Mortality Burden Due to Short-term Exposure to Fine Particulate Matter in Korea.

OBJECTIVES: Excess mortality associated with long-term exposure to fine particulate matter (PM2.5) has been documented. However, research on the disease burden following short-term exposure is scarce. We investigated the cause-specific mortality burden of short-term exposure to PM2.5 by considering the potential non-linear concentration-response relationship in Korea. METHODS: Daily cause-specific mortality rates and PM2.5 exposure levels from 2010 to 2019 were collected for 8 Korean cities and 9 provinces. A generalized additive mixed model was employed to estimate the non-linear relationship between PM2.5 exposure and cause-specific mortality levels. We assumed no detrimental health effects of PM2.5 concentrations below 15 µg/m3. Overall deaths attributable to short-term PM2.5 exposure were estimated by summing the daily numbers of excess deaths associated with ambient PM2.5 exposure. RESULTS: Of the 2 749 704 recorded deaths, 2 453 686 (89.2%) were non-accidental, 591 267 (21.5%) were cardiovascular, and 141 066 (5.1%) were respiratory in nature. A non-linear relationship was observed between all-cause mortality and exposure to PM2.5 at lag0, whereas linear associations were evident for cause-specific mortalities. Overall, 10 814 all-cause, 7855 non-accidental, 1642 cardiovascular, and 708 respiratory deaths were attributed to short-term exposure to PM2.5. The estimated number of all-cause excess deaths due to short-term PM2.5 exposure in 2019 was 1039 (95% confidence interval, 604 to 1472). CONCLUSIONS: Our findings indicate an association between short-term PM2.5 exposure and various mortality rates (all-cause, non-accidental, cardiovascular, and respiratory) in Korea over the period from 2010 to 2019. Consequently, action plans should be developed to reduce deaths attributable to short-term exposure to PM2.5.

Developing a national surveillance system for stroke and acute myocardial infarction using claims data in the Republic of Korea: a retrospective study.

BACKGROUND: Limited information is available concerning the epidemiology of stroke and acute myocardial infarction (AMI) in the Republic of Korea. This study aimed to develop a national surveillance system to monitor the incidence of stroke and AMI using national claims data. METHODS: We developed and validated identification algorithms for stroke and AMI using claims data. This validation involved a 2-stage stratified sampling method with a review of medical records for sampled cases. The weighted positive predictive value (PPV) and negative predictive value (NPV) were calculated based on the sampling structure and the corresponding sampling rates. Incident cases and the incidence rates of stroke and AMI in the Republic of Korea were estimated by applying the algorithms and weighted PPV and NPV to the 2018 National Health Insurance Service claims data. RESULTS: In total, 2,200 cases (1,086 stroke cases and 1,114 AMI cases) were sampled from the 2018 claims database. The sensitivity and specificity of the algorithms were 94.3% and 88.6% for stroke and 97.9% and 90.1% for AMI, respectively. The estimated number of cases, including recurrent events, was 150,837 for stroke and 40,529 for AMI in 2018. The age- and sex-standardized incidence rate for stroke and AMI was 180.2 and 46.1 cases per 100,000 person-years, respectively, in 2018. CONCLUSION: This study demonstrates the feasibility of developing a national surveillance system based on claims data and identification algorithms for stroke and AMI to monitor their incidence rates.

Relationship of bisphenol A substitutes bisphenol F and bisphenol S with adiponectin/leptin ratio among children from the environment and development of children cohort.

BACKGROUND: Bisphenol A (BPA) is known as an obesogenic endocrine disruptor. Bisphenol S (BPS) and F (BPF) are substitutes that have recently replaced BPA. OBJECTIVES: To investigate the relationships of urinary bisphenols (BPA, BPS and BPF) with adiposity measurements (obesity, BMI z-score, and fat mass), serum adipokine levels (adiponectin and leptin), and adiponectin/leptin ratio (A/L ratio) in 6- and 8-year-old children. METHODS: A total of 561 children who participated in the Environment and Development of Children cohort (482 and 516 children visited at age 6 and 8, respectively) at Seoul National University Children's Hospital during 2015-2019 were included. Urinary BPA levels were log-transformed. BPS levels were categorized into three groups (non-detected, lower-half, and higher-half of detected), and BPF levels were classified into two groups (non-detected and detected). RESULTS: The urinary BPS higher-half group had a higher BMI z-score (ß = 0.160, P= 0.044), higher fat mass (ß = 0.104, P< 0.001), lower adiponectin concentration (ß =- 0.069, P< 0.001), higher leptin concentration (ß = 0.360, P< 0.001), and lower A/L ratio (ß =- 0.428, P< 0.001) compared with the non-detected group. The urinary BPF-detected group had a higher fat mass (ß = 0.074, P< 0.001), lower adiponectin concentration (ß =- 0.069, P< 0.001), higher leptin concentration (ß = 0.360, P< 0.001), and lower A/L ratio (ß =- 0.428, P< 0.001) compared with the non-detected group. The BPA levels showed no consistent associations with outcomes, except for isolated associations of BPA at age 6 with a higher BMI z-score at age 6 (P= 0.016) and leptin at age 8 (P= 0.021). CONCLUSIONS: Increased exposure to BPS and BPF is associated with higher fat mass and leptin concentration, lower serum adiponectin, and lower A/L ratio in children. These findings suggest potential adverse effects of BPA substitutes on adiposity and adipokines. No consistent association of BPA exposure with outcomes could be partly explained by the decreasing BPA levels over time.

Ambient particulate matter and surrounding greenness in relation to sleep quality among pregnant women: A nationwide cohort study.

Background: Particulate air pollution and residential greenness are associated with sleep quality in the general population; however, their influence on maternal sleep quality during pregnancy has not been assessed. Objective: This cross-sectional study investigated the individual and interactive effects of exposure to particulate matter (PM) air pollution and residential greenness on sleep quality in pregnant women. Methods: Pregnant women (n = 4933) enrolled in the Korean Children's Environmental Health Study with sleep quality information and residential address were included. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The average concentrations of PM (PM2.5 and PM10) during pregnancy were estimated through land use regression, and residential greenness in a 1000 m buffer area around participants' residences was estimated using the Normalized Difference Vegetation Index (NDVI1000-m). Modified Poisson regression models were used to estimate the associations between PM and NDVI and poor sleep quality (PSQI >5) after controlling for a range of covariates. A four-way mediation analysis was conducted to examine the mediating effects of PM. Results: After adjusting for confounders, each 10 µg/m3 increase in PM2.5 and PM10 exposure was associated with a higher risk of poor sleep quality (relative risk [RR]: 1.06; 95% confidence interval [CI]: 1.01, 1.11; and RR: 1.09; 95% CI: 1.06, 1.13, respectively), and each 0.1-unit increase in NDVI1000-m was associated with a lower risk of poor sleep quality (RR: 0.97; 95% CI: 0.95, 0.99). Mediation analysis showed that PM mediated approximately 37%-56% of the association between residential greenness and poor sleep quality. Conclusions: This study identified a positive association between residential greenness and sleep quality. Furthermore, these associations are mediated by a reduction in exposure to particulate air pollution and highlight the link between green areas, air pollution control, and human health.

Infantile allergic diseases: a cohort study prenatal fish intake and mercury exposure context.

BACKGROUND: Allergic diseases (ADs) have been increasingly reported in infants and children over the last decade. Diet, especially the inclusion of fish intake, may help to lower the risk of ADs. However, fish also, can bioaccumulate environmental contaminants such as mercury. Hence, our study aims to determine what effects the type and frequency of fish intake have on ADs in six-month-old infants, independently and jointly with mercury exposure. METHODS: This study is part of the prospective birth cohort: Mothers and Children's Environmental Health (MOCEH) study in South Korea. Data was collected on prenatal fish intake, prenatal mercury concentration and ADs for infants aged six months for 590 eligible mother-infant pairs. Logistic regression analysis was conducted to evaluate the risk of prenatal fish intake and mercury concentration on ADs in infants. Finally, interaction between fish intake and mercury concentration affecting ADs in infants was evaluated. Hazard ratios of prenatal fish intake on ADs in 6 month old infants were calculated by prenatal mercury exposure. RESULTS: Logistic regression analysis showed that white fish (OR: 0.53; 95% CI 0.30-0.94; P < 0.05) intake frequency, once a week significantly decreased the risk of ADs in infants. Stratification analysis showed that consuming white fish once a week significantly reduced the hazard of ADs (HR: 0.44; 95% CI 0.21-0.92; P < 0.05) in infants in the high-mercury (≥ 50th percentile) exposure group. CONCLUSION: The result indicates that prenatal white fish intake at least once a week reduces the risk of ADs in infants, especially in the group with high prenatal mercury exposure.

Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies.

BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. RESULTS: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior. CONCLUSIONS: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. IMPACT: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.

CYP2A6 Activity and Cigarette Consumption Interact in Smoking-Related Lung Cancer Susceptibility.

Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis. Single-variant and gene-based associations of 43 tobacco carcinogen-metabolizing genes with lung cancer were analyzed using summary statistics and individual-level genetic data, followed by causal inference of Mendelian randomization, mediation analysis, and structural equation modeling. Cigarette smoke-exposed cell models were used to detect gene expression patterns in relation to specific alleles. Data from the International Lung Cancer Consortium (29,266 cases and 56,450 controls) and UK Biobank (2,155 cases and 376,329 controls) indicated that the genetic variant rs56113850 C>T located in intron 4 of CYP2A6 was significantly associated with decreased lung cancer risk among smokers (OR = 0.88, 95% confidence interval = 0.85-0.91, P = 2.18 × 10-16), which might interact (Pinteraction = 0.028) with and partially be mediated (ORindirect = 0.987) by smoking status. Smoking intensity accounted for 82.3% of the effect of CYP2A6 activity on lung cancer risk but entirely mediated the genetic effect of rs56113850. Mechanistically, the rs56113850 T allele rescued the downregulation of CYP2A6 caused by cigarette smoke exposure, potentially through preferential recruitment of transcription factor helicase-like transcription factor. Together, this study provides additional insights into the interplay between host susceptibility and carcinogen exposure in smoking-related lung tumorigenesis. SIGNIFICANCE: The causal pathway connecting CYP2A6 genetic variability and activity, cigarette consumption, and lung cancer susceptibility in smokers highlights the need for behavior modification interventions based on host susceptibility for cancer prevention.

Increased breast cancer incidence among nurses in a tertiary university hospital in South Korea.

Background: A series of breast cancer cases were recently reported in a tertiary university hospital in South Korea. Nurses are generally exposed to risk factors for breast cancer such as night shift work, antineoplastic agents, and job strain. However, the epidemiological evidence of excess incidence among nurses remains lacking. This study aims to investigate the excess incidence of breast cancer among nurses in a tertiary university hospital and provide epidemiological evidence of occupational risk factors. Methods: A retrospective cohort was developed using personnel records of female workers in the nursing department who worked from January 2011 to June 2021 in a tertiary university hospital in South Korea. Sick leave records were used to identify cases of breast cancer. The standardized incidence ratio of breast cancer among nurses was compared to the general population. Results: A total of 5,509 nurses were followed up for 30,404 person-years, and 26 breast cancer cases were identified. This study revealed a significantly increased breast cancer incidence among all included nurses, with a standardized incidence ratio of 1.65 (95% confidence interval [CI]: 1.08-2.41), compared to the general population. Workers, who handle antineoplastic agents in their representative department and current and/or former department, had significantly elevated breast cancer standardized incidence ratios of 2.73 (95% CI: 1.008-5.94) and 3.39 (95% CI: 1.46-6.68), respectively. Conclusions: This study provides significant evidence of increased breast cancer risk among nursing staff in a hospital setting, particularly those who handle antineoplastic drugs. Measures that reduce exposure to risk factors should be implemented, especially anticancer drugs, to protect healthcare professionals. Further research at a national level that focuses on healthcare workers is necessary to validate breast cancer incidence and its contributing factors.

Effects of iodine status on thyroid volume and goiter in children living in an iodine-replete area.

Objective: Adequate iodine intake is essential for growing children, and thyroid volume (Tvol) is considered as an indicator of iodine status. We investigated Tvol and goiter using ultrasonography (US) and their association with iodine status in 228 6-year-old children living in Korea. Methods: Iodine status was assessed using urine iodine concentration (UIC) and categorized as deficient (<100 µg/L), adequate (100-299 µg/L), mild excess (300-499 µg/L), moderate excess (500-999 µg/L), and severe excess (≥1000 µg/L). Tvol was measured using US, and a goiter on the US (goiter-US) was defined as Tvol greater than 97th percentile value by age- and body surface area (BSA)-specific international references. Results: The median Tvol was 2.4 mL, larger than the international reference value (1.6 mL). The age- and BSA-specific goiter-US rates were 25.9% (n = 59) and 34.6% (n = 79), respectively. The prevalence of excess iodine was 73.7% (n = 168). As iodine status increased from adequate to severe excess, the goiter-US rate significantly increased (P for trend <0.05). The moderate and severe iodine excess groups showed higher risk of goiter-US (adjusted odds ratio (aOR) = 3.1 (95% CI: 1.1-9.2) and aOR = 3.1 (95% CI: 1.2-8.3), respectively; age-specific criteria) than the iodine-adequate group. Conclusions: Excess iodine was prevalent in Korean children, and their Tvol was higher than the international reference values. Goiter rate was associated with iodine excess, which significantly increased in the moderate and severe iodine excess groups. Further studies are warranted to define optimal iodine intake in children.

The effect of residential greenness during pregnancy on infant neurodevelopment using propensity score weighting: A prospective mother-infant paired cohort study.

BACKGROUND: While prior studies have suggested an association between green spaces and infant neurodevelopment, the causal effect of green space exposure during pregnancy has not been fully investigated. This study aimed to identify with causal inference the effect of exposure to residential greenness during pregnancy on infants' mental-psychomotor development and the role of maternal education in modifying this association. METHODS: We prospectively collected data of pregnant women and their infants from Mothers and Children Environmental Health cohort study. Based on residential addresses, we compiled information on the percent of green space using different buffer distances (100 m, 300 m, and 500 m) and air pollution (PM2.5). Infant neurodevelopment was measured at 6 months of age using the Korean Bayley Scales of Infant Development II Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI). Generalized propensity scores (GPSs) were estimated from machine-learning (ML) algorithms. We deduced causal inference through GPS adjustment and weighting approaches. Further analyses confirmed whether the association was altered by maternal academic background. RESULTS: A total of 845 mother-infant pairs from the cohort study were included. We found that exposure to green spaces was robustly associated with infants' mental development. For example, an increase in % green space within 300 m increased the MDI by 14.32 (95 % confidence interval [CI], 3.44-25.2) in the weighting approach. Additionally, the association was even more noticeable for mothers with college degrees or above: an increase in % green space within 300 m increased the MDI by 23.69 (95 % CI, 8.53-38.85) and the PDI by 22.45 (95 % CI, 2.58-42.33) in the weighting approach. This association did not appear in mothers without college degrees. CONCLUSION: Exposure to green spaces during pregnancy showed a beneficial relationship with infant mental development. Maternal academic background could modify the impact of green space exposure on infant neurodevelopment.

Mosaic Chromosomal Alterations Are Associated With Increased Lung Cancer Risk: Insight From the INTEGRAL-ILCCO Cohort Analysis.

INTRODUCTION: Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer. METHODS: In this study, we investigated the association between mCAs and lung cancer using the high-density genotyping data from the OncoArray study of INTEGRAL-ILCCO, the largest single genetic study of lung cancer with 18,221 lung cancer cases and 14,825 cancer-free controls. RESULTS: We identified a comprehensive list of autosomal mCAs, ChrX mCAs, and mosaic ChrY (mChrY) losses from these samples. Autosomal mCAs were detected in 4.3% of subjects, in addition to ChrX mCAs in 3.6% of females and mChrY losses in 9.6% of males. Multivariable logistic regression analysis indicated that the presence of autosomal mCAs in white blood cells was associated with an increased lung cancer risk after adjusting for key confounding factors, including age, sex, smoking status, and race. This association was mainly driven by a specific type of mCAs: copy-neutral loss of heterozygosity on autosomal chromosomes. The association between autosome copy-neutral loss of heterozygosity and increased risk of lung cancer was further confirmed in two major histologic subtypes, lung adenocarcinoma and squamous cell carcinoma. In addition, we observed a significant increase of ChrX mCAs and mChrY losses in smokers compared with nonsmokers and racial differences in certain types of mCA events. CONCLUSIONS: Our study established a link between mCAs in white blood cells and increased risk of lung cancer.

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Urinary Phthalate Metabolites and Slow Walking Speed in the Korean Elderly Environmental Panel II Study.

BACKGROUND: Previous epidemiological studies have suggested that phthalate exposure may contribute to neurocognitive and neurobehavioral disorders and decreased muscle strength and bone mass, all of which may be associated with reduced physical performance. Walking speed is a reliable assessment tool for measuring physical performance in adults age 60 y and older. OBJECTIVE: We investigated associations between urinary phthalate metabolites and slowness of walking speed in community-dwelling adults ages 60-98 y. METHODS: We analyzed 1,190 older adults [range, 60-98 y of age; mean±standard deviation (SD) , 74.81±5.99] from the Korean Elderly Environmental Panel II study and measured repeatedly up to three times between 2012 and 2014. Phthalate exposure was estimated using the following phthalate metabolites in urine samples: mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-n-butyl phthalate (MnBP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono-benzyl phthalate (MBzP). Slowness was defined as a walking speed of <1.0meter/second. We used logistic and linear regression models to evaluate the association between each urinary phthalate metabolite and slowness or walking-speed change. We also used Bayesian kernel machine regression (BKMR) to examine overall mixture effects on walking speed. RESULTS: At enrollment, MBzP levels were associated with an increased odds of slowness [odds ratio (OR) per doubling increase: 1.15, 95% confidence interval (CI): 1.02, 1.30; OR for the highest vs. lowest quartile: 2.20 (95% CI: 1.12, 4.35) with p-trend across quartiles=0.031]. In longitudinal analyses, MEHHP levels showed an increased risk of slowness [OR per doubling increase: 1.15 (95% CI: 1.02, 1.29), OR for the highest vs. lowest quartile: 1.47 (95% CI: 1.04, 2.06), p- trend=0.035]; whereas those with higher MnBP showed a reduced risk of slowness [OR per doubling increase: 0.84 (95% CI: 0.74, 0.96), OR in the highest (vs. lowest) quartile: 0.64 (95% CI: 0.47, 0.87), p-trend=0.006]. For linear regression models, MBzP quartiles were associated with slower walking speed (p-trend=0.048) at enrollment, whereas MEHHP quartiles were associated with slower walking speed, and MnBP quartiles were associated with faster walking speed in longitudinal analysis (p-trend=0.026 and <0.001, respectively). Further, the BKMR analysis revealed negative overall trends between the phthalate metabolite mixtures and walking speed and DEHP group (MEHHP, MEOHP, and MECPP) had the main effect of the overall mixture. DISCUSSION: Urinary concentrations of prevalent phthalates exhibited significant associations with slow walking speed in adults ages 60-98 y. https://doi.org/10.1289/EHP10549.

Association between early-childhood exposure to perfluoroalkyl substances and ADHD symptoms: A prospective cohort study.

There is evidence that exposure to perfluoroalkyl substances (PFAS) is associated with attention-deficit/hyperactivity disorder (ADHD) symptoms. Previous studies have focused on prenatal exposure to PFAS, and only few studies have examined the associations of early-childhood exposure, especially at low exposure levels. This study explored the association between early-childhood exposure to PFAS and ADHD symptoms later in childhood. In 521 children, we measured the serum levels of six PFAS in peripheral blood at the ages of 2 and 4 years, including perfluorooctanoate (PFOA), perfluornonanoicacid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonate (PFOS). The ADHD Rating Scale IV (ARS) was utilized to measure ADHD traits at 8 years of age. We explored the relationship between PFAS and ARS scores using Poisson regression models after adjusting for potential confounders. Levels of exposure to individual PFAS and the summed value were divided into quartiles to examine possible nonlinear relationships. All six PFAS exhibited inverted U-shaped curves. Children in the 2nd and 3rd quartile levels of each PFAS showed higher ARS scores than those in the1st quartile level. Below the 3rd quartile of the summed levels of six PFAS (ΣPFAS), a doubling of the ΣPFAS was associated with an 20.0 % (95 % CI: 9.5 %, 31.5 %) increase in ADHD scores. However, at the age of 4 years, none of the evaluated PFAS exhibited linear or nonlinear associations with the ARS scores. Thus, school-aged children may be vulnerable to the neurotoxic effects of exposure to PFAS at age 2 that contribute to ADHD, particularly at low to mid-levels.

DNA methylation is associated with prenatal exposure to sulfur dioxide and childhood attention-deficit hyperactivity disorder symptoms.

Epigenetic influence plays a role in the association between exposure to air pollution and attention deficit hyperactivity disorder (ADHD); however, research regarding sulfur dioxide (SO2) is scarce. Herein, we investigate the associations between prenatal SO2 exposure and ADHD rating scale (ARS) at ages 4, 6 and 8 years repeatedly in a mother-child cohort (n = 329). Whole blood samples were obtained at ages 2 and 6 years, and genome-wide DNA methylation (DNAm) was analyzed for 51 children using the Illumina Infinium HumanMethylation BeadChip. We analyzed the associations between prenatal SO2 exposure and DNAm levels at ages 2 and 6, and further investigated the association between the DNAm and ARS at ages 4, 6 and 8. Prenatal SO2 exposure was associated with ADHD symptoms. From candidate gene analysis, DNAm levels at the 6 CpGs at age 2 were associated with prenatal SO2 exposure levels. Of the 6 CpGs, cg07583420 (INS-IGF2) was persistently linked with ARS at ages 4, 6 and 8. Epigenome-wide analysis showed that DNAm at 6733 CpG sites were associated with prenatal SO2 exposure, of which 58 CpGs involved in Notch signalling pathway were further associated with ARS at age 4, 6 and 8 years, persistently. DNAm at age 6 was not associated with prenatal SO2 exposure. Changes in DNAm levels associated with prenatal SO2 exposure during early childhood are associated with increases in ARS in later childhood.

Relationship of iodine excess with thyroid function in 6-year-old children living in an iodine-replete area.

Background: Adequate iodine intake is essential for growing children, as both deficient and excessive iodine status can result in thyroid dysfunction. We investigated the iodine status and its association with thyroid function in 6-year-old children from South Korea. Methods: A total of 439 children aged 6 (231 boys and 208 girls) were investigated from the Environment and Development of Children cohort study. The thyroid function test included free thyroxine (FT4), total triiodothyronine (T3), and thyroid-stimulating hormone (TSH). Urine iodine status was evaluated using urine iodine concentration (UIC) in morning spot urine and categorized into iodine deficient (< 100 µg/L), adequate (100-199 µg/L), more than adequate (200-299 µg/L), mild excessive (300-999 µg/L), and severe excessive (≥ 1000 µg/L) groups. The estimated 24-hour urinary iodine excretion (24h-UIE) was also calculated. Results: The median TSH level was 2.3 µIU/mL, with subclinical hypothyroidism detected in 4.3% of patients without sex differences. The median UIC was 606.2 µg/L, with higher levels in boys (684 µg/L vs. 545 µg/L, p = 0.021) than girls. Iodine status was categorized as deficient (n = 19, 4.3%), adequate (n = 42, 9.6%), more than adequate (n = 54, 12.3%), mild excessive (n = 170, 38.7%), or severe excessive (n = 154, 35.1%). After adjusting for age, sex, birth weight, gestational age, body mass index z-score, and family history, both the mild and severe excess groups showed lower FT4 (ß = - 0.04, p = 0.032 for mild excess; ß = - 0.04, p = 0.042 for severe excess) and T3 levels (ß = - 8.12, p = 0.009 for mild excess; ß = - 9.08, p = 0.004 for severe excess) compared to the adequate group. Log-transformed estimated 24h-UIE showed a positive association with log-transformed TSH levels (ß = 0.04, p = 0.046). Conclusion: Excess iodine was prevalent (73.8%) in 6-year-old Korean children. Excess iodine was associated with a decrease in FT4 or T3 levels and an increase in TSH levels. The longitudinal effects of iodine excess on later thyroid function and health outcomes require further investigation.

The association between occupational stress level and health-related productivity loss among Korean employees.

OBJECTIVES: Occupational stress management is particularly important for successful business operations, since occupational stress adversely affects workers' health, eventually lowering their productivity. Therefore, this study aimed to investigate the correlation between occupational stress and health-related productivity loss (HRPL) among Korean workers. METHODS: In 2021, 1,078 workers participated in a web-based questionnaire survey. HRPL was measured using the Work Productivity and Activity Impairment Questionnaire, and occupational stress was measured using the Korean Occupational Stress Scale-Short Form. The occupational stress level was divided into tertiles (low, intermediate, and high), and the low occupational stress group was used as the reference group. Using a generalised linear model, differences in labour productivity loss according to the level of occupational stress were tested after adjusting for demographic characteristics such as age, gender, education level, household income, occupation, and underlying medical conditions. RESULTS: Non-parametric regression analysis of HRPL according to occupational stress showed a direct association between occupational stress and HRPL. A statistically significant difference was observed in HRPL between participants with intermediate and high occupational stress and those with low occupational stress. CONCLUSIONS: Our results support the hypothesis that high occupational stress is associated with decreased labour productivity.

Association of paternal cadmium and other heavy metal exposure to birth outcomes using propensity score matching.

BACKGROUND: Human exposure to cadmium has various effects on health, especially on male reproductive organs. Although it is widely known that prenatal maternal cadmium exposure can affect birth outcomes, the effect of paternal exposure to cadmium remains unclear. OBJECTIVES: This study aimed to evaluate the effect of paternal cadmium exposure on fetal growth by considering maternal cadmium exposure and exposure to other heavy metals, namely mercury and lead. METHODS: The Mothers and Children's Environmental Health (MOCEH) study is a prospective birth cohort study in Korea. Overall, 1313 families (father-mother-child triple) without child abnormalities and who completed paternal whole blood cadmium assessments were included in this study. Families were divided into two subgroups based on the blood sampling periods, namely early and late pregnancy. Subjects were selected as follows: one family triple with a high level of paternal cadmium and two triples with low levels of paternal cadmium, using the method of propensity score matching. And linear regression analyses were performed. RESULTS: The group with high paternal cadmium exposure (80% or more; 1.93 µg/L) had lower birth weight infants compared to the group with low cadmium concentrations (ß(se) = -0.21(0.10); p-value = 0.0283). After stratification by infant sex, prenatal paternal cadmium exposure significantly reduced the birth weight of females in subgroups of different sampling times, namely early pregnancy (ß(se) = -0.52 (0.22); p-value = 0.0170) and late pregnancy (ß(se) = -0.43 (0.18); p-value = 0.0160). Finally, after performing propensity score matching in the early pregnancy measurement group, it was found that the prenatal exposure of father to cadmium significantly reduced birth weight in females (ß(se) = -0.72(0.25); p-value = 0.0047). CONCLUSION: This study assessed the effect of paternal cadmium exposure on birth outcomes in family units consisting of a father, mother, and child. Prenatal paternal cadmium exposure negatively affected birth weight, especially that of female, considering covariates and other heavy metals exposure, namely mercury and lead.

Association of long-term exposure to PM2.5 and survival following ischemic heart disease.

BACKGROUND: Numerous studies have suggested that long-term exposure to particulate matter ≤2.5 µm (PM2.5) may cause cardiovascular morbidity and mortality. However, susceptibility among those with a history of ischemic heart disease is less clearly understood. We aimed to evaluate whether long-term PM2.5 exposure is related to mortality among patients with ischemic heart disease. METHODS: We followed up 306,418 patients hospitalized with ischemic heart disease in seven major cities in South Korea between 2008 and 2016 using the National Health Insurance Database. We linked the modeled PM2.5 data corresponding to each patient's administrative districts and estimated hazard ratios (HRs) of cause-specific mortality associated with the long-term exposure to PM2.5 in time-varying Cox proportional hazard models after adjusting for individual- and area-level characteristics. We also estimated HRs by sex, age group (65-74 vs. ≥75 years), and household income. RESULTS: Of the patients with ischemic heart disease, mean age at the discharge was 76.8 years, and 105,913 died during a mean follow-up duration of 21.4 months. The HR of all-cause mortality was 1.10 [95% confidence intervals (CI): 1.07, 1.14] per 10 µg/m3 increase in a 12-month moving average PM2.5. The HRs of cardiovascular, stroke, and ischemic heart disease were 1.17 (95% CI: 1.11, 1.24), 1.17 (95% CI: 1.06, 1.30), and 1.25 (95% CI: 1.15, 1.35), respectively. The subgroup analyses showed that participants aged 65-74 years were more susceptible to adverse effects of PM2.5 exposure. We did not observe any differences in the risk by sex and household income. CONCLUSION: Mortality from all-cause and cardiovascular disease following hospitalization due to ischemic heart disease was higher among individuals with greater PM2.5 exposure in seven major cities in South Korea. The result supports the association of long-term exposure to air pollution with poor prognosis among patients with ischemic heart disease.

Working From Home, Work-Life Balance, and Depression/Anxiety Among Korean Workers in the COVID-19 Pandemic Period: A Mediation Analysis.

OBJECTIVE: We aimed to investigate the association between working from home (WFH), depression/anxiety, and work-family conflict (WFC) among Korean workers during the COVID-19 pandemic. METHODS: We surveyed a total of 1074 workers online. Depression and anxiety were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D) and Beck Anxiety Inventory (BAI). Mediating effects of WFC on the relationship between WFH and depression/anxiety were examined. RESULTS: The WFH group had higher depression and anxiety scores than the daily commuting group. As WFC increased, the CES-D and BAI scores also increased. A possible mediating effect of WFC on the relationship between WFH and high CES-D and BAI scores was found. CONCLUSION: We observed a significant difference in depression/anxiety between WFH and daily commute workers, which was mediated by WFC, especially for young, child-growing, and precarious workers.