offspring being small for gestational age (SGA), and preterm birth. The outcome was hospitalised infections before 5 years age. Using Cox regression, we estimated hazard ratios (HR) of hospitalised infections for: (1) each exposure individually; (2) the cumulative number of exposures; (3) each unique combination of the seven exposures; (4) pairwise interactions between exposures. Results were combined through meta-analysis. Each exposure was individually associated with greater hospitalised infection risk with pooled HR estimates ranging from 1.08 (95% CI 1.08-1.09) for SGA to 1.45 (95% CI 1.43-1.46) for preterm birth. Cumulative risk was observed for increasing number of exposures from a pooled HR of 1.17 (95% CI 1.17-1.18) for one exposure to 1.88 (95% CI 1.78-1.99) for five or more exposures. Analyses of unique combinations of the exposures showed a particularly increased risk among preterm children with one or more additional exposures. Our findings can inform targeted strategies for the prevention and management of childhood infections. We highlight a simple, intuitive method for measuring risk associated with co-occurring exposures.
The relationship between PFAS exposure and dyslipidemia: an updated review, meta-analysis, and evaluation of bias.
Hussey MR, Kornberg TG, Sherrick JM … +3 more , Olson AM, Kind JA, Perez AL
Eur J Epidemiol · 2025 Sep · PMID 40801989 · Publisher ↗
There is concern that widespread exposure to per- and polyfluoroalkyl substances (PFAS) may induce changes in serum lipids, however, current evidence is insufficient to establish causality in humans. This systematic revi...
There is concern that widespread exposure to per- and polyfluoroalkyl substances (PFAS) may induce changes in serum lipids, however, current evidence is insufficient to establish causality in humans. This systematic review evaluated 69 articles examining exposure to perfluorooctanoic acid (PFOA) or perfluorooctane sulfonic acid (PFOS) and alterations in adult serum lipid outcomes. The majority of associations for PFOA or PFOS with serum lipids were either not significant, significantly negative, or were mixed versus significantly positive findings, suggesting non-consensus of any associations. A subset of 37 studies were examined via meta-analysis and reviewed for biases. Using pooled estimates, PFOA and PFOS exposure were significantly positively associated with total cholesterol (TC) and low-density lipoprotein (LDL). PFOA was significantly positively associated with triglycerides (TG), whereas PFOS had a non-significant positive association with high-density lipoprotein (HDL). TC and LDL estimates demonstrated high heterogeneity, peaking within cross-sectional and non-occupational studies that comprised the majority of the meta-analysis. Conversely, pooled estimates from longitudinal investigations trended towards null and were not significant. Potential reasons for heterogeneity were identified in a bias analysis and primarily included inconsistent confounding controls and possible subject recruitment bias from regions with known PFAS contamination. These factors indicate inconsistencies in PFAS-lipid literature that require further prospective investigations.
Circulating inflammation-related proteome improves cardiovascular risk prediction. Results from two large European cohort studies.
Xie R, Sha S, Brenner H … +1 more , Schöttker B
Eur J Epidemiol · 2025 Oct · PMID 40801988 · Full text
BACKGROUND: Inflammation plays a crucial role in cardiovascular disease (CVD), but the value of inflammation-related proteins in predicting major adverse cardiovascular events (MACE) is unclear. This study evaluated whet...
BACKGROUND: Inflammation plays a crucial role in cardiovascular disease (CVD), but the value of inflammation-related proteins in predicting major adverse cardiovascular events (MACE) is unclear. This study evaluated whether incorporating inflammation-related proteins into the SCORE2 model improves 10-year MACE risk prediction. METHODS: This study included 47,382 participants from the UK Biobank and 4,135 participants from the German ESTHER study without prior CVD or diabetes. We tested C-reactive protein (CRP) and 73 inflammation-related proteins measured with Olink panels. Biomarker selection was performed using least absolute shrinkage and selection operator (LASSO) regression with bootstrapping separately for males and females. Selected proteins were added to the SCORE2 model variables. Model performance was evaluated using Harrell's C-index, net reclassification index (NRI), and integrated discrimination index (IDI). RESULTS: Seven inflammation-related proteins but not CRP were selected, including two for both sexes, three specifically for males, and two specifically for females. Incorporating these proteins significantly improved the C-index (95% confidence interval (95%CI)) of the refitted SCORE2 model from 0.716 (0.698, 0.734) to 0.750 (0.732, 0.768) in internal validation in the UK Biobank and from 0.677 (0.644, 0.710) to 0.713 (0.681, 0.745) in external validation in the ESTHER study. The NRI with 95%CI was 12.4% (5.2%, 16.3%) in internal validation and 4.2% (0.5%, 23.6%) in external validation. The IDI also improved significantly. CONCLUSION: Incorporating inflammation-related proteins into the SCORE2 model significantly improves the prediction of 10-year MACE risk among individuals without prior CVD or diabetes. Measuring these proteins may enhance risk stratification in clinical practice.
Is educational attainment protective against developing dementia? A twin study of genetic and environmental contributions.
Walters EE, Luczak SE, Beam CR … +15 more , Ericsson M, Kremen WS, Krueger RF, Markon KE, McGue M, Nygaard M, Panizzon MS, Plassman BL, Reynolds CA, Sachdev PS, Thalamuthu A, Whitfield KE, Pedersen NL, Gatz M, IGEMS Consortium
Eur J Epidemiol · 2025 Oct · PMID 40794236 · Full text
Low educational attainment is recognized as a modifiable risk factor for dementia. Despite the commonly accepted notion that greater educational attainment confers lower dementia risk, few family-based studies have inves...
Low educational attainment is recognized as a modifiable risk factor for dementia. Despite the commonly accepted notion that greater educational attainment confers lower dementia risk, few family-based studies have investigated the causal bases for the association. Using data from seven twin samples from Sweden, Denmark, Australia, and the US participating in the IGEMS (Interplay of Genes and Environment in Multiple Studies) consortium (N = 60,027, 10.92% with dementia), we tested whether twins who achieve higher education than their co-twins have lower risk of dementia. The primary analysis applied a multilevel between-within regression framework, supported by descriptive statistics of within-pair differences. Results confirmed an overall association between educational attainment and dementia risk, such that individuals with higher educational attainment had less likelihood of developing dementia (phenotypic regression coefficient = -0.68, p <.0001). Within twin pairs, however, twins who achieved greater education than their co-twins did not uniformly show lower dementia risk (within-family regression coefficient = -0.07, p =.0983, while between-family regression coefficient = -0.98, p <.0001). Taken together, the pattern of results shows that the effect of educational attainment on dementia risk is largely attributable to genetic influences in common to educational attainment and dementia, although there are also contributions from environmental influences shared between members of the same family. Results were similar in men and women. These findings add to the literature by using a co-twin control design to address possible reasons that low educational attainment is associated with greater dementia risk.
Complex methods for complex data: key considerations for interpretable and actionable results in exposome research.
Ponzano M, Rotem RS, Bellavia A
Eur J Epidemiol · 2025 Dec · PMID 40768123 · Publisher ↗
Complex multidimensional data are becoming more widely available and are drastically affecting the way epidemiological studies are designed and conducted. Novel frameworks such as the exposome-which encompasses the compr...
Complex multidimensional data are becoming more widely available and are drastically affecting the way epidemiological studies are designed and conducted. Novel frameworks such as the exposome-which encompasses the comprehensive and cumulative set of exposures affecting individuals throughout their lifetime and the complex mechanisms through which they act - provide a unique opportunity to transform how public health recommendations are identified at the population and individual level. This data revolution is accompanied by a growing interest in analytical approaches that can handle the complexity of these novel research questions. These include semi-parametric and non-parametric statistical and machine learning methodologies that provide compelling frameworks for analyzing large-scale databases while mitigating overfitting. Nevertheless, interpreting results from these complex methods is often challenging. While discussions on interpretability have largely focused on statistical inference, causal considerations and the practical applicability of the findings to inform the design of tangible interventions have received less attention-despite being essential components of epidemiological research. With this commentary we provide a general overview of these three levels of interpretability-statistical, causal, and actionable-and discuss available tools that can aid epidemiologists to improve results interpretability as they start utilizing more complex analytical approaches.
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