ENVIRONMENTAL LEAD, REPRODUCTION, AND INFANT DEVELOPMENT

We propose to continue to study the relation of chronic lead (Pb) exposure to several health outcomes during childhood. This large prospective cohort study, founded upon a previous study of pregnancy outcome, involves a unique community surrounding a Pb smelter in Yugoslavia; comparison groups are studies in a non-Pb-exposed town 25 miles away. The scientific conduct of our study continues to proceed smoothly and has not been influenced by the conflict in Bosnia. We seek funding to analyze existing data (to age 9) and for additional field studies and analyses to age 12. We aim to test whether Pb exposure, measured by concurrent and past blood Pb (BPb), is associated with: a) cognitive development; b) behavioral problems; c) physical growth; d) blood pressure; e) proteinuria; and f) postural sway. We have observed associations with most of these outcomes at ages 2-5.5 yrs. We will examine the persistence and dose-response patterns of these relationships in later childhood. We also propose to repeat the above analyses at ages 10-12 using K-XRF bone Pb, a more refined measure of body burden, to estimate associations. K-XRF bone Pb measurements will be conducted on site by Dr. Andrew Todd of Mount Sinai Medical Center. In addition, we report herein that children with elevated BPb's maintain a normal hemoglobin concentration but require hyperproduction of erythropoietin to do so. We hypothesize that children with even moderately elevated BPb's have shortened red cell survival, a phenomenon described at much higher exposures. In other words, to maintain a normal steady-state red cell mass, children with elevated BPb must produce a "supernormal" hormonal stimulus for red cell production. Thus, we propose to conduct analyses which may reveal indirect evidence of shortened red cell survival. We will also test the hypothesis that chronic Pb exposure and hyperproduction and erythropoietin during childhood may lead to the eventual failure, as we have observed in adults, of renal erythropoietin production. In sum, we aim to elucidate the pathophysiologic mechanism(s) whereby Pb exposure induces anemia.