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Preterm birth in relation to the bisphenol A replacement, bisphenol S, and other phenols and parabens.

ABSTRACT: INTRODUCTION:Preterm birth continues to be a significant public heath concern and is a leading cause of perinatal and infant mortality. Environmental exposures to phenols and parabens are suspected to potentially contribute to the pathology of preterm birth, yet limited human studies have characterized the extent to which these toxicants are associated with birth outcomes. METHODS:We examined the associations between phenols, parabens, and preterm birth, within pregnant women who were recruited early in gestation into the LIFECODES cohort at Brigham and Women's Hospital in Boston, Massachusetts. Urine samples were collected at up to 4 time points in pregnancy and analyzed for phenols and parabens. We selected 130 cases of preterm birth (defined as delivery before 37 weeks gestation), and 350 random controls. We categorized preterm birth subtypes based on clinical presentation and identified 75 cases of spontaneous preterm birth (characterized by spontaneous preterm labor and/or preterm premature rupture of membranes), and 37 cases of placental preterm birth (characterized by preeclampsia and/or intrauterine growth restriction). We used multivariate logistic regression with visit specific and geometric averages of phenols and parabens to determine associations with preterm birth. RESULTS:We observed moderate variability in urinary phenol and paraben concentrations over pregnancy with intraclass correlation coefficients ranging between 0.45 and 0.68. Regression analyses indicated mostly null associations. We observed inverse associations, notably between 2,5-dichlorophenol and overall preterm birth (adjusted odds ratio [95% confidence interval, CI]: 0.79 [0.67 - 0.94]), and this relationship was consistent by study visit. Conversely, ethyl paraben was associated with increased risk for placental preterm birth (adjusted odds ratio [95% CI]: 1.47 [1.14 - 1.91]). Bisphenol-S detection at visit 4 was associated with overall preterm birth (adjusted odds ratio [95% CI]: 2.05 [1.09, 3.89]). CONCLUSIONS:While the findings from this study largely indicate null associations, we observed some relationships between select phenols, parabens and preterm birth, which warrants further investigation of these toxicants and birth outcomes.

SUBMITTER: Aung MT

PROVIDER: S-EPMC6347500 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Preterm birth in relation to the bisphenol A replacement, bisphenol S, and other phenols and parabens.

Aung Max T MT Ferguson Kelly K KK Cantonwine David E DE McElrath Thomas F TF Meeker John D JD

Environmental research 20181101

<h4>Introduction</h4>Preterm birth continues to be a significant public heath concern and is a leading cause of perinatal and infant mortality. Environmental exposures to phenols and parabens are suspected to potentially contribute to the pathology of preterm birth, yet limited human studies have characterized the extent to which these toxicants are associated with birth outcomes.<h4>Methods</h4>We examined the associations between phenols, parabens, and preterm birth, within pregnant women who ...[more]

PMID: 30448626

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Project description:Phenols and parabens are ubiquitous environmental contaminants. Evidence from animal studies and limited human data suggest they may be endocrine disruptors. In the current study, we examined associations of phenols and parabens with reproductive and thyroid hormones in 106 pregnant women recruited for the prospective cohort, "Puerto Rico Testsite for Exploring Contamination Threats (PROTECT)".Urinary exposure biomarkers (bisphenol A, triclosan, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, butyl, methyl and propyl paraben) and serum hormone levels (estradiol, progesterone, sex hormone-binding globulin (SHBG), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone) were measured at up to two time points during pregnancy (16-20 weeks and 24-28 weeks). We used linear mixed models to assess relationships between exposure biomarkers and hormone levels across pregnancy, controlling for urinary specific gravity, maternal age, BMI and education. In sensitivity analyses, we evaluated cross-sectional relationships between exposure and hormone levels stratified by study visit using linear regression.An IQR increase in methyl paraben was associated with a 7.70% increase (95% CI 1.50, 13.90) in SHBG. Furthermore, an IQR increase in butyl paraben as associated with an 8.46% decrease (95% CI 16.92, 0.00) in estradiol, as well as a 9.34% decrease (95% CI -18.31,-0.38) in estradiol/progesterone. Conversely, an IQR increase in butyl paraben was associated with a 5.64% increase (95% CI 1.26, 10.02) in FT4. Progesterone was consistently negatively associated with phenols, but none reached statistical significance. After stratification, methyl and propyl paraben were suggestively negatively associated with estradiol at the first time point (16-20 weeks), and suggestively positively associated with estradiol at the second time point (24-28 weeks).Within this ongoing birth cohort, certain phenols and parabens were associated with altered reproductive and thyroid hormone levels during pregnancy. These changes may contribute to adverse health effects in mothers or their offspring, but additional research is required.

Project description:BackgroundPhenol exposure during pregnancy has been associated with preterm birth, but the potential effect of preconception exposure in either parent is unknown. There is a growing body of evidence to suggest that the preconception period is a critical window of vulnerability for adverse pregnancy outcomes.ObjectiveWe examined whether maternal and paternal preconception urinary concentrations of select phenols were associated with the risk of preterm birth among couples attending fertility care.MethodsThe analysis included 417 female and 229 male participants of the Environment and Reproductive Health (EARTH) Study who gave birth to 418 singleton infants between 2005 and 2018 and for whom we had phenol biomarkers quantified in at least one urine sample collected before conception. Mothers and fathers provided an average of 4 and 3 urine samples during the preconception period, respectively. We calculated the geometric mean of bisphenol A (BPA), bisphenol S (BPS), benzophenone-3, triclosan, and the molar sum of parabens (ΣParabens) urinary concentrations to estimate each participant's preconception exposure. Risk ratios (RRs) of preterm birth (live birth before 37 completed weeks' gestation) were estimated using modified Poisson regression models adjusted for covariates.ResultsThe mean (SD) gestational age among singletons was 39.3 (1.7) weeks with 8% born preterm. A natural log-unit increase in maternal preconception BPA (RR 1.94; 95% CI: 1.20, 3.14) and BPS (RR 2.42; 95% CI: 1.01, 5.77) concentration was associated with an increased risk of preterm birth. These associations remained after further adjustment for maternal prenatal and paternal preconception biomarker concentrations. Paternal preconception ΣParabens concentrations showed a possible elevated risk of preterm birth (RR 1.36; 95% CI: 0.94, 1.96). No consistent pattern of association was observed for benzophenone-3 or triclosan biomarkers in either parent.DiscussionMaternal preconception urinary BPA and BPS concentrations, as well as paternal preconception urinary parabens concentrations were prospectively associated with a higher risk of preterm birth. Subfertile couples' exposure to select phenols during the preconception period may be an unrecognized risk factor for adverse pregnancy outcomes.

Project description:BackgroundEpidemiologic evidence suggests that environmental factors acting as endocrine disrupting chemicals (EDCs) are associated with mammographic breast density and the risk of breast cancer. Exposure to EDCs during puberty, a period of rapid breast development, may affect susceptibility to breast carcinogenesis.MethodsIn a cohort of 366 Chilean adolescents from the Growth and Obesity Cohort Study, we evaluated the relation between urinary concentrations of 15 suspected EDC biomarkers across three pubertal time points (Tanner breast stage 1 (B1), 4 (B4), and 1-year post-menarche) and breast fibroglandular volume (FGV; percent FGV [%FGV] and absolute FGV [aFGV]) and total breast volume (tBV) at 2-years post-menarche. We used linear mixed models to test differences in creatinine-corrected EDC biomarker concentrations at B4 and 1-year post-menarche compared to B1 and calculated intraclass correlation coefficients (ICC) of EDC concentrations across time points to appraise the consistency of measurements. We fit multivariable generalized estimating equations (GEEs) to evaluate windows of susceptibility for the association between log10-transformed EDCs and log10-transformed breast outcomes. GEEs were adjusted for age, body fat percentage, total caloric intake, and maternal education.ResultsUrinary EDC biomarker concentrations highly varied across pubertal time points (ICC range 0.01-0.30). For 12 EDCs, biomarker concentrations decreased over time. Triclosan measured at 1-year post-menarche was inversely associated with %FGV at 2-years post-menarche (β = -0.025, 95 % confidence interval = -0.041, -0.008). Mono(2-ethyl-5-carboxypentyl) phthalate and the sum of di(2-ethylhexyl) phthalate metabolite concentrations at B4 were positively associated with aFGV and tBV at 2-years post-menarche. No measured phenols were associated with aFGV and tBV, while no measured parabens were associated with %FGV and aFGV.ConclusionsOur study suggests relatively high variability in EDC biomarker concentrations across the peripubertal time period. We also found evidence to suggest that there may be pubertal windows of susceptibility to select EDCs for the association with adolescent breast density.

Project description:BackgroundPreterm birth (PTB), a leading cause of infant mortality and morbidity, has a complex etiology with a multitude of interacting causes and risk factors. The role of environmental contaminants, particularly bisphenol A (BPA), is understudied with regard to PTB.ObjectivesIn the present study we examined the relationship between longitudinally measured BPA exposure during gestation and PTB.MethodsA nested case-control study was performed from women enrolled in a prospective birth cohort study at Brigham and Women's Hospital in Boston, Massachusetts, during 2006-2008. Urine samples were analyzed for BPA concentrations at a minimum of three time points during pregnancy on 130 cases of PTB and 352 randomly assigned controls. Clinical classifications of PTB were defined as "spontaneous," which was preceded by spontaneous preterm labor or preterm premature rupture of membranes, or "placental," which was preceded by preeclampsia or intrauterine growth restriction.ResultsGeometric mean concentrations of BPA did not differ significantly between cases and controls. In adjusted models, urinary BPA averaged across pregnancy was not significantly associated with PTB. When examining clinical classifications of PTB, urinary BPA late in pregnancy was significantly associated with increased odds of delivering a spontaneous PTB. After stratification on infant's sex, averaged BPA exposure during pregnancy was associated with significantly increased odds of being delivered preterm among females, but not males.ConclusionsThese results provide little evidence of a relationship between BPA and prematurity, though further research may be warranted given the generalizability of participant recruitment from a tertiary teaching hospital, limited sample size, and significant associations among females and within the clinical subcategories of PTB.CitationCantonwine DE, Ferguson KK, Mukherjee B, McElrath TF, Meeker JD. 2015. Urinary bisphenol A levels during pregnancy and risk of preterm birth. Environ Health Perspect 123:895-901; http://dx.doi.org/10.1289/ehp.1408126.

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:BackgroundMany phenols and parabens are applied in cosmetics, pharmaceuticals and food, to prevent growth of bacteria and fungi. Whether these chemicals affect inflammatory diseases like allergies and overweight is largely unexplored. We aimed to assess the associations of use of personal care products with urine biomarkers levels of phenols and paraben exposure, and whether urine levels (reflecting body burden of this chemical exposures) are associated with eczema, rhinitis, asthma, specific IgE and body mass index.MethodsDemographics, clinical variables, and self-report of personal care products use along with urine samples were collected concurrently from 496 adults (48% females, median age: 28 years) and 90 adolescents (10-17 years of age) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan (TCS), triclocarban (TCC), parabens and benzophenone-3, bisphenols and dichlorophenols (DCP) were quantified by mass spectrometry.ResultsDetection of the urine biomarkers varied according to chemical type and demographics. TCC was detected in 5% of adults and in 45% of adolescents, while propyl (PPB) and methyl (MPB) parabens were detected in 95% of adults and in 94% (PPB) and 99% (MPB) of adolescents. Women had higher median urine concentrations of phenolic chemicals and reported a higher frequency of use of personal care products than men. Urine concentration of MPB increased in a dose-dependent manner with increased frequency of use of several cosmetic products. Overall, urinary biomarker levels of parabens were lower in those with current eczema. The biomarker concentrations of bisphenol S was higher in participants with positive specific IgE and females with current asthma, but did not differ by eczema or rhinitis status. MPB, ethylparaben (EPB), 2,4-DCP and TCS were inversely related to BMI in adults; interaction by gender were not significant.ConclusionsReported frequency of use of personal care products correlated very well with urine biomarker levels of paraben and phenols. Several chemicals were inversley related to BMI, and lower levels of parabens was observed for participants with current eczema. There is a need for further studies of health effects of chemicals from personal care products, in particular in longitudinally designed studies.

Project description:BackgroundLittle is known about the associations of bisphenol A, chlorophenols, benzophenones, and parabens with reproductive hormone levels in women. Our goal was to evaluate the associations between repeated measures of these chemicals and their mixtures with reproductive hormones in women.MethodsLongitudinal urine samples from healthy, premenopausal women (n = 143 with 3-5 urine samples each) were measured for bisphenol A, five chlorophenols (2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol, 2,4,5-trichlorophenol, 2,4,6-trichlorophenol, triclosan), two ultraviolet (UV) filters (benzophenone-1, benzophenone-3), and eight parabens and their metabolites (benzyl, butyl, ethyl, heptyl, methyl, propyl, 4-hydroxybenzoic acid (4-HB), 3,4-dihydroxybenzoic acid (3,4-DHB)) over two menstrual cycles. Estradiol, progesterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured in blood up to 8 times each menstrual cycle. Linear mixed models were used for both single and multi-chemical exposures estimated using principal component analysis. Four factors were identified including: paraben; paraben metabolites and BPA, phenols, and UV filters. Models were adjusted for creatinine, age, race, and body mass index and weighted with inverse probability of exposure weights to account for time varying confounding.ResultsIn single-chemical models, 3,4-DHB was associated with estradiol (0.06 (95% confidence interval (CI): 0.001, 0.12)), 2-4-DCP with increased progesterone 0.14 (0.06, 0.21) and decreased FSH -0.08 (-0.11, -0.04), and 4-HB was associated with increased FSH 0.07 (0.01, 0.13). In multi-chemical models, all factors were associated with increased progesterone (beta coefficient range: 0.15 for UV filter factor to 0.32 for paraben factor). The paraben factor and the paraben metabolite and BPA factor were associated with increased estradiol [0.21 (0.15, 0.28); 0.12 (0.07, 0.18)]. The phenol and UV filter factors were associated with decreased estradiol, FSH, and LH. The UV filter factor showed the strongest inverse association with estradiol -0.16 (-0.22, -0.10), FSH -0.12 (-0.17, -0.07), and LH -0.17 (-0.23, -0.10).ConclusionMixtures of phenols were associated with changes in reproductive hormones. Such changes could contribute to adverse health in women but additional research is necessary.

Dataset Information

Preterm birth in relation to the bisphenol A replacement, bisphenol S, and other phenols and parabens.

Publications

Preterm birth in relation to the bisphenol A replacement, bisphenol S, and other phenols and parabens.

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