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Associations between maternal plasma measurements of inflammatory markers and urinary levels of phenols and parabens during pregnancy: A repeated measures study.

ABSTRACT: BACKGROUND:Maternal immune system regulation is critical for maintenance of a healthy pregnancy and fetal development. Exposure to phenols and parabens is widespread, and may be linked to systemic inflammation and alteration of circulating immunological biomarkers. OBJECTIVE:We sought to characterize associations between repeated measures of individual urinary phenols, parabens and plasma inflammatory markers across pregnancy. METHODS:In the LIFECODES prospective birth cohort, we conducted a nested preterm birth case-control study, including 130 cases and 352 controls. In urine samples collected from each participant at up to four study visits during pregnancy, we measured concentrations of six phenols and four parabens, as well as five plasma inflammatory markers. We used multivariable linear mixed models to analyze repeated measures of exposures on inflammatory markers. We created and applied inverse probability weights to account for the sampling approach. RESULTS:We observed bidirectional associations between select phenols and parabens and inflammatory markers. An interquartile range increase in triclosan (55.2?ng/mL) was associated with a 12.5% (95% CI: 3.67, 22.0) increase in C-reactive protein, a 7.95% (95% CI: 1.95, 14.3) increase in interleukin 10, and a 7.93% (95% CI: 3.82, 12,2) increase in tumor necrosis factor-?. Additionally, an interquartile range increase in 2,5-dichlorophenol (11.0?ng/mL) was associated with a 10% increase in C-reactive protein (95% CI: 1.92, 18.7). Conversely, an interquartile range increase in ethyl paraben (10.4?ng/mL) was associated with a 7.7% decrease in interleukin?1? (95% CI: -14.1, -0.86). CONCLUSIONS:Our findings can be organized into two thematic frameworks, one where concentrations of urinary phenols and parabens during pregnancy reflected a pro-inflammatory relationship with immunological biomarkers, and the other contrary theme - an anti-inflammatory relationship. These findings have implications for fetal development and reproductive outcomes, and emphasize the need for further research on immunological mechanisms of phenol and paraben action during pregnancy.

SUBMITTER: Aung MT

PROVIDER: S-EPMC6236678 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Associations between maternal plasma measurements of inflammatory markers and urinary levels of phenols and parabens during pregnancy: A repeated measures study.

Aung Max T MT Ferguson Kelly K KK Cantonwine David E DE Bakulski Kelly M KM Mukherjee Bhramar B Loch-Caruso Rita R McElrath Thomas F TF Meeker John D JD

The Science of the total environment 20180829 Pt 1

<h4>Background</h4>Maternal immune system regulation is critical for maintenance of a healthy pregnancy and fetal development. Exposure to phenols and parabens is widespread, and may be linked to systemic inflammation and alteration of circulating immunological biomarkers.<h4>Objective</h4>We sought to characterize associations between repeated measures of individual urinary phenols, parabens and plasma inflammatory markers across pregnancy.<h4>Methods</h4>In the LIFECODES prospective birth coho ...[more]

PMID: 30308801

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Project description:BACKGROUND:A number of phenols and parabens are added to consumer products for a variety of functions, and have been found at detectable levels in the majority of the U.S. POPULATION:Among other functions, thyroid hormones are essential in fetal neurodevelopment, and could be impacted by the endocrine disrupting effects of phenols and parabens. The present study investigated the association between ten maternal urinary phenol and paraben biomarkers (bisphenol S, triclosan, triclocarban, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, and ethyl, butyl, methyl and propyl paraben) and four plasma thyroid hormones in 439 pregnant women in a case-control sample nested within a cohort study based in Boston, MA. METHODS:Urine and blood samples were collected from up to four visits during pregnancy (median weeks of gestation at each visit: Visit 1: 9.64, Visit 2: 17.9, Visit 3: 26.0, Visit 4: 35.1). Linear mixed models were constructed to take into account the repeated measures jointly, followed by multivariate linear regression models stratified by gestational age to explore potential windows of susceptibility. RESULTS:We observed decreased total triiodothyronine (T3) in relation to an IQR increase in benzophenone-3 (percent change [%?]?=?-2.07; 95% confidence interval [CI]?=?-4.16, 0.01), butyl paraben (%??=?-2.76; 95% CI?=?-5.25, -0.26) and triclosan (%??=?-2.53; 95% CI?=?-4.75, -0.30), and triclocarban at levels above the LOD (%??=?-5.71; 95% CI?=?-10.45, -0.97). A 2.41% increase in T3 was associated with an IQR increase in methyl paraben (95% CI?=?0.58, 4.24). We also detected a negative association between free thyroxine (FT4) and propyl paraben (%??=?-3.14; 95% CI?=?-6.12, -0.06), and a suggestive positive association between total thyroxine (T4) and methyl paraben (%??=?1.19; 95% CI?=?-0.10, 2.47). Gestational age-specific multivariate regression analyses showed that the magnitude and direction of some of the observed associations were dependent on the timing of exposure. CONCLUSION:Certain phenols and parabens were associated with altered thyroid hormone levels during pregnancy, and the timing of exposure influenced the association between phenol and paraben, and hormone concentrations. These changes may contribute to downstream maternal and fetal health outcomes. Additional research is required to replicate the associations, and determine the potential biological mechanisms underlying the observed associations.

Project description:BACKGROUND:Maintaining thyroid homeostasis during pregnancy is essential for normal fetal growth and development. Growing evidence suggests that phthalates interfere with normal thyroid function. Few human studies have investigated the degree to which phthalates may affect thyroid hormone levels in particularly susceptible populations such as pregnant women. OBJECTIVES:We examined the associations between repeated measures of urinary phthalate metabolites and plasma thyroid hormone levels in samples collected at up to four time points per subject in pregnancy. Additionally, we investigated the potential windows of susceptibility to thyroid hormone disturbances related to study visit of sample collection. METHODS:Data were obtained from pregnant women (n = 439) participating in a nested case-control study of preterm birth with 116 cases and 323 controls. We measured 9 phthalate metabolite concentrations in urine samples collected at up to four study visits per subject during pregnancy (median = 10, 18, 26, and 35 weeks of gestation, respectively). We also measured a panel of thyroid function markers in plasma collected at the same four time points per subject during pregnancy. RESULTS:Although our results were generally null, in repeated measures analyses we observed that phthalate metabolites were largely inversely associated with thyrotropin and positively associated with free and total thyroid hormones. Cross-sectional analyses by study visit revealed that the magnitude and/or direction of these relationships varied by timing of exposure during gestation. CONCLUSIONS:These results support previous reports showing the potential for environmental phthalate exposure to alter circulating levels of thyroid hormones in pregnant women. Citation: Johns LE, Ferguson KK, McElrath TF, Mukherjee B, Meeker JD. 2016. Associations between repeated measures of maternal urinary phthalate metabolites and thyroid hormone parameters during pregnancy. Environ Health Perspect 124:1808-1815;?http://dx.doi.org/10.1289/EHP170.

Project description:BackgroundExposure to certain phenols is ubiquitous because of their use in many consumer and personal care products. However, predictors of exposure have not been well characterized in most populations.ObjectivesWe sought to identify predictors of exposure and to assess the reproducibility of phenol concentrations across serial spot urine samples among Chinese adults.MethodsWe measured 2,4-dichlorophenol, 2,5-dichlorophenol, butyl paraben, methyl paraben, propyl paraben, benzophenone-3, bisphenol A, and triclosan in urine collected during 1997-2006 from 50 participants of the Shanghai Women's Health Study cohort and during 2002-2006 from 50 participants of the Shanghai Men's Health Study cohort. We investigated predictors of concentrations using the Satterthwaite t-test, and assessed reproducibility among serial samples using intraclass correlation coefficients (ICCs) and Spearman correlation coefficients (SCCs).ResultsCreatinine-corrected phenol concentrations were generally higher among women than men. Participants who had taken medicine within the previous 24 hr had higher concentrations of propyl paraben. Cigarette smoking was associated with lower concentrations of propyl and methyl parabens among men. Bottled water consumption was associated with higher bisphenol A, 2,4-dichlorophenol, and 2,5-dichlorophenol concentrations among women. Among men, reproducibility across serial samples was moderate for 2,4-dichlorophenol and 2,5-dichlorophenol (ICC = 0.54-0.60, SCC = 0.43-0.56), but lower for other analytes (ICC = 0.20-0.29). Reproducibility among women was low (ICC = 0.13-0.39), but increased when restricted to morning-only urine samples.ConclusionsAmong these 100 Shanghai residents, urinary phenol concentrations varied by sex, smoking, and consumption of bottled water. Our results suggest that a single urine sample may be adequate for ranking exposure to the precursors of 2,4-dichlorophenol and 2,5-dichlorophenol among men and, under certain circumstances, among women.

Project description:Adipokines, cytokines secreted by adipose tissue, may contribute to obesity-related metabolic disease. The role of environmental phenols and parabens in racial difference in metabolic disease burden has been suggested, but there is limited evidence. We examined the cross-sectional associations of urinary phenols and parabens with adipokines and effect modification by race. Urinary concentrations of 6 phenols (bisphenol-A, bisphenol-F, 2,4-diclorophenol, 2,5-diclorophenol, triclosan, benzophenone-3) and 4 parabens (methyl-paraben, ethyl-paraben, propyl-paraben, butyl-paraben) were measured in 2002-2003 among 1200 women (mean age = 52.6) enrolled in the Study of Women's Health Across the Nation Multi-Pollutant Study. Serum adipokines included adiponectin, high molecular weight (HMW)-adiponectin, leptin, soluble leptin receptor (sOB-R). Linear regression models were used to estimate the adjusted percentage change in adipokines per inter-quantile range (IQR) increase in standardized and log-transformed levels of individual urinary phenols and parabens. Bayesian kernel machine regression (BKMR) was used to evaluate the joint effect of urinary phenols and parabens as mixtures. Participants included white (52.5%), black (19.3%), and Asian (28.1%) women. Urinary 2,4-dichlorophenol was associated with 6.02% (95% CI: 1.20%, 10.83%) higher HMW-adiponectin and urinary bisphenol-F was associated with 2.60% (0.48%, 4.71%) higher sOB-R. Urinary methyl-paraben was associated with lower leptin in all women but this association differed by race: 8.58% (-13.99%, -3.18%) lower leptin in white women but 11.68% (3.52%, 19.84%) higher leptin in black women (P interaction = 0.001). No significant associations were observed in Asian women. Additionally, we observed a significant positive overall effect of urinary phenols and parabens mixtures in relation to leptin levels in black, but not in white or Asian women. Urinary bisphenol-F, 2,4-dichlorophenol and methyl-paraben may be associated with favorable profiles of adipokines, but methyl-paraben, widely used in hair and personal care products, was associated with unfavorable leptin levels in black women. Future studies are needed to confirm this racial difference.

Project description:BackgroundThe balance between oxidative stress and antioxidant enzymes is one biological mechanism by which environmental and lifestyle exposures affect health outcomes. Yet, no studies have examined the relationship between environmental phenolic compounds and parabens or their mixtures in relation to antioxidant enzyme activity in women of reproductive age.MethodsSixteen environmental phenols and parabens were measured in urine 2-5 times across two months of follow-up in 143 women aged 18-44 years. Four antioxidant enzymes, erythrocyte and plasma glutathione peroxidase (eGPx, pGPx), glutathione reductase (GSHR), superoxide dismutase (SOD) were measured in plasma. Linear mixed models were adjusted for age, body mass index, race, and creatinine and were weighted with inverse probability of exposure weights. Multi-chemical exposures were estimated using hierarchical principal component analysis (PCA).ResultsIn line with our hypothesis that environmental phenols and parabens would be associated with decreased antioxidant enzymes, butyl, benzyl, ethyl, and propyl parabens were associated with lower levels of eGPx. Methyl paraben, 2,4-dichlorophenol and 2,5-dichlorophenol were associated with reduced SOD. 2,4,6-trichlorophenol was associated with increased levels of pGPx and GSHR. Several parabens were associated with modest decreases in eGPx and SOD, biomarkers of antioxidant defense. Increases in pGPx and GSHR were noted in relation to butyl and ethyl parabens. Co-exposures to parabens were associated with decreased eGPx (β = -1.08, 95% CI: -1.74, -0.43) in principal components mixed models, while co-exposure to benzophenones-3 and -1 were associated with increased eGPx (β = 0.92, 95% CI: 0.20, 1.64).ConclusionThese findings indicate that nonpersistent chemicals altered antioxidant enzyme activity. Further human studies are necessary to delineate the relationship between environmental phenol and paraben exposures with erythrocyte and plasma activities of antioxidant enzymes.

Dataset Information

Associations between maternal plasma measurements of inflammatory markers and urinary levels of phenols and parabens during pregnancy: A repeated measures study.

Publications

Associations between maternal plasma measurements of inflammatory markers and urinary levels of phenols and parabens during pregnancy: A repeated measures study.

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