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1.
JAMA Netw Open ; 4(10): e2131327, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34705012

RESUMO

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.

2.
PLoS One ; 15(12): e0243761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315949

RESUMO

BACKGROUND: Because there are no published biochemical reference intervals (RI) for pregnant Taiwanese women, we used an established islandwide birth cohort, the Taiwan Maternal and Infant Cohort Study, to establish RIs for important biochemical parameters in women during their 3rd trimester in Taiwan. Additionally, we compared the differences in these biochemical parameters between early third trimester (weeks 28 to 31) and late third trimester (weeks 37 to 40) of pregnant women as well as the differences in them between the third trimester and after delivery. METHODS: Between 2012 and 2015, we recruited a total of 2,136 pregnant women from nine hospitals located in northern (n = 3), central (n = 3), southern (n = 2), and eastern Taiwan (n = 1) to receive regular prenatal health examinations during their third trimester (weeks 28 to 40). After exclusion, samples obtained from 993 eligible pregnant women were analyzed. RESULTS: There were increases in both lower and upper normal limits for blood neutrophil, thyroid profile (triiodothyronine (T3) and thyroxine (T4)), testosterone, estradiol, and progesterone and decreases for RBC, hemoglobin (Hb), alanine aminotransferase (ALT) and creatinine (Cr) during their third trimesters. Women in their late third trimester (n = 378) had higher median RBC, Hb, aspartate aminotransferase (AST), Cr, thyroid-stimulating hormone (TSH), testosterone, estradiol, and progesterone and lower median platelet and insulin, compared with those in their early third trimester (n = 490). Twenty-three of the women had both third trimester and post-pregnancy data. After delivery, the women had lower median AST, ALT, insulin, T3, T4, testosterone, estradiol, and progesterone and higher median Cr, free T4, FSH, and luteinizing hormone (LH), compared to their third trimesters. CONCLUSIONS: Gestation-related changes in important biochemical parameters should be considered when evaluating clinical laboratory values in pregnant women.


Assuntos
Testes de Química Clínica/normas , Testes Hematológicos/normas , Primeiro Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/sangue , Adulto , Alanina Transaminase/sangue , Alanina Transaminase/normas , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/normas , Índice de Massa Corporal , Estudos de Coortes , Estradiol/sangue , Estradiol/normas , Feminino , Humanos , Contagem de Leucócitos , Neutrófilos/citologia , Período Pós-Parto , Gravidez , Gestantes , Valores de Referência , Hormônios Tireóideos/sangue , Hormônios Tireóideos/normas
3.
Environ Int ; 145: 106134, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33011549

RESUMO

Phthalic acid esters (PAE) are widely used during chemical synthesis and do not form covalent linkages with products. It has been reported that exposure to PAE affects the immune response. However, their effect on antibody concentrations in children is still under investigation. We aimed to examine the association between early-life phthalate exposure and antibody concentrations in children in a longitudinal birth cohort established in 2000-2001. We recruited 398 neonates in central Taiwan and followed them up every 2-3 years, with various antibody-related studies at 11- and 14-year follow-ups. Seven urinary phthalate metabolites were quantified in mothers during pregnancy and children aged 11 years. Four antibody concentrations were analyzed in children aged 11 and 14 years. The percent change in antibody concentrations from ages 11 to 14 years was calculated and its association with phthalate exposure was evaluated via multivariate regression analysis. Eighty-one followed-up children were with sufficient data. After adjusting for prenatal exposure and other confounders, double concentrations of the urinary sum of di-2-ethylhexyl phthalate (ΣDEHPm) and mono-n-butyl phthalate (MnBP) were associated with a 18.06% (95% CI = 3.34%, 32.78%) and 22.53% decrease (95% CI = 3.39%, 41.66%) in antibody concentration against hepatitis B, respectively. Phthalate exposure was found to be related to decreased antibody concentrations against hepatitis B (DEHP, DBnP) in the early teens. This exposure is suggested to be considered for clinical re-booster vaccines among junior high school students. Further verification with additional cohorts and studies on the underlying mechanisms of phthalate exposure are warranted.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Criança , Estudos de Coortes , Exposição Ambiental , Ésteres , Feminino , Seguimentos , Humanos , Recém-Nascido , Gravidez , Taiwan , Vacinação
4.
Environ Res ; 181: 108902, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31785779

RESUMO

BACKGROUND: Phthalic acid esters are established as endocrine disruptors. The study aimed to evaluate the association between urinary phthalate metabolites and prostate cancer occurrence. METHODS: The study was based on the Taiwan Community-Based Cancer Screening Program, which was set up in 1991-1992 and followed periodically. By 2010, 80 incident prostate cancer cases were identified in the 12,020 men. For each case, 2 controls were randomly selected, matched by age (±3 years), urine collection date (±3 months), and residential township. Frequently used phthalate metabolites from the urine samples were quantified by liquid chromatography/electrospray ionization tandem mass spectrometry. Logistic regression was conducted to assess the association between the exposure levels and prostate cancer occurrence. RESULTS: Exposure to di (2-ethylhexyl), butyl-benzyl and di-isobutyl phthalates (DEHP, BBzP, DiBP) was positively associated with prostate cancer in men with waist circumference (WC) ≥90 cm but not in the leans. Odds ratio for the DEHP metabolite summary score (upper tertile compared to the rest) and prostate cancer were 7.76 (95% CI = 1.95-30.9) for WC ≥ 90 cm. CONCLUSIONS: DEHP, BBzP, and DiBP exposure were associated with prostate cancer occurrence in abdominally obese men. The main limitation remains the lack of mechanistic experiments and comparable toxicological data.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Neoplasias da Próstata/epidemiologia , Estudos de Casos e Controles , Exposição Ambiental , Humanos , Masculino , Taiwan/epidemiologia
5.
Sci Total Environ ; 699: 134053, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31678884

RESUMO

Temperamental tendencies may form the basis of personality development, and specific personality constellations are associated with increased incidences of behavioural problems. Phthalic acid ester (PAE) has been associated with symptoms of attention deficit hyperactivity disorder (ADHD) in cross-sectional studies. We hypothesised that early-life exposure to PAE affects the temperaments of children, particularly ADHD traits. In this study, we analysed the temperament evaluations completed at least once by maternal-infant pairs (n = 208) when the child was aged 2, 5, and/or 11 years between 2000 and 2012. We measured seven PAE metabolites in the urine of the mothers during pregnancy and their children using liquid chromatography-electrospray ionisation-tandem mass spectrometry. These metabolites included mono-methyl phthalate, mono-ethyl phthalate, mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), and three metabolites of di (2-ethylhexyl) phthalate. The phthalate metabolite levels in pregnant women were significantly associated with a decreased threshold of responsiveness (coefficients from -0.21 to -0.46) and increased distractibility (coefficients from 0.23 to 0.46) in pre-school children. After adjustment for maternal exposure, the phthalate metabolite concentrations of the children exhibited significantly increased odds ratios (ORs) with respect to the ADHD symptom traits. Specifically, mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), the sum of the DEHP metabolites, and MBzP yielded ORs and 95% confidence intervals of 2.98 (1.05-8.48), 3.28 (1.15-9.35), and 9.12 (1.07-78.06), respectively, for every log10 creatinine unit (g/g creatinine) increase. Thus, early-life phthalate exposure was found to be associated with the behavioural characteristics of children, particularly temperamental traits associated with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Poluentes Ambientais/metabolismo , Exposição Materna/estatística & dados numéricos , Ácidos Ftálicos/metabolismo , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Gravidez
6.
Environ Res ; 172: 569-577, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30875510

RESUMO

OBJECTIVE: Longitudinal studies on neurobehavioral development in relation to prenatal and postnatal exposure to phthalates in school-age children and adolescents are limited. We investigated the association of prenatal and childhood phthalate exposure with the development of behavioral syndromes in 8-14-year-old children. METHOD: We recruited 430 pregnant women from 2000 to 2001 and followed their children at the ages of 2, 5, 8, 11, and 14 years, yielding 153 mother-child pairs in total. Urine samples from pregnant women in the third trimester and from children at 2-8 years of age were analyzed for the concentrations of seven urinary phthalate metabolites: monomethyl phthalate, monoethyl phthalate, monobutyl phthalate, monobenzyl phthalate (MBzP), and three di(2-ethylhexyl) phthalate (DEHP) metabolites, namely mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate. Behavioral syndromes in children aged 8-14 years were assessed using the Child Behavior Checklist. We constructed mixed models to examine these associations after adjustments for potential covariates. RESULTS: Maternal urinary MEHP levels were associated with higher scores for internalizing problems (ß = 0.028, 95% confidence interval [CI]: 0.0004, 0.055) and externalizing problems (ß = 0.040, 95% CI: 0.013, 0.066). Associations of the maternal urinary sum of DEHP metabolite levels with delinquent behavior scores and externalizing problems scores were positive (ß = 0.035, 95% CI: 0.013, 0.057 for delinquent behavior; ß = 0.026, 95% CI: 0.001, 0.050 for externalizing problems). Furthermore, children's urinary MBzP levels were associated with higher scores for social problems (ß = 0.018, 95% CI: 0.001, 0.035). Similar patterns were observed for borderline and clinical ranges. CONCLUSION: Early-life exposure to phthalates may influence behavioral syndrome development in children. Future studies are needed to replicate these findings, and efforts to reduce exposures to phthalates during critical early life stages may be warranted.


Assuntos
Comportamento , Poluentes Ambientais , Ésteres , Sistema Nervoso , Ácidos Ftálicos , Adolescente , Adulto , Comportamento/efeitos dos fármacos , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental , Poluentes Ambientais/toxicidade , Poluentes Ambientais/urina , Ésteres/toxicidade , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Sistema Nervoso/efeitos dos fármacos , Ácidos Ftálicos/análise , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/urina , Gravidez , Problemas Sociais
7.
Ecotoxicol Environ Saf ; 173: 37-44, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30753939

RESUMO

Cross-sectional studies have described an association between exposure to phthalate esters and cardiovascular risk factors. However, the association with coronary heart disease (CHD) is still unclear. A total of 180 subjects randomly selected from 336 CHD patients, and 360 age- and sex-matched non-CHD controls were included from 2008 to 2011. Urinary metabolites of phthalate esters were measured by liquid chromatography-tandem mass spectrometry. The geometric means of urinary phthalates metabolites were significantly higher for the three Di-(2-ethylhexyl)-phthalate (DEHP) metabolites, mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate among CHD patients in-hospital than those of being discharged. Excluding 89 CHD patients of in-hospital and hospital discharge within 2 days, we found the urinary concentrations of MEHP, mono-n-butyl phthalate (MnBP), and mono-isobutyl phthalate (MiBP) of 91 CHD patients discharged ≥ 3 days were higher than those of controls. Among 451 participants, those with higher tertile levels of urinary MEHP, MnBP, and MiBP showed an increased risk for CHD compared to those with lowest tertile levels; the corresponding odds ratios (95% CI) were 2.77 (1.22-6.28), 2.90 (1.32-6.4), and 3.19 (1.41-7.21), respectively, after adjustment for confounders. Higher levels of hs-CRP, fibrinogen, and D-dimer were linked with increased levels of all DEHP metabolites in CHD patients. In conclusion, exposure to DEHP and dibutyl phthalates was positively associated with CHD and this relationship may be probably mediated via atherothrombosis.


Assuntos
Doença das Coronárias/sangue , Doença das Coronárias/urina , Exposição Ambiental/análise , Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Adulto , Biomarcadores/sangue , Estudos Transversais , Poluentes Ambientais/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Ftálicos/química , Fatores de Risco
8.
Environ Sci Pollut Res Int ; 26(6): 6048-6064, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30612372

RESUMO

Toxic metal contamination in food products and the environment is a public health concern. Therefore, understanding human exposure to cadmium (Cd), lead (Pb), cobalt (Co), and copper (Cu) levels in the general population of Taiwan is necessary and urgent. We aimed to establish the human biomonitoring data of urine toxic metals, exposure profile changes, and factors associated with metal levels in the general population of Taiwan. We randomly selected 1601 participants older than 7 years of age (36.9 ± 18.7 years (7-84 years)) from the Nutrition and Health Survey in Taiwan (NAHSIT) conducted during 1993-1996 (93-96) and 2005-2008 (05-08) periods and measured the levels of four metals in the participants' urine samples using inductively coupled plasma-mass spectrometry. The median (range) levels of urinary Cd, Pb, Co, and Cu in participants from the NAHSIT 93-96 (N = 821)/05-08 (N = 780) were 0.60 (ND-13.90)/0.72 (ND-7.44), 2.28 (ND-63.60)/1.09 (0.04-48.88), 0.91 (0.08-17.30)/1.05 (0.05-22.43), and 16.87 (2.62-158.28)/13.66 (1.67-189.70) µg/L, respectively. We found that the urinary median levels of Pb and Cu in our participants were significantly lower in the NAHSIT 05-08 (Pb 1.09 µg/L, Cu 13.66 µg/L) than in the NAHSIT 93-96 (Pb 2.28 µg/L, Cu 16.87 µg/L; P < 0.01), whereas those of Cd and Co were significantly higher in the NAHSIT 05-08 (Cd 0.72 µg/L, Co 1.05 µg/L; P < 0.01). Youths had higher exposure levels of Pb, Co, and Cu than adults. Participants with alcohol consumption, betel quid chewing, or cigarette smoking had significantly higher median levels of urinary Pb or Cu (P < 0.01) than those without. Principal components and cluster analysis revealed that sex had different exposure profiles of metals. We concluded that levels of urinary Cd, Pb, Co, and Cu exposure in the general Taiwanese varied by age, sex, and lifestyles.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/urina , Metais Pesados/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Cádmio/urina , Criança , Cobalto/urina , Cobre/urina , Exposição Ambiental/estatística & dados numéricos , Monitoramento Ambiental , Feminino , Humanos , Chumbo/urina , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Taiwan , Adulto Jovem
9.
Sci Total Environ ; 648: 135-143, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30114584

RESUMO

BACKGROUND: Fetuses are susceptible to phthalates, known endocrine disrupting chemicals, within sensitive windows of development. It is crucial to determine the major sources of phthalates to reduce exposure. This study aims to examine the associations between usage patterns of personal care products (PCPs) and urinary levels of phthalate metabolites across pregnancy in a multi-hospital based birth cohort. METHODS: During 2012-2015, we conducted a birth cohort study named the Taiwan Mother Infant Cohort Study (TMICS). Usage patterns of PCPs were obtained using structured questionnaires during the third trimester of pregnancy. Spot urine samples were collected at each trimester, and levels of eleven phthalate metabolites were measured by liquid chromatography tandem mass spectrometry. The association of PCPs use with urinary phthalate metabolite concentrations was assessed using GEE models. RESULTS: Among the 1676 pregnant women participated in TMICS, 281 who provided two or three urine samples across pregnancy were included. The levels of several phthalate metabolites were significantly associated with the use of PCPs, particularly leave-on PCPs. With the increasing use of skin toners (11.7%; 95% CI: 1.5%, 22.9%), lipsticks (13.2%; 95% CI: 4.6%, 22.5%), and essential oils (21.8%; 95% CI: 9.1%, 36.0%), individuals are exposed to higher concentrations of mono-ethyl phthalate (MEP). Additionally, a positive trend was found regarding the number of leave-on PCPs used and the measured change in MEP concentrations (P for trend = 0.01). Other positive associations included MBzP and body lotions (7.9%; 95% CI: 0.1%, 16.2%). With regard to rinse-off PCPs, we found a positive association between urinary MBzP and shampoo use, and a negative association between urinary MMP and face wash. CONCLUSION: Leave-on PCPs were found to be a more probable source of phthalate exposure than the use of rinse-off PCPs. We suggest pregnant women reduce the frequency of leave-on PCPs use during pregnancy to avoid such phthalate exposure.


Assuntos
Cosméticos/metabolismo , Monitoramento Ambiental , Poluentes Ambientais/metabolismo , Exposição Materna , Ácidos Ftálicos/metabolismo , Adulto , Cromatografia Líquida , Estudos de Coortes , Feminino , Humanos , Gravidez , Terceiro Trimestre da Gravidez , Taiwan , Espectrometria de Massas em Tandem , Adulto Jovem
10.
Environ Int ; 118: 97-105, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29859944

RESUMO

BACKGROUND: Inorganic arsenic (iAs) exposure potentially causes diabetes and cardiovascular diseases in adults. However, its effect on glucose and lipid metabolism in early life remains unknown. OBJECTIVE: We evaluated the associations between early-life arsenic exposure and profiles of glucose and lipids in a 15-year birth cohort in central Taiwan. METHODS: We studied 237 adolescents through 5 waves of follow-up interviews and examinations at ages of approximately 2, 5, 8, 11, and 14 y. We obtained at least one follow-up urine measurement for arsenic species and blood sample collection up to 14 y of age and identified group-based trajectories of serial iAs by semiparametric mixture modeling. Multiple linear and logistic regressions were performed to assess the effect of the arsenic exposure trajectory on serum fasting glucose, total cholesterol (TCHO), triglycerides (TGs), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL). RESULTS: Three trajectories of postnatal arsenic exposure were identified, namely stable-low (31.4%), stable-high (48.2%), and rising-high (20.4%) groups. Compared with the stable-low trajectory group, the percent changes in TCHO and LDL was 14% (95% confidence interval 4-24%) and 23% (9-38%) for the group with "rising-high" trajectory and was 8% (-1-16%) and 16% (4-29%) for the group with "stable-high" trajectory. The rising-high group was also associated with an increase in the TCHO/HDL ratio by 14% (95% CI 3%-25%). The adjusted odds ratios of high developmental trajectories of TCHO, TG, LDL, and non-HDL levels were 4.0 (95% CI 1.2-13.7), 12.2 (2.2-67), 7.3 (1.8-30), and 3.6 (0.9-14.6), respectively, in the rising-high group (reference: stable-low group). CONCLUSION: Our findings suggest that conversion to an atherogenic lipid profile in adolescents may be associated with early-life exposure to environmental arsenic, particularly during the pre-adolescent period. An environmental modification approach for preventing As-related cardiovascular disease is recommended to begin early in life.


Assuntos
Arsênio/efeitos adversos , Aterosclerose/sangue , Aterosclerose/epidemiologia , Exposição Ambiental/estatística & dados numéricos , Lipídeos/sangue , Adolescente , Criança , Pré-Escolar , Seguimentos , Humanos , Metabolismo dos Lipídeos , Taiwan/epidemiologia
12.
Environ Res ; 162: 261-270, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29367177

RESUMO

BACKGROUND: Phthalic acid esters are ubiquitous and antiandrogenic, and may cause systemic effects in humans, particularly with in utero exposure. Epigenetic modification, such as DNA methylation, has been hypothesized to be an important mechanism that mediates certain biological processes and pathogenic effects of in utero phthalate exposure. OBJECTIVE: The aim of this study was to examine the association between genome-wide DNA methylation at birth and prenatal exposure to phthalate. METHODS: We studied 64 infant-mother pairs included in TMICS (Taiwan Maternal and Infant Cohort Study), a long-term follow-up birth cohort from the general population. DNA methylation levels at more than 450,000 CpG sites were measured in cord blood samples using Illumina Infinium HumanMethylation450 BeadChips. The concentrations of three metabolites of di-(2-ethylhexyl) phthalate (DEHP) were measured using liquid chromatography tandem-mass spectrometry (LC-MS/MS) in urine samples collected from the pregnant women during 28-36 weeks gestation. RESULTS: We identified 25 CpG sites whose methylation levels in cord blood were significantly correlated with prenatal DEHP exposure using a false discovery rate (FDR) of 5% (q-value < 0.05). Via gene-set enrichment analysis (GSEA), we also found that there was significant enrichment of genes involved in the androgen response, estrogen response, and spermatogenesis within those genes showing DNA methylation changes in response to exposure. Specifically, PA2G4, HMGCR, and XRCC6 genes were involved in genes in response to androgen. CONCLUSIONS: Phthalate exposure in utero may cause significant alterations in the DNA methylation in cord blood. These changes in DNA methylation might serve as biomarkers of maternal exposure to phthalate in infancy and potential candidates for studying mechanisms via which phthalate may impact on health in later life. Future investigations are warranted.


Assuntos
Metilação de DNA , Dietilexilftalato , Disruptores Endócrinos , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Cromatografia Líquida , Estudos de Coortes , Disruptores Endócrinos/toxicidade , Feminino , Humanos , Hidroximetilglutaril-CoA Redutases/metabolismo , Recém-Nascido , Autoantígeno Ku/metabolismo , Masculino , Exposição Materna , Ácidos Ftálicos/toxicidade , Gravidez , Proteínas de Ligação a RNA/metabolismo , Taiwan , Espectrometria de Massas em Tandem
13.
Epidemiology ; 28 Suppl 1: S10-S18, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29028671

RESUMO

BACKGROUND: Phthalates are widely used in industry, personal care products, and medications. Recent studies have suggested that phthalate exposure alters thyroid hormones. However, longitudinal studies concerning the association between phthalate exposure and thyroid function in children are scant. Therefore, we examined the association between pre- and postnatal phthalate exposure and thyroid function in children born in 2000-2001. METHODS: We studied 181 mother-child pairs in central Taiwan and followed-up the children from 2000 to 2009 at 2, 5, and 8 years old. We measured serum levels of thyroxine (T4), free T4, triiodothyronine (T3), and thyroid-stimulating hormone in children by using radioimmunoassay. We quantified seven phthalate metabolites, representing the five most commonly used phthalates, in maternal and child urine samples by using liquid chromatography-tandem mass spectrometry. The metabolites were monoethylhexyl phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) derived from di(2-ethylhexyl) phthalate (DEHP), monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), and monobenzyl phthalate (MBzP). We constructed a linear mixed model to examine these associations after adjustments for covariates. RESULTS: The T4 levels were inversely associated with maternal urinary MEHHP (ß = -0.028 [95% confidence interval (CI) = -0.051, -0.006]) and MEOHP (ß = -0.027 [-0.050, -0.003]), with similar T3 levels being observed in boys, even when the children exposure levels were considered spontaneously. In the girls, the free T4 levels were inversely associated with levels of maternal urinary MEP (ß = -0.042), maternal urinary MBzP (ß = -0.050), and children's urinary MEHP (ß = -0.027). CONCLUSIONS: Early life phthalate exposure was associated with decreased thyroid hormone levels in young children.


Assuntos
Exposição Ambiental , Ácidos Ftálicos/urina , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Dietilexilftalato/análogos & derivados , Dietilexilftalato/urina , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos , Taiwan , Testes de Função Tireóidea , Adulto Jovem
14.
J Epidemiol ; 27(11): 516-523, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28576446

RESUMO

BACKGROUND: Phthalate diesters are commonly used and have been well established as environmental endocrine disruptors. However, few studies have examined their effects on sex steroid hormones in children. We followed children over time to examine the association between pre- and post-natal phthalate exposure and sex steroid hormone levels at 2, 5, 8, and 11 years of age. METHODS: We recruited 430 pregnant women from central Taiwan from 2000 to 2001 and assessed their children at birth, 2, 5, 8, and 11 years of age. We studies children with at least one measurement for both phthalate and hormone levels during each any of the follow-up time point (n = 193). Estradiol, free testosterone, testosterone, and progesterone were measured from venous blood. Three monoesters of di-2-ethylhexyl phthalate (DEHP), mono-benzyl phthalate, mono-n-butyl phthalate, mono-ethyl phthalate, and mono-methyl phthalate were measured in maternal urine collected during the 3rd trimester and child urine collected at each follow-up point. The sum of mono-2-ethylhexyl phthalate (∑MEHP) was calculated by summing the concentrations of the three DEHP monoesters. Generalized estimating equation regression analysis with repeated measures was used to estimate associations between phthalate metabolites and hormone levels. RESULTS: After adjustment for potential confounders, maternal ∑MEHP level was associated with decreased levels of progesterone in girls (ß = -0.309 p = 0.001). The child ∑MEHP concentration was associated with decreased levels of progesterone for girls (ß = -0.194, p = 0.003) and with decreased levels of free testosterone for boys (ß = -0.124, p = 0.004). CONCLUSIONS: Early-life DEHP exposure may alter sex steroid hormones of children over time, which may pose potential reproductive health risks.


Assuntos
Exposição Ambiental/efeitos adversos , Hormônios Esteroides Gonadais/sangue , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/urina , Efeitos Tardios da Exposição Pré-Natal , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Projetos Piloto , Gravidez , Taiwan
15.
Int J Hyg Environ Health ; 220(5): 869-879, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28457892

RESUMO

Phthalate exposure is omnipresent and known to have developmental and reproductive effects in children. The aim of this study was to determine the phthalate exposure sources and their relative contributions among children in Taiwan. During the first wave of the Risk Assessment of Phthalate Incident in Taiwan (RAPIT), in 2012, we measured 8 urinary phthalate metabolites in 226 children aged 1-11 years old and in 181 children from the same cohort for the wave 2 study in 2014. A two-stage statistical analysis approach was adopted. First, a stepwise regression model was used to screen 80 questions that explored the exposure frequency and lifestyle for potential associations. Second, the remaining questions with positive regression coefficients were grouped into the following 6 exposure categories: plastic container/packaging, food, indoor environment, personal care products, toys, and eating out. A mixed model was then applied to assess the relative contributions of these categories for each metabolite. The use of plastic container or food packaging were dominant exposure sources for mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). The indoor environment was a major exposure source of mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), and mono-isobutyl phthalate (MiBP). The consumption of seafood showed a significant correlation with MEHP. The children's modified dietary behavior and improved living environment in the second study wave were associated with lower phthalate metabolite levels, showing that phthalate exposures can be effectively reduced.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Plastificantes/análise , Animais , Criança , Pré-Escolar , Crustáceos , Dieta , Feminino , Peixes , Contaminação de Alimentos , Embalagem de Alimentos , Humanos , Lactente , Masculino , Alimentos Marinhos , Inquéritos e Questionários , Taiwan
16.
PLoS One ; 12(4): e0175536, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28410414

RESUMO

BACKGROUND: In May 2011, a major incident involving phthalates-contaminated foodstuffs occurred in Taiwan. Di-(2-ethylhexyl) phthalate (DEHP) was added to foodstuffs, mainly juice, jelly, tea, sports drink, and dietary supplements. Concerns arose that normal pubertal development, especially reproductive hormone regulation in children, could be disrupted by DEHP exposure. OBJECTIVE: To investigate the association between phthalate exposure and reproductive hormone levels among children following potential exposure to phthalate-tainted foodstuffs. METHODS: A total of 239 children aged <12 years old were recruited from 3 hospitals in north, central, and south Taiwan after the episode. Structured questionnaires were used to collect the frequency and quantity of exposures to 5 categories of phthalate-contaminated foodstuffs to assess phthalate exposure in children. Urine samples were collected for the measurement of phthalate metabolites. The estimated daily intake of DEHP exposure at the time of the contamination incident occurred was calculated using both questionnaire data and urinary DEHP metabolite concentrations. Multiple regression analyses were applied to assess associations between phthalate exposure and reproductive hormone levels in children. RESULTS: After excluding children with missing data regarding exposure levels and hormone concentrations and girls with menstruation, 222 children were included in the statistical analyses. After adjustment for age and birth weight, girls with above median levels of urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and sum of mono-(2-ethylhexyl) phthalate concentrations had higher odds of above median follicle-stimulating hormone concentrations. Girls with above median estimated average daily DEHP exposures following the contamination episode also had higher odds of sex hormone-binding globulin above median levels. CONCLUSIONS: Phthalate exposure was associated with alterations of reproductive hormone levels in girls.


Assuntos
Dietilexilftalato/toxicidade , Contaminação de Alimentos , Puberdade/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Globulina de Ligação a Hormônio Sexual/metabolismo , Adolescente , Adulto , Criança , Suplementos Nutricionais , Dietilexilftalato/sangue , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hospitais , Humanos , Imunoensaio , Hormônio Luteinizante/sangue , Masculino , Taiwan , Testosterona/sangue , Adulto Jovem
17.
PLoS One ; 11(3): e0151070, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26960145

RESUMO

BACKGROUND: In May 2011, di(2-ethylhexyl) phthalates (DEHP) and, to a lesser extent, di-iso-nonyl phthalate (DiNP) were found to have been illegally used for many years in Taiwan as clouding agents in foods including sports drinks, juice beverages, tea drinks, fruit jam/nectar/jelly, and health or nutrient supplements. OBJECTIVE: To estimate the DEHP exposure for the study participants for the follow-up epidemiological study and health risk assessment. METHODS: A total of 347 individuals possibly highly exposed to phthalate-tainted foods participated in the study. Exposure assessment was performed based on the participants' responses to a structured questionnaire, self-report of exposure history, urinary metabolite concentrations, and DEHP concentration information in 2449 food records. A Bayesian statistical approach using Markov chain Monte Carlo simulation was employed to deal with the uncertainties in the DEHP concentrations of the contaminated foods and the participants' likelihood of being exposed. RESULTS: An estimated 37% and 15% of children younger than 12 years old were exposed to DEHP at medium (20-50 µg / kg_bw / day) and high AvDIs (50-100 µg / kg_bw / day), respectively, prior to the episode (9% and 3% in adults, respectively). Moreover, 11% of children and 1% of adults were highly exposed (> 100 µg / kg_bw / day), with a maximum of 414.1 µg / kg_bw / day and 126.4 µg / kg_bw / day, respectively. CONCLUSIONS: The phthalate exposure-associated adverse health effects for these participants warrant further investigation. The estimation procedure may be applied to other exposure assessment with various sources of uncertainties.


Assuntos
Bebidas/análise , Monitoramento Ambiental , Ácidos Ftálicos/análise , Adolescente , Adulto , Teorema de Bayes , Criança , Pré-Escolar , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/análise , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Medição de Risco , Inquéritos e Questionários , Taiwan/epidemiologia , Adulto Jovem
18.
Int J Hyg Environ Health ; 218(7): 603-15, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26163779

RESUMO

BACKGROUND: Some phthalic acid esters (PAEs) and nonylphenol (NP) are endocrine-disrupting chemicals (EDCs) that are widely used in consumer products. Consequently, the general population is exposed simultaneously to both groups of chemicals. OBJECTIVE: To investigate the single- and co-exposure effects of PAEs (DMP, DEP, DnBP, DiBP, BBzP, and DEHP) and NP on obesity and pubertal maturity to compare the body sizes of general adolescents with the complainants of the phthalate-tainted foods scandal that occurred in Taiwan. METHODS: This study included 270 general adolescents aged 6.5-15.0 years and 38 complainants aged 6.5-8.5 years. Nine metabolites of the five PAEs and of NP were measured in urine. We used a questionnaire to evaluate pubertal maturity, measured anthropometric indices (APs) to assess body size, and collected urine samples to measure the two groups of chemicals. RESULTS: We found that urinary PAE metabolite concentrations (specifically, metabolites of DEP, DnBP, DiBP, and DEHP) were positively associated with the APs for abdominal obesity (including skinfold thickness, waist circumference, waist-to-height ratio, and waist-to-hip) and indicated a dose-response relationship. Mono-methyl phthalate (MMP) exposure was inversely associated with pubarche among boys. The daily intake of DEHP in general adolescents exceeded the reference doses (RfD-20 µg/kgbw/day) and tolerable daily intake (TDI-50 µg/kgbw/day) by 3.4% and 0.4%, respectively. No associations were observed between NP exposure or co-exposure and the APs or pubertal maturity. No significant differences were observed between general adolescents and the complainants with regard to weight, height, or BMI. CONCLUSIONS: The study suggests that PAE (specifically, DEP, DnBP, DiBP, and DEHP) exposure is associated with abdominal obesity in adolescents and that the APs for abdominal obesity are more sensitive than BMI for measuring obesity among adolescents. We suggest that the RfD and TDI for PAEs should be revised to provide sufficient protection.


Assuntos
Peso Corporal/efeitos dos fármacos , Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Obesidade Pediátrica/etiologia , Fenóis/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Puberdade/efeitos dos fármacos , Adolescente , Antropometria , Tamanho Corporal/efeitos dos fármacos , Criança , Dietilexilftalato/efeitos adversos , Dietilexilftalato/urina , Disruptores Endócrinos/urina , Exposição Ambiental/análise , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/urina , Feminino , Contaminação de Alimentos , Humanos , Masculino , Obesidade Abdominal/etiologia , Obesidade Abdominal/urina , Obesidade Pediátrica/urina , Fenóis/urina , Ácidos Ftálicos/urina , Valores de Referência , Caracteres Sexuais , Taiwan
19.
PLoS One ; 10(6): e0131910, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26121592

RESUMO

Few studies have examined the association between environmental phthalate exposure and children's neurocognitive development. This longitudinal study examined cognitive function in relation to pre-and postnatal phthalate exposure in children 2-12 years old. We recruited 430 pregnant women in their third trimester in Taichung, Taiwan from 2001-2002. A total of 110, 79, 76, and 73 children were followed up at ages 2, 5, 8, and 11, respectively. We evaluated the children's cognitive function at four different time points using the Bayley and Wechsler tests for assessing neurocognitive functions and intelligence (IQ). Urine samples were collected from mothers during pregnancy and from children at each follow-up visit. They were analyzed for seven metabolite concentrations of widely used phthalate esters. These esters included monomethyl phthalate, monoethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, and three metabolites of di(2-ethylhexyl) phthalate, namely, mono-2-ethylhexyl phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate. We constructed a linear mixed model to examine the relationships between the phthalate metabolite concentrations and the Bayley and IQ scores. We found significant inverse associations between the children's levels of urinary mono(2-ethyl-5-oxohexyl) phthalate and the sum of the three metabolites of di(2-ethylhexyl) phthalate and their IQ scores (ß = -1.818; 95% CI: -3.061, -0.574, p = 0.004 for mono(2-ethyl-5-oxohexyl) phthalate; ß = -1.575; 95% CI: -3.037, -0.113, p = 0.035 for the sum of the three metabolites) after controlling for maternal phthalate levels and potential confounders. We did not observe significant associations between maternal phthalate exposure and the children's IQ scores. Children's but not prenatal phthalate exposure was associated with decreased cognitive development in the young children. Large-scale prospective cohort studies are needed to confirm these findings in the future.


Assuntos
Cognição/efeitos dos fármacos , Ácidos Ftálicos/toxicidade , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal
20.
Environ Sci Pollut Res Int ; 21(24): 13964-73, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25030786

RESUMO

Evidence has shown that polymorphisms of various genes known to be involved in estrogen biosynthesis and function are associated with estrogen-dependent diseases (EDDs). These genes include CYP17A1, estrogen receptor 1 (ESR1), and 2 (ESR2). Phthalates are considered estrogenic endocrine disruptors, and recent research has suggested that they may act as a risk factor for EDDs. However, extremely few studies have assessed the effects of gene-environment interaction on these diseases. We recruited 44 patients with endometriosis or adenomyosis, 36 patients with leiomyoma, and 69 healthy controls from a medical center in Taiwan between 2005 and 2007. Urine samples were collected and analyzed for seven phthalate metabolites using liquid chromatography tandem mass spectrometry. Peripheral lymphocytes were used for DNA extraction to determine the genotype of CYP17A1, ESR1, and ESR2. Compared to controls, patients with leiomyoma had significantly higher levels of total urinary mono-ethylhexyl phthalate (ΣMEHP) (52.1 vs. 29.6 µg/g creatinine, p = 0.040), mono-n-butyl phthalate (MnBP) (75.4 vs. 51.3 µg/g creatinine, p = 0.019), and monoethyl phthalate (MEP) (103.7 vs. 59.3 µg/g creatinine, p = 0.031). In contrast, patients with endometriosis or adenomyosis showed a marginally increased level of urinary MEHP only. Subjects who were homozygous for both the ESR1 C allele (rs2234693) and CYP17A1 C allele (rs743572) showed a significantly increased risk for leiomyoma (OR = 19.8; 95 % CI, 1.70; 231.5; p = 0.017) relative to subjects with other genotypes of ESR1 and CYP17A1. These results were obtained after adjusting for age, cigarette smoking, MEHP level, GSTM1 genotype and other covariates. Our results suggested that both CYP17A1 and ESR1 polymorphisms may modulate the effects of phthalate exposure on the development of leiomyoma.


Assuntos
Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Estrogênios/metabolismo , Ácidos Ftálicos/toxicidade , Polimorfismo Genético , Esteroide 17-alfa-Hidroxilase/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Poluentes Ambientais/toxicidade , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Regulação da Expressão Gênica , Genótipo , Humanos , Leiomioma/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Esteroide 17-alfa-Hidroxilase/genética , Taiwan
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