Associations between exposure to phthalates and subclinical hypothyroidism in pregnant women during early pregnancy: A pilot case-control study in China

Phthalates are environmental endocrine disruptors with thyroid-disrupting properties; however, the association between phthalate exposure and subclinical hypothyroidism (SCH) during pregnancy is unknown. We recruited a study population from a cohort of pregnant women in Beijing, China, and conducted the present pilot case-control study of 42 SCH cases and 84 non-SCH controls matched with age and body mass index (BMI). Serum levels of thyroid peroxidase antibody, free thyroxine (FT₄), thyroid-stimulating hormone (TSH), and urinary levels of ten phthalate metabolites during early pregnancy were measured. Urinary monoethyl phthalate (MEP) levels in SCH cases were observably higher than those in controls (p = 0.01). Conditional logistic regression analysis revealed that mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), MEP, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and di-(2-ethylhexyl) phthalate (ΣDEHP) were significantly associated with a higher risk of SCH during early pregnancy (adjusted odds ratios = 1.89, 1.42, 1.81, and 1.92, respectively). Concomitantly, multiple linear regression analysis showed that MECPP, MEOHP, and ΣDEHP were positively associated with TSH and FT₄ × TSH in the entire study population. Bayesian kernel machine regression analysis and stratified analysis by BMI revealed upward tendencies in the serum levels of TSH and FT₄ × TSH. In summary, exposure to phthalates, especially DEHP, may be associated with a higher risk of SCH during early pregnancy, and a possible mechanism is the disruption of the hypothalamus-pituitary-thyroid axis.