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Maternal ethylenethiourea levels, newborn thyroid function & infant development

a PSC Research Project

Investigators:   Sioban D. Harlow, Niko Kaciroti, Betsy Lozoff

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, leading to adverse reproductive outcomes including pregnancy loss, preterm delivery, intrauterine growth restriction, as well as to disruptions in fetal central nervous system and brain development and consequent impaired cognitive and motor function, very few epidemiological studies to date have evaluated the effects of prenatal exposure to ETU on newborn thyroid function or the subsequent neurobehavioral development of young children. This study proposes to follow pregnant women and their infants, incorporating prenatal urinary biomarkers of ETU exposure, survey data of environmental ETU exposure, and sensitive growth and neurobehavioral developmental measures in infants. We hypothesize that higher maternal urinary ETU levels during pregnancy will be associated with higher mean thyroid-stimulating hormone and lower mean free thyroxine levels in newborns and with delayed growth measures and with poorer cognitive, visual, and psychomotor developmental assessment scores at 6, 12, and 18 months of age. The proposed research takes advantage of a unique opportunity to investigate this question in a highly exposed population in Ecuador. Using a community-based research approach, we will enroll 420 pregnant women at 10-12 weeks gestation, follow them through delivery and follow-up the mother-infant pair for 18 months. We will obtain monthly prenatal urine samples from the mother and will ask about her health, working conditions during pregnancy, maternal stress levels and depression, maternal-child interactions, and socio-demographic factors. We will obtain neonatal blood samples to assess thyroid hormone levels at birth. We will administer highly sensitive developmental assessment 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. We will quantify levels of ETU exposure in pregnancy and will analyze levels by trimester. We will assess trends, correlations, and associations between prenatal ETU metabolite levels with both neonatal thyroid function and infant developmental outcomes. This study will further scientific understanding of the neurobehavioral health consequences of exposure to fungicides, which have become the most commonly used pesticides in agricultural industry in the Unites States and globally.

Funding Period: 09/30/2017 to 07/31/2022

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