BACKGROUND:Current evidence remains inconclusive regarding the developmental toxicity of specific fine particulate matter (PM2.5) components during critical fetal growth periods, particularly concerning key toxic components and exposure windows. METHODS:This prospective birth cohort included 2680 mother-newborn pairs with 9339 growth ultrasound measurements [abdominal circumference, head circumference (HC), femur length (FL), estimated fetal weight (EFW)] in Guangzhou, China, from 2017 to 2020. Weekly exposures to PM2.5 components-black carbon (BC), organic matter (OM), nitrate (NO3-), sulfate (SO42-), and ammonium (NH4+)-were quantified by using the Tracking Air Pollution in China database (TAP) real-time air-pollutant-exposure model. Distributed lag models with generalized estimating equations were employed to identify critical exposure windows and machine-learning approaches were used to assess constituent mixture effects and identify dominant toxic components. RESULTS:FL, HC, and EFW demonstrated component-specific vulnerability. FL reduction at gestational Weeks 12-15 was most strongly associated with BC exposure, followed by OM and SO42-; HC deficits in Weeks 5-12 and 22-24 were predominantly linked to NO3- exposure; EFW reductions during Weeks 6-8 were most sensitive to NO3- exposure. BC and NO3- were identified as the most impactful constituents. CONCLUSION:Our findings identify gestational Weeks 12-15 for BC exposure and Weeks 5-12 and 22-24 for NO3- exposure as critical vulnerable windows for adverse fetal development associated with PM2.5 components. These results support the need for further research into component-specific air-quality guidelines targeting sensitive gestational periods.
BACKGROUND:Physical activity is recommended for obesity prevention, but the evidence is limited by possible biases from reverse causation and confounding, and there are limited data on the long-term effects of physical activity through middle age on the development of obesity. METHODS:We emulated a target trial by using 10 waves of observational data from the 1946-51 Australian Longitudinal Study on Women's Health collected between 1996 and 2022. The target trial would determine the effect of randomizing women to either meeting or not meeting the World Health Organization's recommended level of physical activity over an 18-year period on the 21-year incidence of obesity. Targeted maximum-likelihood estimation controlling for time-constant and time-varying confounders was used to emulate the target trial, assuming conditional exchangeability, positivity, consistency, and no interference. RESULTS:In total, 779 women aged 47-52 years at study entry were included. The cumulative incidence of obesity was 9.9% [99.5% confidence interval (CI): 8.6%, 11.1%] in the scenario with 18-year adherence to the recommendation and 15.1% (99.5% CI: 12.8%, 17.4%) with consistent non-adherence (risk ratio: 1.5, 99.5% CI: 1.2, 1.9; risk difference: 5.3%-point, 99.5% CI: 2.3%, 8.3%). Each additional survey with non-adherence increased the risk of obesity (risk ratio: 1.1, 99.5% CI: 1.0, 1.1). There was no additional benefit of meeting a higher physical-activity target. CONCLUSION:The results of our analysis, designed specifically to address the key limitations of previous evidence, underscore the benefits of long-term adherence to the recommended ≥150 minutes of moderate-to-vigorous physical activity per week for obesity prevention in middle-aged women.
BACKGROUND:Ozone is known to have harmful health impacts, and its concentration is projected to rise with climate change; however, little is known about how ozone impacts the health of people with disabilities and its interaction with temperature. We aimed to estimate the association between ozone exposure and emergency department (ED) visits, stratified by disability status and type. METHODS:ED visit data spanning 2015-19 and 2022-23 were collected from the Korean National Health Insurance Service. We included the 3-day moving average (the same day, 1 day prior, and 2 days prior; lag 0-2) ozone concentration at the 8-hour maximum and adjusted for daily mean temperature and national holidays. Using a time-stratified case-crossover design and conditional logistic regression, we estimated the association between ozone concentration and natural-cause ED visits. Furthermore, an interaction term between temperature strata and ozone was included to assess potential effect modification across temperature value. RESULTS:Overall, 3 484 877 ED visits were recorded. An interquartile range (∼22 ppb) increase in daily 8-hour maximum ozone (lag 0-2) was associated with a 1.94% increase [95% confidence interval (CI): 1.64-2.25] and a 1.93% increase (95% CI: 1.62-2.25) in ED visits during the warm season (April-September) and the entire year (January-December), respectively, among persons with disabilities. These estimates were higher than those observed among persons without disabilities [1.36% (95% CI: 0.92-1.80) and 1.42% (95% CI: 1.03-1.82) during the warm season and the entire year, respectively]. Greater risks were observed in brain lesion disorders, developmental and mental disabilities, ED visits due to respiratory diseases during June, and on days with high temperatures. CONCLUSIONS:These findings underscore the importance of tailoring strategies to specific disability types and early-season public health interventions-beginning in April or May-incorporating both ozone levels and daily temperature to effectively mitigate the heightened risks identified in this population.
BACKGROUND:The frequency and severity of extreme temperatures have been increasing and are expected to continue to escalate in the coming decades. Relationships between extreme temperatures and early deliveries are not well understood. METHODS:Data were obtained from 201 759 pregnancies with gestational age (GA) of >27 weeks in the Consortium on Safe Labor retrospective cohort study from 19 hospitals across the USA for 2002-8. Location-specific bulk temperatures were obtained from the Parameter-Elevation Regressions on Independent Slopes Model (4-km resolution), from which participants were linked to minimum, maximum, and mean daily temperatures across each day of pregnancy. Days were categorized for each site as cold (both minimum and maximum temperatures ≤ 20th percentile), hot (both minimum and maximum temperatures ≥ 80th percentile), or neither for each pregnancy. Cold and hot days were then analysed individually or as the proportion within specific pregnancy windows by using Cox regression and fetuses-at-risk logistic regression models. RESULTS:Detrimental relations in fetuses-at-risk models were consistently observed between exposure to chronic cold and chronic heat and early delivery: odds ratio (ORcold)= 1.66, 1.40, and 1.16; ORheat = 1.20, 1.13, and 1.32 for early-preterm (GA < 34 weeks), preterm (34 ≤ GA < 37 weeks), and early-term (37 ≤ GA < 39), respectively. Associations for exposures in Trimesters 1 and 2 were mixed but clearly more detrimental in Trimester 1. The likelihood of early delivery increased with daily exposure to extreme temperatures after 27 weeks. CONCLUSION:Future work should seek to elucidate the underlying mechanisms and to validate these findings by using more recent diverse global data.
Negative controls have gained traction as a useful tool for causal research to address confounding and bias. However, general guidance on how to select and apply negative controls and how to report and interpret their findings is lacking. This paper lays out the key steps of conducting a negative-control analysis and provides all relevant background information, important feasibility and validity considerations, and practical suggestions for the implementation and interpretation of each step. This includes a convenient overview of all methods, complete with their rationale, key considerations, and illustrative examples, and practical checklists that both researchers and reviewers can use to facilitate the complete and rigorous reporting of negative-control analyses.
BACKGROUND:Previous research on moderate-to-vigorous physical activity (MVPA) and ovarian cancer risk have shown inconsistent results. Most studies measured recreational MVPA once during late adulthood, which does not consider the way in which timing may differently influence risk or account for MVPA from other activities. Life-course epidemiology models (critical-period, sensitive-period, and accumulation) can evaluate whether the timing and cumulative burden of total MVPA across the lifespan influences risk. Here, we identify which model best describes the association between total MVPA, encompassing recreational, occupational, household, and transportation activities, and invasive ovarian cancer risk. METHODS:A population-based case-control study of ovarian cancer in Montreal, Canada (2011-16) included 268 invasive cases and 668 controls aged ≥52 years. Total MVPA was determined by using recalled information on the frequency and duration of various physical activities across adulthood. A Bayesian relevant life course exposure model was used to estimate the relative importance of total MVPA, represented as average energy expenditure in units of metabolic equivalent (MET)-hours/week, during three pre-specified periods (early reproductive years, late reproductive years/perimenopause, and postmenopause) on invasive ovarian cancer risk. RESULTS:The lifetime-effect odds ratio comparing ≥50 vs <50 MET-hours/week across adulthood was 0.59 (95% credible interval: 0.35-0.93). MVPA during late reproductive years/perimenopause showed the highest relative importance, suggesting that this may be a sensitive period. Associations were similar for serous and non-serous subtypes. CONCLUSION:Our results support that higher MVPA across the adult life course is associated with a reduced invasive ovarian cancer risk and mid-adulthood, represented by late reproductive years/perimenopause, may be a sensitive period.
BACKGROUND:Although polysomnography (PSG) is the diagnostic gold standard, PSG data on obstructive sleep apnea (OSA) presence and severity are rarely available at the population level. Health administrative databases offer broad coverage for OSA case ascertainment but require methods that address inherent misclassification. We utilized a previously validated probabilistic case ascertainment model of OSA to estimate population-level prevalence and correlates of OSA. METHODS:We conducted a population-based retrospective cohort study in Ontario, Canada. First, using a clinical cohort with PSG-confirmed OSA severity (measurement cohort; n = 18 581), we quantified misclassification in probabilistic OSA case definitions. We then applied the externally validated probability models to all adults 18 years and older in Ontario who underwent in-laboratory overnight PSG between 2010 and 2018 (provincial PSG cohort; n = 834 361). OSA prevalence and correlates were estimated using multiple probability thresholds and a threshold-free bootstrap imputation approach (BIA). RESULTS:Compared to the PSG-based gold standard, the BIA surrogate definition had the lowest average relative bias in OSA prevalence estimation (BIA: 5% versus >38% probability threshold: 11.4%). Using BIA, we estimate a 44.3% prevalence of moderate-severe OSA in the provincial PSG cohort, which in scenario-based projections yields a 3.4%-17.1% general population prevalence dependent on an assumed OSA underdiagnosis rate. OSA prevalence was higher in men, older ages, and previous comorbidity and was stable annually. CONCLUSION:Probabilistic case ascertainment using health administrative data enables robust population-level estimation of OSA epidemiology despite the absence of clinical diagnostic data and provides a framework for studying OSA prevalence, correlates, and outcomes over time.
BACKGROUND:Extreme temperatures are projected to increase; however, comprehensive mapping of associations between temperature extremes and kidney diseases across age groups and disease subtypes remains limited. METHODS:Data were collected for all emergency department (ED) visits for kidney diseases across all ages from South Korea's national health insurance claims between 2011 and 2019. A time-stratified case-crossover design was used to assess the association between ambient temperature and ED visits for kidney diseases. RESULTS:The study included around 1.9 million ED visits due to kidney diseases. Heat-related risks of kidney disease-related ED visits (99th vs. 75th percentile) were highest among adults aged 50-59 years [odds ratio (OR): 1.28, 95% confidence interval (CI): 1.22-1.34), while cold-related risks (1st vs. 25th percentile) were highest among those aged 30-39 years (OR: 1.13, 95% CI: 1.05-1.20). Heat-related hospitalization risk was primarily driven by urinary tract infection among individuals in their 30s (OR: 1.37; 95% CI: 1.09-1.72) and by acute kidney injury among those in their 40s (OR: 2.29; 95% CI: 1.52-3.44). From a cost-burden perspective, urinary tract infections among adults aged ≥70 years contributed the largest medical cost burden attributable to high and low temperatures. CONCLUSIONS:This nationwide study demonstrated age- and disease subtype-specific heterogeneity in temperature-related kidney disease risks. Our findings suggest that, in addition to older adults, younger and middle-aged populations should also be primarily considered in climate change adaptation strategies targeting kidney health.
BACKGROUND:Increased childhood adiposity contributes to higher type 2 diabetes (T2D) risk, but the underlying mechanisms remain unclear. Furthermore, whether these mechanistic pathways are shared across ethnic groups has not been explored. METHODS:We conducted a two-step Mendelian randomization (MR) using European-based summary statistics from genome-wide association studies of childhood body mass index (BMI) (n = 61 111), adulthood proteomics (n = 35 559), and later life T2D (cases: 242 283; controls: 1 569 734). We also conducted a recall-by-genotype (RbG) study in a Chinese birth cohort (n = 250) to assess whether childhood BMI was associated with the identified proteomic signals in an East Asian population. Analyses included multi-instrument MR methods (inverse variance weighted and MR-Egger) and, for single-instrument proteins, cis-MR using the Wald ratio, with colocalization validation. Multiple testing was adjusted using false discovery rate (FDR). RESULTS:Higher genetically predicted childhood BMI was associated with 1299 proteins (FDR-adjusted P < .05), of which 36 proteins were associated with higher T2D risk. Six proteins were supported by colocalization (PPH4 > 80%). Genetically predicted higher childhood BMI was positively associated with GCKR, RBP1, ENTPD6, and GST A1-1, and inversely associated with PRSS27 and SHBG. The proportion of the BMI-T2D effect mediated by these proteins ranged from 1.87% to 12.92%. However, only SHBG was replicated in Asians in the RbG study. CONCLUSIONS:Our study identified putative actionable proteins that could reduce the elevated T2D risk attributable to childhood adiposity in Europeans, but their relevance in Asian populations requires further investigation.
BACKGROUND:Under the top-secret Manhattan Project, improperly stored radioactive byproducts from the processing of uranium contaminated Coldwater Creek in north St. Louis County, Missouri. We used the original 1958 Baby Tooth Survey (BTS) linked with the National Death Index (NDI) to investigate whether childhood residential proximity to the creek, as a proxy for radiation exposure, was associated with mortality. METHODS:There were 43 876 eligible participants from the BTS (those outside Greater St. Louis and/or had incomplete covariates were excluded). In December 2023, the NDI was searched for BTS participants who had died. We estimated the hazard ratio (HR) and 95% confidence intervals between distance to Coldwater Creek (per 10 km) and mortality (all-cause, cancer, and cardiovascular disease) adjusting for sex, birth year, and census tract-level socioeconomic indicators. RESULTS:Living closer to Coldwater Creek was associated with a higher rate of all-cause mortality (HR: 1.05; 95% CI: 1.01-1.09; P = .01). There was suggestive evidence of an increased rate for cancer mortality: any cancer (HR: 1.06; 95% CI: 1.00-1.14; P = .06), solid cancer (HR: 1.07, 95% CI: 1.00-1.16; P = .06) and radiosensitive cancer (HR: 1.10; 95% CI: 1.00-1.21; P = .05). There was no association with non-radiosensitive cancer and cardiovascular mortality. CONCLUSIONS:Our study provides new data that suggest living near Coldwater Creek in childhood was positively associated with the rate of all-cause mortality, and to a lesser extent cancer mortality, but not cardiovascular disease mortality. However, these findings should be interpreted cautiously given the lack of data on internal radiation exposure and individual socioeconomic status.
