Abstract
BackgroundHuman populations, including susceptible subpopulations such as pregnant women and their fetuses, are continuously exposed to phthalates. Phthalates may affect the thyroid hormone system, causing concern for pregnancy health, birth outcomes and child development. Few studies have investigated the joint effect of phthalates on thyroid function in pregnant women, although they are present as a mixture with highly inter-correlated compounds. Additionally, no studies have investigated if the key nutrient for thyroid health, iodine, modifies these relationships. MethodsIn this study, we examined the cross-sectional relationships between concentrations of 12 urinary phthalate metabolites and 6 plasma thyroid function biomarkers measured mid-pregnancy (~17 week gestation) in pregnant women (N = 1072), that were selected from a population-based prospective birth cohort, The Norwegian Mother, Father and Child Cohort study (MoBa). We investigated if the phthalate metabolite-thyroid function biomarker associations differed by iodine status by using a validated estimate of habitual dietary iodine intake based on a food frequency questionnaire from the 22nd gestation week. We accounted for the phthalate metabolite mixture by factor analyses, ultimately reducing the exposure into two uncorrelated factors. These factors were used as predictors in multivariable adjusted linear regression models with thyroid function biomarkers as the outcomes. ResultsFactor 1, which included high loadings for mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and monobenzyl phthalate (MBzP), was associated with increased total triiodothyronine (TT3) and free T3 index (fT3i). These associations appeared to be driven primarily by women with low iodine intake (<150 µg/day, ~70% of our sample). Iodine intake significantly modified (p-interaction < 0.05) the association of factor 1 with thyroid stimulating hormone (TSH), total thyroxine (TT4) and free T4 index (fT4i), such that only among women in the high iodine intake category (≥150 µg/day, i.e. sufficient) was this factor associated with increased TSH and decreased TT4 and FT4i, respectively. In contrast, factor 2, which included high loadings for di-2-ethylhexyl phthalate metabolites (∑DEHP) and di-iso-nonyl phthalate metabolites (∑DiNP), was associated with a decrease in TT3 and fT3i, which appeared fairly uniform across iodine intake categories. ConclusionWe find that phthalate exposure is associated with thyroid function in mid-pregnancy among Norwegian women, and that iodine intake, which is essential for thyroid health, could influence some of these relationships.
Highlights
Phthalate diesters are a group of synthetic chemicals used extensively in our modern society, as plasticizers in polyvinyl chloride (PVC) products such as building material, food containers, medical products and children’s toys as well as ingredients in cosmetics, personal care products and some medication and dietary supplements (Cao, 2010; Wormuth et al, 2006)
As sensitivity analyses, we investigated the factor models in a population restricted to MoBa participants who were randomly sampled to be in the sub-cohort and where the child did not have Attention-deficit/hyperactivity disorder (ADHD) case status, to ensure that results were not driven by mothers of these cases
Even though all initial phthalate measurement were above limit of quantification (LOQ), after adjustment for batch and specific gravity, some of the lower concentrations fell below the analytic LOQ
Summary
Phthalate diesters are a group of synthetic chemicals used extensively in our modern society, as plasticizers in polyvinyl chloride (PVC) products such as building material, food containers, medical products and children’s toys as well as ingredients in cosmetics, personal care products and some medication and dietary supplements (Cao, 2010; Wormuth et al, 2006). Methods: In this study, we examined the cross-sectional relationships between concentrations of 12 urinary phthalate metabolites and 6 plasma thyroid function biomarkers measured mid-pregnancy (~17 week gestation) in pregnant women (N = 1072), that were selected from a population-based prospective birth cohort, The Norwegian Mother, Father and Child Cohort study (MoBa). We accounted for the phthalate metabolite mixture by factor analyses, reducing the exposure into two uncorrelated factors These factors were used as predictors in multivariable adjusted linear regression models with thyroid function biomarkers as the outcomes. Results: Factor 1, which included high loadings for mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and monobenzyl phthalate (MBzP), was associated with increased total triiodothyronine (TT3) and free T3 index (fT3i) These associations appeared to be driven primarily by women with low iodine intake (< 150 μg/day, ~70% of our sample). Conclusion: We find that phthalate exposure is associated with thyroid function in mid-pregnancy among Norwegian women, and that iodine intake, which is essential for thyroid health, could influence some of these relationships
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