We are studying the relation of chronic lead (Pb) exposure to physical, behavioral and cognitive-linguistic development during infancy and childhood. This prospective cohort study, founded upon a previous study of pregnancy outcome, involves a unique community surrounding a Pb smelter in Titova Mitrovica, Yugoslavia; comparison groups are studied in Pristina, a non-Pb-exposed town 25 miles away. In Mitrovica, 237 infants were selected at birth on cord blood lead concentration (BPb): low, mid and high. In Pristina, a cohort of 225 infants includes one group frequency-matched on maternal and paternal education to the high cord BPb group, and one group with the highest cord BPb's. We describe herein three findings of major importance: 1) After adjustment for sociodemographic variables, there is a strong, significant effect of post-natal Pb exposure on cognitive function at 24-months of age; 2) Hemoglobin concentration (Hgb) , presumably an indicator of iron status, also has a significant effect on cognitive function which is independent of the Pb effect; parameter estimates of the Hgb effect are comparable in both towns; and, 3) Elevated BPb is associated with depressed serum erythropoietin (EPO) levels. The anemia of Pb toxicity may therefore be due, in part, to impaired renal production of EPO. Indeed, serum EPO may be a sensitive indicator of Pb-induced renal toxicity. We propose to evaluate the relationships between chronic Pb exposure, iron deficiency and development through age 7.5 years to determine whether the observed deficits persist during the transition from home to school. In addition, we will describe the dose-response relationship between BPb and EPO, utilizing a serum bank created during the pregnancy and infant development studies. This study is unique in that it permits the separation of pre-and postnatal effects of Pb, and can explore biologic hypotheses concerning measures of BPb, Hgb, EPO, EP and ferritin.
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