Population-based Prospective Cohort Study Research Articles

Automated Deep Learning-Based Segmentation of Abdominal Adipose Tissue on Dixon MRI in Adolescents: A Prospective Population-Based Study.

BACKGROUND. The prevalence of childhood obesity has increased significantly worldwide, highlighting a need for accurate noninvasive quantification of body fat distribution in children. OBJECTIVE. The purpose of this study was to develop and test an automated deep learning method for subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) segmentation using Dixon MRI acquisitions in adolescents. METHODS. This study was embedded within the Generation R Study, a prospective population-based cohort study in Rotterdam, The Netherlands. The current study included 2989 children (1432 boys, 1557 girls; mean age, 13.5 years) who underwent investigational whole-body Dixon MRI after reaching the age of 13 years during the follow-up phase of the Generation R Study. A 2D competitive dense fully convolutional neural network model (2D-CDFNet) was trained from scratch to segment abdominal SAT and VAT using Dixon MRI-based images. The model underwent training, validation, and testing in 62, eight, and 15 children, respectively, who were selected by stratified random sampling, with manual segmentations used as reference. Segmentation performance was assessed using the Dice similarity coefficient and volumetric similarity. Two observers independently performed subjective visual assessments of automated segmentations in 504 children, selected by stratified random sampling, with undersegmentation and oversegmentation scored on a scale of 0-3 (with a score of 3 denoting nearly perfect segmentation). For 2820 children for whom complete data were available, Spearman correlation coefficients were computed among MRI measurements and BMI and dual-energy x-ray absorptiometry (DEXA)-based measurements. The model used (gitlab.com/radiology/msk/genr/abdomen/cdfnet) is publicly available. RESULTS. In the test dataset, the mean Dice similarity coefficient and mean volu-metric similarity, respectively, were 0.94 ± 0.03 [SD] and 0.98 ± 0.01 [SD] for SAT and 0.85 ± 0.05 and 0.92 ± 0.04 for VAT. The two observers assigned a score of 3 for SAT in 94% and 93% for the undersegmentation proportion and in 99% and 99% for the oversegmentation proportion, and they assigned a score of 3 for VAT in 99% and 99% for the undersegmentation proportion and in 95% and 97% for the oversegmentation proportion. Correlations with SAT and VAT were 0.808 and 0.698 for BMI and 0.941 and 0.801 for DEXA-derived fat mass. CONCLUSION. We trained and evaluated the 2D-CDFNet model on Dixon MRI in adolescents. Quantitative and qualitative measures of automated SAT and VAT segmentations indicated strong model performance. CLINICAL IMPACT. The automated model may facilitate large-scale studies investigating abdominal fat distribution on MRI among adolescents as well as associations of fat distribution with clinical outcomes.

Development and validation of the chemotherapy-induced peripheral neuropathy integrated assessment – oxaliplatin subscale: a prospective cohort study

BackgroundCurrent chemotherapy-induced peripheral neuropathy (CIPN) assessment tools mostly have poor sensitivity and weak anti-interference, so that it is sometimes difficult to provide substantive guidance for clinical intervention. This study aimed to develop an assessment tool dedicated for oxaliplatin to address these limitations.MethodsThis study screened 445 OIPN-related literatures for producing a symptom list, and developed the questionnaire module through expert supplement, item generation, content correlation analysis, pre-testing, and item improvement. The validation phase used a Chinese population-based prospective cohort study from June 2021 to July 2022. Patients were requested to complete the tested questionnaire, QLQ-CIPN20 and the CTCAE grading one day before cycles 2–6 of chemotherapy. Cronbach’s α coefficient and intraclass correlation coefficient (ICC) were calculated for the internal consistency and stability analysis, respectively. Exploratory factor analysis was conducted to investigate the construct validity. The correlations among the tested questionnaire, QLQ-CIPN20 and CTCAE were compared for the criterion validity analysis. Wilcoxon signed-rank sum test was utilized to compare the sensitivity between the tested questionnaire and QLQ-CIPN20.ResultA 20-item CIPN assessment tool named chemotherapy-induced peripheral neuropathy integrated assessment – oxaliplatin subscale (CIPNIA-OS) was developed. The validation phase included 186 patients. Cronbach's α coefficient of CIPNIA-OS was 0.764 (> 0.7), and ICC was 0.997 (between 0.9 and 1). The structure of CIPNIA-OS containing seven factors was examined. The correlation coefficient between CIPNIA-OS and CTCAE was 0.661 (95%CI 0.623 to 0.695), which was significantly higher than that between QLQ-CIPN20 and CTCAE (0.417, 95%CI 0.363 to 0.469, p < 0.01). Besides, the total score of CIPNIA-OS was mostly higher than QLQ-CIPN20, with an average difference of 2.189 (CI 95% 2.056 to 2.322), and the difference gradually expanded with the progress of chemotherapy (p < 0.05).ConclusionThis study developed an original CIPN questionnaire which was dedicated for OIPN assessment. It was a comprehensive tool that covered acute OIPN symptoms and integrated features from several proven CIPN assessment tools. The validation results supported that CIPNIA-OS had satisfactory reliability, stability, construct, criterion validity, and was more accuracy and sensitive than QLQ-CIPN20 in the evaluation of OIPN.

L-Shaped Association of Serum Chloride Level With All-Cause and Cause-Specific Mortality in American Adults: Population-Based Prospective Cohort Study.

Chloride is the most abundant anion in the human extracellular fluid and plays a crucial role in maintaining homeostasis. Previous studies have demonstrated that hypochloremia can act as an independent risk factor for adverse outcomes in various clinical settings. However, the association of variances of serum chloride with long-term mortality risk in general populations has been rarely investigated. This study aims to assess the association of serum chloride with all-cause and cause-specific mortality in the general American adult population. Data were collected from 10 survey cycles (1999-2018) of the National Health and Nutrition Examination Survey. All-cause mortality, cardiovascular disease (CVD) mortality, cancer mortality, and respiratory disease mortality data were obtained by linkage to the National Death Index through December 31, 2019. After adjusting for demographic factors and relevant lifestyle, laboratory items, and comorbid factors, weighted Cox proportional risk models were constructed to estimate hazard ratios and 95% CIs for all-cause and cause-specific mortality. A total of 51,060 adult participants were included, and during a median follow-up of 111 months, 7582 deaths were documented, 2388 of CVD, 1639 of cancer, and 567 of respiratory disease. The weighted Kaplan-Meier survival analyses showed consistent highest mortality risk in individuals with the lowest quartiles of serum chloride. The multivariate-adjusted hazard ratios from lowest to highest quartiles of serum chloride (≤101.2, 101.3-103.2, 103.2-105.0, and ≥105.1 mmol/L) were 1.00 (95% CI reference), 0.77 (95% CI 0.67-0.89), 0.72 (95% CI 0.63-0.82), and 0.77 (95% CI 0.65-0.90), respectively, for all-cause mortality (P for linear trend<.001); 1.00 (95% CI reference), 0.63 (95% CI 0.51-0.79), 0.56 (95% CI 0.43-0.73), and 0.67 (95% CI 0.50-0.89) for CVD mortality (P for linear trend=.004); 1.00 (95% CI reference), 0.67 (95% CI 0.54-0.84), 0.65 (95% CI 0.50-0.85), and 0.65 (95% CI 0.48-0.87) for cancer mortality (P for linear trend=.004); and 1.00 (95% CI reference), 0.68 (95% CI 0.41-1.13), 0.59 (95% CI 0.40-0.88), and 0.51 (95% CI 0.31-0.84) for respiratory disease mortality (P for linear trend=.004). The restricted cubic spline analyses revealed the nonlinear and L-shaped associations of serum chloride with all-cause and cause-specific mortality (all P for nonlinearity<.05), in which lower serum chloride was prominently associated with higher mortality risk. The associations of serum chloride with mortality risk were robust, and no significant additional interaction effect was detected for all-cause mortality and CVD mortality (P for interaction>.05). In American adults, decreased serum chloride concentrations were independently associated with increased all-cause mortality, CVD mortality, cancer mortality, and respiratory disease mortality. Our findings suggested that serum chloride may serve as a promising cost-effective health indicator in the general adult population. Further studies are warranted to explore the potential pathophysiological mechanisms underlying the association between serum chloride and mortality.

Elevated remnant cholesterol in atherosclerotic cardiovascular disease in diabetes: a population-based prospective cohort study

Abstract Background Elevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population; the association in individuals with diabetes is not known. Purpose We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of peripheral artery disease, myocardial infarction, ischemic stroke, and any ASCVD in individuals with diabetes. Methods We studied 4,569 individuals with diabetes and 102,674 individuals without diabetes from the Copenhagen General Population Study (2003-2015). In those with diabetes, during up to 15 years of follow-up, 236 were diagnosed with peripheral artery disease, 234 with myocardial infarction, 226 with ischemic stroke, and 498 with any ASCVD in national Danish health registries. Remnant cholesterol was calculated from a standard lipid-profile as total cholesterol minus HDL cholesterol minus LDL cholesterol. Results Individuals with diabetes had higher levels of remnant cholesterol, but lower levels of LDL cholesterol, compared to individuals without diabetes (Figure 1). Statin use could explain the lower levels of LDL cholesterol but did not associate with levels of remnant cholesterol. Multivariable adjusted hazard ratios (95% confidence interval) per doubling of remnant cholesterol and LDL cholesterol were 1.8 (1.2-2.5) and 0.9 (0.6-1.2) for peripheral artery disease, 1.8 (1.3-2.6) and 1.0 (0.7-1.4) for myocardial infarction, 1.6 (1.1-2.3) and 1.1 (0.8-1.6) for ischemic stroke, and 1.7 (1.4-2.2) and 0.9 (0.7-1.1) for any ASCVD, respectively. Excess risk conferred by diabetes was 2.5-fold for peripheral artery disease, 1.6-fold for myocardial infarction, 1.4-fold for ischemic stroke, and 1.6-fold for any ASCVD. Elevated remnant cholesterol explained 14% (95% confidence interval: 6-23%) of excess risk of PAD; corresponding numbers were 26% (10-41%) for myocardial infarction, 34% (5-64%) for ischemic stroke, and 24% (12-36%) for any ASCVD (Figure 2). LDL cholesterol was lower in individuals with diabetes than in individuals without diabetes and could therefore not explain excess risk. Conclusions Elevated remnant cholesterol was associated with increased risk of ASCVD in individuals with diabetes and explained 24% of their excess risk of ASCVD. Clinical trials should determine if remnant cholesterol lowering can prevent ASCVD in individuals with diabetes.

Association of adverse pregnancy outcomes with cardiovascular risk profile in later life - lessons learned from a large prospective population-based cohort-study

Abstract Background An increased cardiovascular risk profile in parous women in later life has been related to maternal outcomes of pregnancy such as hypertension, diabetes, excessive weight gain as well as fetal outcomes such as preterm birth or excessive birth weight. Methods Using data from a large, monocenter, prospective, long-term, population-based cohort, we analysed self-reported data on pregnancy, risk factors and health status of 1,970 women. We examined the correlations between gestational hypertension (gHTN), gestational diabetes (gDM) and excessive weight gain during pregnancy with hypertension (HTN), diabetes (DM), hyperlipoproteinemia (HLP) and body-mass-index (BMI) in later life. Regarding adverse fetal outcomes, we investigated correlations between preterm birth and later hysterectomy/ovariectomy of parous women and birth weight of &amp;gt;4,000 g with parous women’s BMI in later life. The Wilcoxon rank sum test and the Pearson's Chi-squared test were carried out to prove associations. Further logistic regression analyses are planned to assess cardiovascular outcomes such as myocardial infarction, stroke, heart failure and atrial fibrillation in these parous women. The p-value of 0.05 was defined as a standard for significance. Results The median age of 1,970 women upon examination was 63 years. The proportion of gestational hypertension was 8.7%. 18% of women gained more than 20 kg and 2.4% had diabetes during pregnancy. 10% delivered newborns with a birth weight of &amp;lt;2,500 g. 14% delivered newborns with a birth weight of &amp;gt;4,000 g. 19% were smokers and had hyperlipoproteinaemia, 59% were hypertensive and 33% had metabolic syndrome. We found positive correlations between gestational hypertension and hypertension in later life as well as between gestational diabetes and diabetes mellitus. Excessive weight gain during pregnancy was found to relate to elevated BMI in later life as well as current smoking status. Excessive weight gain during pregnancy did, however, not relate to HLP. High birth weight of &amp;gt;4,000 g correlated with elevated BMI in later life. Conclusions In a population-based sample, we were able to demonstrate that pregnancy-related manifestations of cardiovascular risk factors are indeed related to an increased risk profile in later life. There is a profound need for better individual risk stratification in women based on pregnancy-related data in order to deliver optimised early preventative strategies and potentially reduce cardiovascular events in later life.

Understanding suicidal transitions in Australian adults: protocol for the LifeTrack prospective longitudinal cohort study

BackgroundThe factors that influence transition from suicidal ideation to a suicide attempt or remission of suicidal thoughts are poorly understood. Despite an abundance of research on risk factors for suicidal ideation, no large-scale longitudinal population-based studies have specifically recruited people with suicidal ideation to examine the mechanisms underlying critical transitions to either suicide attempt or recovery from suicidal ideation. Without longitudinal data on the psychological, behavioural, and social determinants of suicide attempt and the remission of suicidal ideation, we are unlikely to see major gains in the prevention of suicide.AimThe LifeTrack Project is a population-based longitudinal cohort study that aims to identify key modifiable risk and protective factors that predict the transition from suicidal ideation to suicide attempt or remission of suicidal ideation. We will assess theory-informed risk and protective factors using validated and efficient measures to identify distinct trajectories reflecting changes in severity of suicidal ideation and transition to suicide attempt over three years.MethodsA three-year prospective population-based longitudinal cohort study will be conducted with adults from the general Australian population who initially report suicidal ideation (n = 842). Eligibility criteria include recent suicidal ideation (past 30 days), aged 18 years or older, living in Australia and fluent in English. Those with a suicide attempt in past 30 days or who are unable to participate in a long-term study will be excluded. Participants will be asked to complete online assessments related to psychopathology, cognition, psychological factors, social factors, mental health treatment use, and environmental exposures at baseline and every six months during this three-year period. One week of daily measurement bursts (ecological momentary assessments) at yearly intervals will also capture short-term fluctuations in suicidal ideation, perceived burdensomeness, thwarted belongingness, capability for suicide, and distress.ConclusionThis study is intended to identify potential targets for novel and tailored therapies for people experiencing suicidal ideation and improve targeting of suicide prevention programs. Even modest improvements in current treatments may lead to important reductions in suicide attempts and deaths.Study RegistrationAustralian New Zealand Clinical Trials Registry identifier: ACTRN12623000433606.

Sex differences in the associations between relative fat mass and all-cause and cardiovascular mortality: A population-based prospective cohort study

Background and aimsThe novel sex-specific anthropometric equation relative fat mass (RFM) is a new estimator of whole-body fat %. The study aimed to investigate the predictive role of RFM in cardiometabolic abnormalities, cardiovascular disease (CVD), all-cause and cardiovascular mortality, and explored potential sex differences. Methods and resultsThe study analyzed data from 26,754 adults in NHANES 1999–2010, with a median follow-up of 13.8 years. The correlation between RFM and body composition as well as fat distribution assessed by dual-energy X-ray absorptiometry was investigated. Weighted multivariable generalized linear models, Cox proportional hazards models and restricted cubic spline were applied to investigate the predictive role of RFM in metabolic markers, cardiovascular risk factors, CVD, all-cause and cardiovascular mortality. RFM exhibited a robust correlation with both whole-body fat % and trunk fat %. Higher RFM exhibited a stronger association with impaired glucose homeostasis, serum lipids, the incidence of hypertension, and coronary heart disease in males, while a stronger association with C-reactive protein in females. A U-shaped association between RFM and all-cause mortality was observed only in males. The hazard ratio (HR) of all-cause and cardiovascular mortality in males increased rapidly when RFM exceeded 30. However, in females, the HR of all-cause and cardiovascular mortality fluctuated until RFM exceeded 45, after which it increased rapidly. ConclusionRFM was a sex-specific estimator for both general and central obesity, sex-specific differences in predicting cardiometabolic abnormalities and adverse events using RFM might be partially attributed to differences in body composition and fat distribution between sexes.

Effects of prenatal single and mixed bisphenol exposure on bone mineral density in preschool children: A population-based prospective cohort study

Exposure to bisphenols can affect bone mineral density (BMD) in animals and humans. However, the effects of maternal exposure to bisphenols during pregnancy on bone health in preschool children remain unknown. We aimed to assess the effects of prenatal exposure to single and multiple bisphenols on bone health in preschool children. A total of 230 mother–child pairs were included in this study. Generalized linear regression, restricted cubic spline (RCS), principal component analysis (PCA), and Bayesian kernel machine regression (BKMR) were utilized to assess the relationship between bisphenol levels and bone health in preschool children. Each natural log (Ln) unit increase in tetrabromobisphenol A was related to a 0.007 m/s (95 % CI: –0.015, 0.000) decrease in Ln-transformed speed of sound (SOS) among girls. Decreased BMD Z scores in preschool children were found only in the high bisphenol S exposure group (β = -0.568; 95 % CI: –1.087, –0.050) in boys. The risk of low BMD (BMDL) was significantly higher in the middle-exposure group (OR = 4.695; 95 % CI: 1.143, 24.381) and high-exposure group of BPS (OR = 6.165, 95 % CI: 1.445, 33.789) compared with the low-exposure group in boys. In girls, the risk of BMDL decreased with increasing bisphenol A concentration (OR = 0.413, 95 % CI: 0.215, 0.721). RCS analysis revealed a U-shaped nonlinear correlation between BPB concentration and BMDL in girls (P-overall = 0.011, P-nonlinear = 0.009). In PCA, a U-shaped dose–response relationship was found between PC2 and the risk of BMDL (P-overall = 0.048, P-nonlinear = 0.032), and a significant association was only noted in girls when stratified by sex. The BKMR model revealed a horizontal S-shaped curve relationship between bisphenol mixtures and BMDL in girls. The results indicated that prenatal exposure to single and mixed bisphenols can affect BMD in preschool children, exerting nonmonotonic and child sex-specific effects.

Year-by-Year Blood Pressure Variability From Midlife to Death and Lifetime Dementia Risk

High visit-to-visit blood pressure variability (BPV) in late life may reflect increased dementia risk better than mean systolic blood pressure (SBP). Evidence from midlife to late life could be crucial to understanding this association. To determine whether visit-to-visit BPV at different ages was differentially associated with lifetime incident dementia risk in community-dwelling individuals. This cohort study analyzed data from the Adult Changes in Thought (ACT) study, an ongoing population-based prospective cohort study in the US. Participants were 65 years or older at enrollment, community-dwelling, and without dementia. The study focused on a subset of deceased participants with brain autopsy data and whose midlife to late-life blood pressure data were obtained from Kaiser Permanente Washington medical archives and collected as part of the postmortem brain donation program. In the ACT study, participants underwent biennial medical assessments, including cognitive screening. Data were collected from 1994 (ACT study enrollment) through November 2019 (data set freeze). Data analysis was performed between March 2020 and September 2023. Visit-by-visit BPV at ages 60, 70, 80, and 90 years, calculated using the coefficient of variation of year-by-year SBP measurements over the preceding 10 years. All-cause dementia, which was adjudicated by a multidisciplinary outcome adjudication committee. A total of 820 participants (mean [SD] age at enrollment, 77.0 [6.7] years) were analyzed and included 476 females (58.0%). A mean (SD) of 28.4 (8.4) yearly SBP measurements were available over 31.5 (9.0) years. The mean (SD) follow-up time was 32.2 (9.1) years in 27 885 person-years from midlife to death. Of the participants, 372 (45.4%) developed dementia. The number of participants who were alive without dementia and had available data for analysis ranged from 280 of those aged 90 years to 702 of those aged 70 years. Higher BPV was not associated with higher lifetime dementia risk at age 60, 70, or 80 years. At age 90 years, BPV was associated with 35% higher dementia risk (hazard ratio [HR], 1.35; 95% CI, 1.02-1.79). Meta-regression of HRs calculated separately for each age (60-90 years) indicated that associations of high BPV with higher dementia risk were present only at older ages, whereas the association of SBP with dementia gradually shifted direction linearly from being incrementally to inversely associated with older ages. In this cohort study, high BPV indicated increased lifetime dementia risk in late life but not in midlife. This result suggests that high BPV may indicate increased dementia risk in older age but might be less viable as a midlife dementia prevention target.

Associations of Fish and Fish Oil Consumption With Incident Inflammatory Bowel Disease: A Population-Based Prospective Cohort Study.

We examined the associations of fish and fish oil consumption with inflammatory bowel disease (IBD) incidence. We conducted a longitudinal analysis based on the UK Biobank, a population-based prospective cohort. Dietary consumption of fish and fish oil was collected by questionnaire. IBD incident cases were identified through links to National Health Services datasets. Cox proportional hazards regression models were used to assess the associations between oily fish, nonoily fish, and fish oil intake and IBD incidence with adjustment for various confounding factors. A total of 265 839 participants free of IBD at baseline were included, and 1554 incident IBD cases were identified during an average follow-up of 11.8 years. In fully adjusted models, we found that compared with participants who never ate oily fish, those having <1 serving/wk, 1 serving/wk, and >1 serving/wk had 9% (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.77-1.08), 19% (HR, 0.81; 95% CI, 0.69-0.96), and 12% (HR, 0.88; 95% CI, 0.73-1.06) lower risks of IBD, respectively, albeit not all statistically significant. A significant association was found between fish oil intake and a reduced risk of IBD (HR, 0.84; 95% CI, 0.75-0.93). We found no significant associations for nonoily fish. In a subsample (n = 105 714) of participants with multiple subsequent dietary reviews, we also found a negative association between the frequency of fish oil intake over time and incident IBD (P trend < .05). Our findings indicate that oily fish and fish oil supplements might be protective factors against IBD.

Body mass index trajectories and mortality risk in Japan using a population-based prospective cohort study: the Japan Public Health Center-based Prospective Study.

Recent studies have found that long-term changes in weight during adulthood are associated with a high risk of mortality. The objective of this study was to characterize body mass index (BMI) trajectories during adulthood and to examine the association between BMI trajectories and risk of death in the Japanese population. The data were extracted from Japan Public Health Center-based Prospective Study-a population-based prospective cohort study in Japan with participants aged 40-69 years followed over 20 years. The participants were categorized into multiple BMI trajectory groups using the latent class growth model. The Cox proportional-hazards model was conducted using all-cause mortality and cause-specific mortality as outcomes and the identified BMI trajectory groups as a predictor. In total, 65 520 participants were included in the analysis. Six BMI trajectory groups were identified: underweight stable (Group 1), low-to-high normal (Group 2), high-to-low normal (Group 3), normal to overweight (Group 4), overweight to normal (Group 5) and normal to obese (Group 6). Our Cox models showed a higher hazard (risk) of all-cause mortality among participants in the BMI-declining groups [Group 3, adjusted hazard ratio (aHR): 1.10, 95% CI: 1.05-1.16; Group 5, aHR: 1.16, 95% CI: 1.08-1.26], underweight stable group (Group 1, aHR: 1.27, 95% CI: 1.21-1.33) and normal to obese group (Group 6, aHR: 1.22, 95% CI: 1.13-1.33) than Group 2 (low-to-high normal BMI trajectory). Stable underweight and weight loss were associated with a high risk of mortality, both of which were uniquely observed in a Japanese population.

The association between maternal prenatal vitamin B12 intake and child cognitive development

Abstract Background Nutrient deficiencies in diet during pregnancy may have an adverse effect on the development of offspring. The association between prenatal vitamin B12 intake and cognitive functioning in children is unclear. Therefore, we examined such association in Czech children. Methods Czech part of European Longitudinal Study of Pregnancy and Childhood is a population-based prospective longitudinal birth cohort study of pregnant women and their children enrolled in 1991-1992. Dietary data was measured at 32 weeks of gestation using 145 items self-reported food frequency questionnaire. Parents reported on their child's speech and language development at 18 months, 3, 5, and 7 years of age (outcomes ranging from n = 1891 to n = 2362), from which single scores for vocabulary, language, early communication, understanding, and intelligibility were calculated. Higher scores indicate better speech and language development. Data were analysed using multiple ordinal and logistic regression models. Results Higher prenatal vitamin B12 intake was associated with higher speech and language test scores in fully adjusted models. Children of mothers with higher B12 intake had increased likelihood of higher scores in vocabulary (OR = 1.06, 95% CI: 1.01; 1.11), language (OR = 1.05, 95% CI: 1.01; 1.10), early communication (OR = 1.06, 95% CI: 1.01; 1.11) and understanding (OR = 1.09, 95% CI: 1.04; 1.14) at 18 months of age. Furthermore, they were more likely to get maximum points in the intelligibility test at age 3 (OR = 1.08, 95% CI: 1.02; 1.14) opposed to children of mothers with lower B12 intake. There were no associations at 5 and 7 years. Conclusions We found consistent and significant associations between prenatal vitamin B12 intake and early speech and language development. The results suggest that a diet during pregnancy low in vitamin B12 may negatively affect children's cognitive development. Thus, a healthy pregnancy diet with sufficient vitamin B12 should be promoted. Key messages • A diet low in vitamin B12 during pregnancy may have negative effects on the cognitive development of offspring, according to a longitudinal birth cohort study. • Adequate prenatal vitamin B12 intake is important for cognitive development, particularly speech and language development.

Prior morbidity and sickness absence with Covid-19 among wholesale and retail blue-collar workers

Abstract Background Cancer, cardiovascular disease, hypertension, diabetes, chronic kidney disorders, chronic lung disorders, neurological disorders, obesity, immunocompromisation, and schizophrenia or bipolar disorders were found to be risk factors for severe Covid-19. The aim was to determine associations between having such diagnoses and future sickness absence (SA) due to Covid-19 or related diagnoses in 2020. Methods A prospective population-based cohort study of all 299,268 blue-collar workers (48% women) in Sweden in 2018, using linked microdata from four nationwide registers covering 2018-2020. People with any of the above diagnoses in 2018 or 2019 were identified using microdata from specialised in- and outpatient healthcare and prescribed drugs. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of a new SA spell &amp;gt;14 days due to diagnosed Covid-19 or one of the diagnoses used by the Social Insurance Agency for suspected Covid-19 in 2020, separately for each diagnosis group and a global estimate for all risk factors together, adjusted for sociodemographic characteristics. Results In total, 38,422 individuals had at least one of the diagnoses that was a risk factor for severe Covid-19. Of them, 284 individuals had SA due to Covid-19 or related diagnoses (0.7%) in 2020, while 1210 of those with no such risk factor for Covid-19 had SA due to Covid-19 or related diagnoses (0.5%). The adjusted OR of SA due to Covid-19 or related diagnoses was 1.37 (95% CI 1.20-1.56) for those who had any risk factors for severe Covid-19. The group of diagnoses with the highest adjusted OR for SA in Covid-19-related diagnoses was lung disease (2.23; 95% CI 1.93-2.56). Conclusions While only a few of those with prior morbidity that was a risk factor for severe Covid-19 had SA due to Covid-19 or related diagnoses in 2020, they had a higher risk than those without such prior morbidity. Key messages • Having prior morbidity with a diagnosis identified as a risk factor for severe Covid-19 was associated with a higher risk of having SA due to Covid-19 or related diagnoses in 2020. • Prior lung disease was the diagnosis group with the highest risk of SA due to Covid-19 or related diagnoses.

Sickness absence and/or disability pension and future work income after age 65 and 70 in Sweden

Abstract Background As retirement ages are increasing in Europe, more knowledge is needed on factors that are associated with extended working life. Our aim was to explore if prior sickness absence (SA) and/or disability pension (DP) due to mental and/or somatic diagnoses were associated with income from work after age 65 and 70, respectively. Methods A 4-year prospective population-based cohort study using microdata from nationwide registers. We included all who in 2014 were aged 65-69 (cohort A; n = 201,263) and ≥70 (cohort B; n = 93,751), respectively, had income from work in 2014 (baseline), and lived in Sweden in 2010-2015. Cox proportional hazard regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for associations between prior SA (in spells &amp;gt;14 days) and/or DP due to mental and/or somatic diagnoses, overall and stratified by the number of net days (2010-2014), and future years with income from work (2015-2018), censored for death and emigration, adjusted for sociodemographic and work-related factors, and stratified by sex. Results The majority had no SA or DP during the exposure interval (cohort A 66.3% women, 75.8% men; cohort B 96.8% women, 97% men). Many had income from work at some point during follow-up (cohort A 77.8% women, 81.6% men, cohort B 81.9% women, 83.4% men). Prior somatic SA/DP was associated with a marginally but significantly higher HR for earlier exit from paid work in cohort A (women 1.08; 95% CI: 1.06-1.10; men 1.10; 1.08-1.12), lower HR for men in cohort B (0.93; 0.86-0.99), and non-significant HR for women in cohort B. The corresponding association for mental SA/DP was significant only for women in cohort A (1.09; 1.06-1.13). Conclusions The likelihood of earlier exit from paid work was slightly higher for those aged 65-69 at baseline with prior somatic SA/DP, but lower for men aged ≥70 at baseline with prior somatic SA/DP. Prior mental SA/DP was associated with earlier exit only for women aged 65-69 at baseline. Key messages • Prior SA/DP was in many cases marginally but significantly associated with future income from work. The direction of association differed depending on the diagnosis of the spell, cohort and sex. • More knowledge is needed on how older workers with different types of morbidities and functional limitations can extend their working life in Sweden as well as in other European countries.

Sickness absence after work injuries and post-traumatic stress among white-collar workers

Abstract Background There is very little knowledge about sickness absence (SA) and disability pension (DP) after work injuries and post-traumatic stress disorder (PTSD) among white collar workers. The aim was to examine diagnosis-specific SA and DP after healthcare due to a workplace injury and PTSD, respectively, among white-collar workers in the wholesale and retail industry in Sweden. Methods A prospective population-based cohort study of all 192,077 such white-collar workers (44% women) in Sweden in 2012, using linked microdata from three nationwide registers covering 2012-2016. We identified individuals who had specialised out- or inpatient healthcare due to a work injury (n = 1114) or to PTSD (n = 216) in the years 2012-2016. Their average number of net days of diagnosis-specific SA and DP was calculated for the 365 days before and 365 days after the healthcare visit. Results 64% of women and 45% of the men had at least one new SA spell during the 365 days after healthcare due to a work injury. On average, women had 14 SA/DP days the year before the injury and 31 days after; corresponding days for men were 9 and 21 days. SA days with fractures and with other injuries increased most, while SA days with mental diagnoses increased slightly. In the PTSD group, 80% of women and 65% of men had a new SA spell. Women's SA/DP days increased from 121 to 157 and men's from 112 to 174. SA with stress-related disorders and other mental diagnoses increased most, while DP with stress-related diagnoses and SA with musculoskeletal diagnoses increased slightly. Conclusions About half of those who had healthcare due to work injuries, and the majority of those who had PTSD, had new SA following the healthcare. SA due to diagnoses related to injury and mental diagnoses, respectively, increased most, however, SA/DP days due to other diagnoses also increased slightly. More knowledge is needed on factors associated with having or not having SA/DP with different diagnoses after work injuries and PTSD. Key messages • About half of those who had specialised healthcare due to work injuries, and the majority of those who had PTSD, had new SA in the following 365 days. • Individuals with healthcare for PTSD had more SA/DP days both before and after their healthcare visit than those with work injuries, but individuals with work injuries had a larger increase.

Assessment of Physical Resilience Using Residual Methods and Its Association With Adverse Outcomes in Older Adults.

Physical resilience (PR) is recognized as the ability to recover from the adverse effects of a stressor. However, there is a lack of consensus on how to optimally measure PR in older adults in general. We aimed to measure PR using residuals from regression analyses and investigated its association with adverse outcomes in older adults. A total of 6 508 older adults were included from the National Health and Aging Trends Study, which was a population-based prospective cohort study. PR was assessed using residual methods from a linear model regressing the short physical performance battery on clinical diseases, age, sex, race/ethnicity, and health condition. Adverse outcomes included all-cause mortality, falls, and overnight hospitalization. The mean age was 77.48 (7.84) years. Increased PR was associated with a lower risk of all-cause mortality (hazard ratio [HR] = 0.85, 95% confidence interval [CI]: 0.83-0.87). Compared to participants with reduced PR, those with normal PR had a lower risk for mortality (HR = 0.51, 95% CI: 0.46-0.56). Specifically, restricted cubic spline regression revealed a dose-response relationship between PR and all-cause mortality (p-overall < .0001, p-nonlinear = .011). Additionally, we also found significant associations of increased PR with lower risks of falls (HR = 0.98, 95% CI: 0.96-0.99) and overnight hospitalization (HR = 0.98, 95% CI: 0.97-1.00). PR, measured by residual methods, was robustly and independently associated with all-cause mortality, falls, and overnight hospitalization. Our findings provide evidence that this approach may be a simple and feasible strategy to assess PR.

Tocolysis after preterm prelabor rupture of membranes and 5-year outcomes: a population-based cohort study

The administration of tocolytics after preterm prelabor rupture of membranes remains a controversial practice. In theory, reducing uterine contractility should delay delivery and allow for optimal antenatal management, thereby reducing the risks for prematurity and adverse consequences over the life course. However, tocolysis may be associated with neonatal death or long-term adverse neurodevelopmental outcomes, mainly related to prolonged fetal exposure to intrauterine infection or inflammation. In a previous study, we showed that tocolysis administration was not associated with short-term benefits. There are currently no data available to evaluate the impact of tocolysis on neurodevelopmental outcomes in school-aged children born prematurely in this clinical setting. This study aimed to investigate whether tocolysis administered after preterm prelabor rupture of membranes is associated with neurodevelopmental outcomes at 5.5 years of age. We used data from a prospective, population-based cohort study of preterm births recruited in 2011 (referred to as the EPIPAGE-2 study) and for whom the results of a comprehensive medical and neurodevelopmental assessment of the infant at age 5.5 years were available. We included pregnant individuals with preterm prelabor rupture of membranes at 24 to 32 weeks' gestation in singleton pregnancies with a live fetus at the time of rupture, birth at 24 to 34 weeks' gestation, and participation of the infant in an assessment at 5.5 years of age. Exposure was the administration of any tocolytic treatment after preterm prelabor rupture of membranes. The main outcome was survival without moderate to severe neurodevelopmental disabilities at 5.5 years of age. Secondary outcomes included survival without any neurodevelopmental disabilities, cerebral palsy, full-scale intelligence quotient, developmental coordination disorders, and behavioral difficulties. A propensity-score analysis was used to minimize the indication bias in the estimation of the treatment effect on outcomes. Overall, 596 of 803 pregnant individuals (73.4%) received tocolytics after preterm prelabor rupture of membranes. At the 5.5-year follow-up, 82.7% and 82.5% of the children in the tocolysis and no tocolysis groups, respectively, were alive without moderate to severe neurodevelopmental disabilities; 52.7% and 51.1%, respectively, were alive without any neurodevelopmental disabilities. After applying multiple imputations and inverse probability of treatment weighting, we found no association between the exposure to tocolytics and survival without moderate to severe neurodevelopmental disabilities (odds ratio, 0.93; 95% confidence interval, 0.55-1.60), survival without any neurodevelopmental disabilities (odds ratio, 1.02; 95% confidence interval, 0.65-1.61), or any of the other outcomes. There was no difference in the neurodevelopmental outcomes at age 5.5 years among children with and without antenatal exposure to tocolysis after preterm prelabor rupture of membranes. To date, the health benefits of tocolytics remain unproven, both in the short- and long-term.

Physical Activity and Bladder Cancer Risk: Findings of the Japan Collaborative Cohort Study.

The association of physical activity with the risk of bladder cancer remains inconsistent among Asian populations. We aimed to examine the association in a large Japanese cohort. In a population-based prospective cohort study, a total of 50,374 Japanese adults aged 40-79 years without a history of cancer or cardiovascular disease who had information on physical activity from self-administrated questionnaires were used for analysis. We performed Cox proportional hazard models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident bladder cancer after adjusting for several potential confounders. During the median 17.5 years of follow-up, 153 incident bladder cancers (116 men and 37 women) were identified. After the multivariable adjustment, HRs (95% CI) of bladder cancer concerning those with recreational sports participation of 1-2 hr/wk, 3-4 hr/wk, and 5 hr/wk and more were 0.67 (0.38-1.20), 0.79 (0.36-1.74), and 0.28 (0.09-0.89), respectively (p for trend=0.017). Compared with mostly sitting at the workplace, occupational physical activity of standing and walking were associated with a lower risk of bladder cancer (HR, 0.53 [95% CI, 0.32 to 0.85]). Hours of daily walking were not associated with the risk. The lower risk of bladder cancer was more evident for recreational sports (HR, 0.33 [95% CI, 0.10 to 1.00]), and for occupational standing and walking activity at work (HR, 0.57 [95% CI, 0.33 to 0.98]) among men. Recreational sports participation and occupational physical activity were inversely associated with the risk of bladder cancer among Japanese, especially in men.

Physical exercise and cardiovascular response: design and implementation of a pediatric CMR cohort study

To examine feasibility and reproducibility and to evaluate the cardiovascular response to an isometric handgrip exercise in low-risk pediatric population using Cardiovascular Magnetic Resonance measurements. In a subgroup of 207 children with a mean age of 16 years participating in a population-based prospective cohort study, children performed an isometric handgrip exercise. During rest and exercise, continuous heart rate and blood pressure were measured. Cardiovascular magnetic resonance (CMR) measurements included left ventricular mass, aortic distensibility and pulse wave velocity at rest and left ventricular end-diastolic and end-systolic volumes, ejection fraction, stroke volume and cardiac output during rest and exercise. 207 children had successful CMR measurements in rest and 184 during exercise. We observed good reproducibility for all cardiac measurements. Heart rate increased with a mean ± standard deviation of 42.6% ± 20.0 and blood pressure with 6.4% ± 7.0, 5.4% ± 6.1 and 11.0% ± 8.3 for systolic, diastolic and mean arterial blood pressure respectively (p-values < 0.05). During exercise, left ventricular end-diastolic and end-systolic volumes and cardiac output increased, whereas left ventricular ejection fraction slightly decreased (p-values < 0.05). Stroke volume did not change significantly. A sustained handgrip exercise of 7 min at 30–40% maximal voluntary contraction is a feasible exercise-test during CMR in a healthy pediatric population, which leads to significant changes in heart rate, blood pressure and functional measurements of the left ventricle in response to exercise. This approach offers great novel opportunities to detect subtle differences in cardiovascular health.

Risk factors and cardio-metabolic outcomes associated with metabolic-associated fatty liver disease in childhood

Non-Alcoholic Fatty Liver Disease (NAFLD) is defined as increased liver fat percentage, and is the most common chronic liver disease in children. Rather than NAFLD, Metabolic-Associated Fatty Liver Disease (MAFLD), defined as increased liver fat with presence of adverse cardio-metabolic measures, might have more clinical relevance in children. We assessed the prevalence, risk-factors and cardio-metabolic outcomes of MAFLD at school-age. This cross-sectional analysis was embedded in an ongoing population-based prospective cohort study started in 2001, in the Netherlands. In 1910 children of 10 years, we measured liver fat fraction by magnetic resonance imaging (MRI), body mass index (BMI), blood pressure, and lipids, insulin, and glucose concentrations. Childhood lifestyle factors were obtained through questionnaires. MAFLD was defined as ≥2% liver fat in addition to excess adiposity (BMI or visceral adiposity), presence of metabolic risk (blood pressure, triglycerides and HDL-concentrations) or prediabetes (glucose). Of all children, 49.6% had ≥2% liver fat, and 25.2% fulfilled the criteria of MAFLD. Only non-European descent was associated with increased odds of MAFLD at nominal significance (Odds Ratio 1.38, 95% Confidence Interval 1.04, 1.82). Compared to children with <2% liver fat, those with MAFLD had increased odds of cardio-metabolic-risk-factor clustering (Odds Ratio 7.65, 95% Confidence Interval 5.04, 11.62). In this study, no NAFLD-associated childhood risk factors were associated with increased odds of childhood MAFLD, yet the findings suggest that ethnicity could be, despite mostly explained by socio-economic factors. Use of MAFLD criteria, rather than NAFLD, may identify children at risk for impaired cardio-metabolic health. Erasmus University MC, the Netherlands Organisation for Health Research and Development, the Ministry of Health, Welfare, and Sport, and the European Research Council.