Maternal intrahepatic cholestasis of pregnancy and neurodevelopmental conditions in offspring: A population-based cohort study of 2 million Swedish children.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is the most common obstetric liver disorder and is associated with an increased risk of iatrogenic preterm birth and adverse infant outcomes. Hence, there are several plausible pathways through which ICP could affect offspring neurodevelopment. However, to the best of our knowledge, no studies have investigated these associations. Thus, we aimed to determine whether ICP is associated with offspring neurodevelopmental conditions. METHODS AND FINDINGS: In this Swedish register-based cohort study, we included singleton non-adopted children born in Sweden between the 1st of January 1987 and the 31st of December 2010, who were resident in Sweden >5 years, with no missing covariate information, which we followed until the 31st of December 2016. Maternal ICP diagnosis and the date of the initial diagnosis during pregnancy were obtained from the National Patient Register. Offspring diagnoses of attention deficit/hyperactivity disorder (ADHD), autism, or intellectual disability were obtained from the National Patient Register, and the dispensation of ADHD medications were obtained from the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression while controlling for observed confounders and unobserved confounders shared among full siblings and maternal full cousins. A total of 2,375,856 children were included in the study; 81.6% of them were of Nordic origin, and 51.4% were male. Of these, 10,378 (0.44%) were exposed to ICP. During a median of 18 years follow-up (interquartile range 11 to 24), 143,746 (6.05%) of children were diagnosed with a neurodevelopmental condition. After adjusting for child's sex, birth year, birth month, maternal age, highest parental education level, maternal birth country, birth order, maternal psychiatric history, ICP was associated with increased odds of offspring neurodevelopmental conditions (OR 1.22, 95% CI 1.13 to 1.31), particularly among those exposed to early-onset ICP (OR 2.38, 95% CI 1.71 to 3.30) as compared to ICP diagnosed after reaching term (≥37 weeks of gestation) (OR 1.08, 95% CI 0.97 to 1.20). The findings of early-onset ICP were consistent in family-based analyses. Within-family comparisons of full maternal cousins yielded an OR of 2.99 (95% CI 1.48 to 6.04), and comparisons of full siblings showed an OR of 1.92 (95% CI 0.92 to 4.02), though the latter was less precise. The findings were consistent across specific neurodevelopmental conditions and different analytical approaches. The primary limitations of this study included its observational design, the absence of data on ICP therapeutics, and the lack of bile acid measures. CONCLUSIONS: In this study, we observed that exposure to ICP during gestation is associated with an increased likelihood of neurodevelopmental conditions in offspring, particularly in cases of early-onset ICP. Further studies are warranted to better understand the role of early-ICP in offspring neurodevelopment.

First-trimester use of antiseizure medications and the risk of miscarriage: a population-based cohort study.

BACKGROUND: Antiseizure medications (ASMs) during the first trimester of pregnancy have been associated with an increased risk of miscarriage. METHODS: We carried out a population-based cohort study using routinely collected healthcare data from the UK, 1995-2018. Pregnancies were identified in the Clinical Practice Research Datalink and we estimated the HR of miscarriage associated with prescriptions of ASMs during the first trimester of pregnancy, using Cox regression, adjusting for potential confounders, including ASM indications. RESULTS: ASMs were prescribed during the first trimester in 7832 (0.8%) of 1 023 787 included pregnancies. 14.5% of pregnancies with first-trimester exposure to ASMs ended in miscarriage, while 12.2% without ASM exposure in the first trimester ended in miscarriage; after adjustment, there was a 1.06-fold relative hazard of miscarriage (95% CI 1.00 to 1.13) in women with first-trimester ASM use. After restricting to women with specific ASM indications, this association was not evident in women with epilepsy (adjusted HR 0.98, 95% CI 0.89 to 1.08), but was observed in women with bipolar or other psychiatric conditions (1.08, 95% CI 1.00 to 1.16) although CIs overlapped. Compared with discontinuation of ASMs prior to pregnancy, there was no evidence of increased risk of miscarriage for first-trimester ASM use in women with bipolar or other psychiatric conditions (1.02, 95% CI 0.87 to 1.20). CONCLUSION: We found no clear evidence to suggest that first-trimester ASM use increased the risk of miscarriage. Taken together, our analyses suggest that apparent associations between first-trimester ASM use and miscarriage may be the result of confounding by the presence of a bipolar disorder or associated unmeasured variables.

Mode of delivery and subsequent self-perceived sexual life satisfaction: a population-based cohort study.

BACKGROUND: The potential association between mode of obstetrical delivery and subsequent sexual outcomes of the birthing parent remains uncertain and has not been well investigated from the perspective of positive sexual life satisfaction. OBJECTIVE: This study aimed to investigate if there was any association between mode of delivery and subsequent sexual life satisfaction of the birthing parent. A secondary aim was to assess the extent to which this association changed when stratified by time elapsed since delivery. STUDY DESIGN: The study matched participants in the Stockholm Public Health Cohort with deliveries recorded in the Swedish Medical Birth Register. Any deliveries recorded in the registry before the participation in the Stockholm Public Health Cohort were included (n=46,078). The length of time from delivery to outcome assessment varied from 1 month to 41 years (mean, 18 years [±10.8]). Mode of delivery was retrieved from the same registry, whereas self-perceived sexual life satisfaction was retrieved from the Stockholm Public Health Cohort Questionnaires where participants had assessed their sexual life satisfaction as 1 out of 5 mutually exclusive options. Multinomial logistic regression was used to test for any association between mode of delivery (cesarean, instrumental, and spontaneous vaginal delivery) and sexual life satisfaction, both overall and stratified by time elapsed since delivery. RESULTS: After adjusting for covariates, no statistically significant (P < .05) difference in subsequent sexual life satisfaction of the birthing parent between modes of delivery was identified. Adjusted odds ratios for assessing sexual life satisfaction as the lowest level ("very unsatisfactory") were 1.11 (95% confidence interval, 0.98-1.25) for cesarean delivery and 1.16 (95% confidence interval, 0.99-1.35) for instrumental delivery, compared with spontaneous vaginal delivery. The difference in covariate-adjusted prevalence of the lowest level of sexual life satisfaction among the different groups categorized by time since delivery was small: 4.0% (95% confidence interval, 2.4%-5.6%) for cesarean delivery as opposed to 2.8% (95% confidence interval, 2.1%-3.6%) for spontaneous vaginal delivery within 2 years since delivery. CONCLUSION: These findings do not support any impact of mode of delivery on the subsequent self-perceived sexual life satisfaction among birthing people, either overall or across different time periods since delivery.

The influence of the COVID-19 pandemic on physical activity in Stockholm County - Evidence from time series models of smartphone measured daily steps data spanning over 3 years.

BACKGROUND: It has been reported that physical activity levels decreased during the COVID-19 pandemic. Previous studies often relied on self-reported physical activity, which has low accuracy. Studies based on objectively measured physical activity have had short data collection periods, thereby not allowing the consideration of pre-pandemic levels of physical activity or the influence over the different waves of the pandemic. METHODS: In this study, we utilize smartphone-measured step data from a nonprobability sample in Stockholm County, Sweden, where measures to limit the spread of COVID-19 differed from those in many other countries. The results are based on 522 individuals and 532,739 person-days with step data spanning from 2019 to 2021. Generalized additive models were fitted for each individual, and meta-regression was used to combine the results from individual models. RESULTS: Daily steps decreased during the first wave but increased during the third wave compared to individual pre-pandemic levels. The decrease in daily steps occurred primarily in young individuals and those with occupations allowing remote work. Individuals of retirement age on the contrary increased their daily steps during the same period. CONCLUSIONS: This study reveal that the influence of the COVID-19 pandemic was temporary and that younger age and the possibility of working from home were associated with a decreasing trend in physical activity.

Trends and patterns of antiseizure medication prescribing during pregnancy between 1995 and 2018 in the United Kingdom: A cohort study.

OBJECTIVE: To examine antiseizure medication (ASM) prescription during pregnancy. DESIGN: Population-based drug utilisation study. SETTING: UK primary and secondary care data, 1995-2018, from the Clinical Practice Research Datalink GOLD version. POPULATION OR SAMPLE: 752 112 completed pregnancies among women registered for a minimum of 12 months with an 'up to standard' general practice prior to the estimated start of pregnancy and for the duration of their pregnancy. METHODS: We described ASM prescription across the study period, overall and by ASM indication, examined patterns of prescription during pregnancy including continuous prescription and discontinuation, and used logistic regression to investigate factors associated with those ASM prescription patterns. MAIN OUTCOME MEASURES: Prescription of ASMs during pregnancy and discontinuation of ASMs before and during pregnancy. RESULTS: ASM prescription during pregnancy increased from 0.6% of pregnancies in 1995 to 1.6% in 2018, driven largely by an increase in women with indications other than epilepsy. Epilepsy was an indication for 62.5% of pregnancies with an ASM prescription and non-epilepsy indications were present for 66.6%. Continuous prescription of ASMs during pregnancy was more common in women with epilepsy (64.3%) than in women with other indications (25.3%). Switching ASMs was infrequent (0.8% of ASM users). Factors associated with discontinuation included age ≥35, higher social deprivation, more frequent contact with the GP and being prescribed antidepressants or antipsychotics. CONCLUSIONS: ASM prescription during pregnancy increased between 1995 and 2018 in the UK. Patterns of prescription around the pregnancy period vary by indication and are associated with several maternal characteristics.

Body mass index and weight gain in pregnancy and cardiovascular health in middle age: A cohort study.

OBJECTIVE: To examine associations between body mass index (BMI) in early pregnancy and gestational weight gain (GWG) with cardiovascular health in middle age using the 'Life's Essential 8' (LE8) concept of the American Heart Association (AHA). DESIGN: Population-based cohort study. SETTING: Swedish CardioPulmonary bioImage Study (SCAPIS). POPULATION: A total of 8871 women from SCAPIS were included. METHODS: Information on cardiovascular health in middle age was collected from SCAPIS and linked to pregnancy weight data obtained from the Swedish Medical Birth Register, with an average follow-up time of 24.5 years. An LE8 score between 0 and 100 was determined, where a score under 60 points was defined as poor cardiovascular health. Binary logistic regression and restricted cubic splines were used. MAIN OUTCOME MEASURES: Cardiovascular health according to LE8 in middle age. RESULTS: The odds of having poor cardiovascular health in middle age were significantly higher in women who had overweight (adjusted odds ratio, aOR 3.30, 95% CI 2.82-3.88) or obesity (aOR 7.63, 95% CI 5.86-9.94), compared with women classified as being of normal weight in pregnancy. Higher odds were also found for excessive GWG (aOR 1.31, 95% CI 1.09-1.57), compared with women who gained weight within the recommendations. CONCLUSIONS: A high BMI in early pregnancy and excessive GWG were associated with greater odds of poor cardiovascular health in middle age. Although further studies are needed, our results highlight pregnancy as an important period to support long-term cardiovascular health.

Life's Essential 8 in relation to self-rated health and health-related quality of life in a large population-based sample: the SCAPIS project.

PURPOSE: To monitor cardiovascular health, in 2022, the American Heart Association (AHA) updated the construct "Life's Simple 7" (LS7) to "Life's Essential 8" (LE8). This study aims to analyze the associations and capacity of discrimination of LE8 and LS7 in relation to self-rated health (SRH) and health-related quality of life (HRQoL). METHODS: This study from the Swedish CArdioPulmonary bioImage Study (SCAPIS) included 28 731 Swedish participants, aged 50-64 years. Three different scores were derived from the SF-12 questionnaire: 1-item question SRH ("In general, would you say your health is …?"), mental-HRQoL and physical-HRQoL. Logistic regression, restricted cubic splines, and ROC analysis were used to study the associations between the AHA scores in relation to SRH and HRQoL. RESULTS: Compared to those with a LE8 score of 80, participants with a LE8 score of 40 were 14.8 times more likely to report poor SRH (OR: 14.8, 95% CI: 13.0-17.0), after adjustments. Moreover, they were more likely to report a poor mental-HRQoL (OR: 4.9, 95% CI: 4.2-5.6) and a poor physical-HRQoL (OR: 8.0, 95% CI: 7.0-9.3). Area under curves for discriminating poor SRH were 0.696 (95% CI: 0.687-0.704), 0.666 (95% CI: 0.657-0.674), and 0.643 (95% CI: 0.634-0.651) for LE8, LS7 (0-14), and LS7 (0-7), respectively, all p values < 0.001 in the DeLong's tests. CONCLUSION: LE8 and LS7 had strong and inverse associations with SRH, mental-HRQoL, and physical-HRQoL, though LE8 had a somewhat higher capacity of discrimination than LS7. The novel LE8, a construct initially conceived to monitor cardiovascular health, also conveys SRH and HRQoL.

Associations of psychological factors with atherosclerosis and cardiovascular health in middle-age: the population-based Swedish CArdioPulmonary bioImage study (SCAPIS).

BACKGROUND: Cardiovascular disease (CVD) is a major global health issue, primarily caused by atherosclerosis. Psychological factors may play a role in the development and progression of CVD. However, the relationship between psychological factors and atherosclerosis is complex and poorly understood. This study, therefore, aimed to examine the association of psychological factors with (i) coronary and carotid atherosclerosis and (ii) cardiovascular health according to Life's Essential 8, in a large Swedish cohort. METHODS: This study utilized data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), a large population-based project including individuals aged 50 to 65 years. Several psychological factors were analysed: general stress, stress at work, financial stress, major adverse life events, locus of control, feeling depressed, and depression. Coronary atherosclerosis was assessed as the degree of stenosis by coronary computed tomography angiography (CCTA) and coronary artery calcification (CAC) scores. Carotid atherosclerosis was examined using ultrasound. In addition, cardiovascular health was examined using the Life's Essential 8 concept created by the American Heart Association, which includes four health behaviors and four health factors. Associations were examined through binomial logistic regression (atherosclerosis variables) and linear regression (Life's Essential 8). RESULTS: A total of 25,658 participants were included in the study. The presence of financial stress, higher locus of control, and depression was weakly associated with increased odds of CCTA stenosis, CAC ≥ 1 and the presence of carotid plaques (all odds ratios: 1.10-1.21, 95% CI: 1.02-1.32) after adjusting for sex, age, and study site. However, these associations were attenuated and not statistically significant after additional adjustments for socioeconomic factors and health behaviors. Conversely, we observed inverse associations between the worst category for all psychological factors and cardiovascular health according to Life's Essential 8 score (all standardized ß-Coefficient ≤-0.033, p < 0.001). CONCLUSION: While there were no strong and consistent associations between psychological factors and atherosclerosis, the consistent associations of psychological factors with cardiovascular health by Life's Essential 8 may have relevance for future CVD risk. However, further studies are needed to elucidate the long-term effects of psychological factors on atherosclerosis development and cardiovascular health.

Physical fitness in male adolescents and atherosclerosis in middle age: a population-based cohort study.

OBJECTIVES: To examine the associations between physical fitness in male adolescents and coronary and carotid atherosclerosis in middle age. METHODS: This population-based cohort study linked physical fitness data from the Swedish Military Conscription Register during adolescence to atherosclerosis data from the Swedish CArdioPulmonary bioImage Study in middle age. Cardiorespiratory fitness was assessed using a maximal cycle-ergometer test, and knee extension muscular strength was evaluated through an isometric dynamometer. Coronary atherosclerosis was evaluated via Coronary Computed Tomography Angiography (CCTA) stenosis and Coronary Artery Calcium (CAC) scores, while carotid plaques were evaluated by ultrasound. The associations were analysed using multinomial logistic regression, adjusted (marginal) prevalences and restricted cubic splines. RESULTS: The analysis included 8986 male adolescents (mean age 18.3 years) with a mean follow-up of 38.2 years. Physical fitness showed a reversed J-shaped association with CCTA stenosis and CAC, but no consistent association was observed for carotid plaques. After adjustments, compared with adolescents in the lowest tertile of cardiorespiratory fitness and muscular strength, those in the highest tertile had 22% (OR 0.78; 95% CI 0.61 to 0.99) and 26% (OR 0.74; 95% CI 0.58 to 0.93) lower ORs for severe (≥50%) coronary stenosis, respectively. The highest physical fitness group (high cardiorespiratory fitness and muscular strength) had 33% (OR 0.67; 95% CI 0.52 to 0.87) lower OR for severe coronary stenosis compared with those with the lowest physical fitness. CONCLUSION: This study supports that a combination of high cardiorespiratory fitness and high muscular strength in adolescence is associated with lower coronary atherosclerosis, particularly severe coronary stenosis, almost 40 years later.

Acetaminophen Use During Pregnancy and Children's Risk of Autism, ADHD, and Intellectual Disability.

Importance: Several studies suggest that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children. If true, this would have substantial implications for management of pain and fever during pregnancy. Objective: To examine the associations of acetaminophen use during pregnancy with children's risk of autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. Design, Setting, and Participants: This nationwide cohort study with sibling control analysis included a population-based sample of 2 480 797 children born in 1995 to 2019 in Sweden, with follow-up through December 31, 2021. Exposure: Use of acetaminophen during pregnancy prospectively recorded from antenatal and prescription records. Main Outcomes and Measures: Autism, ADHD, and intellectual disability based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes in health registers. Results: In total, 185 909 children (7.49%) were exposed to acetaminophen during pregnancy. Crude absolute risks at 10 years of age for those not exposed vs those exposed to acetaminophen were 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability. In models without sibling control, ever-use vs no use of acetaminophen during pregnancy was associated with marginally increased risk of autism (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]; risk difference [RD] at 10 years of age, 0.09% [95% CI, -0.01% to 0.20%]), ADHD (HR, 1.07 [95% CI, 1.05-1.10]; RD, 0.21% [95% CI, 0.08%-0.34%]), and intellectual disability (HR, 1.05 [95% CI, 1.00-1.10]; RD, 0.04% [95% CI, -0.04% to 0.12%]). To address unobserved confounding, matched full sibling pairs were also analyzed. Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, -0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, -0.02% [95% CI, -0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, -0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively. Conclusions and Relevance: Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding.

Bias amplification of unobserved confounding in pharmacoepidemiological studies using indication-based sampling.

PURPOSE: Estimating causal effects in observational pharmacoepidemiology is a challenging task, as it is often plagued by confounding by indication. Restricting the sample to those with an indication for drug use is a commonly performed procedure; indication-based sampling ensures that the exposed and unexposed are exchangeable on the indication-limiting the potential for confounding by indication. However, indication-based sampling has received little scrutiny, despite the hazards of exposure-related covariate control. METHODS: Using simulations of varying levels of confounding and applied examples we describe bias amplification under indication-based sampling. RESULTS: We demonstrate that indication-based sampling in the presence of unobserved confounding can give rise to bias amplification, a self-inflicted phenomenon where one inflates pre-existing bias through inappropriate covariate control. Additionally, we show that indication-based sampling generally leads to a greater net bias than alternative approaches, such as regression adjustment. Finally, we expand on how bias amplification should be reasoned about when distinct clinically relevant effects on the outcome among those with an indication exist (effect-heterogeneity). CONCLUSION: We conclude that studies using indication-based sampling should have robust justification - and that it should by no means be considered unbiased to adopt such approaches. As such, we suggest that future observational studies stay wary of bias amplification when considering drug indications.

Low prevalence of ideal cardiovascular health in the general Swedish population: Results from the Swedish CArdioPulmonary bioImage Study (SCAPIS).

The aim of the current study was to examine the prevalence of ideal cardiovascular health (iCVH) in the general Swedish middle-aged population. To address this aim, we utilised data from the Swedish CArdioPulmonary bioImage Study (SCAPIS) which is a large Swedish population-based study (N=30,154) that combined comprehensive state-of-the-art imaging technology with clinical examinations and included all iCVH components. A total iCVH score was calculated as the number of iCVH metrics at an ideal level for the seven components and classified as: ideal (⩾5 ideal components), intermediate (3-4 ideal components) and poor (⩽2 ideal components). Our results showed that only 18.2% of the population reached ideal status (i.e. ⩾5 components at the ideal level), whereas 51.9% were classified as intermediate status and 29.9% as poor status of iCVH. Women had a higher prevalence of iCVH status (23.9% vs. 12.0%) and a lower prevalence of poor iCVH status (23.5% vs. 36.8%). Our data may serve as benchmarks for future national and international comparisons and motivate efforts to promote cardiovascular health in the general population, given the strong link between iCVH with all-cause and cardiovascular disease mortality and morbidity.

Mode of delivery and maternal sexual wellbeing: A longitudinal study.

OBJECTIVES: To investigate the association between mode of delivery and subsequent maternal sexual wellbeing. DESIGN: Prospective birth cohort study. SETTING: Avon (in Bristol area), UK. POPULATION: Participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). METHODS: Mode of delivery was abstracted from obstetric records and sexual wellbeing measures were collected via a self-report questionnaire. Missing data were imputed using multiple imputation, and ordinal logistic regression models for ordered categorical outcomes were adjusted for the covariates maternal age at delivery, pre-pregnancy body mass index, diabetes during pregnancy, socio-economic position, parity, depression and anxiety. MAIN OUTCOME MEASURES: Sexual enjoyment and frequency at four time points postpartum (between 33 months and 18 years) and two types of sex-related pain (pain in the vagina during sex and elsewhere after sex) at 11 years postpartum. RESULTS: We found no association between mode of delivery and sexual enjoyment (e.g. adjusted odds ratio [OR] 1.11, 95% confidence interval [95% CI] 0.97-1.27 at 33 months) or sexual frequency (OR 0.99, 95% CI 0.88-1.12 at 33 months). Caesarean section was associated with an increased odds of pain in the vagina during sex at 11 years postpartum as compared with vaginal delivery in the adjusted model (OR 1.74, 95% CI 1.46-2.08). CONCLUSIONS: These findings provide no evidence supporting associations between caesarean section and sexual enjoyment or frequency. However, mode of delivery was shown to be associated with dyspareunia, which may not be limited to abdominal scarring.

HMG-CoA reductase inhibitors and COVID-19 mortality in Stockholm, Sweden: A registry-based cohort study.

BACKGROUND: The relationship between statin treatment and Coronavirus Disease 2019 (COVID-19) mortality has been discussed due to the pleiotropic effects of statins on coagulation and immune mechanisms. However, available observational studies are hampered by study design flaws, resulting in substantial heterogeneity and ambiguities. Here, we aim to determine the relationship between statin treatment and COVID-19 mortality. METHODS AND FINDINGS: This cohort study included all Stockholm residents aged 45 or older (N = 963,876), followed up from 1 March 2020 until 11 November 2020. The exposure was statin treatment initiated before the COVID-19-pandemic, defined as recorded statin dispensation in the Swedish Prescribed Drug Register between 1 March 2019 and 29 February 2020. COVID-19-specific mortality was ascertained from the Swedish Cause of Death Registry. Hazard ratios (HRs) were calculated using multivariable Cox regression models. We further performed a target trial emulation restricted to initiators of statins. In the cohort (51.6% female), 169,642 individuals (17.6%) were statin users. Statin users were older (71.0 versus 58.0 years), more likely to be male (53.3% versus 46.7%), more often diagnosed with comorbidities (for example, ischemic heart disease 23.3% versus 1.6%), more frequently on anticoagulant and antihypertensive treatments, less likely to have a university-level education (34.5% versus 45.4%), and more likely to have a low disposable income (20.6% versus 25.2%), but less likely to reside in crowded housing (6.1% versus 10.3%). A total of 2,545 individuals died from COVID-19 during follow-up, including 765 (0.5%) of the statin users and 1,780 (0.2%) of the nonusers. Statin treatment was associated with a lowered COVID-19 mortality (adjusted HR, 0.88; 95% CI, 0.79 to 0.97, P = 0.01), and this association did not vary appreciably across age groups, sexes, or COVID-19 risk groups. The confounder adjusted HR for statin treatment initiators was 0.78 (95% CI, 0.59 to 1.05, P = 0.10) in the emulated target trial. Limitations of this study include the observational design, reliance on dispensation data, and the inability to study specific drug regimens. CONCLUSIONS: Statin treatment had a modest negative association with COVID-19 mortality. While this finding needs confirmation from randomized clinical trials, it supports the continued use of statin treatment for medical prevention according to current recommendations also during the COVID-19 pandemic.

Associations of participation in organized sports and physical activity in preschool children: a cross-sectional study.

BACKGROUND: Participation in organized sports is associated with higher physical activity (PA) levels in school-aged-children. Yet, little is known about PA determinants in preschool-aged-children. We examined associations between organized sports participation and preschoolers' daily PA. METHODS: The study comprised 290 3-5 years old children and PA was measured for 1 week via accelerometers. Organized sports participation was parent-reported and preschool arrival and departure time was teacher-recorded. The preschool duration reported by teachers was matched with time-stamped accelerometer data to distinguish PA during preschool time and PA outside preschool time. Linear mixed models, nested on preschool level, were used to examine associations between organized sports participation and children's PA outside preschool time, during preschool time and throughout the day. RESULTS: In total, 146 children (50.3%) participated in organized sports at least 1 h/week. Participation in organized sports was associated with 6.0 more minutes of moderate-to-vigorous PA (MVPA) (95% CI: 0.6, 11.3) throughout the day and 5.7 more minutes of MVPA (95% CI: 1.6, 9.7) outside preschool time after adjustment. There was no association between organized sports participation and PA during preschool time. CONCLUSIONS: This is the first study to show positive associations between organized sports participation and preschoolers' PA levels outside preschool time and throughout the day. In addition, findings from this study do not support PA compensation. Therefore, targeting organized sports may be successful in improving PA, even among preschoolers.

Elective and nonelective cesarean section and obesity among young adult male offspring: A Swedish population-based cohort study.

BACKGROUND: Previous studies have suggested that cesarean section (CS) is associated with offspring overweight and obesity. However, few studies have been able to differentiate between elective and nonelective CS, which may differ in their maternal risk profile and biological pathway. Therefore, we aimed to examine the association between differentiated forms of delivery with CS and risk of obesity in young adulthood. METHODS AND FINDINGS: Using Swedish population registers, a cohort of 97,291 males born between 1982 and 1987 were followed from birth until conscription (median 18 years of age) if they conscripted before 2006. At conscription, weight and height were measured and transformed to World Health Organization categories of body mass index (BMI). Maternal and infant data were obtained from the Medical Birth Register. Associations were evaluated using multinomial and linear regressions. Furthermore, a series of sensitivity analyses were conducted, including fixed-effects regressions to account for confounders shared between full brothers. The mothers of the conscripts were on average 28.5 (standard deviation 4.9) years old at delivery and had a prepregnancy BMI of 21.9 (standard deviation 3.0), and 41.5% of the conscripts had at least one parent with university-level education. Out of the 97,291 conscripts we observed, 4.9% were obese (BMI ≥ 30) at conscription. The prevalence of obesity varied slightly between vaginal delivery, elective CS, and nonelective CS (4.9%, 5.5%, and 5.6%, respectively), whereas BMI seemed to be consistent across modes of delivery. We found no evidence of an association between nonelective or elective CS and young adulthood obesity (relative risk ratio 0.96, confidence interval 95% 0.83-1.10, p = 0.532 and relative risk ratio 1.02, confidence interval 95% 0.88-1.18, p = 0.826, respectively) as compared with vaginal delivery after accounting for prepregnancy maternal BMI, maternal diabetes at delivery, maternal hypertension at delivery, maternal smoking, parity, parental education, maternal age at delivery, gestational age, birth weight standardized according to gestational age, and preeclampsia. We found no evidence of an association between any form of CS and overweight (BMI ≥ 25) as compared with vaginal delivery. Sibling analysis and several sensitivity analyses did not alter our findings. The main limitations of our study were that not all conscripts had available measures of anthropometry and/or important confounders (42% retained) and that our cohort only included a male population. CONCLUSIONS: We found no evidence of an association between elective or nonelective CS and young adulthood obesity in young male conscripts when accounting for maternal and prenatal factors. This suggests that there is no clinically relevant association between CS and the development of obesity. Further large-scale studies are warranted to examine the association between differentiated forms of CS and obesity in young adult offspring. TRIAL REGISTRATION: Registered as observational study at ClinicalTrials.gov Identifier: NCT03918044.

Life's Essential 8 and Life's Simple 7 in Relation to Coronary Atherosclerosis: Results From the Population-Based SCAPIS Project.

OBJECTIVE: To examine the associations between the American Heart Association scores ("Life's Essential 8" [LE8] and "Life's Simple 7" [LS7]) and 2 subclinical coronary atherosclerosis indicators: coronary computed tomographic angiography (CCTA)-stenosis and coronary artery calcium (CAC). PATIENTS AND METHODS: We included a population-based sample, aged 50 to 64 years, recruited between 2013 and 2018 from the Swedish Cardiopulmonary Bioimage Study (n=24,819, 50.3% women). CCTA-stenosis was graded as no stenosis, stenosis (1%-49%) or severe stenosis (≥50%), whereas CAC was graded as 0, 1 to 99, 100 to 399, or ≥400 Agatston units. Multinomial logistic regression and receiver operating characteristic (ROC) curves were used to study the associations between cardiovascular health scores and subclinical coronary atherosclerosis. RESULTS: Odds ratios (ORs) for CCTA-stenosis and severe CCTA-stenosis between the lowest (<50 points) vs the highest (≥80 points) LE8 group were 4.18 (95% CI, 3.56 to 4.91) and 11.17 (95% CI, 8.36 to 14.93), respectively. For corresponding CAC results, ORs were 3.36 (95% CI, 2.84 to 3.98), 7.72 (95% CI, 6.03 to 9.89), and 14.94 (95% CI, 10.47 to 21.31) for CAC scores of 1 to 99, 100 to 399, and ≥400, respectively. Area under ROC curves for predicting any stenosis were 0.642 (95% CI, 0.635 to 0.649) and 0.631 (95% CI, 0.624 to 0.638, P<.001) for LE8 and LS7, respectively. CONCLUSION: Our data indicate that LE8 showed a strong, graded, and inverse association with CCTA-stenosis and CAC score. The capacity to predict CCTA-stenosis was comparable between LE8 and LS7, although LE8 had slightly higher prediction capacity of any stenosis. This study provides novel evidence that the LE8 score may be a useful tool for monitoring cardiovascular health.

Life's Essential 8 is inversely associated with high-sensitivity C-reactive protein.

Life's Essential 8 (LE8) is a score that includes modifiable risk factors for cardiovascular disease. Four health behaviors (diet, physical activity, nicotine exposure and sleep health) and four health factors (non-HDL cholesterol, blood glucose, blood pressure and body mass index) are included. These modifiable risk factors promote inflammation, and inflammation is one of the biological mechanisms of cardiovascular disease development. Thus, we examined the relationship between cardiovascular health measured by LE8 and low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) in the cross-sectional population-based Swedish CArdioPulmonary bioImage Study (SCAPIS). The study consisted of 28,010 participants between 50 and 64 years (51.5% women, mean age 57.5 years). All individual LE8 components were assigned a score between 0 (unhealthy) and 100 (healthy) points, and a global score was calculated. The association between LE8 scores and high-risk hs-CRP (defined as > 3.0 mg/L) was analyzed using adjusted logistic regression with spline analyses. There was a strong, dose response and inverse association between LE8 scores and levels of hs-CRP. Thus, those with a low LE8 score (= 50.0 points) had 5.8 higher (95% confidence interval [CI] 5.2-6.4) odds ratio (OR) of having high hs-CRP as compared to those with a high LE8 score (= 80.0 points). In conclusion, our findings show strong inverse associations between LE8 scores and levels of hs-CRP.

Genetic and Environmental Factors and Cardiovascular Disease Risk in Adolescents.

Importance: Cardiovascular risk factors in youth have been associated with future cardiovascular disease (CVD), but conventional observational studies are vulnerable to genetic and environmental confounding. Objective: To examine the role of genetic and environmental factors shared by full siblings in the association of adolescent cardiovascular risk factors with future CVD. Design, Setting, and Participants: This is a nationwide cohort study with full sibling comparisons. All men who underwent mandatory military conscription examinations in Sweden between 1972 and 1995 were followed up until December 31, 2016. Data analysis was performed from May 1 to November 10, 2022. Exposures: Body mass index (BMI), cardiorespiratory fitness, blood pressure, handgrip strength, and a combined risk z score in late adolescence. Main Outcomes and Measures: The primary outcome was fatal or nonfatal CVD, as recorded in the National Inpatient Register or the Cause of Death Register before 2017. Results: A total of 1 138 833 men (mean [SD] age, 18.3 [0.8] years), of whom 463 995 were full brothers, were followed up for a median (IQR) of 32.1 (26.7-37.7) years, during which 48 606 experienced a CVD outcome (18 598 among full brothers). All risk factors were associated with CVD, but the effect of controlling for unobserved genetic and environmental factors shared by full siblings varied. In the sibling analysis, hazard ratios for CVD (top vs bottom decile) were 2.10 (95% CI, 1.90-2.32) for BMI, 0.77 (95% CI, 0.68-0.88) for cardiorespiratory fitness, 1.45 (95% CI, 1.32-1.60) for systolic blood pressure, 0.90 (95% CI, 0.82-0.99) for handgrip strength, and 2.19 (95% CI, 1.96-2.46) for the combined z score. The percentage attenuation in these hazard ratios in the sibling vs total cohort analysis ranged from 1.1% for handgrip strength to 40.0% for cardiorespiratory fitness. Consequently, in the sibling analysis, the difference in cumulative CVD incidence at age 60 years (top vs bottom decile) was 7.2% (95% CI, 5.9%-8.6%) for BMI and 1.8% (95% CI, 1.0%-2.5%) for cardiorespiratory fitness. Similarly, in the sibling analysis, hypothetically shifting everyone in the worst deciles of BMI to the middle decile would prevent 14.9% of CVD at age 60 years, whereas the corresponding number for cardiorespiratory fitness was 5.3%. Conclusions and Relevance: In this Swedish national cohort study, cardiovascular risk factors in late adolescence, especially a high BMI, were important targets for CVD prevention, independently of unobserved genetic and environmental factors shared by full siblings. However, the role of adolescent cardiorespiratory fitness in CVD may have been overstated by conventional observational studies.