OBJECTIVES:Although previous epidemiological studies have reported the effects of fetal exposure to phthalates and phenols on birth outcomes, evidence is still limited. The objective of this study was to investigate whether prenatal exposure to endocrine-disrupting chemicals [EDCs; phthalates and bisphenol A (BPA)] is associated with birth outcomes and whether there are sex-specific effects. METHODS:We used data from the Korean CHildren's ENvironmental health Study (Ko-CHENS) cohort. Exposure to phthalates and BPA was measured by urine tests, and the information on outcomes and confounders was obtained from delivery records, biomarker assessment, and a self-reported questionnaire. We performed multivariate logistic regression to estimate the association between exposure to individual phthalates and bisphenol A and birth outcomes. Additionally, to evaluate the effects of EDC mixture exposure, we performed weighted quantile sum regression analysis. Subgroup analysis stratified by maternal age and sex at birth was performed to examine potential differences in associations. RESULTS:This study included 2,176 mother-child pairs from the Ko-CHENS. We observed a significant association between the risk of PTB and exposure to BPA during early pregnancy and mono-carboxyoctyl phthalate (MCOP) during late pregnancy, with odds ratios of 1.23 (95% CI: 1.01, 1.49) and 1.29 (95% CI: 1.03, 1.62), respectively. Additionally, there was a significant association between exposure to MCOP during early pregnancy and the risk of LBW (OR: 1.39, 95% CI: 1.03, 1.89). For male infants in particular, exposure to MCOP during early pregnancy was associated with the risk of LBW (OR: 2.44, 95% CI: 1.43, 4.15), and exposure to MCOP during late pregnancy was associated with the risk of PTB (OR 1.45, 95% CI: 1.05, 2.02). CONCLUSIONS:This study suggests a potential association between exposure to BPA during early pregnancy and PTB, while exposure to MCOP during late pregnancy was associated with increased PTB risk in male infants.

Objective Optimal metabolically healthy status is important to prevent various chronic diseases. This study investigated the association between lifelog-derived physical activity and metabolically healthy status. Methods This cross-sectional study included 51 Korean adults aged 30–40 years with no history of chronic diseases. Physical activity data were obtained by the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Lifelog-derived physical activity was defined by step counts and walking speed for 1 week, as recorded by the Samsung Health application on both the Samsung Galaxy Fit2 and mobile phones. Participants without metabolic syndrome components were categorized as the metabolically healthy group ( n = 31) and the remaining participants as the metabolically unhealthy group ( n = 20). Prevalence ratios and 95% confidence intervals were estimated using Poisson regression models. The predictive ability of each physical activity measure was evaluated according to the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) values. Results Among the physical activity measures, lifelog-derived walking speed was significantly inversely associated with prevalent metabolically unhealthy status. The lifelog component model including walking speed, age, and sex had the highest AUC value for metabolically unhealthy status. Adding lifelog-derived step counts to the IPAQ-SF-derived metabolic equivalent (MET) model (including age, sex, and IPAQ-SF-METs) yielded 37% and 13% increases in the NRI and IDI values, respectively. Incorporating walking speed into the IPAQ-SF-derived MET model improved metabolically unhealthy status prediction by 42% and 21% in the NRI and IDI analyses, respectively. Conclusions Slow walking speed derived from the lifelog was associated with a higher prevalence of metabolically unhealthy status. Lifelog-derived physical activity information may aid in identifying individuals with metabolic abnormalities.

Objective: Metabolic syndrome (MetS) is a global problem that reduces the quality of life and threatens health such as cardiovascular disease and type 2 diabetes. It is known that the risk of cardiovascular disease increases in middle-aged women due to menopause, so management of metabolic syndrome is essential. We investigated the association between dietary metabolic syndrome index (DMetSI) and MetS, MetS unhealthy, insulin resistance (HOMA-IR), and non-alcoholic fatty liver disease (NAFLD) in middle-aged women. Methods: We used the data of a cohort study of midlife Korean women. MetS were defined as three or more of the five items of waist circumference, blood triglyceride, blood high-density cholesterol, blood pressure, and fasting blood sugar that was out of the standard range. DMetSI was calculated using the scoring method established by Shivappa from KNHANES (Korea National Health and Nutrition Examination Survey) and CANVAS (sub-study of the Korean Genome and Epidemiology Study) data. We were named K-DMetSI and C-DMetS, respectively, and divided DMetSI scores into 3 quartiles. A Poisson regression model was used to analyze the association between DII and MetS, MetS unhealthy (divided into over one items), NAFLD, and insulin resistance(divided 75th percentile). Results: A total of 2,552 subjects were studied. The K-DMetSI scores of the subjects were –1.23 to 1.96 and the C-DMetS were -2.05 to 2.75. The prevalence of MetS was 36.8%, MetS unhealthy was 5.4%, NAFLD was 19.7%, and insulin resistance was 22.2%. The risk of MetS in the Q3 group which had the highest K-DMetS was 1.97 (1.29, 3.01) higher than that in the Q1 group. The risk of MetS in the Q3 group which had the highest C-DMetS was 1.68 (1.10, 2.57) higher than that in the Q1 group. Then we found that the level of K-DMetS and C-DMetS were significantly positively associated with the MetS unhealthy, NAFLD, and insulin resistance. Conclusions: K-DMetS and C-DMetS were associated with the prevalence of MetS, Mets unhealthy, NALFD, and insulin resistance. To prevent chronic metabolic diseases, it is necessary to conduct investigations and dietary interventions for middle-aged women.

Obejectives: We examined the association between vasomotor symptoms (VMSs) and arterial stiffness, using brachial-ankle pulse wave velocity (baPWV), among Korean women in menopausal transition. Study design: This cross-sectional study comprised 945 women aged 42-52 years. Methods: VMSs, including hot flashes and night sweats, were assessed using the Menopause-Specific Quality of Life questionnaire (Korean version). Moderate/severe VMSs were defined as having a score of equal to or greater than 3 points (range: 0 to 6, 6 being most bothersome). Arterial stiffness was measured by baPWV. The high-risk group was defined as baPWV over the 90th percentile. Multivariable logistic regression models were performed to determine whether prevalent VMSs were significantly associated with high level of baPWV in menopausal transitioning women. Results: Compared to women without VMSs, those with VMSs had a prevalence ratio (PR) of 2.12 (95% confidence interval (CI), 1.17-3.84) for high baPWV after adjusted for age, menopausal status, education levels, body mass index, total and low-density lipoprotein cholesterol, triglycerides, diabetes, hypertension, physical activity, amount of alcohol intakes, and smoking status. The multivariable-adjusted PRs for high baPWV were 1.54 (95% CI: 0.73-3.23) and 2.72 (95% CI: 1.36-5.44) in women with mild and moderate/severe VMSs, respectively (P for trend = 0.005). Conclusion: Our findings suggest that VMSs, including moderate/severe VMSs, were significantly associated with arterial stiffness among Korean menopausal transitioning women.

BACKGROUND AND AIM: Phthalates, endocrine-disrupting chemicals that are commonly found in consumer products, may adversely affect thyroid hormones, but findings from prior epidemiologic studies have been inconsistent. In a prospective cohort study, we investigated whether maternal urinary phthalate metabolite concentrations and phthalate mixtures measured during pregnancy were associated with thyroid hormones among pregnant women. METHODS: We measured five phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate, mono-isobutyl phthalate, monobenzyl phthalate (MBzP), and four monoesthers of di(2-ethylhexyl) phthalate] in urine collected at pregnant women in MAKE Study. Thyroid stimulating hormone (TSH) and free and total thyroxine and triiodothyronine were measured in maternal serum (n = 215). We used multivariable linear regression to assess associations between individual urinary phthalate metabolites and concentrations of maternal thyroid hormones. We used weighted quantile sum regression (WQS) to create a phthalate index describing combined concentrations of phthalate metabolites and to investigate associations of the phthalate index with individual thyroid hormones. RESULTS: The geometric mean urinary concentrations of specific gravity adjusted MEPm MBzP and MECCP were 2.1, 0.2, and 0.1 μg/L, respectively. The phthalate index was had a significantly positive effect on the maternal serum TSH (WQS beta = 0.13; p = 0.02). However, no significant association was found with both maternal serum TT3 (WQS beta = -0.23; 0.89) or and TT4 (WQS beta = -0.02; p=0.83) CONCLUSIONS: Our results suggest that co-exposure to multiple phthalates was positively associated with TSH in pregnant women in this birth cohort. These findings highlight the need to study chemical mixtures in environmental epidemiology. KEYWORDS: Phthalates; Pregnancy; Thyroid hormones; Weighted quantile sum regression.

ABSTRACT Objective This study aimed to investigate the association between gut microbiota and depressive symptoms in a large population cohort of Korean adults. Methods Overall, 1238 participants were included in the study. Participants were categorized into depressed or non-depressed groups, based on the depressive symptoms reported on the Center for Epidemiologic Studies Rating Scale for Depression, with a cutoff score of 16, and their fecal microbiota was profiled using 16S ribosomal RNA gene sequencing. Several alpha and beta diversity measures were also estimated. The association between depressive symptoms and gut microbiota was analyzed using generalized linear models. The inferred function of the metagenomes was compared between the two groups. Results There were no consistent differences in alpha and beta diversity between the depressed and non-depressed groups. However, the continuous measure of depressive symptoms was inversely associated with one of four measures of alpha diversity (Shannon’s diversity, p = .021). We also found a substantial difference between the depressed and non-depressed groups in the Bray-Curtis dissimilarity among the four beta diversity indices (p = .004). Participants whose depressive symptoms exceeded a clinical cutoff score had a lower relative abundance of the genus Faecalibacterium when compared with controls (coefficient = −0.025, q = 0.047). However, the depressed group had a significantly higher abundance of the genus Oscillospira than did the non-depressed group (coefficient = 0.002, q = 0.023). Conclusions Our findings contribute to the identification of potential relationships between the gut microbiota and depressive symptoms and provide useful insights for developing microbiota-based interventions for patients with depressive symptoms.

Introduction: Human exposure to parabens is very common in daily life, and prenatal exposure to these chemicals is associated with poor birth outcomes. Therefore, the aim of this study was to investigate the effect of glutathione S-transferase (GST) polymorphisms on the association between prenatal exposure to parabens and birth outcomes. Methods: We conducted a multivariate analysis involving 177 subjects to determine the association between paraben concentrations and birth outcomes in mothers with GST mu 1 (GSTM1) and GST theta 1 (GSTT1) polymorphisms from 2017 to 2019. Furthermore, we determined the interactive effect between paraben levels and GSTM1/GSTT1 polymorphisms using regression analysis, in addition to a generalized linear model after stratifying GSTM1/GSTT1 genotype into three categories. Results: Methyl and propyl paraben concentrations were significantly and positively associated with birth weight (methyl, β = 116.525, 95% confidence interval (CI) = 22.460–210.590; propyl, β = 82.352, 95% CI = 9.147–155.557) in individuals with the GSTM1-null genotype. Moreover, the propyl paraben concentration was significantly associated with an increase in gestational age (β = 0.312, 95% CI = 0.085–0.539) in individuals with the GSTM1-null genotype. Conclusions: This study reported the association between prenatal paraben exposure and birth outcomes in individuals with GST polymorphisms. We found positive relationships of maternal exposure to methyl parabens with birth weight in both mothers with GSTM1 and GSTT1-null genotypes.

A person high in neuroticism is more likely to experience anxiety, stress, worry, fear, anger, and depression. Previous studies have shown that the gut microbiota can influence personality and mental disorders, including stress, anxiety, and depression, through the gut–brain axis. Here, we investigated the correlations between the sub-facet of neuroticism and gut microbiota using the Revised NEO Personality Inventory and the 16S rRNA gene sequencing data 784 adults. We found that the high anxiety and vulnerability group showed significantly lower richness in microbial diversity than a group with low anxiety and vulnerability. In beta diversity, there was a significant difference between the low and high groups of anxiety, self-consciousness, impulsiveness, and vulnerability. In taxonomic compositions, Haemophilus belonging to Gammaproteobacteria was correlated with the Neuroticism domain as well as N1 anxiety and N6 vulnerability facets. The high N1 anxiety and N6 vulnerability group was correlated with a low abundance of Christensenellaceae belonging to Firmicutes Clostridia. High N4 self-consciousness was correlated with a low abundance of Alistipes and Sudoligranulum. N5 impulsiveness was correlated with a low abundance of Oscillospirales. Our findings will contribute to uncovering the potential link between the gut microbiota and neuroticism, and the elucidation of the correlations of the microbiome–gut–brain axis with behavioral changes and psychiatric cases in the general population.

Bisphenols are endocrine disruptors that may be associated with altered fetal growth in humans, and they have similar biological functions to mimic hormones. In addition, aggregated chemicals showed an adverse effect although individual concentration was at a low level. However, most studies between bisphenols and birth outcomes have focused on the effect of individual bisphenol. Thus, we explored the associations of urinary bisphenol mixtures with birth outcomes. We conducted a prospective birth cohort study in South Korea. One hundred eighty mother-infant pairs were recruited from 2017 to 2019. Bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS) in one spot urine were analyzed using ultra-performance liquid chromatography–tandem mass spectrometry. We used two statistical approaches to examine potential associations of BPA, BPF, and BPS with birth weight and gestational age: (1) multivariable linear regression; (2) Bayesian kernel machine regression (BKMR). The geometric means of BPA, BPF, and BPS were 2.1, 0.2, and 0.1 μg/L, respectively. In stratified linear analyses by each median value, a higher BPF was positively associated with birth weight (g) (β = 125.5; 95% CI: 45.0 to 205.9). Mixture analyses using BKMR suggested an inverse association between bisphenol mixtures and birth weight. Our findings suggest that in utero bisphenol exposure may influence birth weight and that such relationships may differ considering non-linearity and the combined effect.

Introduction: Bisphenol F (BPF) and bisphenol S (BPS) are chemical substitutes for, and may have similar physiological effects to, bisphenol A (BPA). Bisphenols provoke endocrine disorders and are cytotoxic, oxidize hemoglobin, and induce morphological changes in human red blood cells (RBC). It is more sensitive to changes in the RBC number and hemoglobin (Hb) level during pregnancy. Therefore, we investigated the effects of bisphenols (BPs) and their substitute compounds on hemopoiesis and the serum biochemical parameters of pregnant women. Methods: The study population comprised 196 pregnant women from the MAKE cohort study, recruitment for which occurred from 2017 to 2019. We measured the levels of BPA, BPF and BPS in urine samples and collected data on socioeconomic, lifestyle, and environmental factors at visits to the hospital. The associations between the levels of the three BPs and biochemical parameters were analyzed by multiple linear regression. Results: The geometric mean urinary concentrations of specific gravity adjusted BPA, BPF, and BPS were 2.1, 0.2, and 0.1 mu g/L, respectively. There was a significant negative association between the urinary concentration of BPA and the Hb level (beta = -0.5, p = 0.02). After stratifying by the median concentrations of the three BPs, the maternal urinary BPA level had a significantly negative effect on the RBC count, HB level, and hematocrit in the high BPA concentration group (RBC, beta = 0.5, p = 0.001; Hb, beta = -1.4, p = 0.002; Hct, beta = - 5.0, p = 0.001). Conclusions: BPA has a harmful effect on hemato-biochemical changes that occur during pregnancy. Further studies should investigate the relation between widespread exposure to bisphenols and effects on human health.

Background: The Mothers and Children's Environmental Health study (MOCEH) is a multi-centric prospective birth cohort study investigating effects of various environmental pollutants like heavy metals, endocrine disruptors, air pollutants, nutrition and lifestyle on birth outcomes, growth and development, health and disease of children. In this study, we report all the outcomes from the MOCEH study describing the different environmental pollutants affecting children's health and disease. Methods: In MOCEH study, 1,751 pregnant women in their first trimester were recruited at 3 centers from 2006 to 2010 in South Korea. The children were followed from birth up to 6 years. Information on health outcomes of children including birth parameters, demographic characteristics, medical and child-rearing history, and nutritional status, were repeatedly obtained through the follow-ups by questionnaires administration, clinical evaluation, and biological specimen collection and measurements. Prenatal and postnatal measurement in biospecimen, i.e., lead, mercury, cadmium, manganese, 1-hydroxypyrene, 2-naphthol, malonadialdehyde, hippuric acid, bisphenol A and phthalate metabolites, and measurement in air samples, i.e., particulate matter, nitrogen dioxide, and total volatile organic compounds were performed. Results: The results show the adverse effect of prenatal exposure to heavy metals like mercury, lead and cadmium on children's physical, cognitive and neurobehavioral development. Exposure to endocrine disruptors, air pollution, second hand smoke, and mother's lifestyle during pregnancy affects children's growth and development. We also identified specific window periods of exposure of pollutants significantly related to children's health outcomes. Conclusion: The collective results from MOCEH study provide strong scientific evidence that exposures to prenatal and postnatal environmental pollutants have a negative effect on growth and development of children, which will be useful in implementing effective national policy to improve children's environmental health.

The gut microbiota has been linked to blood lipids. However, the relationship between the gut microbiome and other lipid markers like apolipoproteins A1 (apoA1) and B (apoB) as well as classical lipid markers in Asians remain unclear. Here, we examined the associations between gut microbial diversity and taxonomic compositions with both apolipoproteins and lipid markers in a large number of Korean patients. The fecal 16S rRNA gene sequencing data from 1141 subjects were analyzed and subjects were categorized into control group (G0) or abnormal group (G1) according to blood lipid measurements. The microbial diversity and several taxa of the gut microbiota were significantly associated with triglyceride, apoA1, and apoB levels, but not with total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. The alpha diversity of the gut microbiota was inversely associated with high triglyceride level. Interestingly, G1 of apoA1 showed increased microbial richness and distinct microbial community compared with G0 of apoA1. A high abundance of Fusobacteria and low abundance of Oscillospira were found in the hypertriglyceridemia group. In this large-scale study, we identified associations of gut microbiota with apolipoproteins and classical lipid markers, indicating that the gut microbiota may be an important target for regulating blood lipids.

Emerging evidence has shown that flavonoids extracted from Artemisia have beneficial effects on metabolic disorders. However, whether and how jaceosidin ameliorates insulin resistance and diabetic nephropathy in type 2 diabetes mellitus is largely unknown. For 8 weeks, db/db diabetic mice were fed with or without jaceosidin. Oral jaceosidin supplementation reduced fasting blood glucose levels and insulin resistance through the upregulation of insulin receptor downstream pathways in the liver and skeletal muscles. While jaceosidin did not noticeably alter kidney filtration function, this dietary intervention contributed to attenuating the accumulation of advanced glycation end products in diabetic kidneys. The levels of VEGF-a (vascular endothelial growth factor-a) proteins in the diabetic kidneys were markedly diminished by jaceosidin treatments, which increased the expression and activity of Cu (copper) and Zn-SOD (zinc-superoxide dismutase). Therefore, it is suggested that jaceosidin supplementation elicits antidiabetic effects and treats diabetic nephropathy by augmenting insulin signaling, suppressing fibrosis, and enhancing antioxidant activity.

Although obesity is associated with numerous diseases, the risks of disease may depend on metabolic health. Associations between the gut microbiota, obesity, and metabolic syndrome have been reported, but differences in microbiomes according to metabolic health in the obese population have not been explored in previous studies. Here, we investigated the composition of gut microbiota according to metabolic health status in obese and overweight subjects. A total of 747 overweight or obese adults were categorized by metabolic health status, and their fecal microbiota were profiled using 16S ribosomal RNA gene sequencing. We classified these adults into a metabolically healthy group (MH, N = 317) without any components of metabolic syndrome or a metabolically unhealthy group (MU, N = 430) defined as having at least one metabolic abnormality. The phylogenetic and non-phylogenetic alpha diversity for gut microbiota were lower in the MU group than the MH group, and there were significant differences in gut microbiota bacterial composition between the two groups. We found that the genus Oscillospira and the family Coriobacteriaceae were associated with good metabolic health in the overweight and obese populations. This is the first report to describe gut microbial diversity and composition in metabolically healthy and unhealthy overweight and obese individuals. Modulation of the gut microbiome may help prevent metabolic abnormalities in the obese population.

Cholecystectomy alters the bile flow into the intestine and the enterohepatic circulation of the bile acids; this may affect the gut microbiota. We assessed the gut microbiota composition of patients who had undergone cholecystectomy and compared with those who had not. From a cohort of 1463 adult participants who underwent comprehensive health screening examinations, 27 subjects who had undergone cholecystectomy (cholecystectomy group) and 81 age- and sex-matched subjects who had not (control group) were selected. Clinical parameters were collected and compared. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from fecal samples. We evaluated differences in the overall microbial composition and in the abundance of taxa. The two groups were comparable with respect to clinical characteristics and laboratory results. The actual number of taxa observed in a sample (observed features) was significantly lower in the cholecystectomy group than in the control group (p = 0.042). The beta diversity of Jaccard distance index was significantly different between the two groups (p = 0.027). Blautia obeum and Veillonella parvula were more abundant in the cholecystectomy group. The difference in the diversity of the gut microbiota between the cholecystectomy and control groups was subtle. However, B. obeum and V. parvula, which have azoreductase activity, were more abundant in the cholecystectomy group. The impact of such changes in the gut microbiota on health remains to be determined.

Background/AimBisphenol-F(BPF) is a substitute substances of bisphenol-A and the manufacturing of plastics and epoxy resins(such as food contact materials, structural adhesive). However, the exposure of BPF in pregnant women is presently unknown. This study aimed to examine urinary BPF concentrations of pregnant women and investigate their associations with environmental factors.MethodsIn order to find out the association with BPF and environmental factors, we plan to recruit more than 300 women during 2nd and 3rd stage pregnancy between 2017 and 2019 in the Korean pregnant women. We also collected information on birth outcome, socio-economic status, use of disposable foods, and consumption habits of consumer products. Multiple regression analysis was performed to assess the effect of BPF exposure by environmental factors.ResultsThe creatinine-adjusted geometric mean of BPF were 0.2μg (95% CI: 0.40-5.49) and that was tended to increase of environmental factors. There were significant associations was observed between BPF and use of plastic cooking tools (β=0.88, p=0.006), intake of wrapping food (β=0.7, p=0.05), habits of using perfume (β=0.69, p=0.05), respectively. None of the BPF concentrations were associated with the other consumer products and food. In addition, we found the associations with BPF and renovation of the house within the last 6 months (β=0.97, p=0.02).ConclusionsWe expect this study to provide evidence to support the hypothesis that the environmental factor has an effect on the exposure during pregnancy.

Objectives: The accumulated evidence shows that adult disease may have origins during the fetal period and maternal environmental exposure may affect fetus and infant health. To assess the environmental health of fetus and infants and examine women's concerns about environmental health, we designed and conducted an environmental health survey in reproductive-aged women in 2011. Methods: A stratified multi-stage design was adopted for our survey, and 1,000 reproductive-aged women aged 25 to 39 years participated. The participants were asked to complete an electronic questionnaire using the computer-assisted web interviewing method. All the participants were married woman, and 80% had experienced pregnancy before completing the survey. Results: In the study, 86.3% of the participants responded that they are worried about the environmental problems that may affect the fetus and infant. The participants responded that they were most worried about global warming and climate change (36.2%), electromagnetic waves (31.4%), and endocrine disrupting chemicals (25.1%). Moreover, participants responded that environmental problem can cause children's allergic disease, such as atopic dermatitis, metabolic syndrome and growth development. Conclusion: We found reproductive-aged women have high awareness of children's environmental health. We also recommended that additional surveys on mother and child environmental health be conducted to make a health policy for women, fetus and infant.