Associations of cold exposure with hospital admission and mortality due to acute kidney injury: A nationwide time-series study in Korea.

BACKGROUND: Emerging evidence supports an association between heat exposure and acute kidney injury (AKI). However, there is a paucity of studies on the association between cold exposure and AKI. OBJECTIVE: We aimed to investigate the associations of cold exposure with hospital admission and mortality due to AKI and to explore whether these associations were influenced by age and sex. METHODS: Information on daily counts of hospital admission and mortality due to AKI in 16 regions of Korea during the cold seasons (2010-2019) was obtained from the National Health Insurance Service (a single national insurer providing universal health coverage) and Statistics Korea. Daily mean temperature and relative humidity were calculated from hourly data obtained from 94 monitoring systems operated by the Korean Meteorological Administration. Associations of low temperatures (<10th percentile of daily mean temperature) and cold spells (≥2 consecutive days with <5th percentile of daily mean temperature) up to 21 days with AKI were estimated using quasi-Poisson regression models adjusted for potential confounders (e.g., relative humidity and air pollutants) with distributed lag models and univariate meta-regression models. RESULTS: Low temperatures were associated with hospital admission due to AKI [relative risk (RR) = 1.12, 95 % confidence interval (CI): 1.09, 1.16]. Cold spells were associated with hospital admission (RR = 1.87, 95 % CI: 1.46, 2.39) and mortality due to AKI (RR = 4.84, 95 % CI: 1.30, 17.98). These associations were stronger among individuals aged ≥65 years than among those aged <65 years. CONCLUSION: Our results underscore the need for the general population, particularly the elderly, physicians, and other healthcare providers to be more vigilant to cold exposure, given the risk of AKI. Government agencies need to develop specific strategies for the prevention and early detection of cold exposure-related AKI.

Associations between cold spells and hospital admission and mortality due to diabetes: A nationwide multi-region time-series study in Korea.

BACKGROUND: Climate change is predicted to increase the frequency, intensity, and duration of extreme cold events in the mid-latitudes. However, although diabetes is one of the most critical metabolic diseases due to its high and increasing prevalence worldwide, few studies have investigated the short-term association between cold exposure and diabetes-related outcomes. OBJECTIVE: The aim of this study was to investigate the associations between cold spells and their characteristics (intensity, duration, and seasonal timing) and hospital admission and mortality due to diabetes. METHODS: This study used claims data from the National Health Insurance Service and cause-specific mortality data from Statistics Korea (2010-2019). Cold spells were defined as ≥2 consecutive days with a daily mean temperature lower than the region-specific 5th percentile during the cold season (November-March). Quasi-Poisson regressions combined with distributed lag models were used to assess the associations between exposures and outcomes in 16 regions across the Republic of Korea. Meta-analyses were conducted to pool the region-specific estimates. RESULTS: Exposure to cold spells was associated with an increased risk of hospital admission [relative risk (RR) = 1.45, 95% confidence interval (CI): 1.26, 1.66] and mortality (RR = 2.02, 95% CI: 1.37, 2.99) due to diabetes. The association between cold spells and hospital admission due to diabetes was stronger for cold spells that were more intense, longer, and occurred later during the cold season. The association between cold spells and diabetes-related mortality was stronger for more intense and longer cold spells. CONCLUSION: This study emphasizes the importance of developing effective interventions against cold spells, including education on the dangers of cold spells and early alarm systems. Further studies are needed to create real-world interventions and evaluate their effectiveness in improving diabetes-related outcomes.

Effect modification of consecutive high concentration days on the association between fine particulate matter and mortality: a multi-city study in Korea.

OBJECTIVES: Although there is substantial evidence for the short-term effect of fine particulate matter (PM2.5) on daily mortality, few epidemiological studies have explored the effect of prolonged continuous exposure to high concentrations of PM2.5. This study investigated how the magnitude of the mortality effect of PM2.5 exposure is modified by persistent exposure to high PM2.5 concentrations. METHODS: We analyzed data on the daily mortality count, simulated daily PM2.5 level, mean daily temperature, and relative humidity level from 7 metropolitan cities from 2006 to 2019. Generalized additive models (GAMs) with quasi-Poisson distribution and random-effects meta-analyses were used to pool city-specific effects. To investigate the effect modification of continuous exposure to prolonged high concentrations, we applied categorical consecutive-day variables to the GAMs as effect modification terms for PM2.5. RESULTS: The mortality risk increased by 0.33% (95% confidence interval [CI], 0.16 to 0.50), 0.47% (95% CI, -0.09 to 1.04), and 0.26% (95% CI, -0.08 to 0.60) for all-cause, respiratory, and cardiovascular diseases, respectively, with a 10 µg/m3 increase in PM2.5 concentration. The risk of all-cause mortality per 10 µg/m3 increase in PM2.5 on the first and fourth consecutive days significantly increased by 0.63% (95% CI, 0.20 to 1.06) and 0.36% (95% CI, 0.01 to 0.70), respectively. CONCLUSIONS: We found increased risks of all-cause, respiratory, and cardiovascular mortality related to daily PM2.5 exposure on the day when exposure to high PM2.5 concentrations began and when exposure persisted for more than 4 days with concentrations of ≥35 µg/m3. Persistently high PM2.5 exposure had a stronger effect on seniors.

Cancer risk in the residents of a town near three industrial waste incinerators in Korea: a retrospective cohort study.

BACKGROUND: Three industrial waste incinerators (IWIs) were built in 1999, 2001, and 2010, within a 3 km radius of a town with a population of around 5000 in Korea. This study evaluated whether residents near these three IWIs had increased cancer incidence than those from other areas in Korea using regional health data. METHODS: Standardized incidence ratios (SIR) were calculated using the frequency of cancer cases in the National Cancer Registry of the exposed area (Buki-myeon), Chungcheongbuk-do (Chungbuk, state including Buki-myeon), and whole Korea from 1999 to 2017. A retrospective cohort was created using National Health Insurance System data from 2002 to 2018. The exposed group was defined as those having a residential history in the exposed area. The control group was defined as those having a residential history in nearby towns or counties in Chungbuk, excluding counties having living and cultural areas in other provinces and cities. Hazard ratio (HR) and 95% confidence intervals (CI) were estimated using the Cox proportional hazard model adjusted for age, level of health insurance fee, and smoking history. RESULTS: In the ecological study using National Cancer Registry data, the risk of all cancers, all cancers excluding thyroid, esophageal, stomach, and lung cancers in the exposed area were 1.13 (95% CI 1.03-1.24), 1.15 (95% CI 1.04-1.26), 1.91 (95% CI 1.13-2.89), 1.39 (95% CI 1.14-1.66), and 1.29 (95% CI 1.03-1.57) times higher than in whole Korea among exposed males, respectively. In the retrospective cohort, 4300 males (26,821 person-years) and 3796 females (24,746 person-years) in exposed group, 150,964 males (1,212,010 person-years) and 134,535 females (1,104,025 person-years) in control group were analyzed. After adjusting for several confounding factors, the risks for gallbladder cancer among males and kidney cancer among females were 2.65 (95% CI 1.38-5.06) and 2.82 (95% CI 1.13-7.03) times higher in the exposed group versus the control group, respectively. CONCLUSIONS: Cancer risk was higher in Koreans having residential history living near IWIs compared to the other areas. Further study warrants nationwide effects and longer follow-up of WIs for cancers in Korea.

Cancer cluster among small village residents near the fertilizer plant in Korea.

OBJECTIVES: In Jang-jeom, a small village in Hamra-myeon, Iksan-si, Jeollabuk-do, South Korea, residents raised concerns about a suspected cancer cluster that they attributed to a fertilizer plant near the village. We aimed to investigate whether the cancer incidence in the village was higher than that in the general Korean population when the factory was in operation (2001-2017) and whether living in the village was associated with a higher risk of cancer. METHODS: Using national population data and cancer registration data of South Korea, we estimated the standardized incidence ratios (SIRs) in the village to investigate whether more cancer cases occurred in the village compared to other regions. The SIRs were standardized by age groups of 5 years and sex. In order to investigate whether residence in the village increased the risk of cancer, a retrospective cohort was constructed using National Health Insurance Service (NHIS) databases. We estimated the cancer hazard ratios (HRs) using the Cox proportional hazard model, and defined the exposed area as the village of Jang-jeom, and the unexposed or control area as the village neighborhood in Hamra-myeon. We considered potential confounding variables such as age, sex, and income index in the models. Additionally, we measured polycyclic aromatic hydrocarbons (PAHs) and tobacco-specific nitrosamines (TSNAs), suspected carcinogens that may have caused the cancer cluster, in samples collected from the plant and the village. RESULTS: Twenty-three cancer cases occurred in Jang-jeom from 2001 to 2017. Between 2010 and 2016, the incidence rates of all cancers (SIR: 2.05, except thyroid cancer: 2.22), non-melanoma skin cancer (SIR: 21.14, female: 25.41), and gallbladder (GB) and biliary tract cancer in men (SIR: 16.01) in the village were higher than those in the national population in a way that was statistically significant. In our cohort analysis that included only Hamra-myeon residents who have lived there for more than 7 years, we found a statistically significant increase in the risk of all cancers (HR: 1.99, except thyroid cancer: 2.20), non-melanoma skin cancer (HR: 11.60), GB and biliary tract cancer (HR: 15.24), liver cancer (HR: 6.63), and gastric cancer (HR: 3.29) for Jang-jeom residents compared to other Hamra area residents. We identified PAHs and TSNAs in samples of deposited dust and residual fertilizer from the plant and TSNAs in dust samples from village houses. CONCLUSIONS: The results of the SIR calculation and cancer risk analyses of Jang-jeom village residents from the retrospective cohort design showed consistency in the effect size and direction, suggesting that there was a cancer cluster in Jang-jeom. This study would be a good precedent for cancer cluster investigation.

Clinical presentation of young people (10-24 years old) with brain tumors: results from the international MOBI-Kids study.

INTRODUCTION: We used data from MOBI-Kids, a 14-country international collaborative case-control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24). METHODS: Information from clinical records was obtained for 899 BT cases, including signs and symptoms, symptom onset, diagnosis date, tumor type and location. RESULTS: Overall, 64% of all tumors were low-grade, 76% were neuroepithelial tumors and 62% gliomas. There were more males than females among neuroepithelial and embryonal tumor cases, but more females with meningeal tumors. The most frequent locations were cerebellum (22%) and frontal (16%) lobe. The most frequent symptom was headaches (60%), overall, as well as for gliomas, embryonal and 'non-neuroepithelial' tumors; it was convulsions/seizures for neuroepithelial tumors other than glioma, and visual signs and symptoms for meningiomas. A cluster analysis showed that headaches and nausea/vomiting was the only combination of symptoms that exceeded a cutoff of 50%, with a joint occurrence of 67%. Overall, the median time from first symptom to diagnosis was 1.42 months (IQR 0.53-4.80); it exceeded 1 year in 12% of cases, though no particular symptom was associated with exceptionally long or short delays. CONCLUSIONS: This is the largest clinical epidemiology study of BT in young people conducted so far. Many signs and symptoms were identified, dominated by headaches and nausea/vomiting. Diagnosis was generally rapid but in 12% diagnostic delay exceeded 1 year with none of the symptoms been associated with a distinctly long time until diagnosis.

Associations of Maternal Cell-Phone Use During Pregnancy With Pregnancy Duration and Fetal Growth in 4 Birth Cohorts.

Results from studies evaluating potential effects of prenatal exposure to radio-frequency electromagnetic fields from cell phones on birth outcomes have been inconsistent. Using data on 55,507 pregnant women and their children from Denmark (1996-2002), the Netherlands (2003-2004), Spain (2003-2008), and South Korea (2006-2011), we explored whether maternal cell-phone use was associated with pregnancy duration and fetal growth. On the basis of self-reported number of cell-phone calls per day, exposure was grouped as none, low (referent), intermediate, or high. We examined pregnancy duration (gestational age at birth, preterm/postterm birth), fetal growth (birth weight ratio, small/large size for gestational age), and birth weight variables (birth weight, low/high birth weight) and meta-analyzed cohort-specific estimates. The intermediate exposure group had a higher risk of giving birth at a lower gestational age (hazard ratio = 1.04, 95% confidence interval: 1.01, 1.07), and exposure-response relationships were found for shorter pregnancy duration (P < 0.001) and preterm birth (P = 0.003). We observed no association with fetal growth or birth weight. Maternal cell-phone use during pregnancy may be associated with shorter pregnancy duration and increased risk of preterm birth, but these results should be interpreted with caution, since they may reflect stress during pregnancy or other residual confounding rather than a direct effect of cell-phone exposure.

Environmental Tobacco Smoke Exposure at Home and Attributable Problem Behaviors in Korean Children and Adolescents for 2012-2014 in a Nationally Representative Survey.

BACKGROUND: This study aimed to examine the environmental tobacco smoke (ETS) exposure at home and associated problem behaviors in Korean children and adolescents. METHODS: Approximately 2,167 children aged 3-18 years were included in the study after excluding 163 active smokers from the Korean Environmental Health Survey in Children and Adolescents (2012-2014). ETS data were obtained using a questionnaire; problem behaviors were measured using the Child Behavior Checklist administered to parents. The relationship between ETS exposure and problem behavior was evaluated using a survey regression model adjusted for region, age, sex, income, and father's education. The population-attributable fraction (PAF%) was calculated based on problem behaviors related to ETS exposure at home. RESULTS: The rates of ETS exposure at home were 20%, 28%, and 39% in children aged 3-5, 6-11, and 12-18 years, respectively; ETS exposure at home was associated with behavioral problems: the exposed group having higher total behavioral problem score (95% confidence interval [CI]) than the non-exposed by 2.46 (0.60-4.32) and 2.74 (0.74-4.74) in children aged 6-11 and 12-18 years, respectively, with no significant association in those aged 3-5 years. The PAF% (95% CI) of total problem behaviors for ETS exposure at home were 2.68 (-10.11-17.78), 10.66 (3.25-17.55), and 11.62 (3.03-18.96) in children aged 3-5, 6-11, and 12-18 years, respectively. Children with externalizing problems had higher PAF% than those with internalizing problems. CONCLUSION: In Korea, ETS exposure at home is associated with problem behaviors in children and adolescents with about more than 10% population attributable fraction.

Maternal cell phone use during pregnancy and child cognition at age 5 years in 3 birth cohorts.

BACKGROUND: There have been few studies of children's cognitive development in relation to mothers' cell phone use, and most were limited to outcomes at age 3 years or younger. We examined the relationship between maternal cell phone use during pregnancy and cognitive performance in 5-year old children. METHODS: This study included data from 3 birth cohorts: the Danish National Birth Cohort (DNBC) (n = 1209), Spanish Environment and Childhood Project (INMA) (n = 1383), and Korean Mothers and Children's Environment Health Study (MOCEH) (n = 497). All cohorts collected information about maternal cell phone use during pregnancy and cognitive performance in children at age 5. We performed linear regression to compute mean differences (MD) and 95% confidence intervals (CI) in children's general, verbal, and non-verbal cognition scores comparing frequency of maternal prenatal cell phone use with adjustments for numerous potential confounding factors. Models were computed separately for each cohort and using pooled data in meta-analysis. RESULTS: No associations were detected between frequency of prenatal cell phone use and children's cognition scores. Scores tended to be lower in the highest frequency of use category; MD (95% CI) in general cognition scores were 0.78 (-0.76, 2.33) for none, 0.11 (-0.81, 1.03) for medium, and -0.41 (-1.54, 0.73) for high compared to low frequency of use. This pattern was seen across all cognitive dimensions, but the results were imprecise overall. CONCLUSION: We observed patterns of lower mean cognition scores among children in relation to high frequency maternal prenatal cell phone use. The causal nature and mechanism of this relationship remain unknown.

Estimation of Cancer Incidence and Mortality Risks Attributed to Diagnostic Medical Radiation Exposure in Korea, 2013.

BACKGROUND: Radiation exposure from medical procedures has been rapidly increasing. We purposed to estimate the fraction of cancer incidence and mortality attributed to diagnostic medical radiation exposure in Korea. METHODS: Using information on diagnostic medical radiation exposure from various sources including national health examination (National Health Insurance Service), private health examination, and conscription health examination; the annual mean exposed organ dose (mGy) from all diagnostic medical radiation use, grouped by sex and 5-year age ranges up to 80 years, was calculated. Cancer incidence and mortality lifetime attributable risks (LARs) up to 85 years using estimated exposed organ doses and biological effects of ionizing radiation (BEIR) VII model (excess relative risk and excess absolute risk) were estimated. Using background cancer incidence and mortality risk based on the national database, along with estimated LARs, we finally estimated population attributable fraction (PAF) of cancer incidence and mortality. RESULTS: The PAF for diagnostic medical radiation exposure among all cancers of Koreans was 0.9% for incidence and mortality, resulting 1,915 cancer cases and 637 cancer deaths a year. The PAF in females was higher than those in males: 1.2% and 1.7% (incidence and mortality) versus 0.6% (same in incidence and mortality), respectively. CONCLUSION: The estimated PAF for diagnostic medical radiation in Korea in 2013 was higher than those reported in the UK in 2004. Optimized management of diagnostic medical radiation use is important in Korea.

Mercury Exposure in Association With Decrease of Liver Function in Adults: A Longitudinal Study.

OBJECTIVES: Although mercury (Hg) exposure is known to be neurotoxic in humans, its effects on liver function have been less often reported. The aim of this study was to investigate whether total Hg exposure in Korean adults was associated with elevated serum levels of the liver enzymes aspartate aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyltransferase (GGT). METHODS: We repeatedly examined the levels of total Hg and liver enzymes in the blood of 508 adults during 2010-2011 and 2014-2015. Cross-sectional associations between levels of blood Hg and liver enzymes were analyzed using a generalized linear model, and nonlinear relationships were analyzed using a generalized additive mixed model. Generalized estimating equations were applied to examine longitudinal associations, considering the correlations of individuals measured repeatedly. RESULTS: GGT increased by 11.0% (95% confidence interval [CI], 4.5 to 18.0%) in women and 8.1% (95% CI, -0.5 to 17.4%) in men per doubling of Hg levels, but AST and ALT were not significantly associated with Hg in either men or women. In women who drank more than 2 or 3 times per week, AST, ALT, and GGT levels increased by 10.6% (95% CI, 4.2 to 17.5%), 7.7% (95% CI, 1.1 to 14.7%), and 37.5% (95% CI,15.2 to 64.3%) per doubling of Hg levels, respectively, showing an interaction between blood Hg levels and drinking. CONCLUSIONS: Hg exposure was associated with an elevated serum concentration of GGT. Especially in women who were frequent drinkers, AST, ALT, and GGT showed a significant increase, with a significant synergistic effect of Hg and alcohol consumption.

The relationship between spontaneous abortion and female workers in the semiconductor industry.

BACKGROUND: This study investigated the relationship between job type and the risk for spontaneous abortion to assess the reproductive toxicity of female workers in the semiconductor industry. METHODS: A questionnaire survey was administered to current female workers of two semiconductor manufacturing plants in Korea. We included female workers who became pregnant at least 6 months after the start of their employment with the company. The pregnancy outcomes of 2,242 female workers who experienced 4,037 pregnancies were investigated. Personnel records were used to assign the subjects to one of three groups: fabrication process workers, packaging process workers, and clerical workers. To adjust for within-person correlations between pregnancies, a generalized estimating equation was used. The logistic regression analysis was limited to the first pregnancy after joining the company to satisfy the assumption of independence among pregnancies. Moreover, we stratified the analysis by time period (pregnancy in the years prior to 2008 vs. after 2009) to reflect differences in occupational exposure based on semiconductor production periods. RESULTS: The risk for spontaneous abortion in female semiconductor workers was not significantly higher for fabrication and packaging process workers than for clerical workers. However, when we stratified by time period, the odds ratio for spontaneous abortion was significantly higher for packaging process workers who became pregnant prior to 2008 when compared with clerical workers (odds ratio: 2.21; 95% confidence interval: 1.01-4.81). CONCLUSIONS: When examining the pregnancies of female semiconductor workers that occurred prior to 2008, packaging process workers showed a significantly higher risk for spontaneous abortions than did clerical workers. The two semiconductor production periods in our study (prior to 2008 vs. after 2009) had different automated processes, chemical exposure levels, and working environments. Thus, the conditions prior to 2008 may have increased the risk for spontaneous abortions in packaging process workers in the semiconductor industry.

Maternal cell phone use during pregnancy and child behavioral problems in five birth cohorts.

INTRODUCTION: Previous studies have reported associations between prenatal cell phone use and child behavioral problems, but findings have been inconsistent and based on retrospective assessment of cell phone use. This study aimed to assess this association in a multi-national analysis, using data from three cohorts with prospective data on prenatal cell phone use, together with previously published data from two cohorts with retrospectively collected cell phone use data. METHODS: We used individual participant data from 83,884 mother-child pairs in the five cohorts from Denmark (1996-2002), Korea (2006-2011), the Netherlands (2003-2004), Norway (2004-2008), and Spain (2003-2008). We categorized cell phone use into none, low, medium, and high, based on frequency of calls during pregnancy reported by the mothers. Child behavioral problems (reported by mothers using the Strengths and Difficulties Questionnaire or Child Behavior Checklist) were classified in the borderline/clinical and clinical ranges using validated cut-offs in children aged 5-7years. Cohort specific risk estimates were meta-analyzed. RESULTS: Overall, 38.8% of mothers, mostly from the Danish cohort, reported no cell phone use during pregnancy and these mothers were less likely to have a child with overall behavioral, hyperactivity/inattention or emotional problems. Evidence for a trend of increasing risk of child behavioral problems through the maternal cell phone use categories was observed for hyperactivity/inattention problems (OR for problems in the clinical range: 1.11, 95%CI 1.01, 1.22; 1.28, 95%CI 1.12, 1.48, among children of medium and high users, respectively). This association was fairly consistent across cohorts and between cohorts with retrospectively and prospectively collected cell phone use data. CONCLUSIONS: Maternal cell phone use during pregnancy may be associated with an increased risk for behavioral problems, particularly hyperactivity/inattention problems, in the offspring. The interpretation of these results is unclear as uncontrolled confounding may influence both maternal cell phone use and child behavioral problems.

Short-term Effect of Fine Particulate Matter on Children's Hospital Admissions and Emergency Department Visits for Asthma: A Systematic Review and Meta-analysis.

OBJECTIVES: No children-specified review and meta-analysis paper about the short-term effect of fine particulate matter (PM2.5) on hospital admissions and emergency department visits for asthma has been published. We calculated more precise pooled effect estimates on this topic and evaluated the variation in effect size according to the differences in study characteristics not considered in previous studies. METHODS: Two authors each independently searched PubMed and EMBASE for relevant studies in March, 2016. We conducted random effect meta-analyses and mixed-effect meta-regression analyses using retrieved summary effect estimates and 95% confidence intervals (CIs) and some characteristics of selected studies. The Egger's test and funnel plot were used to check publication bias. All analyses were done using R version 3.1.3. RESULTS: We ultimately retrieved 26 time-series and case-crossover design studies about the short-term effect of PM2.5 on children's hospital admissions and emergency department visits for asthma. In the primary meta-analysis, children's hospital admissions and emergency department visits for asthma were positively associated with a short-term 10 µg/m3 increase in PM2.5 (relative risk, 1.048; 95% CI, 1.028 to 1.067; I2=95.7%). We also found different effect coefficients by region; the value in Asia was estimated to be lower than in North America or Europe. CONCLUSIONS: We strengthened the evidence on the short-term effect of PM2.5 on children's hospital admissions and emergency department visits for asthma. Further studies from other regions outside North America and Europe regions are needed for more generalizable evidence.

Associations of Low Environmental Exposure to Multiple Metals with Renal Tubular Impairment in Korean Adults.

Recently several studies reported that the renal toxicity of lead (Pb) and cadmium (Cd) may exist in even a low level exposure. In terms of the deterioration of tubular function, it affects the loss of divalent metals and leads to other complications, so renal tubular effect of heavy metals should be well managed. Considering the exposure to heavy metals in reality, it is hard to find the case that human is exposed to only one heavy metal. We designed a cross-sectional study using Korean Research Project on the Integrated Exposure Assessment (KRIEFS) data to investigate the renal effects of multiple metal exposure in general population. We used blood Pb and urinary Cd as exposure measures, and urinary N-acetyl-ß-D-glucosaminidase (NAG) and ß2-microglobulin (ß2-MG) as renal tubular impairment outcome. We conducted linear regression to identify the association between each heavy metal and urinary NAG and ß2-MG. And then, we conducted linear regression including the interaction term. Of 1953 adults in KRIEFS (2010~2011), the geometric mean of blood Pb and urinary Cd concentration was 2.21 µg/dL (geometric SD = 1.49 µg/dL) and 1.08 µg/g cr (geometric SD = 1.98 µg/g cr), respectively. In urinary Cd, the strength of the association was also high after adjusting (urinary NAG: ß = 0.44, p < 0.001; urinary ß2-MG: ß = 0.13, p = 0.002). Finally, we identified the positive interactions for the two renal biomarkers. The interaction effect of the two heavy metals of ß2-MG was greater than that of NAG. It is very important in public health perspective if the low level exposure to multiple heavy metals has an interaction effect on kidney. More epidemiological studies for the interaction and toxicological studies on the mechanism are needed.

Association of current phthalate exposure with neurobehavioral development in a national sample.

BACKGROUND: Previous studies have indicated that phthalate exposure may influence the development of children, but the current data are limited, and controversy remains regarding the sex-specific and age-specific effects of phthalate exposure. METHODS: We investigated the sex- and age-specific associations of current phthalate exposure with neurobehavioral development scores in a nationally representative sample of 6-18-year-olds participating in the Korean Environmental Health Survey in Children and Adolescents (KorEHS-C). Neurobehavioral development was assessed using the Korean Child Behavior Checklist (CBCL, N=1723) and the Korean Attention Deficit Hyperactivity Disorder Rating Scale (ARS, N=867). We measured the concentrations of phthalate metabolites in urine samples using high-performance liquid chromatography tandem mass spectrometry. The associations between urine phthalate metabolite concentrations and neurobehavioral development were examined by survey regression analysis for complex sampling and penalized regression splines using a generalized additive model. RESULTS: Survey regression analysis revealed that a higher mono-n-butyl phthalate (MnBP) level was associated with social (ß=0.60; 95% confidence interval=0.15-1.05), thought (0.55; 0.08-1.03), and attention (0.68; 0.21-1.14) problems on the CBCL. A significant association was found between the MnBP level and the ARS hyperactivity subscale score (0.42; 0.05-0.58). Higher levels of MnBP (0.87; 0.20-1.54), mono-2-ethyl-5-oxohexyl phthalate (MEOHP, 0.61; 0.11-1.11) and mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP, 0.51; 0.04-0.97) were associated with an increase in thought problems among the girls. Among the younger children aged 6-11 years, significant positive associations between the MnBP (0.71; 0.09-1.33), MECPP (0.74, 0.14-1.34), MEOHP (0.65; 0.10-1.20), and MEHHP (0.71; 0.21-1.21) levels and social problems and between the MnBP (1.11; 0.37-1.84), MEOHP (0.64; 0.13-1.15), and MEHHP (0.66; 0.18-1.14) levels and attention problems were observed. The penalized regression splines for the age-specific relationships between the urinary MnBP, MEOHP, and MEHHP levels and social and attention problems exhibited positive supralinear relationships with downward curvature in the 6-11 year age group. In contrast, the score for social problems exhibited nearly linear relationships with these levels in the 12-18 year age group. CONCLUSIONS: In this national sample, increased phthalate exposure exhibited supralinear associations with social, thought and attention problems in children aged 6-11 years, who showed greater vulnerability to phthalate exposure. The results highlight the need for the environmental regulation of phthalate exposure in younger children, even at low dosages.