Heavy metal exposure is increasingly linked to impaired childhood growth, but the biological mechanisms are poorly understood. Here, we assessed associations between heavy metal exposure and growth impairment (idiopathic short stature [ISS] and growth hormone deficiency [GHD]) in 36 children (24 cases, 12 controls, males 41.7%), identifying related alterations in circulating exosomal miRNAs. Blood/urine concentrations of nine metals, including Pb, As, and Hg were measured, and serum exosomal miRNAs were profiled via sequencing. Elevated heavy metal exposure was associated with significantly increased proportions of ISS and GHD. Specifically, high blood Pb was associated with ISS (p = 0.01) and high urinary As with overall short stature (p = 0.03). Elevated urinary Hg showed a marginal association with GHD (p = 0.07). Differentially expressed miRNAs were identified: hsa-miR-4488 was downregulated in high-Pb and ISS groups, whereas hsa-miR-133a-3p and hsa-miR-4516 were upregulated in high urinary Hg/As and GHD groups. Predicted targets of these miRNAs involved growth hormone (GH)-insulin-like growth factor-1 (IGF-1) signaling and endochondral ossification. In conclusion, Pb, As, and Hg exposures were associated with impaired growth in children. The dysregulation of related miRNAs suggests biological mechanisms involving both local growth-plate dysfunction and GH-IGF1 signaling disruption.

Background/Objectives: Congenital cleft earlobes are a rare deformity with variable degrees of severity. Because no widely accepted classification or corrective methods exist, we report a case of a 7-year-old boy who presented with a right defective-type cleft earlobe that was successfully reconstructed. We also elucidate the various types of congenital cleft earlobes and corrective methods through a scoping review of the literature. Methods: PubMed searches were performed using the terms ear deformity and cleft earlobe. We analyzed 14 articles to establish a classification system for congenital cleft earlobe and to identify appropriate corrective methods. Results: Our case was successfully reconstructed using a simple local flap technique that can be easily applied to defective-type cleft earlobes of moderate to severe degree. Based on this case and our systematic analysis, we have synthesized existing classification systems and surgical techniques for correcting congenital cleft earlobes according to subtype. Conclusions: We present a unified classification system for congenital cleft earlobes consisting of four subtypes based on external appearance: defective type, simple type, tag with or without hypoplasia, and triple lobe. Various reconstructive techniques-including simple suture, Z-plasty, Y-V advancement, and flap procedures-can be applied according to the specific earlobe subtype.

Emerging evidence indicates that environmental exposure to per- and polyfluoroalkyl substances (PFASs) may influence lipid metabolism, though studies on adolescents remain scarce. This study aimed to investigate the association between PFAS mixture exposure and lipid profiles in Korean adolescents. Using data from the Korean National Environmental Health Survey (2018–2020), we analyzed 824 adolescents aged 12–17 years. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorodecanoic acid (PFDeA), and lipid profiles were assessed. In multivariate regression models, PFDeA and PFNA were positively associated with elevated total cholesterol and low-density lipoprotein cholesterol levels, and PFDeA was associated with hypercholesterolemia risk in boys. In girls, PFDeA was associated with higher high-density lipoprotein cholesterol and lower triglycerides, though no significant association with hypercholesterolemia risk was observed. Bayesian kernel machine regression demonstrated positive associations between PFAS mixture exposure and hypercholesterolemia risk in boys but not in girls. The quantile g-computation model also demonstrated an odds ratio (OR) of 1.47 (95% CI: 0.99–2.19, p = 0.057) for PFAS mixture exposure in boys, suggesting borderline statistical significance. These findings suggest that PFAS exposure may disrupt lipid metabolism, elevating hypercholesterolemia risk in adolescents, particularly boys.

Disclosure: M. Shin: None. S. Kim: None. Background: Exposure to heavy metals is a growing public health concern, particularly for its potential impact on childhood growth. However, the relationship between heavy metal exposure and growth outcomes, such as short stature, idiopathic short stature (ISS), and growth hormone deficiency (GHD), remains poorly understood. This study aimed to evaluate the association between heavy metal exposure and these growth-related conditions in children. Methods: This cross-sectional study included 24 children with short stature and 12 controls. Blood and urinary levels of heavy metals—mercury (Hg), lead (Pb), arsenic (As), aluminum (Al), cesium (Cs), cadmium (Cd), antimony (Sb), thallium (Tl), and nickel (Ni)—were measured and categorized into tertiles or dichotomized at the median. The prevalence of short stature, ISS, and GHD was compared between groups using the Fisher’s exact test. Odds ratios (ORs) for short stature in the highest versus lowest tertile of heavy metal exposure were calculated after adjusting for sex and age. Quantile G-computation models were used to assess the combined effects of metal mixtures on growth outcomes. Results: The prevalence of short stature, ISS, and GHD increased significantly with higher heavy metal exposure levels. A significantly higher prevalence of short stature was observed in children with elevated blood Pb (50% vs. 83.3%, P=0.03) and urinary As levels (50% vs. 83.3%, P=0.03). ISS prevalence was significantly higher in children with elevated Pb levels (16.7% vs. 55.6%, P=0.01), while GHD prevalence was marginally higher in those with elevated urinary Hg levels (16.7% vs. 44.4%, P=0.07). Adjusted ORs indicated a significant association between high blood Pb levels and ISS and between high urinary As levels and short stature . Quantile G-computation revealed that blood Pb and urinary As were key contributors to ISS, while urinary As and Hg were significant contributors to GHD. Significant associations were observed between heavy metal mixture exposure and both ISS and GHD, with OR of 2.32 (95% CI: 1.12-4.79) for ISS and 3.01 (95% CI: 1.83-2.25) for GHD. Conclusion: This study demonstrates an association between elevated heavy metal exposure and impaired growth outcomes in children, including short stature, ISS, and GHD. These findings highlight the need for targeted interventions to reduce environmental heavy metal exposure and mitigate its impact on pediatric health. Further longitudinal studies are warranted to confirm causality and explore underlying mechanisms. Presentation: Saturday, July 12, 2025

Investigating the impact of urinary mercury and cadmium on anthropometric parameters in Korean children is crucial amid growing concerns about heavy metal exposure and childhood growth. Using data from the Korean National Environmental Health Survey (2015–2017), we assessed age- and sex-specific associations of urinary mercury and cadmium with height and body mass index (BMI) z-scores in 1458 children aged 3–5 (n = 571) and 6–11 years (n = 887). Overall, 5.0% had stunted height (3–5 years: 6.9%, 6–11 years: 3.8%), whereas older children exhibited higher overweight/obesity prevalence (29.2%) than younger ones did (22.2%). In 3–5-year-old boys, urinary mercury correlated negatively with height z-scores (p < 0.001), whereas in girls, urinary cadmium correlated positively (p = 0.015). Boys aged 6–11 years showed positive associations between mercury/cadmium levels and BMI z-scores (p = 0.012). Logistic regression indicated associations between urinary mercury and stunted height likelihood (p = 0.001) and between urinary cadmium and reduced overweight likelihood (p = 0.039) in 3–5-year-old boys. In boys aged 6–11 years, urinary cadmium levels were positively associated with overweight likelihood (p = 0.003). This study underscores the link between elevated urinary mercury, cadmium levels, and growth disruptions in Korean children, emphasizing the need for public health strategies for reducing childhood heavy metal exposure.

AIMS:Recent epidemiologic research has examined the relationship between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and diabetes mellitus with inconclusive findings. In this cross-sectional study, we aimed to explore the association between serum PFAS concentrations and the prevalence of prediabetes and pre-diagnostic diabetes in the general Korean population as well as the combined effects of exposure to mixed PFAS compounds. METHODS:We analyzed data from participants aged ≥19 years enrolled in the Korean National Environmental Health Survey Cycle 4 (2018-2020). Individuals diagnosed with diabetes were excluded to minimize potential bias. We identified cases of pre-diagnostic diabetes based on the HbA1c level ≥6.5% and prediabetes as HbA1c levels of 5.7-6.49%. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were quantified using high-performance liquid chromatography-tandem mass spectrometry. Survey-weighted logistic regression models were used to assess the relationships between PFAS levels and diabetes risk, adjusting for covariates. Additionally, Bayesian kernel machine regression (BKMR) was used to investigate the combined effects of exposure to mixed PFAS compounds. RESULTS:In the study population excluding participants with diagnosed diabetes (n = 2709), the prevalence of pre-diagnostic diabetes and prediabetes was 4.8% and 30.1%, respectively. Significant positive associations were found between serum PFHxS and PFOS quartiles and pre-diagnostic diabetes risk. Likewise, among those without diagnosed or pre-diagnostic diabetes (n = 2579), the highest quartiles of PFDeA, PFHxS, and PFOS and the overall PFAS level were associated with an increased risk of prediabetes compared with the lowest quartiles. BKMR analysis revealed a significant positive association between overall serum PFAS level and prediabetes risk, which was most marked for PFOS. CONCLUSIONS:These findings highlight the potential health implications of PFAS exposure and prediabetes risk. Further research is needed to validate these associations and identify potential mechanistic pathways.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022-2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980-2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

The increasing prevalence of pediatric obesity has emerged as a significant public health concern. Among various contributing factors, exposure to endocrine-disrupting chemicals (EDCs) has gained recognition for its potential role. EDCs, including bisphenols, phthalates, per- and polyfluoroalkyl substances, polycyclic aromatic hydrocarbons, and organochlorines, disrupt hormonal regulation and metabolic processes, contributing to alterations in fat storage, appetite regulation, and insulin sensitivity. This study offers a comprehensive review of the current research linking EDC exposure to pediatric obesity by integrating the findings from experimental and epidemiological studies. It also addresses the complexities of interpreting this evidence in the context of public health, highlighting the urgent need for further research.

BackgroundOver the last few decades, there has been growing evidence of earlier onset and progression of puberty worldwide. This population-based longitudinal cohort study aimed to analyze the change in the annual incidence rate of central precocious puberty (CPP) among Korean children over the most recent decade, using the national registry data.MethodThe International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) and insurance claims for gonadotropin-releasing hormone agonist (GnRHa) treatment were used to identify CPP patients who were using the Korean Health Insurance Review & Assessment Service (HIRA) database between 2008 and 2020. Patients who began GnRHa therapy before the age of 9 and 10 for girls and boys, respectively, were included in the study.ResultsA total of 6,906 boys and 126,377 girls were diagnosed with CPP between 2008 and 2020. The annual incidence of CPP increased by 83.3 times in boys (from 1.2 to 100 per 100,000 persons) and by 15.9 times in girls (from 88.9 to 1414.7 per 100,000 persons). The age-specific annual incidence of CPP increased remarkably more in older children than in younger ones; the 2020 CPP incidence among 9-year-old boys and 8-year-old girls reached 705.2 and 7,967.3 per 100,000 persons, respectively. The annual prevalence of CPP in boys and girls increased from 2.7 to 206.5 (76.5 times) and from 141.8 to 3439.9 (24.3 times) per 100,000 persons, respectively.ConclusionBased on GnRHa treatment insurance claims, our study suggests that the annual incidence of CPP has substantially increased in Korea during the past 13 years. These findings highlight the importance of meticulous judgment by doctors in determining GnRHa treatment.

Objectives: Existing literature provides limited information on the association between childhood obesity and polycyclic aromatic hydrocarbons (PAHs), which are potentially obesogenic. We examined the association between urinary concentrations of PAH metabolites and obesity in the Korean pediatric population. Methods: We analyzed the data of 2286 children/adolescents aged 3–17 years who participated in the Korean National Environmental Health Survey between 2015 and 2017. Urinary concentrations of 2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 1-hydroxypyrene were assayed using gas chromatography–mass spectrometry. Overweight/obesity was defined as a body mass index (BMI) for age ≥85th percentile. Multiple linear and logistic regression models were used to analyze the relationship of BMI z-score and overweight with urinary concentrations of PAH metabolites after adjusting for age, sex, household income, parental education level, physical activity, fast-food consumption, and environmental tobacco smoke exposure. Results: BMI z-score was positively associated with 2-naphthol concentrations in children aged 6–11 and 12–17 years and with 1-hydroxypyrene concentrations in children aged 6–11 years. In the overall population, a significant rise in odds ratios for overweight/obesity across 2-naphthol quartiles was noted. Specifically, the 3rd and 4th quartiles displayed odds ratios of 1.39 [1.03, 1.88] and 1.46 [1.08, 1.99] respectively, compared to the 1st quartile (P-for-trend = 0.006). Similar associations between 2-naphthol and overweight/obesity status were observed in the 6–11- and 12–17-year age groups. There was little evidence of an association between overweight/obesity and other PAH hydroxy derivatives. Conclusions: PAH exposure may be associated with increased childhood adiposity, a potential risk factor for adult obesity and adverse metabolic outcomes.

Congenital cleft earlobes are a rare type of deformity. The degree of cleft earlobe deformity can vary. For this reason, there are no widely accepted classifications and corrective methods. Herein, we report a case of a 7-year-old boy who presented with right defective type cleft earlobe. Moreover, we clarify the various types of congenital cleft earlobes and possible corrective methods reported until now. We performed PubMed searches to identify all studies on ‘ear deformity’ and ‘cleft earlobe’, and analyzed 14 articles to organize the classification of congenital cleft earlobe and their corrective methods. The case was successfully reconstructed with a simple local flap technique, and our technique can be easily applied in defective type cleft earlobe of moderate to severe degree. Prompted by this case, we have organized two classifications and the surgical techniques to correct congenital cleft earlobe from a scoping review of the literature. The congenital cleft earlobe can be classified into four subtypes according to the external appearance: defective type, simple type, tag, and cleft with or without hypoplasia, and triple lobe. Various reconstructive methods including simple suture, Z-plasty, Y–V advancement, and several flap techniques have been described according to the 4 subtypes of congenital cleft earlobes.

Abstract Disclosure: S. Kim: None. Objectives: Recent epidemiologic research has studied the relationship between Per- and polyfluoroalkyl substances (PFAS) and diabetes mellitus (DM), yet the findings have been inconsistent. We examined the association between serum PFAS concentrations and the prevalence of diabetes in the Korean general population. Methods: We analyzed the data of 2,993 participants aged ≥ aged 19 years who participated in the Korean National Environmental Health Survey (KoNEHS) Cycle 4 (2018-2020). Serum concentrations of 5 PFAS [perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS)] were quantified using using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Individuals with DM were identified by the presence of one or more of the following conditions: (1) self-reported diabetes; (2) use of a glucose-lowering medication; (3) hemoglobin A1c ≥6.5%. Multiple logistic regression models were used to examine the associations between PFAS concentrations and DM after adjusting for age, sex, central obesity, education levels, smoking status, alcohol consumption, physical activity, and frequency of delivery food consumption. Bayesian kernel machine regression (BKMR) was used to investigate the independent and combined relationship between PFAS exposure and DM prevalence. Results: The prevalence of DM was 11.8%. The odds ratios (95% confidence intervals) of DM in the highest quartile relative to the lowest were 0.85 (0.56, 1.32) for PFOA, 1.39 (0.87, 2.23) for PFNA, 0.95 (0.63, 1.43) for PFDeA, 1.52 (1.01, 2.35) for PFHsS, 1.26 (0.77, 2.05) for PFOS and 1.01 (0.66, 1.55) for the sum of PFAS. According to the BKMR model results, PFNA and PFHxS were positively associated with an increased risk of DM, while PFOA and PFDeA were negatively associated. The risk of DM appeared to rise in correlation with the PFAS mixture quartile, but the association was statistically insignificant. Conclusions: Different associations between PFAS concentrations and DM were observed according to the PFAS isomers. Further studies are needed to clarify the mechanism of action of different PFAS isomers on the development of DM. Presentation: Thursday, June 15, 2023

See the article "Predictors of associated and multiple autoimmunity in children and adolescents with type 1 diabetes mellitus" on page 192.

Background: There is a lack of recent research on the changes in risk factors for metabolic syndrome (MetS) in the Asian pediatric population. We aimed to determine the 12-year trends in the prevalence of MetS and relevant lifestyle factors such as smoking, exercise, and calorie intake among Korean adolescents.Methods: We investigated trends in MetS and lifestyle factors among 6,308 adolescents aged 12 to 18 years from the Korea National Health and Nutrition Examination Survey, 2007 to 2018.Results: The prevalence of MetS was stable from 2007 to 2018 (1.7% to 2.2%). There were significant increases in the prevalence of central obesity (from 8.1% to 11.2%, P=0.012) and hyperglycemia (from 5.3% to 10.4%, P<0.001) and decreases in hypo-high-density lipoprotein (HDL)-cholesterolemia (from 22.4% to 14.8%, P<0.001). Total calorie intake and calorie intake from fat significantly increased (P<0.001), whereas calorie intake from carbohydrates significantly decreased (P<0.001) during the study period. The proportions of tobacco smokers and regular walkers significantly decreased from 2007 to 2018. After controlling for all covariates, total calorie intake was positively correlated with waist circumference (P<0.05). HDL-cholesterol was negatively associated with carbohydrate consumption (P<0.01) and positively associated with fat consumption (P<0.001). Regular walking and regular strength training were associated with lower waist circumference (P<0.05). Smoking was associated with lower fasting glucose levels (P<0.01).Conclusion: Although the prevalence rate of MetS is stable among Korean adolescents, the prevalence of central obesity and hyperglycemia has increased greatly in the recent decade. Public education on proper dietary intake and lifestyle modification is required.

This study was aimed to evaluate the association between urinary bisphenol A (BPA) levels and risk of obesity in Korean adults. We analyzed data from the Korean National Environmental Health Survey (KoNEHS) Cycle 2 (2012–2014) and Cycle 3 (2015–2017). A total of 10,021 participants aged ≥ 19 years were included. Urine dilution was corrected by the covariate-adjusted standardization (CAS) method. We performed meta-analysis, logistic regression analysis by matching all covariates with a 1:1 propensity score, and a 4-knot restricted cubic spline plot model to calculate the odds ratios (ORs) for obesity according to natural log-transformed BPA levels. Mean urinary BPA concentration was 1.12 µg/L in KoNEHS Cycle 2 and 1.32 µg/L in Cycle 3. BPA levels were significantly higher among obese adults than among non-obese adults in both KoNEHS Cycles 2 and 3. In pooled data of KoNEHS Cycles 2 and 3, BPA showed significant positive associations with ORs for obesity in both sexes, which were more prominent in females (linear) than in males (non-linear). These associations were confirmed in spline analyses. CAS-applied BPA concentrations were positively associated with obesity in nationwide representative samples of Korean adults. Further studies are warranted to confirm and elucidate the underlying mechanism.

Off-vertical axis rotation (OVAR) is a laboratory test to assess the otolith function. This study aimed to analyze the parameters of OVAR in patients with unilateral vestibular hypofunction (UVH) and bilateral vestibulopathy (BVP), and to correlate the parameters of OVAR with those of VEMPs. Ten healthy volunteers, 41 UVH, and 13 BVP patients performed OVAR. Bias component (BIC) and modulation component (MOC) of UVH and BVP patients were compared with those of healthy controls. BIC and MOC were correlated with amplitude and interaural difference (IAD) of cervical VEMP (cVEMP) and ocular VEMP (oVEMP). In UVH patients, the direction of BICs to affected side rotation were reversed and the absolute value of BICs were decreased when they were compared to healthy controls. In BVP patients, BICs were markedly attenuated. MOCs were not changed in UVH and BVP patients. There was no statistically significant correlation between VEMPs and OVAR.

Phthalate exposure has been reported to be more associated with obesity in children than in adults. The concentration of di(2-ethylhexyl)phthalate (DEHP) was high temporal variability in spot urine, so additional tools of assessing DEHP exposure were required. Therefore, we used relative metabolite ratios (RMRs) as well as concentrations, and RMRs did not need to be corrected to the creatinine concentration. We aimed to evaluate the levels of urinary DEHP metabolites and their RMRs in obese children in South Korea, and to investigate the potential of RMRs for assessing the risks for childhood obesity. We analyzed the four urinary DEHP metabolites (mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)) in 240 children aged 5–16 years, using isotope dilution GC-MS/MS. The children were placed into three groups (“normal weight,” “overweight,” and “obese”) according to body mass index (BMI) percentiles. We statistically compared the concentrations and RMRs of DEHP metabolites among these groups. The obese group had lower MEHP levels, and higher secondary metabolite (MEHHP, MEOHP, and MECPP) levels, than the normal weight group. DEHP metabolite levels did not differ significantly between the normal weight and obese groups, whereas RMRA2 (as the ratio of the molar concentrations of MEOHP to MEHHP) was found to be negatively associated with BMI percentile (β= −0.236, p <0.01) and weight percentile (β= −0.282, p<0.001). Therefore, we suggest that RMRs are an additional tool for assessing the health risks of DEHP.