Giehae Choi1, Alexander P Keil2, Gro D Villanger3, David B Richardson2, Julie L Daniels2, Kate Hoffman4, Amrit K Sakhi3, Cathrine Thomsen3, Amy H Herring5, Samantha S M Drover2, Rachel Nethery6, Heidi Aase3, Stephanie M Engel2. 1. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: gchoi8@jhmi.edu. 2. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 3. Norwegian Institute of Public Health, Oslo, Norway. 4. Nicholas School of the Environment, Duke University, Durham, NC, USA. 5. Department of Statistical Science and Global Health Institute, Duke University, Durham, NC, USA. 6. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Abstract
BACKGROUND: Contemporary human populations are exposed to elevated concentrations of organophosphate esters (OPEs) and phthalates. Some metabolites have been linked with altered thyroid function, however, inconsistencies exist across thyroid function biomarkers. Research on OPEs is sparse, particularly during pregnancy, when maintaining normal thyroid function is critical to maternal and fetal health. In this paper, we aimed to characterize relationships between OPEs and phthalates exposure and maternal thyroid function during pregnancy, using a cross-sectional investigation of pregnant women nested within the Norwegian Mother, Father, and Child Cohort (MoBa). METHODS: We included 473 pregnant women, who were euthyroid and provided bio-samples at 17 weeks' gestation (2004-2008). Four OPE and six phthalate metabolites were measured from urine; six thyroid function biomarkers were estimated from blood. Relationships between thyroid function biomarkers and log-transformed concentrations of OPE and phthalate metabolites were characterized using two approaches that both accounted for confounding by co-exposures: co-pollutant adjusted general linear model (GLM) and Bayesian Kernal Machine Regression (BKMR). RESULTS: We restricted our analysis to common-detect OPE and phthalate metabolites (>94%): diphenyl phosphate (DPHP), di-n-butyl phosphate (DNBP), and all phthalate metabolites. In GLM, pregnant women with summed di-isononyl phthalate metabolites (∑DiNP) concentrations in the 75th percentile had a 0.37 ng/μg lower total triiodothyronine (TT3): total thyroxine (TT4) ratio (95% credible interval: [-0.59, -0.15]) as compared to those in the 25th percentile, possibly due to small but diverging influences on TT3 (-1.99 ng/dL [-4.52, 0.53]) and TT4 (0.13 μg/dL [-0.01, 0.26]). Similar trends were observed for DNBP and inverse associations were observed for DPHP, monoethyl phthalate, mono-isobutyl phthalate, and mono-n-butyl phthalate. Most associations observed in co-pollutants adjusted GLMs were attenuated towards the null in BKMR, except for the case of ∑DiNP and TT3:TT4 ratio (-0.48 [-0.96, 0.003]). CONCLUSIONS: Maternal thyroid function varied modestly with ∑DiNP, whereas results for DPHP varied by the type of statistical models.
BACKGROUND: Contemporary human populations are exposed to elevated concentrations of organophosphate esters (OPEs) and phthalates. Some metabolites have been linked with altered thyroid function, however, inconsistencies exist across thyroid function biomarkers. Research on OPEs is sparse, particularly during pregnancy, when maintaining normal thyroid function is critical to maternal and fetal health. In this paper, we aimed to characterize relationships between OPEs and phthalates exposure and maternal thyroid function during pregnancy, using a cross-sectional investigation of pregnant women nested within the Norwegian Mother, Father, and Child Cohort (MoBa). METHODS: We included 473 pregnant women, who were euthyroid and provided bio-samples at 17 weeks' gestation (2004-2008). Four OPE and six phthalate metabolites were measured from urine; six thyroid function biomarkers were estimated from blood. Relationships between thyroid function biomarkers and log-transformed concentrations of OPE and phthalate metabolites were characterized using two approaches that both accounted for confounding by co-exposures: co-pollutant adjusted general linear model (GLM) and Bayesian Kernal Machine Regression (BKMR). RESULTS: We restricted our analysis to common-detect OPE and phthalate metabolites (>94%): diphenyl phosphate (DPHP), di-n-butyl phosphate (DNBP), and all phthalate metabolites. In GLM, pregnant women with summed di-isononyl phthalate metabolites (∑DiNP) concentrations in the 75th percentile had a 0.37 ng/μg lower total triiodothyronine (TT3): total thyroxine (TT4) ratio (95% credible interval: [-0.59, -0.15]) as compared to those in the 25th percentile, possibly due to small but diverging influences on TT3 (-1.99 ng/dL [-4.52, 0.53]) and TT4 (0.13 μg/dL [-0.01, 0.26]). Similar trends were observed for DNBP and inverse associations were observed for DPHP, monoethyl phthalate, mono-isobutyl phthalate, and mono-n-butyl phthalate. Most associations observed in co-pollutants adjusted GLMs were attenuated towards the null in BKMR, except for the case of ∑DiNP and TT3:TT4 ratio (-0.48 [-0.96, 0.003]). CONCLUSIONS: Maternal thyroid function varied modestly with ∑DiNP, whereas results for DPHP varied by the type of statistical models.
Authors: Mary E Ingle; Deborah Watkins; Zaira Rosario; Carmen M Vélez Vega; Gredia Huerta-Montanez; Antonia M Calafat; Maria Ospina; José F Cordero; Akram Alshawabkeh; John D Meeker Journal: Environ Res Date: 2019-09-23 Impact factor: 6.498
Authors: Megan E Romano; Melissa N Eliot; R Thomas Zoeller; Andrew N Hoofnagle; Antonia M Calafat; Margaret R Karagas; Kimberly Yolton; Aimin Chen; Bruce P Lanphear; Joseph M Braun Journal: Int J Hyg Environ Health Date: 2018-03-23 Impact factor: 5.840
Authors: Elizabeth M Kamai; Gro D Villanger; Rachel C Nethery; Cathrine Thomsen; Amrit K Sakhi; Samantha S M Drover; Jane A Hoppin; Gun Peggy Knudsen; Ted Reichborn-Kjennerud; Pål Zeiner; Kristin Overgaard; Amy H Herring; Heidi Aase; Stephanie M Engel Journal: Environ Epidemiol Date: 2021-07-01