Maternal ethylenethiourea levels, newborn thyroid function & infant development

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Project Summary An estimated 1 in 6 children in the U.S. and over 200 million children in the developing world are not reaching their full developmental potential. Although fungicide use is growing exponentially in the United States and globally, a significant gap exists in scientific knowledge about the neurodevelopmental toxicity of fungicides. Ethylenebisdithiocarbamates, or EBDCs, are commonly-used fungicides in agricultural production as well as in floriculture and horticulture. EBDCs are metabolized into a more toxic carcinogenic and teratogenic compound, ethylenethiourea (ETU), which has been associated with decreased serum thyroxine levels, increased thyroid stimulation hormone levels, and thyroid gland disorders. Although research indicates that prenatal ETU exposure may cause maternal and neonatal thyroid dysfunction, potentially leading to adverse outcomes including pregnancy loss, preterm delivery, intrauterine growth restriction, disruptions in fetal central nervous system and brain development and impaired cognitive and motor function, no epidemiological studies to date has evaluated the effects of prenatal exposure to ETU on newborn thyroid function or the subsequent neurobehavioral development of infants. This study proposes to follow pregnant women and their infants, incorporating prenatal urinary biomarkers of ETU exposure, survey data of environmental ETU exposure and key social and economic factors, and sensitive growth and neurobehavioral developmental measures. We hypothesize that higher maternal urinary ETU levels during pregnancy will be associated with delayed growth measures and lower cognitive, visual, and psychomotor developmental assessment scores at birth, 6, 12, and 18 months of age and that this association will be mediated through an impact on newborn thyroid function. The proposed research takes advantage of a unique opportunity to investigate this question in a highly exposed population in Ecuador. We will enroll 420 pregnant women at 10-12 weeks gestation and follow them through pregnancy up to 18 months post-partum. We will obtain monthly prenatal urine samples. We will obtain neonatal blood samples to assess thyroid hormone levels at birth. We will administer highly sensitive tests (BSID-III, Teller cards) that will assess cognitive, motor, language, and social-behavioral development, and visual function in infants. Infants will also be measured for growth and nutritional status. At each visit throughout the study, data will be collected on working conditions, stress, environmental exposures in home and work environments, social support, maternal health and lifestyle factors, socio-economic and demographic factors. We will quantify levels of prenatal ETU exposure and will analyze levels by trimester. We will assess associations between prenatal urinary ETU metabolite levels and infant developmental outcomes and will run a multivariate path analysis to test for a mediating effect of newborn thyroid dysfunction on this association. This study will further scientific understanding of the developmental consequences of exposure to fungicides, which have become the most commonly used pesticides in agricultural industry in the U.S. and globally.