Early-life phthalate exposure, thyroid function and child cognitive development

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DESCRIPTION (provided by applicant): The competitive renewal is responsive to recent epidemiologic and experimental evidence indicating that certain phthalates modulate thyroid function and reduce circulating thyroid hormone levels. The phthalates implicated include those already being studied under the current RO1 (Prenatal Phthalates, Placental Function and Fetal Growth R01 ES013543, Robin Whyatt, PI): di(2-ethylhexyl) phthalate (DEHP), butylbenzyl phthalate (BBzP) and dibutyl phthalate (DBP). Exposures to these phthalates are substantial among cohort subjects. Our proposed renewal will determine whether these exposures are associated with perturbations in thyroid function in children followed from birth through age 10-11 years. The study will also determine whether the phthalates are associated with deficits in child neuropsychological function, including in domains that might be associated with phthalate-induced reductions in thyroid function (intelligence, attention, executive function and motor skills). In addition, given that the purported mechanism whereby phthalates affect thyroid levels is through modulation of the Sodium Iodide Symporter (NIS) mediated iodide uptake activity in the thyroid gland, we will also evaluate whether prenatal phthalate exposures modulate expression of the NIS in placental tissue. Such a finding could have important implications for fetal thyroid function, as the NIS is the transport gene responsible for the active transfer of iodide across the placenta. Thyroid hormones during pregnancy and early childhood are critical to brain development, and even modest reductions in hormone levels may have long-lasting effects on child mental, motor and neuropsychological function. However, while prior studies have assessed the relationship between phthalates and thyroid hormones in adults, no prior studies have assessed these relationships in children, or evaluated the effects of prenatal and early-life phthalates exposures on child neuropsychological function. In our preliminary analyses, we found a significant inverse association between maternal prenatal DEHP exposure and child mental development at age 3 years among cohort children. This proposed renewal will build on these preliminary findings to evaluate the role of prenatal and early childhood phthalate exposures on: (1) measures of thyroid function in children from birth through age 11 years; (2) child cognition (language, working memory, executive function, problem solving); (3) child behavior (attention and impulsivity ); (4) child motor development (fine manual control, manual coordination, body coordination, strength and agility, motor speed and visual scanning) and (5) expression of the NIS in placental tissue.