Environmental Lead, Thyroid Function &Neurodevelopment

Severe deficiency of thyroid hormone during the prenatal and neonatal periods is associated with adverse neurodevelopmental outcomes in infancy and childhood. Maternal iodine deficiency during pregnancy leads to a lowered production of activated (i.e., iodinated) thyroid hormone (T3) and an increased risk of cretinism (with associated severe mental retardation) in the child. Congenital hypothyroidism and transient hypothyroidism of prematurity are associated with deficits in cognition during early life. In light of these observations, it is appropriate to ask whether sub-optimal maternal thyroid function, particularly during the first half of pregnancy when maternal contribution to fetal thyroid hormone is maximal, is associated with neurodevelopment of the child. Recent data suggest that children of mothers with 'low-normal' thyroid function are at risk for small deficits in cognition and increased reports of behavior problems. The overall goal of this project is to assess whether mild deficiencies in maternal thyroid function are associated with adverse neurodevelopment in the child, and, if so, to elucidate possible biologic mechanism. One possible mechanism is through damage to the choroid plexus, the site of production of the brain-specific transport protein for thyroid hormone. Animal studies suggest that the choroid plexus is damaged by exposure to environmental lead, raising the possibility that associations between lead exposure and cognition in the child arise through an effect of lead on transport of thyroid hormone to the brain. The proposed study draws on data from a prospective study designed to examine the associations between pre- and post-natal lead exposure and childhood development. The cohort comprises approximately 300 children, born in 1984-1985 in two towns in Kosovo, Yugoslavia who were followed through age 12. Sera are available to measure thyroid function in the mothers at mid-pregnancy and in the children at ages 4, 7 and 12. Outcomes, including cognition, motor function, behavior problems and anthropometric measurements, were measured repeatedly during infancy and childhood. This project will expand the findings of the Yugoslavia study to examine first, whether maternal thyroid function in the first half of pregnancy is associated with cognitive, behavioral and growth outcomes and second, whether the associations between Pb and these outcomes are mediated by exposure to thyroid hormone.