Association between long-term PM2.5 exposure and risk of Kawasaki disease in children: A nationwide longitudinal cohort study.

BACKGROUND: Based on previous studies suggesting air pollution as a potential risk factor for Kawasaki Disease (KD), we examined the association of long-term exposure to childhood fine particulate matter (PM2.5) with the risk of KD. METHODS: We used National Health Insurance Service-National Sample Cohort data from 2002 to 2019, which included beneficiaries aged 0 years at enrollment and followed-up until the onset of KD or age 5 years. The onset of KD was defined as the first hospital visit record with a primary diagnostic code of M30.3, based on the 10th revision of the International Classification of Diseases, and with an intravenous immunoglobulin (IVIG) prescription. We assigned PM2.5 concentrations to 226 districts, based on mean annual predictions from a machine learning-based ensemble prediction model. We performed Cox proportional-hazards modeling with time-varying exposures and confounders. RESULTS: We identified 134,634 individuals aged five or less at enrollment and, of these, 1220 individuals who had a KD onset and an IVIG prescription during study period. The average annual concentration of PM2.5 exposed to the entire cohort was 28.2 µg/m³ (Standard Deviation 2.9). For each 5 µg/m³ increase in annual PM2.5 concentration, the hazard ratio of KD was 1.21 (95% CI 1.05-1.39). CONCLUSIONS: In this nationwide, population-based, cohort study, long-term childhood exposure to PM2.5 was associated with an increased incidence of KD in children. The study highlights plausible mechanisms for the association between PM2.5 and KD, but further studies are needed to confirm our findings.

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.

BMI trajectory and inflammatory effects on metabolic syndrome in adolescents.

BACKGROUND: Various life course factors can affect susceptibility to diseases during adolescence and adulthood, and those relationships are complex. However, few studies have assessed the potential mediating factors. Therefore, we assessed the mediating effects of factors related to growth and inflammation between perinatal factors and metabolic syndrome risk during adolescence. METHODS: The study was conducted on adolescents who participated in the follow-up in the Ewha Birth and Growth Cohort. We considered the ponderal index (PI) as a perinatal factor and the continuous metabolic syndrome score (cMetS) as the outcome and confirmed the mediating effects of body mass index (BMI) trajectory pattern in childhood and inflammation levels by using the PROCESS macro for SAS. RESULTS: Although the direct effect of BMI trajectory on the relationship between PI and cMetS was not significant (0.545), the indirect effect was significant (1.044). In addition, the indirect effect was statistically significant in the pathways mediating the BMI trajectory pattern and inflammation (ß = 1.456). CONCLUSIONS: The direct and indirect effects on the relationship between PI and cMetS suggest that childhood factors related to growth may be involved in disease susceptibility. Therefore, appropriate interventions for the management of obesity during the growth phase are necessary. IMPACT: Unlike other existing studies, this study assessed multiple mediating effects by considering the BMI trajectory pattern and inflammatory indexes as mediating factors between the ponderal index and the continuous metabolic syndrome score during adolescence. We found significant indirect effects of the BMI trajectory between PI and cMetS, and also significant indirect effects in the pathways mediating the BMI trajectory and hs-CRP. The significant indirect mediating effects support that childhood factors related to growth may be involved in disease susceptibility.

Prospective association between phthalate exposure in childhood and liver function in adolescence: the Ewha Birth and Growth Cohort Study.

BACKGROUND: Phthalate exposure is ubiquitous due to the widespread use of plastic products in daily life, and affects several health outcomes, including metabolic diseases. In this study, we evaluated the effects of phthalate exposure in childhood on liver function in adolescence.  METHODS: Among 164 Ewha Birth and Growth Cohort Study participants followed up during two exposure periods (when the children were aged 3-5 and 7-9 years), 126 were followed up at age 10-15 years. To investigate the relationship between phthalate exposure during the two periods and liver enzyme levels (ALT, AST, γ-GTP) in adolescence, differences between groups and the dose-response relationship were analyzed. In addition, we investigated differences in liver enzymes between groups based on the combined exposure levels (high or low) during the two periods. The interaction effect between phthalates and BMI on liver enzyme levels was evaluated, stratified by sex.  RESULTS: In the 3-5 year-old exposure period, ALT levels tended to increase as MECPP levels increased, while γ-GTP levels tended to increase as MiBP, MnBP, and ∑DBP levels increased. In addition, the group exposed to consistently high levels of phthalates at both time points had higher liver enzyme levels compared to the group that had lower exposure. In particular, the interaction effect between some phthalate metabolites and BMI in 3-5 year olds affected AST and γ-GTP levels in adolescence only in girls. CONCLUSIONS: Exposure to phthalates in daily life during childhood affects liver enzyme levels in adolescence. Elevated liver enzyme levels are associated with the development of metabolic syndrome, implying that attention should be paid to phthalate exposure during childhood.

Mortality Risk within 14 Days after Coronavirus Disease 2019 Diagnosis in Dementia Patients: A Nationwide Analysis.

INTRODUCTION: The study evaluated the increased mortality risk within 14 days of coronavirus disease 2019 (COVID-19) diagnosis in dementia patients. METHODS: This retrospective study was conducted from February to April 2020 using the COVID-19 patients' database from the Korea Disease Control and Prevention Agency. The risk factors for early death within 14 days were determined using generalized logistic regression performed in a stepwise manner. Dementia patients diagnosed with COVID-19 were used for the study. The propensity score-matched cohort was included as controls. The differences in mortality within 14 days after COVID-19 diagnosis between the dementia patients and controls were evaluated. RESULTS: We enrolled 5,349 COVID-19 patients from the database; 224 had dementia as comorbidity. The mortality rate within 14 days after COVID-19 diagnosis in dementia patients and the controls was 23.7% versus 1.7%, respectively, before propensity score matching (PSM) (p < 0.001), and 23.7% versus 9.2% after PSM (p < 0.001). The hazard ratio (HR) for mortality within 14 days in COVID-19 patients with dementia was significant even after PSM (HR 5.104, 95% confidence interval 2.889-5.673, p < 0.001). The survival curve of dementia patients was steeply inclined within 14 days after COVID-19 diagnosis, resulting in 70.7% of all deaths in dementia patients. CONCLUSIONS: COVID-19 patients with dementia had a higher risk of early death within 14 days. Thus, prompt intervention is necessary for dementia patients after COVID-19 diagnosis.

The Association of Ovarian Reserve with Exposure to Bisphenol A and Phthalate in Reproductive-aged Women.

BACKGROUND: Exposure to endocrine disrupting chemicals (EDCs) that influence the hormonal and homeostatic systems is known to be associated with gynecologic health risks in many countries. In this study, we evaluated exposure to EDCs associated with diminished ovarian reserve (DOR) and gynecologic health risks. METHODS: This cross-sectional study was performed from September 2014 to November 2014 and included 307 Korean reproductive-aged women. Anthropometric measurements, laboratory tests with urine and blood sampling and pelvic ultrasound examinations were performed. RESULTS: Urinary bisphenol A (BLA) level was significantly higher in the DOR group with anti-Müllerian hormone lower than 25 percentile (1.89 ± 2.17 ug/g and 1.58 ± 1.08 ug/g, P < 0.05). Urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate and mono-N-butyl phthalate, and substrates of phthalate were evaluated and no significant difference was observed between the DOR group and non-DOR group. Logistic regression analysis suggested an increase in infertility in high BPA exposure group and the odds ratio (OR, 4.248) was statistically significant after adjustment for age, birth control pills, and the age of menarche, parity, and waist circumference. High phthalate exposure was associated with endometrial polyp after adjustment (OR, 2.742). CONCLUSION: BPA exposure might be associated with DOR and infertility. Meanwhile, endometrial polyp is increased in women with high phthalate exposure. Therefore, the risk of exposures to EDCs for reproduction should be a matter of concern in reproductive-aged women.

Macrophage-derived progranulin promotes allergen-induced airway inflammation.

BACKGROUND: Progranulin (PGRN), mainly produced by immune and epithelial cells, has been known to be involved in the development of various inflammatory diseases. However, the function of PGRN in allergic airway inflammation has not been clearly elucidated, and we investigated the role of PGRN in allergic airway inflammation. METHODS: Production of PGRN and various type 2 cytokines was evaluated in mouse airways exposed to house dust mite allergen, and main cellular sources of these molecules were investigated using macrophage, airway epithelial cell, and NKT cell lines. We elucidated the role of PGRN in allergic airway inflammation in mouse models of asthma using macrophage-derived PGRN-deficient mice and NKT cell knockout mice by evaluating cytokine levels in bronchoalveolar lavage fluids and histopathology. We also supplemented recombinant PGRN in the mouse models to confirm the role of PGRN in allergic airway inflammation. RESULTS: PGRN production preceded other cytokines, mainly from macrophages, in the airway exposed to allergen. PGRN induced IL-4 and IL-13 production in NKT cells and IL-33 and TSLP in airway epithelial cells. PGRN-induced Th2 cytokine production was abolished in NKT-deficient mice. Finally, allergic inflammation was significantly attenuated in allergen-exposed PGRN-deficient mice, but inflammation was restored when recombinant PGRN was supplemented during the allergen sensitization period. CONCLUSION: The presence of macrophage-derived PGRN in airways in the early sensitization period may be critical for mounting a Th2 immune response and for following an allergic airway inflammation pathway via induction of type 2 cytokine production in NKT and airway epithelial cells.

Development of novel NLRP3-XOD dual inhibitors for the treatment of gout.

Gout is a crystalline-related arthropathy caused by the deposition of monosodium urate (MSU). Acute gouty arthritis is the most common first symptom of gout. Studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome as pattern recognition receptors can be activated by uric acid crystallization, triggering immune inflammation and causing acute gouty arthritis symptoms. Currently, the treatment of gout mainly includes two basic methods: reducing uric acid and alleviating inflammation. In this paper, 22 novel benzoxazole and benzimidazole derivatives were synthesized from deoxybenzoin oxime derivatives. These compounds have good inhibitory effects on NLRP3 and XOD screened by our research group in the early stage. The inhibitory activities of XOD and NLRP3 and their derivatives were also screened. Notably, compound 9b is a multi-targeting inhibitor of NLRP3 and XOD with excellent potency in treating hyperuricemia and acute gouty arthritis.

Prenatal exposure to mixtures of heavy metals and neurodevelopment in infants at 6 months.

BACKGROUND: Exposure to mixture of neurotoxic metals such as lead, mercury and cadmium occurs at a specific point of time. When exposed to metal mixtures, one metal may act as an agonist or antagonist to another metal. Thus, it is important to study the effects of exposure to a combination of metals on children's development using advance statistical methods. OBJECTIVES: In this study, we explored the effects of prenatal metal exposure including lead, mercury and cadmium in early pregnancy (12-20 weeks), late pregnancy (>28 weeks), and at birth on neurodevelopment of infants at 6 months of age. METHODS: We included 523 eligible mother-child pairs from the mothers and children environmental health (MOCEH) study, a prospective birth cohort study in Korea. We used linear regression, Bayesian kernel machine regression (BKMR) and generalized additive models (GAM), to evaluate the effects of exposure to metal mixtures on neurodevelopment of infants aged 6 months. The Korean version of Bayley scale of infant and toddler development-II was used to measure the child's neurodevelopment. RESULTS: Linear regression models showed a significant negative effect of lead exposure during late pregnancy on the mental development index (MDI) [ß = -2.51 (-4.92, -0.10)] scores of infants aged 6 months following co-exposure to mercury. Further, linear regression analysis showed a significant interaction between late pregnancy lead and mercury concentrations. BKMR analysis showed similar results as those obtained in linear regression models. These results were also replicated in the GAM. Stratification analysis showed that greater than 50 percentile concentration of mercury in late pregnancy potentiated the adverse effects of lead in late pregnancy on MDI [ß = -4.33 (-7.66, -1.00)] and psychomotor development index (PDI) [ß = -5.30 (-9.13, -1.46)] at 6 months of age. Prenatal cadmium exposure did not show a significant association with MDI and PDI at 6 months in the linear regression or BKMR analysis. CONCLUSION: Based on all the statistical methods used, we demonstrated the effect of combined exposure to metals on the neurodevelopment of infants aged 6 months, with significant interaction between lead and mercury.

Adverse effects of prenatal mercury exposure on neurodevelopment during the first 3 years of life modified by early growth velocity and prenatal maternal folate level.

BACKGROUND AND AIMS: Previous studies have suggested that mercury exposure and folate levels during pregnancy may influence early childhood neurodevelopment. Rapid catch-up growth in children is associated with an increased risk of pathological nervous system development. We evaluated whether the association between prenatal folate and mercury-related neuropsychological dysfunction was modified by growth velocity during childhood. METHODS: The Mothers and Children's Environmental Health (MOCEH) birth cohort study began in 2006 and by 2010, 1751 women had been enrolled before the second trimester of their pregnancy along with their partners. Participants visited the research center at birth and 6, 12, 24, and 36 months. We measured mercury levels in maternal and cord blood and folate in maternal serum. Questionnaires to evaluate the environment and health of their child were administered and anthropometric factors including body weight and height were measured. Certified investigators used the Bayley test to measure neurobehavioral outcomes. We calculated postnatal growth change as the change in infant weight for-age z-score between birth and 3 years. Multiple linear regression and mixed models were used to examine the association between mercury exposure and children's neurodevelopment as well as the modifying effects of folate and growth velocity. RESULTS: A total of 30.6% of children experienced rapid growth during the first 3 years of life. Median values of mercury in the low folate group were significantly higher in rapid growers (3.41 µg/L in maternal blood and 5.63 µg/L in cord blood) than in average/slow growers (3.05 µg/L in maternal blood and 5.19 µg/L in cord blood). Rapid growers were also significantly associated with decreased psychomotor development scores during the first 3 years of life and with having mothers who had low prenatal folate levels, even after adjusting for potential confounders. CONCLUSION: Prenatal mercury exposure adversely affects infant neurodevelopment and is associated with rapid growth during the first 3 years of life. This effect was limited to children whose mothers had low prenatal folate levels, suggesting a protective effect of folate against developmental neurotoxicity due to mercury exposure and rapid catch-up growth.

Association between pre-and postnatal growth and longitudinal trends in serum uric acid levels and blood pressure in children aged 3 to 7 years.

BACKGROUND: Uric acid has been identified as an important factor in the development of hypertension. If low birth weight (LBW) combined with catch-up growth (CUG) is associated with continuously elevated serum uric acid levels (SUA) level trajectories, LBW children who experience CUG may have an increased risk of hypertension later in life. Therefore, this cohort study analyzed longitudinal trends in SUA levels and changes in blood pressure in relation to pre- and postnatal growth over an extended follow-up period. METHODS: This prospective cohort study of 364 children from the Ewha Birth and Growth Cohort assessed the effects of pre- and postnatal growth status on SUA at 3, 5, and 7 years of age using a linear mixed model and the change in blood pressure over the 7-year follow-up period using a generalized linear model (analysis of covariance). CUG was defined as a change in weight (between birth and age 3) with a z-score > 0.67 for LBW subjects. The multivariate model considered sex, gestational age, and uric acid, height, and weight at 3 years of age. RESULTS: Children with LBW and CUG had higher SUA for the first 7 years of life compared to the normal birth weight group. This trend was particularly evident when comparing LBW children at term to children with normal birth weight. Within the group with LBW at term, children with greater CUG had higher SUA than children with normal birth weight, and this difference increased with age. Changes in the systolic blood pressure between 3 and 7 years of age were higher by 7.9 mmHg in children who experienced LBW and CUG compared with those who had a normal birth weight after adjusting for sex, gestational age, and height, weight, and uric acid at 3 years of age (p-value = 0.08). CONCLUSIONS: The uric acid levels and changes in systolic blood pressure were consistently higher among LBW children who experienced CUG compared with NBW children for the first 7 years of life. LBW children who experienced greater weight gain from birth to age 3 had even higher uric acid levels compared with NBW children.

Endothelial Sox17 promotes allergic airway inflammation.

BACKGROUND: IL-33, levels of which are known to be increased in patients with eosinophilic asthma and which is suggested as a therapeutic target for it, activates endothelial cells in which Sry-related high-mobility-group box (Sox) 17, an endothelium-specific transcription factor, was upregulated. OBJECTIVE: We investigated the relationship between Sox17 and IL-33 and the possible role of Sox17 in the pathogenesis of asthma using a mouse model of airway inflammation. METHODS: We used ovalbumin (OVA) to induce airway inflammation in endothelium-specific Sox17 null mutant mice and used IL-33 neutralizing antibody to evaluate the interplay between IL-33 and Sox17. We evaluated airway inflammation and measured levels of various cytokines, chemokines, and adhesion molecules. We also carried out loss- or gain-of-function experiments for Sox17 in human endothelial cells. RESULTS: Levels of IL-33 and Sox17 were significantly increased in the lungs of OVA-challenged mice. Anti-IL-33 neutralizing antibody treatment attenuated not only OVA-induced airway inflammation but also Sox17 expression in pulmonary endothelial cells. Importantly, endothelium-specific deletion of Sox17 resulted in significant alleviation of various clinical features of asthma, including airway inflammation, immune cell infiltration, cytokine/chemokine production, and airway hyperresponsiveness. Sox17 deletion also resulted in decreased densities of Ly6chigh monocytes and inflammatory dendritic cells in the lungs. In IL-33-stimulated human endothelial cells, Sox17 showed positive correlation with CCL2 and intercellular adhesion molecule 1 levels. Lastly, Sox17 promoted monocyte adhesion to endothelial cells and upregulated the extracellular signal-regulated kinase-signal transducer and activator of transcription 3 pathway. CONCLUSION: Sox17 was regulated by IL-33, and its genetic ablation in endothelial cells resulted in alleviation of asthma-related pathophysiologic features. Sox17 might be a potential target for asthma management.

The Association Between Mercury Exposure and Atopic Dermatitis in Early Childhood: A Mothers and Children's Environmental Health Study.

BACKGROUND: Atopic dermatitis is a chronic and relapsing inflammatory skin disease. Although mercury has been suggested as a risk factor, the underlying mechanism and the relationship between mercury and atopic dermatitis remains unclear. The objective of the present study was to investigate the relationship between mercury exposure and the presence of atopic dermatitis in early childhood. METHODS: This study is part of the prospective Mothers and Children's Environmental Health cohort study. A total of 1,751 pregnant women were enrolled in Mothers and Children's Environmental Health. After delivery, children were followed up. Blood samples were collected and mothers were asked about the presence of atopic dermatitis in their children via a questionnaire at 6, 12, 24, 36, and 60 months of age. RESULTS: After excluding participants who did not meet the inclusion criteria, a total of 1,061 mother-children pairs were included in the analysis. The geometric mean of mercury concentrations in cord blood was 5.1 µg/L. In adjusted models, cord blood mercury exposure (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 1.0, 1.2 at 12-24 months) and postnatal mercury exposure (OR = 1.2; 95% CI = 1.0, 1.5 at 24-36 months, OR = 1.4; 95% CI = 1.1, 1.8 at 48-60 months) were associated with the presence of atopic dermatitis in children. CONCLUSIONS: Postnatal mercury exposure at 24 months of age increases the risk of atopic dermatitis in children.

Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment.

Recruitment and activation of dendritic cells (DCs) in the lungs are critical for Th2 responses in asthma, and CCL20 secreted from bronchial epithelial cells (BECs) is known to influence the recruitment of DCs. Because asthma is a disease that is closely associated with oxidative stress, we hypothesized that clusterin, an oxidative stress regulatory molecule, may have a role in the development of allergic airway inflammation. The aim of this study was to examine whether clusterin regulates CCL20 production from the BECs and the subsequent DC recruitment in the lungs. To verify the idea, clusterin knockout (Clu(-/-)), clusterin heterogeneous (Clu(+/-)), and wild-type mice were exposed intranasally to house dust mite (HDM) extract to induce allergic airway inflammation. We found that the total number of immune cells in bronchoalveolar lavage fluid and the lung was increased in Clu(-/-) and Clu(+/-) mice. Of these immune cells, inflammatory DCs (CD11b(+)CD11c(+)) and Ly6C(high) monocyte populations in the lung were significantly increased, which was accompanied by increased levels of various chemokines, including CCL20 in bronchoalveolar lavage fluid, and increased oxidative stress markers in the lung. Moreover, HDM-stimulated human BECs with either up- or downregulated clusterin expression showed that CCL20 secretion was negatively associated with clusterin expression. Interestingly, clusterin also reduced the level of intracellular reactive oxygen species, which is related to induction of CCL20 expression after HDM stimulation. Thus, the antioxidant property of clusterin is suggested to regulate the expression of CCL20 in BECs and the subsequent recruitment of inflammatory DCs in the airway.

A prospective cohort study of the association between bisphenol A exposure and the serum levels of liver enzymes in children.

BACKGROUND: Bisphenol A (BPA) is an endocrine disrupter that acts in an estrogen-like manner. Few studies have investigated the association between urinary BPA concentrations and adverse liver function. Additionally, most studies were cross-sectional in nature and included only adults. OBJECTIVES: We evaluated BPA exposure levels and prospectively explored the association between BPA exposure and liver function in children. METHODS: Data were retrieved from the ongoing prospective Ewha Birth and Growth Cohort Study. Urinary BPA concentrations were measured in 164 children at 3-5 and 7-9 years of age. At each visit, fasting blood and urine samples were collected, and questionnaires were completed. The associations between the BPA concentrations at these ages and the serum levels of liver enzymes measured at 10-13 years of age were analyzed (n = 113). Multiple regression analysis was performed with adjustment for covariates. We also explored whether the BPA level exhibited dose-response relationships with liver enzyme levels. RESULTS: The median urinary BPA concentrations were 0.76µg/g creatinine at 3-5 years and 0.61µg/g creatinine at 7-9 years of age. The urinary BPA concentrations at the two ages were correlated significantly (r = 0.23, p < 0.01). The urinary BPA concentrations at 7-9 years, but not that at 3-5 years, was associated significantly with the serum levels of liver enzymes at 10-13 years of age (p < 0.05). Those in the top tertile of urinary BPA concentration had higher levels of liver enzymes than did others. After adjustment for covariates, dose-response relationships of the BPA level with liver enzyme levels were evident at 7-9 years, but not at 3-5 years. Notably, the effect size was larger and the dose-response relationships were more evident in boys than in girls. CONCLUSIONS: Exposure of children to even low doses of BPA may adversely affect later liver function.

Association of maternal omega-6 fatty acid intake with infant birth outcomes: Korean Mothers and Children's Environmental Health (MOCEH).

BACKGROUND: Maternal fatty acids (FAs) intake has an effect on birth weight, birth length, and gestational age, as fetal development is entirely dependent on the maternal essential FA supply. This study aimed to identify the association between the maternal intake of FAs and birth outcomes among pregnant women who participated in the Mothers and Children's Environmental Health (MOCEH) prospective cohort study in South Korea. METHODS: A total of 1407 pregnant women, aged 30.2 ± 3.7 years, at 12 to 28 weeks' gestation were recruited between August 2006 and December 2010. Their dietary intake during pregnancy was investigated by the 1-day 24-h dietary recall method. The pregnancy outcome data-namely infant's gestational age, birth weight, and birth length-were analyzed for their associations with their mothers' intake of FAs. RESULTS: When adjusted for confounding factors, multiple regression analysis revealed adverse effects on birth weight (P = 0.031) and birth length (P = 0.025) with high maternal intake of omega-6 FAs. In the multiple logistic regression analysis, the odds ratio (OR) for the risk of being below the 10th percentile for birth weight was higher in the highest quintile (Q5) compared to the lowest quintile (Q1) of omega-6 FA intake levels (OR = 2.444; 95% CI = 1.038-5.751; P for trend = 0.010). Also, the OR for being above the 90th percentile of birth length was lower in the highest quintile (Q5) compared to that in the lowest quintile (Q1) of omega-6 FA intake (OR = 0.432; 95% CI = 0.211-0.884; P for trend = 0.020). However, the maternal intake of omega-3 FAs was not related to gestational age, birth weight, or birth length. CONCLUSIONS: A high maternal omega-6 FA intake was negatively associated with birth weight and birth length.

Association between the DNA methylations of POMC, MC4R, and HNF4A and metabolic profiles in the blood of children aged 7-9 years.

BACKGROUND: Proopiomelanocortin (POMC), melanocortin 4 receptor (MC4R), and hepatocyte nuclear factor 4 alpha (HNF4A) are closely associated with weight gain and metabolic traits. In a previous study, we demonstrated associations between the methylations of POMC, MC4R, and HNF4A and metabolic profiles at birth. However, little is known about these associations in obese children. To evaluate the clinical utility of epigenetic biomarkers, we investigated to determine whether an association exists between the methylations of POMC, MC4R, and HNF4A and metabolic profiles in blood of normal weight and overweight and obese children. METHODS: We selected 79 normal weight children and 41 overweight and obese children aged 7-9 years in the Ewha Birth and Growth Cohort study. POMC methylation levels at exon 3, and MC4R and HNF4A methylation levels in promoter regions were measured by pyrosequencing. Serum glucose, total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-c), and insulin levels were analyzed using a biochemical analyzer and an immunoradiometric assay. Partial correlation and multiple regression analysis were used to assess relationships between POMC, MC4R, and HNF4A methylation levels and metabolic profiles. RESULTS: Significant correlations were found between POMC methylation and HDL-c levels, and between HNF4A methylation and both TC and HDL-c levels. Interestingly, associations were found between POMC methylation status and HDL-c levels, and between HNF4A methylation status and TC levels independent of body mass index. CONCLUSIONS: These findings show that POMC, MC4R, and HNF4A methylation status in the blood of children are associated with metabolic profiles. Therefore, we suggest that the DNA methylation status might serve as a potential epigenetic biomarkers of metabolic syndrome.

Birth Cohort Consortium of Asia: Current and Future Perspectives.

BACKGROUND: The environmental health of children is one of the great global health concerns. Exposures in utero and throughout development can have major consequences on later health. However, environmental risks or disease burdens vary from region to region. Birth cohort studies are ideal for investigating different environmental risks. METHODS: The principal investigators of three birth cohorts in Asia including the Taiwan Birth Panel Study (TBPS), the Mothers and Children's Environmental Health Study (MOCEH), and the Hokkaido Study on Environment and Children' Health (Hokkaido Study) coestablished the Birth Cohort Consortium of Asia (BiCCA) in 2011. Through a series of five PI meetings, the enrolment criteria, aim of the consortium, and a first-phase inventory were confirmed. RESULTS: To date, 23 birth cohorts have been established in 10 Asian countries, consisting of approximately 70,000 study subjects in the BiCCA. This article provides the study framework, environmental exposure and health outcome assessments, as well as maternal and infant characteristics of the participating cohorts. CONCLUSIONS: The BiCCA provides a unique and reliable source of birth cohort information in Asian countries. Further scientific cooperation is ongoing to identify specific regional environmental threats and improve the health of children in Asia.

The effect of prenatal TVOC exposure on birth and infantile weight: the Mothers and Children's Environmental Health study.

BACKGROUNDVolatile organic compounds (VOCs) might restrict prenatal and postnatal growth. However, the effect of the exposure of prenatal VOCs on postnatal growth has not been studied sufficiently. Thus, we investigated the relationship between the exposure of total volatile organic compounds (TVOCs) during pregnancy and its effects on postnatal growth.METHODSA total of 383 pregnant participants were enrolled from 2006 to 2008. We investigated maternal characteristics using a questionnaire. Personal air samples of TVOCs were obtained in mid or late pregnancy. After these mothers had given birth, 360 singleton newborns were selected and postnatal follow-up data were collected at 6, 12, 24, and 36 months, as well as anthropometric factors including body weight. Multiple general linear and mixed models were applied for statistical analyses.RESULTSThe mean concentration of prenatal exposure to TVOCs was 284.2 µg/m3 and that of formaldehyde was 81.6 µg/m3. The birth weight of newborns decreased significantly with prenatal TVOC exposure (ß=-45.89, P=0.04). The adjusted mean body weight was 300 g lower in the high-TVOC group (⩾75th) compared with that in the low-exposure group (<75th).CONCLUSIONThese results indicate that elevated exposure to TVOCs during the prenatal period may adversely influence early postnatal growth.

Neurodevelopment for the first three years following prenatal mobile phone use, radio frequency radiation and lead exposure.

BACKGROUND: Studies examining prenatal exposure to mobile phone use and its effect on child neurodevelopment show different results, according to child's developmental stages. OBJECTIVES: To examine neurodevelopment in children up to 36 months of age, following prenatal mobile phone use and radiofrequency radiation (RFR) exposure, in relation to prenatal lead exposure. METHODS: We analyzed 1198 mother-child pairs from a prospective cohort study (the Mothers and Children's Environmental Health Study). Questionnaires were provided to pregnant women at ≤20 weeks of gestation to assess mobile phone call frequency and duration. A personal exposure meter (PEM) was used to measure RFR exposure for 24h in 210 pregnant women. Maternal blood lead level (BLL) was measured during pregnancy. Child neurodevelopment was assessed using the Korean version of the Bayley Scales of Infant Development-Revised at 6, 12, 24, and 36 months of age. Logistic regression analysis applied to groups classified by trajectory analysis showing neurodevelopmental patterns over time. RESULTS: The psychomotor development index (PDI) and the mental development index (MDI) at 6, 12, 24, and 36 months of age were not significantly associated with maternal mobile phone use during pregnancy. However, among children exposed to high maternal BLL in utero, there was a significantly increased risk of having a low PDI up to 36 months of age, in relation to an increasing average calling time (p-trend=0.008). There was also a risk of having decreasing MDI up to 36 months of age, in relation to an increasing average calling time or frequency during pregnancy (p-trend=0.05 and 0.007 for time and frequency, respectively). There was no significant association between child neurodevelopment and prenatal RFR exposure measured by PEM in all subjects or in groups stratified by maternal BLL during pregnancy. CONCLUSIONS: We found no association between prenatal exposure to RFR and child neurodevelopment during the first three years of life; however, a potential combined effect of prenatal exposure to lead and mobile phone use was suggested.