Maternal urinary phthalate metabolites during pregnancy and thyroid function: The MAKE Study

BACKGROUND AND AIM: Phthalates, endocrine-disrupting chemicals that are commonly found in consumer products, may adversely affect thyroid hormones, but findings from prior epidemiologic studies have been inconsistent. 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. METHODS: We measured five 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 pregnant women in MAKE Study. Thyroid stimulating hormone (TSH) and free and total thyroxine and triiodothyronine were measured in maternal serum (n = 215). We used multivariable linear regression to assess associations between individual urinary phthalate metabolites and concentrations of maternal 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: The geometric mean urinary concentrations of specific gravity adjusted MEPm MBzP and MECCP were 2.1, 0.2, and 0.1 μg/L, respectively. The phthalate index was had a significantly positive effect on the maternal serum TSH (WQS beta = 0.13; p = 0.02). However, no significant association was found with both maternal serum TT3 (WQS beta = -0.23; 0.89) or and TT4 (WQS beta = -0.02; p=0.83) CONCLUSIONS: Our results suggest that co-exposure to multiple phthalates was positively associated with TSH in pregnant women in this birth cohort. These findings highlight the need to study chemical mixtures in environmental epidemiology. KEYWORDS: Phthalates; Pregnancy; Thyroid hormones; Weighted quantile sum regression.