Prenatal phthalate exposure and sex steroid hormones in newborns: Taiwan Maternal and Infant Cohort Study.

BACKGROUND: Newborn anogenital distance (AGD) has been associated with prenatal exposure of phthalates. The association between prenatal phthalate exposure and sex steroid hormones in newborns is unclear. OBJECT: This study aimed to examine whether cord-blood sex hormone levels were associated with prenatal phthalate exposure and newborn anogenital distance (AGD). METHODS: In the Taiwan Maternal and Infant Cohort Study, we recruited 1,676 pregnant women in their third trimester in 2012-2015 in Taiwan. We determined 11 urinary phthalate metabolites in pregnant women, three maternal and five cord-blood steroid sex-hormone concentrations. Five hundred and sixty-five mother-infant pairs with sufficient data were included. Trained neonatologists measured 263 newborns' AGD. We examined the associations of prenatal phthalate metabolite levels with AGD and hormones using linear regression models and evaluated correlations between maternal and cord-blood sex hormone levels and AGD. RESULTS: Compared with the male newborns exposed to maternal phthalate metabolites at the first tertile, AGD was -3.75, -3.43, and -3.53 mm shorter among those exposed at the median tertile of di-2-ethylhexyl phthalate (DEHP) metabolites, monobenzyl phthalate (MBzP), and monomethyl phthalate (MMP), respectively. Compared with those who had exposed at the first tertile, cord-blood follicle-stimulating hormone (FSH) decreased among male newborns exposed at higher levels of MMP, mono-n-butyl phthalate (MnBP), MBzP and DEHP, and among female newborns exposed at higher levels of MMP, MBzP and mono(2-ethyl-5-hydroxyhexyl) phthalate. However, we did not observe significant correlations of maternal or cord-blood sex steroid hormones with newborns' AGDs. CONCLUSIONS: Alterations in cord-blood sex steroid hormone levels were associated with prenatal phthalate exposures, particularly in male newborns. Women aspiring to be pregnant should be alerted of the need of reducing phthalate exposure.

Long-term PM2.5 exposure is associated with asthma prevalence and exhaled nitric oxide levels in children.

BACKGROUND: Exhaled nitric oxide concentration (FENO) is a marker of airway inflammation. This study aimed to evaluate the association of air pollution exposure with FENO levels and asthma prevalence with respiratory symptoms in school children. METHODS: We analyzed 4736 school children who reside in six townships near industrial areas in central Taiwan. We evaluated asthmatic symptoms, FENO, and conducted the environmental questionnaire. The personal exposure of PM2.5, NO, and SO2 was estimated using land-use regression models data on children's school and home addresses. RESULTS: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma (OR = 1.595), exercise-induced wheezing (OR = 1.726), itchy eyes (OR = 1.417), and current nasal problems (OR = 1.334) (P < 0.05). FENO levels in the absence of infection were positively correlated with age, previous wheezing, allergic rhinitis, atopic eczema, near the road, and for children with high exposure to PM2.5 (P < 0.05). An increase of 1 µg/m3 PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels for children after adjusting for potential confounding variables, including exposures to NO and SO2. CONCLUSIONS: Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children. IMPACT: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma and nasal problems and itchy eyes. Long-term exposures to PM2.5 were significantly associated with FENO levels after adjusting for potential confounding variables. This is first study to assess the association between FENO levels and long-term air pollution exposures in children near coal-based power plants. An increase of 1 µg/m3 annual PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children.

The factors of perceived disease knowledge and self-care behavior in type 2 diabetic patients with chronic kidney disease: A cross-sectional study.

Chronic kidney diseases (CKD) is an important public health issue worldwide, and diabetes mellitus is the main cause of CKD. Having sufficient disease knowledge and good self-care behavior both help to prevent the progression of diabetes mellitus and CKD. This cross-sectional study enrolled 181 type 2 diabetic patients with CKD from July 2017 to October 2017. Perceived Kidney Knowledge survey and structured questionnaires of self-care behavior were used to measure perceived disease knowledge and CKD Self-Care (CKDSC) scales respectively with the determinants analyzed by linear regression. Meanwhile, socio-demographic information, kidney function and laboratory data were collected. Of 181 enrolled patients, the mean age was 66.8 ±â€…9.7 years, 59.1% were male and the mean estimated glomerular filtration rate was 33.1 ±â€…23.1 mL/min/1.73 m2. The mean scores of CKDSC and perceived disease knowledge were 63.2 and 22.4, respectively. High scores of disease knowledge were significantly correlated with low glycated hemoglobin (P = .03) and high scores of overall self-care behavior (P = .03) and aspects of self-care behavior, including diet (P = .003), exercise (P = .02), and home blood pressure monitoring (P = .04). The relationship between young age and high scores of disease knowledge was found (P = .001); however, old age was significantly associated with high scores of overall self-care behavior (P < .001) while additionally, married patients had high scores of regular medication behavior (P = .03). Our findings identified the significant factors correlated with disease knowledge and self-care behavior in type 2 diabetic patients with CKD. Healthcare givers should establish personalized health education plans to improve perceived disease knowledge and self-care behavior.

Low-to-Moderate Arsenic Exposure and Urothelial Tract Cancers with a Long Latent Period of Follow-Up in an Arseniasis Area.

BACKGROUND: Arsenic exposure can cause adverse health effects. The effects of long-term low-to-moderate exposure and methylations remain unclear. OBJECTIVE: This study aims to examine the association between low-to-moderate arsenic exposure and urothelial tract cancers while considering the effects of methylation capacity. METHODS: In this study, 5,811 participants were recruited from an arseniasis area in Taiwan for inorganic arsenic metabolite analysis. This follow-up study was conducted between August 1995 and December 2017. We identified 85 urothelial tract cancers in these participants, including 49 bladder and 36 upper urothelial tract cancer cases. A Cox proportional hazards model was employed. RESULTS: The analyses revealed a significant association between concentrations of inorganic arsenic in water > 100 ug/L and bladder cancer occurrence, with a hazard ratio (HR) of 4.88 (95% CI 1.35-17.61). A monotonic trend was observed between concentrations of inorganic arsenic in water (from 0 to > 100 ug/L) and the incidence of urothelial tract cancer, including bladder cancer (p < 0.05) and upper urothelial tract cancers (p < 0.05). Participants with a lower primary methylation index or higher secondary methylation index had a prominent effect. CONCLUSIONS: Rigorous regulations and active interventions should be considered for populations with susceptible characteristics.

Shared decision-making for renal replacement treatment and illness perception in patients with advanced chronic kidney disease.

BACKGROUND: Current healthcare trends emphasize the use of shared decision-making (SDM) for renal replacement treatment (RRT) in patients with chronic kidney disease (CKD). This is crucial to understand the relationship between SDM and illness perception of CKD patients. Few studies have focused on SDM and illness perception status of CKD patients and the impact of illness perception on RRT after SDM. METHODS: In this cross-sectional study, we used a questionnaire with purposive sampling from March 2019 to February 2020 at the nephrology outpatient department of a medical center in southern Taiwan. The nephrology medical team in this study used the SHARE five-step model of SDM to communicate with the patients about RRT and Brief Illness Perception Questionnaire (BIPQ) was applied to evaluate illness perception of these patients at the beginning of SDM. According to the SDM decision time, the study participants were classified general and delayed SDM groups. The distribution between SDM groups was estimated using independent two sample t-test, chi-squared test or Fisher's exact test. The correlation between illness perception and SDM decision time were illustrated and evaluated using Spearman's correlation test. A p-value less than 0.05 is statistically significant. RESULTS: A total of 75 patients were enrolled in this study. The average time to make a dialysis decision after initiating SDM was 166.2 ± 178.1 days. 51 patients were classified as general group, and 24 patients were classified as delayed group. The median SDM decision time of delayed group were significantly longer than general group (56 vs. 361 days, P < 0.001). Our findings revealed that delayed group was significantly characterized with not created early surgical assess (delayed vs. general: 66.7% vs. 27.5%, p = 0.001) compared to general group. The average BIPQ score was 54.0 ± 8.1 in our study. We classified the patients into high and low illness perception group according to the median score of BIPQ. The total score of BIPQ in overall participants might increase by the SDM decision time (rho = 0.83, p = 0.830) and the linear regression line also showed consistent trends between BIPQ and SDM decision time in correspond cohorts. However, no statistically significant findings were found. CONCLUSIONS: The patients with advanced chronic kidney disease took an average of five and a half months to make a RRT decision after undergoing SDM. Although there is no statistical significance, the trend of illness perception seems correlated with decision-making time. The stronger the illness perception, the longer the decision-making time. Furthermore, shorter decision times may be associated with earlier establishment of surgical access. We need more research exploring the relationship between illness perception and SDM for RRT in CKD patients.

[Treg Cells, FoxP3 and TGF-ß Expression and Significance in Chronic Myeloid Leukemia].

OBJECTIVE: To investigate the expression and significance of regulatory T cells (Tregs), FoxP3 and transforming growth factor-ß (TGF-ß) in different phase of chronic myeloid leukemia (CML). METHODS: Peripheral blood of 73 CML patients in Department of Hematology, Heze Municipal Hospital from March 2018 to March 2021 were collected. According to patient's period in CML, they were divided into ND CML group (newly diagnosed), CP CML group (chronic period), and BP CML group (blast phase). The percentage of Tregs, expression level of FoxP3 mRNA and TGF-ß were detected by flow cytometry, RT-qPCR, and ELISA, respecitively. The roles of above indices in clinical pathogenesis of patients with CML were analyzed. RESULTS: The proportion of Treg in the ND CML group was slightly higher than the CP CML group, but the difference was not statistically significant (P =0.695), while the BP CML group was significantly higher than the other two groups (P =0.008, P <0.001). The expression levels of FoxP3 mRNA in ND CML group, CP CML group and BP CML group were 11.61±2.21, 6.46±1.35 and 8.54±2.13, respectively. Significant difference in FoxP3 mRNA levels was observed among patients in different phases of CML (F =55.199, P <0.001). The expression levels of FoxP3 mRNA both in ND CML group and BP CML group were significantly higher than that in CP CML group (P <0.001), and the ND CML group was the highest (P <0.001). However, the expression levels of TGF-ß in different phases of CML showed no statistical differences (H =0.634, P =0.728). CONCLUSION: The abnormal distribution of Treg subset in different phases of CML and the significant increase of the expression level of FoxP3 mRNA in the new onset and blast phase of CML suggest that Tregs may promote the occurrence and progression of CML through immune regulation.

Associations of urinary phthalate metabolites with household environments among mothers and their preschool-age children.

Phthalates have become a matter of public health concern due to their extensive use worldwide and negative health effects. The evaluation of potential sources of phthalate exposure is crucial to design prevention strategies, especially for vulnerable populations. This study included 528 mother-child pairs in the Taiwan Mother Infant Cohort Study who were followed up at ages 3-6 years between 2016 and 2020. Each mother was interviewed by using a structured questionnaire containing questions on demographic characteristics and household environment factors, such as the use of plastic food packaging, residential visible mold, insecticide sprays, and electric mosquito repellents. Eleven phthalate metabolites were analyzed in urine samples simultaneously collected from the mother-child pairs. The phthalate metabolite urinary concentrations were higher among the children than among their mothers, except those of mono-ethyl phthalate (MEP) and mono-2-ethylhexyl phthalate (MEHP). Multiple linear regression analyses showed that urine samples collected during the summer showed higher concentrations of phthalate metabolites than those collected during the winter. Family income levels had negative associations with the concentrations of MnBP and metabolites of di-2-ethylhexyl phthalate (DEHP) in children. The use of plastic food packaging was positively associated with mono-n-butyl phthalate (MnBP) and metabolites of DEHP in mothers. Residential visible mold or mold stains were significantly associated with higher MnBP and DEHP metabolite concentrations in children. The use of insecticide sprays was positively associated with MnBP concentrations in children. Significant associations between household environmental factors and phthalate exposure were mostly found in children, potentially indicating different exposure pathways between mothers and their children. Findings from this study provide additional information for the design of prevention strategies to protect the health of children and women.

Phthalates exposure and pubertal development in a 15-year follow-up birth cohort study in Taiwan.

Purpose: Phthalates are ubiquitous endocrine disruptors that can affect pubertal development in children. The association of fetal and childhood levels of phthalates with pubertal development were explored. Methods: We conduct a population-based birth cohort study to investigate the association between prenatal and childhood exposure to phthalates and pubertal development. Initially, a total of 445 children were recruited from 2000 to 2001, of which 90 children were followed for 15 years which measurements of urine and development assessed at 2, 5, 8, 11, and 14 years. We defined higher Tanner stage as the 14-year-old Tanner stage ≥ 4 and 5 for boys and girls, respectively. A logistic regression analysis was conducted to estimate the crude and adjusted odds ratio of a higher Tanner stage at 14 years old. The Pearson correlation coefficient and multiple linear regression were used to estimate the association of testicular volume, uterine volume, ovarian volume, and blood hormones at 14 years of age with the log-transformed concentration of phthalates at 2, 5, 8, 11, and 14 years. Results: In boys, a significantly different geometric mean of mono-benzyl phthalate (MBzP) was observed in 11-year-olds; 6.82 and 2.96 in the lower Tanner stage group and higher Tanner stage group. In girls, a significant difference in the geometric mean of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in 11-year-olds and mono-ethyl phthalate (MEP) in 2-year-olds was observed; MEHHP was 32.97 and 18.13 in the lower Tanner stage group and higher Tanner stage group, and MEP was 26.54 and 65.74 in the lower Tanner stage group and higher Tanner stage group, respectively. Uterine volume at 14 years old was negatively associated with several phthalate metabolites (MEHP at 8 years old, MnBP at 8 years old, MBzP at 14 years old, MMP prenatally, MMP at 8 years old, and MEP at 8 years old) after adjusting for covariates. However, no significant correlations were found between phthalate metabolites and ovarian or testicular volume. Conclusion: Phthalate exposure at certain time points may influence the reproductive development of children during puberty; however, further studies should be conducted to determine the causal nature of this association.

Serum neurofilament light chain as a predictive marker of neurologic outcome after cardiac arrest: a meta-analysis.

OBJECTIVE: Recently, an increasing number of studies have suggested using serum neurofilament light (NfL) chain to predict the neurologic outcome after cardiac arrest. However, the predictive ability of this approach remains inconclusive. Meta-analysis was performed on related studies to assess the ability of serum NfL to predict the neurologic outcome after cardiac arrest. MATERIALS AND METHODS: PubMed, ScienceDirect and Embase were systematically searched from the date of their inception until June 2022. Data were extracted to calculate the area under the receiver operating characteristic curve (AUC), the sensitivity, the specificity and the publication bias to evaluate the predictive power of serum NfL using Stata 14.0. RESULTS: Nine studies were included in the present meta-analysis. Seven studies involving 1296 participants reported serum NfL 24 h post arrest for predicting the neurological outcome, and the AUC was 0.92 (77% sensitivity and 96% specificity). Seven studies involving 1020 participants reported serum NfL 48 h post arrest for predicting the neurological outcome, and the AUC was 0.94 (78% sensitivity and 98% specificity). Four studies involving 804 participants reported serum NfL 72 h post arrest for predicting the neurological outcome, and the AUC was 0.96 (90% sensitivity and 98% specificity). No significant publication bias was observed among the included studies. CONCLUSION: The present meta-analysis results support the potential use of serum NfL as an early biomarker of neurologic outcome, especially 72 h post arrest.

Reference intervals for thyroid hormone, sex hormone, and clinical biochemical tests in cord blood from Taiwanese newborn - TMICS cohort.

BACKGROUND/PURPOSE: This study aims to establish reference intervals for important biochemical parameters in cord blood of newborn male and female infants in Taiwan and to investigate their sex difference. We also examined the correlation of the same markers between maternal blood levels and neonatal cord blood levels. METHODS: 2,136 pregnant women receiving regular routine prenatal health assessments in their third trimester (weeks 29-40) were recruited from nine hospitals in Taiwan between 2012 and 2015. After exclusion, we were left with 580 cord blood samples to include in this study. RESULTS: Cord blood thyroid-stimulating hormone was higher in males than females (p < 0.05). Males also had significantly higher sex hormone levels (estradiol, follicle-stimulating hormone, and sex hormone-binding globulin), while females had higher levels of luteinizing hormone. Male newborns had higher cord blood immunoglobulin E (IgE), while females had higher insulin-like growth factor-1 (IGF-1) levels. We found a slight positive link between maternal blood and cord blood in thyroid hormones and sex hormones. CONCLUSION: This study found sex differences in cord blood thyroid hormone, sex hormone, IGF-1, and IgE levels and a link between maternal blood levels of thyroid and sex hormones and those in the cord blood of their infants.

Co-exposure to toxic metals and phthalates in pregnant women and their children's mental health problems aged four years - Taiwan Maternal and Infant Cohort Study (TMICS).

BACKGROUND: Childhood and adolescent mental health problems may increase the global burden of disease. Neurotoxic metals are associated with inflammation and cytotoxicity in the brain. In addition, prenatal phthalate ester (PAE) exposure is associated with cognitive function deficits. However, the effect of co-exposure to toxic metals, PAEs, and their association with child behavior is less well studied. Hence, we aimed to investigate prenatal co-exposure to the metals and PAEs and the consequent behavioral outcomes in early childhood. METHODS: We followed pregnant women and their newborns from the Taiwan Maternal and Infant Cohort Study between 2015 and 2017, with a focus on women from the central, southern, and eastern areas of Taiwan. We quantified maternal urinary concentrations of metals and metabolites of PAEs as surrogates of prenatal exposure. We recorded the Child Behavior Checklist scores according to caregiver reports at 4 years of age, and identified Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)-oriented problems. RESULTS: Ultimately, 408 children were included in the statistical analysis. Maternal urinary copper levels were significantly associated with depressive problems (odds ratio [OR] = 2.13) in children. Maternal urinary concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) were also significantly associated with depressive symptoms (odds ratio [OR] = 1.51 and 1.53, respectively). Further analysis considering prenatal co-exposure to metals and PAEs showed that co-exposure to these materials was significantly associated with autism spectrum problems (OR = 3.11). CONCLUSIONS: We observed that prenatal single exposure or co-exposure to metals and PAEs may play a role in some DSM-5-oriented problems in children at 4 years of age. Reduction of exposure to toxic metals and PAEs in pregnancy is suggested to prevent increased mental health problems in children.

Associations between maternal phthalate exposure and neonatal neurobehaviors: The Taiwan maternal and infant cohort study (TMICS).

Previous studies have shown associations between prenatal phthalate exposure and neurobehavioral changes in children. However, few studies have focused on neonatal neurobehavioral development. This study aimed to examine the associations between prenatal phthalate exposure and neonatal neurobehavioral development in the early days of life after birth. This cohort study included 283 mother-infant pairs who participated in the Taiwan Mother Infant Cohort Study during 2012-2015. Each mother was interviewed, and urine samples were collected during the third trimester of pregnancy (weeks 29-40). Eleven common phthalate metabolites in maternal urine were analyzed. The Chinese version of the Neonatal Neurobehavioral Examination was used to evaluate early infant neurobehavioral development within five days of birth. We performed multiple linear regressions to explore the associations between phthalate exposure and neonatal neurobehavioral development. Sex differences in the association between phthalate metabolites and neonatal neurobehaviors were noted. Among girls, tertiles of phthalate metabolite concentrations were associated with worse behavioral responses and tone and motor patterns in the high-molecular-weight phthalate (HMW) and low-molecular-weight phthalate (LMW) groups. Girls in the highest tertile of di-2-ethylhexyl phthalate (DEHP) and mono-isobutyl phthalate (MiBP) had a negative association with tone and motor patterns. Girls in the highest tertile of mono-n-butyl phthalate (MnBP) and MiBP showed a negative association with behavioral responses. In contrast, tertiles of phthalate metabolite exposure were associated with improved neurobehaviors in mono-methyl phthalate (MMP) among boys. The highest tertile of MMP was positively associated with behavioral responses, primitive reflexes, and tone and motor patterns. Our findings suggest that maternal phthalate exposure affects neonatal neurobehavioral development in a sex-specific manner. Despite the relatively small sample size, our findings add to the existing research linking maternal phthalate exposure to neonatal neurobehavioral development. Additional research is needed to determine the potential long-term effects of prenatal phthalate exposure on children.

Aspergillus sensitization associated with current asthma in children in the United States: an analysis of data from the 2005-2006 NHANES.

OBJECTIVES: This study investigated the association between allergen sensitization and current asthma in children in the United States using data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES). METHODS: Children who participated in the 2005-2006 NHANES, aged 6 years to 19 years, were included in this study. A structured questionnaire was used to assess asthma status (without asthma, asthma in remission, or current asthma). Nineteen specific immunoglobulin E (sIgE) levels were measured using the Pharmacia Diagnostics ImmunoCAP 1000 System (Kalamazoo, MI, USA). A machine-learning method was applied to select important sIgEs related to childhood asthma. Multivariate regression analysis was used to test this hypothesis. RESULTS: In total, 2,875 children were recruited. The prevalence of ever having asthma and current asthma was 16.5% and 5.6%, respectively. Six sIgE levels were found to contribute to asthma using bootstrap forest selection. After adjusting for the child's sex, age, and family income, children with double the sIgE levels of Dermatophagoides farinae, dogs, and Aspergillus were more likely to have current asthma than children without asthma (odds ratio [95% confident interval]: 1.11 [1.04 to 1.19], 1.30 [1.16 to 1.46], and 1.55 [1.39 to 1.72], respectively). CONCLUSIONS: Our findings suggest that allergen sensitization, especially to Aspergillus, is associated with current asthma in children. Strategies to reduce sensitization may help prevent and manage asthma.

Benchmark dose in the presence of coexposure to melamine and diethylhexyl phthalate and urinary renal injury markers in pregnant women.

Environmental exposures to mixtures of toxic chemicals have potential interaction effects that may lead to hazard index values exceeding one. However, current regulation levels, such as tolerable daily intake (TDI), are mostly based on experimental studies conducted with a single chemical compound. In this study, we assessed the relationships between melamine and di-(2-ethylhexyl) phthalate (DEHP) exposure and their coexposure with the early renal injury markers N-acetyl -D-glucosaminidase (NAG), albumin/creatinine ratio (ACR), and microalbuminuria in 1236 pregnant women. Various generalized linear models with interaction terms and Bayesian kernel machine regression models were used for the (co-)exposure response associations. We derived the benchmark dose (BMD) and the corresponding one-sided 95% confidence bound BMDL based on the estimated (covariate-adjusted) average daily intake of melamine and DEHP metabolites measured in spot urine of the women collected during the third trimester. Given a benchmark response of 0.1, the BMDL level of melamine (DEHP) exposure on NAG (ACR, microalbuminuria) was 2.67 (11.20, 4.45) µg/kg_bw/day, and it decreased to as low as 1.46 (3.83, 2.73) µg/kg_bw/day when considering coexposure to DEHP (melamine) up to the 90th percentile. Both the exposure threshold levels of melamine and DEHP for early renal injuries in pregnant women were several-fold to one order lower than the current recommended TDIs by the WHO and the US FDA and EPA and were even lower considering coexposure. Because of concurrent exposures in real-world environments, more stringent regulation levels are recommended in susceptible populations, such as pregnant women, due to potential synergistic mixture effects.

Di-(2-ethylhexyl) phthalate exposure links to inflammation and low bone mass in premenopausal and postmenopausal females: Evidence from ovariectomized mice and humans.

OBJECTIVE: Phthalates induce inflammation and are ubiquitously used in daily life. We aim to study the impact of di-(2-ethylhexyl) phthalate (DEHP) exposure on inflammation and osteoporosis in premenopausal and postmenopausal females. METHODS: Female 8-week-old C57BL/6JNarl mice received an ovariectomy (OVX) or a sham operation and were fed with DEHP or vehicle by oral gavage for 4 or 8 weeks. Their femurs were isolated for micro-computed tomography, and their serum was collected for inflammatory cytokine assays. Correlations between urinary phthalate metabolites and the lumbar spine bone mineral density (BMD) in premenopausal and postmenopausal volunteers were performed. RESULTS: Among the OVX mice treated for 4 weeks, significant lower bone volume, bone volume/tissue volume, and trabecular number but significant higher trabecular bone pattern factor and structure model index were identified in the mice treated with DEHP than with vehicle. The OVX mice treated with DEHP for 4 weeks had significantly higher serum interleukin (IL)-1ß, IL-10, IL-17A, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and Dickkopf-1 levels than those treated with vehicle. The sham mice treated with DEHP for 8 weeks showed an impaired femur trabecular microstructure and had significantly higher serum IL-1ß, IL-6, IL-10, IL-17A, IFN-γ, and TNF-α than those treated with vehicle. DEHP metabolites were inversely correlated with the BMD of premenopausal women and the T-score of postmenopausal women. CONCLUSION: DEHP treatment in OVX and sham mice results in osteoporosis and impairs the microstructure of the femur trabecula through inflammation. Phthalate exposure negatively affects the bone mass in both premenopausal and postmenopausal women. Thus, long-term avoidance is suggested.

Relationship of maternal body weight and gestational diabetes mellitus with large-for-gestational-age babies at birth in Taiwan: The TMICS cohort.

OBJECTIVE: To determine if both gestational diabetes mellitus (GDM) and maternal overweight/obesity are independently associated with delivery of large-for-gestational-age (LGA) babies in Taiwan. MATERIALS AND METHODS: Anthropometric parameters were measured and 75-g oral glucose-tolerance tests were administered to a cohort of 1428 pregnant women at 24-28 weeks gestation at nine hospitals in Taiwan. GDM was diagnosed based on the International Association of Diabetes and Pregnancy Study Groups criteria. Reported pre-pregnancy BMI and measured BMI during pregnancy were recorded at the late stage of the second trimester and the third trimester. Neonatal anthropometrics were measured at delivery. Primary outcome was LGA, defined in this study as having a birth weight ≥90th percentile for gestational age defined by WHO or a Chinese growth reference, taking into consideration the racial/ethnic and environmental differences in growth around the world. Multiple logistic regression was used to examine associations of GDM and maternal overweight/obesity with outcomes. RESULTS: Based on WHO growth reference definition of LGA, subjects with pre-pregnancy BMI ≥24 and pregnancy BMI >28.4 were found to be 2.46 times (0.76-7.97) and 3.28 times (1.01-10.60), respectively, more likely to deliver LGA babies than subjects with normal pre-pregnancy and pregnancy BMIs. Compared to those without GDM, subjects with GDM were 7.55 (1.62-35.25) times more likely to deliver LGA babies. The odds ratios for delivering a baby with a birth weight ≥90th percentile were 11.40 (1.65-78.75) for those with GDM alone, 4.10 (1.07-15.65) for those with overweight/obesity alone and 15.75 (1.30-190.40) for those with both GDM and overweight/obesity, compared to those with no GDM and no overweightness. Women with both pre-pregnancy and pregnancy overweightness/obesity were 3.64 (1.07-12.34) times more likely to deliver LGA. The above results remained similar when analyzing data based on Chinese growth reference definition of LGA. CONCLUSION: Maternal overweightness/obesity and GDM are independently associated with LGA. Their combination had a greater impact than either one alone.

Longitudinal changes in oxidative stress and early renal injury in children exposed to DEHP and melamine in the 2011 Taiwan food scandal.

In 2011, phthalates, mainly di-(2-ethylhexyl) phthalate (DEHP), were found to have been added to a variety of foods in Taiwan, increasing the risk of microalbuminuria in children. Exposure to melamine perhaps modifies that risk. This prospective cohort study investigates whether renal injury resulting from exposure to DEHP-tainted foods from the 2011 Taiwan Food Scandal is reversed over time. The temporal and interactive effects of past daily DEHP intake, current daily DEHP intake, and urinary melamine levels on oxidative stress and renal injury were also examined. Two hundred possibly DEHP-affected children (aged < 18 years) were enrolled in the first survey wave (August 2012-January 2013), with 170 and 159 children in the second (July 2014-February 2015) and third waves (May 2016-October 2016), respectively. The first wave comprised questionnaires that were used to collect information about possible past daily DEHP intake from DEHP-tainted foods. One-spot first morning urine samples were collected to measure melamine levels, phthalate metabolites, and markers indicating oxidative stress (malondialdehyde and 8-oxo-2'-deoxyguanosine), and renal injury (albumin/creatinine ratio (ACR) and N-acetyl-beta-D-glucosaminidase) in all three waves. Generalized estimating equation (GEE) modeling revealed that both past daily DEHP intake and time might affect urinary ACR. However, most interactions were negative and significant correlation was observed only during the second wave (P for interaction = 0.014) in the group with the highest past daily DEHP intake (>50 µg/kg/day). Urinary melamine levels were found to correlate significantly with both urinary ACR and oxidative stress markers. The highest impact associated with exposure to DEHP-tainted foods in increasing urinary ACR of children was observed during the first wave, and the effect may partially diminish over time. These results suggest that continuous monitoring of renal health and other long-term health consequences is required in individuals who were affected by the scandal in 2011.

The sex-specific association of prenatal phthalate exposure with low birth weight and small for gestational age: A nationwide survey by the Taiwan Maternal and Infant Cohort Study (TMICS).

The Taiwan Maternal and Infant Cohort Study (TMICS) was launched with the aim to assess the effects of prenatal exposure to phthalic acid esters (PAEs) on infant health. A total of 1102 pregnant women were enrolled in this study from 2012 to 2015. All participants completed a structured questionnaire, and provided urine specimens. The urinary concentrations of PAE metabolites in the third trimester were measured using liquid chromatography-electrospray ionization tandem mass spectrometry. Generalized additive model-penalized regression splines and logistic regression models were employed to determine the risk for low birth weight (LBW) or small for gestational age (SGA) among pregnant women exposed to PAEs. After adjustments for other covariates, each incremental unit of ln-transformed mono-n-butyl phthalate (MnBP) for pregnant women increased the odds of SGA in male neonates by 1.44 (95% CI: 0.92-2.23). An inverse association between SGA and maternal MnBP exposure level was observed in female neonates. An increase in one ln-transformed MnBP concentration unit decreased the risk of female SGA to 0.50 (95% CI: 0.24-0.97). In the penalized regression splines, increased risks of LBW/SGA in male neonates were presented while pregnant women exposed to increased MnBP levels. However, an association in the opposite direction was observed between maternal MnBP and LBW or SGA for male and female neonates. This study indicated that high maternal MnBP exposure in the third trimester was associated with LBW or SGA for male infants. Adverse effects on susceptible populations exposed to high levels of PAEs should be of concern.

Food Processing and Phthalate Exposure: The Nutrition and Health Survey in Taiwan (1993-1996 and 2005-2008).

Background: Phthalates esters are widely used commercially and can leach from a food container or food packaging. Few studies have been conducted in Asia regarding food processed to varying levels and human phthalate exposure. This study aimed to evaluate the association between unprocessed and ultra-processed food intake and urinary phthalate metabolite levels in the Taiwanese adult population. Methods: A total of 516 participant data were extracted from the cross-sectional 1993-1996 and 2005-2008 Nutrition and Health Survey in Taiwan of those aged over 18 years, where urinary measures and one 24-h dietary recall were collected. Urinary concentrations of dimethyl phthalate, diethyl phthalate, dibutyl phthalate, butyl benzyl phthalate, and di-(2-ethylhexyl) phthalate metabolites including monomethyl phthalate, monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate, mono-(2-ethylhexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate were measured in spot urine samples. The NOVA food processing classification system was applied to divide all consumed foods into four mutually exclusive groups including unprocessed or minimally processed, processed culinary ingredients, processed and ultra-processed food. Generalized linear models were employed to examine the associations between the percentage quartiles (Qs) of unprocessed and ultra-processed foods in the total weight of food and the urinary phthalate metabolites. Results: Compared with participants in the lowest quartiles (Q1) of ultra-processed food intake, highest ultra-processed food intake (Q4) had 65.7% (95% confidence interval [CI]: 4.83, 162) higher urinary concentrations of MEP after adjusted for covariates. In contrast, the higher unprocessed food consumption was inversely associated with urinary concentrations of MEP and MBP (P for trend = 0.03). When compared to the lowest unprocessed food consumers (Q1), higher consumers (Q4) presented 38.6% (95% CI: -61.3, -2.59) lower MEP concentrations and 23.1% (95% CI: -38.5, -3.71) lower MBP concentrations. Conclusion: Ultra-processed food consumption was associated with increased concentrations of urinary MEP. Conversely, consuming unprocessed food was associated with lower concentrations of MEP and MBP in the Asian Taiwanese adult population.

Association Between Prenatal Exposure to Metals and Atopic Dermatitis Among Children Aged 4 Years in Taiwan.

Importance: The prevalence of atopic dermatitis has substantially increased in recent decades, and atopic dermatitis could lead to allergic airway inflammation later in life. A previous study found that inorganic arsenic exposure was associated with allergic airway inflammation in children aged 8 to 14 years. However, the association between prenatal exposure to arsenic and other metals and the risk of atopic dermatitis among young children remains unknown. Objective: To assess the association between prenatal exposure to arsenic and other metals and the occurrence of atopic dermatitis in children at age 4 years. Design, Setting, and Participants: In total, 1152 pregnant women were enrolled in the original Taiwan Maternal and Infant Cohort Study (TMICS), a multicenter birth cohort study conducted at 9 hospitals in northern, central, southern, and eastern Taiwan from October 2012 to May 2015. Of those, 586 mothers and children aged 4 years participated in follow-up questionnaire interviews from August 2016 to January 2019. After excluding 216 participants with missing data, the final statistical analysis of follow-up data included 370 mother and child pairs from the central and eastern regions of Taiwan. Data were analyzed from February 2 to August 12, 2021. Exposures: Arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc during pregnancy. Main Outcomes and Measures: The outcome was parent-reported atopic dermatitis history among children aged 4 years. The presence of atopic dermatitis was defined as a positive response to the question, "Has your child ever had atopic dermatitis diagnosed by a physician?" During the initial TMICS study period, concentrations of arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc were measured in maternal urine during the third trimester of pregnancy using an inductively coupled plasma mass spectrometer. Estimated total inorganic arsenic exposure was calculated using a model that included data on both total arsenic and arsenic species (arsenite, arsenate, monomethylarsonate, and dimethylarsenate) obtained from a previous TMICS cohort. Results: Among 370 children included in the analysis, the mean (SD) age was 3.94 (0.59) years; 208 children (56.2%) were male, and 267 children (72.2%) were from the central region of Taiwan. A total of 110 children (29.7%) had atopic dermatitis at age 4 years. Maternal estimated total inorganic arsenic exposure during pregnancy was associated with increased odds of atopic dermatitis among children at age 4 years (odds ratio [OR], 2.42 [95% CI, 1.33-4.39] for every doubled increase of total inorganic arsenic) after adjusting for parental allergies, child's sex, geographic area, maternal educational level, and exposure to tobacco smoke. Every increased unit in the weighted quantile sum index of maternal metal exposure was significantly associated with atopic dermatitis (OR, 1.63; 95% CI, 1.28-2.07). Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal mixture index. Conclusions and Relevance: This cohort study found that prenatal exposure to inorganic arsenic and coexposure to inorganic arsenic and cadmium were associated with a higher risk of atopic dermatitis in young children. These findings suggest that prevention of exposure to inorganic arsenic and cadmium during pregnancy may be helpful for the control of atopic dermatitis and other potential allergies in children.