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Thyroid hormone parameters during pregnancy in relation to urinary bisphenol A concentrations: A repeated measures study.

ABSTRACT: BACKGROUND:Maternal supply of thyroid hormones during pregnancy serves a critical role in fetal development. Although animal and in vitro studies provide evidence for thyroid hormone disruption as a result of bisphenol A (BPA) exposure, there is still a lack of evidence in human studies, particularly in the context of pregnancy. OBJECTIVES:We aimed to explore the associations between urinary BPA concentrations and plasma thyroid hormone parameters during gestation in pregnant women, and also investigated potential windows of vulnerability during gestation. METHODS:Our study population included 116 cases of preterm birth and 323 controls from a nested case-control study. We measured BPA in urine and thyroid hormone parameters in plasma samples collected at up to four study visits during pregnancy (median for each visit: 9.64, 17.9, 26.0, and 35.1weeks gestation). We used linear mixed models for repeated measures analyses, and multivariate linear regression models stratified by study visit to explore potential windows of susceptibility. RESULTS:In our repeated measures analysis, BPA and thyrotropin (TSH) were inversely associated. An interquartile range (IQR) increase in BPA was associated with an 8.21% decrease in TSH (95% confidence interval [CI]: -14.2, -1.83), and a 4.79% increase in free T4 (95% CI: 0.82, 8.92). BPA and TSH were also inversely associated in our cross-sectional analyses at visits 3 and 4. CONCLUSIONS:Our results suggest that TSH is inversely associated with urinary BPA in a consistent manner across pregnancy. Disruption of TSH levels during pregnancy can potentially impact child development and interfere with normal birth outcomes.

SUBMITTER: Aung MT

PROVIDER: S-EPMC5497503 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Thyroid hormone parameters during pregnancy in relation to urinary bisphenol A concentrations: A repeated measures study.

Aung Max T MT Johns Lauren E LE Ferguson Kelly K KK Mukherjee Bhramar B McElrath Thomas F TF Meeker John D JD

Environment international 20170413

<h4>Background</h4>Maternal supply of thyroid hormones during pregnancy serves a critical role in fetal development. Although animal and in vitro studies provide evidence for thyroid hormone disruption as a result of bisphenol A (BPA) exposure, there is still a lack of evidence in human studies, particularly in the context of pregnancy.<h4>Objectives</h4>We aimed to explore the associations between urinary BPA concentrations and plasma thyroid hormone parameters during gestation in pregnant wome ...[more]

PMID: 28410473

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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:BACKGROUND:Phthalates, endocrine-disrupting chemicals that are commonly found in consumer products, may adversely affect thyroid hormones, but findings from prior epidemiologic studies are inconsistent. OBJECTIVES:In a prospective cohort study, we investigated whether maternal urinary phthalate metabolite concentrations and phthalate mixtures measured during pregnancy were associated with thyroid hormones among pregnant women and newborns. METHODS:We measured nine phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate, mono-isobutyl phthalate, monobenzyl phthalate (MBzP), and four monoesthers of di(2-ethylhexyl) phthalate] in urine collected at approximately 16 and 26 weeks' gestation among women in the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, Ohio). Thyroid stimulating hormone (TSH) and free and total thyroxine and triiodothyronine were measured in maternal serum at 16 weeks' gestation (n?=?202) and cord serum at delivery (n?=?276). We used multivariable linear regression to assess associations between individual urinary phthalate metabolites and concentrations of maternal or cord serum thyroid hormones. We used weighted quantile sum regression (WQS) to create a phthalate index describing combined concentrations of phthalate metabolites and to investigate associations of the phthalate index with individual thyroid hormones. RESULTS:With each 10-fold increase in 16-week maternal urinary MEP, maternal serum total thyroxine (TT4) decreased by 0.52??g/dL (95% CI: -1.01, -0.03). For each 10-fold increase in average (16- and 26-week) maternal urinary MBzP, cord serum TSH decreased by 19% (95% CI: -33.1, -1.9). Among mothers, the phthalate index was inversely associated with maternal serum TT4 (WQS beta?=?-0.60; 95% CI: -1.01, -0.18). Among newborns, the phthalate index was inversely associated with both cord serum TSH (WQS beta?=?-0.11; 95% CI: -0.20, -0.03) and TT4 (WQS beta?=?-0.53; 95% CI: -0.90, -0.16). CONCLUSION:Our results suggest that co-exposure to multiple phthalates was inversely associated with certain thyroid hormones (TT4 in pregnant women and newborns, and TSH in newborns) in this birth cohort. These findings highlight the need to study chemical mixtures in environmental epidemiology.

Project description:BackgroundIncreasing scientific evidence suggests that exposure to phthalates during pregnancy may be associated with an elevated risk of adverse reproductive outcomes such as preterm birth. Maternal endocrine disruption across pregnancy may be one pathway mediating some of these relationships. We investigated whether urinary phthalate metabolites were associated with maternal serum thyroid (free thyroxine [FT4], free triiodothyronine [FT3], and thyroid-stimulating hormone [TSH]), and sex (estradiol, progesterone, and sex hormone-binding globulin [SHBG]) hormone levels at multiple time points during pregnancy.MethodsPreliminary data (n = 106) were obtained from an ongoing prospective birth cohort in Northern Puerto Rico. We collected urine and serum sample at the first and third study visits that occurred at 18 +/- 2 and 26 +/- 2 weeks of gestation, respectively. To explore the longitudinal relationships between urinary phthalate metabolites and serum thyroid and sex hormone concentrations, we used linear mixed models (LMMs) adjusted for prepregnancy body mass index (BMI) and maternal age. An interaction term was added to each LMM to test whether the effect of urinary phthalate metabolites on serum thyroid and sex hormone levels varied by study visit. In cross-sectional analyses, we stratified BMI- and age-adjusted linear regression models by study visit.ResultsIn adjusted LMMs, we observed significant inverse associations between mono-3-carboxypropyl phthalate (MCPP) and FT3 and between mono-ethyl phthalate (MEP) and progesterone. In cross-sectional analyses by study visit, we detected stronger and statistically significant inverse associations at the third study visit between FT3 and MCPP as well as mono-carboxyisooctyl phthalate (MCOP); also at the third study visit, significant inverse associations were observed between FT4 and metabolites of di-(2-ethylhexyl) phthalate (DEHP). The inverse association between MEP and progesterone was consistent across study visits.ConclusionsIn this group of pregnant women, urinary phthalate metabolites may be associated with altered maternal serum thyroid and sex hormone levels, and the magnitude of these effects may depend on the timing of exposure during gestation.

Project description:BACKGROUND:Phthalates and bisphenol A (BPA) are environmental contaminants that may affect early embryonic development. OBJECTIVE:To assess the association between phthalate metabolites and BPA with early pregnancy endpoints in a cohort of women followed from before conception. METHODS:We quantified 11 phthalate metabolites and BPA in 137 conception cycles from naturally conceived clinical pregnancies. Phthalate metabolites and BPA concentrations were measured in a pooled sample of three daily morning urine specimens. Daily urinary hormone measurements had previously been used to define ovulation, implantation, and corpus luteum rescue. We assessed associations between conception cycle exposures (phthalate biomarkers and BPA) and 1) time from ovulation to implantation; 2) type of corpus luteum rescue (timing and pattern of rise in progesterone: early, late, or no rise); and 3) rate of initial rise in hCG. RESULTS:Mono(3-carboxypropyl) phthalate (MCPP) and mono-isobutyl phthalate (MiBP) were associated with earlier implantation (6-8 days vs. 9 days (the most commonly observed); per natural log-unit, OR (95% CI) =?2.8 (1.2, 6.7) and OR (CI) =?2.1 (1.2, 3.7), respectively). Monoethyl phthalate (MEP) was associated with later implantation (10-12 days vs. 9 days); OR (CI) =?1.5 (1.0, 2.1). Compared with implantation on day 9, BPA was significantly associated with both earlier and later implantation (OR=2.2 for both). Women with concentrations above the median of monobenzyl phthalate (MBzP) (p?=?0.04) or above the median of the molar sum of four di(2-ethylhexyl) phthalate metabolites (?DEHP) (p?=?0.08) had a slower initial rise in hCG. Increasing MCPP was associated with an increased odds of a late rise rescue (OR (CI) =?2.9 (1.0, 8.5); late rise vs. early rise), while increasing MEP was associated with a no rise rescue (OR (CI) =?1.6 (0.9, 2.8); no rise vs. early rise). CONCLUSIONS:The reported associations varied in their direction of effect, some potentially protective, others adverse. This may reflect the complexity with which these potential endocrine disrupting chemicals can be acting, but chance findings are also possible. Given that women continue to be exposed to these compounds (or their precursors), continued research on the effects they may have on pregnancy is warranted.

Project description:BackgroundFew epidemiologic studies have evaluated the impact of paternal environmental exposures, particularly as mixtures, on couples' pregnancy outcomes.ObjectiveWe investigated whether mixtures of paternal urinary bisphenol A (BPA), paraben, and phthalates were associated with pregnancy outcomes among couples attending a fertility center.MethodsWe included 210 couples undergoing 300 in vitro fertilization (IVF) between 2004 and 2017 in this prospective analysis. We quantified paternal urinary biomarker concentrations in one sample per cycle using isotope-dilution tandem mass spectrometry. We used principal component analysis (PCA) to identify correlations of biomarker concentrations and multivariable Cox proportional hazards models for discrete survival time to estimate the hazard ratios (HRs) and 95% CIs for the associations between PCA-derived factor scores and probability of failing to achieve a live birth. Interactions were also included in the models to examine strength of associations over three vulnerable periods [embryo transfer to implantation, implantation to clinical pregnancy, and clinical pregnancy to live birth]. Models were adjusted for paternal and maternal ages and body mass indexes, urinary dilution (specific gravity) and year of collection, infertility diagnosis, and other PCA factor scores. Sensitivity analyses with further adjustment for maternal PCA factor scores were performed.ResultsWe identified three factors, representing di-2-ethylhexyl phthalate (DEHP) metabolites, BPA and non-DEHP metabolites, and parabens, accounting for 56%, 15% and 10%, respectively, of the total variance explained. An interquartile range (25th and 75th percentiles) increase in the DEHP-related factor score was associated with elevated probability of failing prior to live birth (HR = 1.41, 95% CI: 1.08, 1.81) and the association was stronger between implantation and clinical pregnancy as well as between clinical pregnancy and live birth compared to before implantation. The overall HRs of failure for the BPA/non-DEHP-related and paraben-related factor scores were HR = 1.24 (95% CI: 0.97, 1.59) and HR = 0.99 (95% CI: 0.80, 1.24). We found similar HRs when additionally adjusting for maternal PCA factor scores.ConclusionPaternal mixtures of urinary concentrations of DEHP metabolites were related to higher infertility treatment failure.

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Thyroid hormone parameters during pregnancy in relation to urinary bisphenol A concentrations: A repeated measures study.

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Thyroid hormone parameters during pregnancy in relation to urinary bisphenol A concentrations: A repeated measures study.

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