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A repeated measures study of phenol, paraben and Triclocarban urinary biomarkers and circulating maternal hormones during gestation in the Puerto Rico PROTECT cohort.

ABSTRACT: INTRODUCTION:Prenatal exposure to some phenols and parabens has been associated with adverse birth outcomes. Hormones may play an intermediate role between phenols and adverse outcomes. We examined the associations of phenol and paraben exposures with maternal reproductive and thyroid hormones in 602 pregnant women in Puerto Rico. Urinary triclocarban, phenol and paraben biomarkers, and serum hormones (estriol, progesterone, testosterone, sex-hormone-binding globulin (SHBG), corticotropin-releasing hormone (CRH), total triiodothyronine (T3), total thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH)) were measured at two visits during pregnancy. METHODS:Linear mixed models with a random intercept were constructed to examine the associations between hormones and urinary biomarkers. Results were additionally stratified by study visit. Results were transformed to hormone percent changes for an inter-quartile-range difference in exposure biomarker concentrations (%?). RESULTS:Bisphenol-S was associated with a decrease in CRH [(%? -11.35; 95% CI: -18.71, -?3.33), and bisphenol-F was associated with an increase in FT4 (%?: 2.76; 95% CI: 0.29, 5.22). Butyl-, methyl- and propylparaben were associated with decreases in SHBG [(%?: -5.27; 95% CI: -9.4, -?1.14); (%?: -3.53; 95% CI: -7.37, 0.31); (%?: -3.74; 95% CI: -7.76, 0.27)]. Triclocarban was positively associated with T3 (%?: 4.08; 95% CI: 1.18, 6.98) and T3/T4 ratio (%?: 4.67; 95% CI: -1.37, 6.65), and suggestively negatively associated with TSH (%?: -10.12; 95% CI: -19.47, 0.32). There was evidence of susceptible windows of vulnerability for some associations. At 24-28?weeks gestation, there was a positive association between 2,4-dichlorophenol and CRH (%?: 9.66; 95% CI: 0.67, 19.45) and between triclosan and estriol (%?: 13.17; 95% CI: 2.34, 25.2); and a negative association between triclocarban and SHBG (%?: -9.71; 95% CI:-19.1, -?0.27) and between bisphenol A and testosterone (%?: -17.37; 95% CI: -26.7, -?6.87). CONCLUSION:Phenols and parabens are associated with hormone levels during pregnancy. Further studies are required to substantiate these findings.

SUBMITTER: Aker AM

PROVIDER: S-EPMC6444601 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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A repeated measures study of phenol, paraben and Triclocarban urinary biomarkers and circulating maternal hormones during gestation in the Puerto Rico PROTECT cohort.

Aker Amira M AM Ferguson Kelly K KK Rosario Zaira Y ZY Mukherjee Bhramar B Alshawabkeh Akram N AN Calafat Antonia M AM Cordero José F JF Meeker John D JD

Environmental health : a global access science source 20190402 1

<h4>Introduction</h4>Prenatal exposure to some phenols and parabens has been associated with adverse birth outcomes. Hormones may play an intermediate role between phenols and adverse outcomes. We examined the associations of phenol and paraben exposures with maternal reproductive and thyroid hormones in 602 pregnant women in Puerto Rico. Urinary triclocarban, phenol and paraben biomarkers, and serum hormones (estriol, progesterone, testosterone, sex-hormone-binding globulin (SHBG), corticotropi ...[more]

PMID: 30940137

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Project description:BACKGROUND:Understanding important sources and pathways of exposure to common chemicals known or suspected to impact human health is critical to eliminate or reduce the exposure. This is particularly important in areas such as Puerto Rico, where residents have higher exposures to numerous chemicals, as well as higher rates of many adverse health outcomes, compared to the mainland US. OBJECTIVE:The aim of this study was to assess distributions, time trends, and predictors of urinary triclocarban, phenol, and paraben biomarkers measured at multiple times during pregnancy among women living in Northern Puerto Rico. METHODS:We recruited 1003 pregnant women between years 2010 and 2016 from prenatal clinics and collected urine samples and questionnaire data on personal care product use at up to three separate visits, between 16 and 28?weeks gestation. Urine samples were analyzed for triclocarban, seven phenols and four parabens: 2,4-dichlorophenol, 2,5-dichlorophenol, benzophenone-3, bisphenol A (BPA), bisphenol S (BPS), bisphenol F, triclosan, butylparaben, ethylparaben, methylparaben, and propylparaben. RESULTS:Detectable triclocarban, phenol and paraben concentrations among pregnant women were prevalent and tended to be higher than levels measured in women of reproductive age from the general US population, especially triclocarban, which had a median concentration 37 times higher in Puerto Rico participants (2.6 vs 0.07?ng/mL). A decreasing temporal trend was statistically significant for urine concentrations of BPA during the study period, while the BPA substitute BPS showed an increasing temporal trend. Significant and positive associations were found between biomarker concentrations with the products use in the past 48-h (soap, sunscreen, lotion, cosmetics). There was an increasing trend of triclocarban/triclosan urinary concentrations with increased concentrations of triclocarban/triclosan listed as the active ingredient in the bar soap/liquid soap products reported being used. CONCLUSION:Our results suggest several potential exposure sources to triclocarban, phenols, and parabens in this population and may help inform targeted approaches to reduce exposure.

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:Phenols and parabens are used in a multitude of consumer products resulting in ubiquitous human exposure. Animal and in vitro studies suggest that exposure to these compounds may be related to a number of adverse health outcomes, as well as potential mediators such as oxidative stress and inflammation. We examined urinary phenol (bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (24-DCP), 2,5-dichlorophenol (25-DCP)) and paraben (butyl paraben (B-PB), methyl paraben (M-PB), propyl paraben (P-PB)) concentrations measured three times during pregnancy in relation to markers of oxidative stress and inflammation among participants in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) project. Serum markers of inflammation (c-reactive protein (CRP), IL-1?, IL-6, IL-10, and tumor necrosis factor-? (TNF-?)) were measured twice during pregnancy (n=105 subjects, 187 measurements) and urinary markers of oxidative stress (8-hydroxydeoxyguanosine (OHdG) and isoprostane) were measured three times during pregnancy (n=54 subjects, 146 measurements). We used linear mixed models to assess relationships between natural log-transformed exposure and outcome biomarkers while accounting for within individual correlation across study visits. After adjustment for urinary specific gravity, study visit, maternal pre-pregnancy BMI, and maternal education, an interquartile range (IQR) increase in urinary BPA was associated with 21% higher OHdG (p=0.001) and 29% higher isoprostane (p=0.0002), indicating increased oxidative stress. The adjusted increase in isoprostane per IQR increase in marker of exposure was 17% for BP-3, 27% for B-PB, and 20% for P-PB (all p<0.05). An IQR increase in triclosan (TCS) was associated with 31% higher serum concentrations of IL-6 (p=0.007), a pro-inflammatory cytokine. In contrast, IQR increases in BP-3 and B-PB were significantly associated with 16% and 18% lower CRP, a measure of systemic inflammation. Our findings suggest that exposure to BPA, select parabens, and TCS during pregnancy may be related to oxidative stress and inflammation, potential mechanisms by which exposure to these compounds may influence birth outcomes and other adverse health effects, but additional research is needed.

Project description:BackgroundPrenatal exposure to certain xenobiotics has been associated with adverse birth outcomes. We examined the associations of triclocarban, phenols and parabens in a cohort of 922 pregnant women in Puerto Rico, the Puerto Rico Testsite for Exploring Contamination Threats Program (PROTECT).MethodsUrinary triclocarban, phenols and parabens were measured at three time points in pregnancy (visit 1: 16-20 weeks, visit 2: 20-24 weeks, visit 3: 24-28 weeks gestation). Multiple linear regression (MLR) models were conducted to regress gestational age and birthweight z-scores against each woman's log average concentrations of exposure biomarkers. Logistic regression models were conducted to calculate odds of preterm birth, small or large for gestational age (SGA and LGA) in association with each of the exposure biomarkers. An interaction term between the average urinary biomarker concentration and infant sex was included in models to identify effect modification. The results were additionally stratified by study visit to look for windows of vulnerability. Results were transformed into the change in the birth outcome for an inter-quartile-range difference in biomarker concentration (Δ).ResultsAverage benzophenone-3, methyl- and propyl-paraben concentrations were associated with an increase in gestational age [(Δ 1.90 days; 95% CI: 0.54, 3.26); (Δ 1.63; 95% CI: 0.37, 2.89); (Δ 2.06; 95% CI: 0.63, 3.48), respectively]. Triclocarban was associated with a suggestive 2-day decrease in gestational age (Δ - 1.96; 95% CI: -4.11, 0.19). Bisphenol A measured at visit 1 was associated with a suggestive increase in gestational age (Δ 1.37; 95% CI: -0.05, 2.79). Triclosan was positively associated with gestational age among males, and negatively associated with gestational age among females. Methyl-, butyl- and propyl-paraben were associated with significant 0.50-0.66 decreased odds of SGA. BPS was associated with an increase in the odds of SGA at visit 3, and a suggestive increase in the odds of LGA at visit 1.ConclusionBenzophenone-3, methyl-paraben and propyl-paraben were associated with an increase in gestational age. Concentrations of triclocarban, which were much higher than reported in other populations, were associated with a suggestive decrease in gestational age. The direction of the association between triclosan and gestational age differed by infant sex. Parabens were associated with a decrease in SGA, and BPS was associated with both SGA and LGA depending on the study visit. Further studies are required to substantiate these findings.

Project description:Phthalates are ubiquitous environmental exposures that may be implicated in inflammatory processes, as demonstrated by previous in vivo and in vitro studies. Few human studies have substantiated these observations. This study sought to examine whether maternal phthalate exposures impact inflammatory processes, as measured by circulating inflammatory biomarkers, in the PROTECT cohort in northern Puerto Rico. Inflammatory biomarkers included matrix metalloproteinases 1, 2, and 9 (MMPs), C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM), and intercellular cell adhesion molecule-1 (ICAM). Biomarkers were measured in maternal serum samples collected during pregnancy. 19 phthalate metabolites were assessed in urinary samples collected at three study visits across pregnancy. Phthalates with <50 % of measurements above the limit of detection were excluded from analysis. We utilized linear mixed effect models to estimate associations between interquartile range increases in phthalate metabolite concentrations and percent changes in inflammatory biomarkers. Our results revealed significant associations between mono-n-butyl phthalate (MBP) and higher MMP1 by 7.86 % (95 % CI: 0.49, 15.76) and between mono oxononyl phthalate (MONP) and higher MMP2 by 8.30 % (95 % CI: 2.22, 14.75). We observed negative or null associations between phthalate metabolites and MMP2, MMP9, ICAM, VCAM, and CRP. Many results were significantly modified by fetal sex, particularly those between di-2-ethylhexyl phthalate (DEHP) metabolites and MMP1 (p-interaction: MEHHP = 0.01, MEOHP = 0.04, MECPP = 0.01) and MMP2 (p-interaction: MEHHP = 0.03, MEOHP = 0.01, MECPP = 0.01), for which associations were positive among only women carrying female fetuses. MMPs have been previously associated with preeclampsia and hypertensive pregnancy disorders as mediators of artery remodeling. Hence, our findings suggest a potential role for phthalates in mediating the maternal inflammatory response, as well as significant sexual dimorphism in these relationships, which has implications for several adverse pregnancy outcomes.

Project description:Context:Phthalates are endocrine-disrupting chemicals that may be associated with adverse birth outcomes. Dysregulation of maternal endocrine homeostasis could be a possible biological pathway between phthalates and birth outcomes. Objective:Examine associations between 19 maternal urinary phthalate or phthalate replacement metabolites and 9 serum hormones measured over two time points during pregnancy. Design:Longitudinal study conducted in the PROTECT pregnancy cohort. Setting:Puerto Rico. Patients:Six hundred seventy-seven women in the first trimester of pregnancy. Main Outcome Measures Serum:CRH, estriol, SHBG, progesterone, TSH, total T3, free T4, total T4, and testosterone. Results:T3 was significantly associated with most metabolites. CRH was inversely associated with mono carboxyisononyl phthalate [MCNP; percent change (%?), -4.08; 95% CI, -7.24, -0.804], mono-3-carboxypropyl phthalate (MCPP; %?, -5.25; 95% CI, -8.26, -2.14), mono-2-ethyl-5-carboxypentyl phthalate (MECPP; %?, -18.4; 95% CI, -30.4, -4.37), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; %?, -13.4; 95% CI, -22.7, -2.92), and mono-2-ethyl-5-oxohexyl phthalate (MEOHP; %?, -12.7; 95% CI, -22.2, -2.20). Positive associations were found between numerous phthalate metabolites and free T4, T4, and the T3/T4 ratio. Testosterone was positively associated with mono hydroxybutyl phthalate (MHBP; %?, 4.71; 95% CI, 0.27, 9.35) and inversely associated with monoethyl phthalate (MEP; %?, -14.5; 95% CI, -24.3, -3.42), and relationships with MCNP and mono carboxyisooctyl phthalate (MCOP) were significantly modified by study visit. Finally, an inverse association was found between mono-2-ethyl-5-hydrohexyl terephthalate (MEHHTP), a terephthalate metabolite, and progesterone at visit 3 only (%?, -13.1; 95% CI, -22.3, -2.75). Conclusions:These results indicate that exposure to phthalates may differentially impact the maternal endocrine system at different points during pregnancy, and that exposures to phthalate replacement chemicals may be particularly important to consider in future human health studies.

Project description:BackgroundPhthalates have been reported to alter circulating lipid concentrations in animals, and investigation of these associations in humans will provide greater understanding of potential mechanisms for health outcomes.ObjectiveTo explore associations between phthalate metabolite biomarkers and lipidomic profiles among pregnant women (n = 99) in the Puerto Rico PROTECT cohort.MethodsWe measured 19 urinary phthalate metabolites during 24-28 weeks of pregnancy. Lipidomic profiles were identified from plasma samples by liquid chromatography-mass spectrometry-based shotgun lipidomics. Relationships between phthalate metabolites and lipid profiles were estimated using compound-by-compound comparisons in multiple linear regression and dimension reduction techniques. We derived sums for each lipid class and sub-class (saturated, mono-unsaturated, polyunsaturated) which were then regressed on phthalate metabolites. Associations were adjusted for false discovery.ResultsAfter controlling for multiple comparisons, 33 phthalate-lipid associations were identified (False discovery rate adjusted p value < 0.05), and diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1 were the most strongly associated with multiple phthalate metabolites. Metabolites of di-2-ethylhexyl phthalate, bis(2-ethylhexyl) phthalate, dibutyl phthalates, and diisobutyl phthalate were associated with increased ceramides, lysophosphatidylcholines, lysophosphatidylethanolamines, and triacylglycerols, particularly those containing saturated and mono-unsaturated fatty acid chains.SignificanceCharacterization of associations between lipidomic markers and phthalate metabolites during pregnancy will yield mechanistic insight for maternal and child health outcomes.ImpactThis study leverages emerging technology to evaluate lipidome-wide signatures of phthalate exposure during pregnancy. The greatest lipid signatures of phthalate exposure were observed for diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1. Polymerized glycerides are important for energy production and regulated through hormone signaling, while plasmenyl-phosphatidylcholines have been implicated in membrane dynamics and important for cell-to-cell signaling. Characterization of these mechanisms are relevant for informing the etiology of maternal and children's health outcomes.

Dataset Information

A repeated measures study of phenol, paraben and Triclocarban urinary biomarkers and circulating maternal hormones during gestation in the Puerto Rico PROTECT cohort.

Publications

A repeated measures study of phenol, paraben and Triclocarban urinary biomarkers and circulating maternal hormones during gestation in the Puerto Rico PROTECT cohort.

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