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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES003460-14
Application #
2634327
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1985-02-01
Project End
1999-12-31
Budget Start
1998-01-01
Budget End
1999-12-31
Support Year
14
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Pharmacology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Kahn, Linda G; Liu, Xinhua; Rajovic, Biljana et al. (2014) Blood lead concentration and thyroid function during pregnancy: results from the Yugoslavia Prospective Study of Environmental Lead Exposure. Environ Health Perspect 122:1134-40
Graziano, Joseph; Slavkovich, Vesna; Liu, XinHua et al. (2004) A prospective study of prenatal and childhood lead exposure and erythropoietin production. J Occup Environ Med 46:924-9
Wasserman, Gail A; Factor-Litvak, Pam; Liu, Xinhua et al. (2003) The relationship between blood lead, bone lead and child intelligence. Child Neuropsychol 9:22-34
Wasserman, G A; Liu, X; Pine, D S et al. (2001) Contribution of maternal smoking during pregnancy and lead exposure to early child behavior problems. Neurotoxicol Teratol 23:13-21
Todd, A C; Buchanan, R; Carroll, S et al. (2001) Tibia lead levels and methodological uncertainty in 12-year-old children. Environ Res 86:60-5
Wasserman, G A; Liu, X; Popovac, D et al. (2000) The Yugoslavia Prospective Lead Study: contributions of prenatal and postnatal lead exposure to early intelligence. Neurotoxicol Teratol 22:811-8
Wasserman, G A; Musabegovic, A; Liu, X et al. (2000) Lead exposure and motor functioning in 4(1/2)-year-old children: the Yugoslavia prospective study. J Pediatr 137:555-61
Factor-Litvak, P; Wasserman, G; Kline, J K et al. (1999) The Yugoslavia Prospective Study of environmental lead exposure. Environ Health Perspect 107:9-15
Factor-Litvak, P; Slavkovich, V; Liu, X et al. (1998) Hyperproduction of erythropoietin in nonanemic lead-exposed children. Environ Health Perspect 106:361-4
Wasserman, G A; Staghezza-Jaramillo, B; Shrout, P et al. (1998) The effect of lead exposure on behavior problems in preschool children. Am J Public Health 88:481-6

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