Long-Term Effects of Environmental Lead on Erythropoietin Production in Young Adults: A Follow-Up Study of a Prospective Cohort in Kosovo.

Background and Aims: Epidemiologic cross-sectional studies examining the relationship between environmental lead (Pb) exposure and erythropoietin (EPO) production have reported contrasting results. It is unknown, however, if exposure to Pb earlier in life has an effect on EPO production later in life. Here, using a prospective study, we evaluate the association between prenatal, early childhood, and concurrent Pb exposure and EPO concentration in young adulthood. Methods: From our prospective birth cohort study in Mitrovica (a mining town) and Pristina (a control town), Kosovo, from 1985 to 1998, we located and assessed blood lead concentration (BPb) and serum EPO in 101 participants (mean age 24.9 years) in 2011. We examined the association between BPb and EPO, stratified by hemoglobin (Hgb), and controlling for potential confounders. Results: These results resemble the findings in the original full cohort at 4.5 and 6.5 years of age, at which time we reported that the maintenance of a normal Hgb required increased EPO production among participants exposed to high levels of environmental Pb. In contrast, when the original cohort was 9.5 and 12 years of age, they were no longer capable of hyper-production of EPO in order to maintain normal levels of Hgb, suggestive of cumulative toxicity to the peritubular cells of the kidney that are responsible for EPO synthesis. Conclusion: Our results, along with previously reported findings on this cohort, suggest that a dramatic reduction of Pb exposure may allow for a reversal of the impact that prolonged Pb exposure may have on EPO production.

Long-Term Effects of Environmental Lead Exposure on Blood Pressure and Plasma Soluble Cell Adhesion Molecules in Young Adults: A Follow-Up Study of a Prospective Cohort in Kosovo.

Background and Aims: Epidemiologic studies examining the relationship between environmental lead (Pb) exposure and blood pressure (BP) generally report small associations between blood lead concentration (BPb) and BP. However, these studies are predominantly cross-sectional. In addition, no epidemiologic studies evaluate associations between either current or past Pb exposure and serum levels of markers of systemic inflammation and endothelial dysfunction, including soluble vascular adhesion molecule (sVCAM-1) and soluble intercellular cell adhesion molecule (sICAM-1). We prospectively investigate these associations later in life: Methods. From our original prospective birth cohort study in Mitrovica (a mining town) and Prishtina (a control town), Kosovo, from 1985 to 1998, we located and assessed BPb and BP in 101 participants (mean age of 24.9 years old) in 2011. Results: We found highly statistically significant association between concurrent BPb and sVCAM-1 in men and a marginally significant association between concurrent PBb and sICAM.-1 in women. We did not find evidence of mediation. Conclusion: Current study results, along with previously reported findings on this cohort, provide evidence for the hypothesis that exposure to Pb leads to small increases in sBP and perhaps to increased circulating levels of sVCAM-1 and sICAM-1 later in life.

The relationship between blood lead, bone lead and child intelligence.

We report associations between serial measures of blood lead and intelligence in children age 10-12 years, half heavily exposed to lead from the prenatal period onward, and half relatively unexposed. For a subsample, we examine bone lead-IQ associations, comparing them with bone lead associations. Both blood and bone lead levels were associated with intelligence decrements, small relative to the contribution of social factors. For each doubling of Tib-Pb, Full Scale, Performance, and Verbal IQ decreased by an estimated 5.5, 6.2, and 4.1 points, respectively. Bone lead-IQ associations were stronger than those for blood lead, which nonetheless provide robust analogues. Current BPb, easy to obtain, provides a useful means for assessing Pb exposure/IQ associations.

Blood lead concentration and thyroid function during pregnancy: results from the Yugoslavia Prospective Study of Environmental Lead Exposure.

BACKGROUND: Although maternal hypothyroidism increases the risk of adverse neonatal and obstetric outcomes as well as lower IQ in children, the environmental determinants of maternal thyroid dysfunction have yet to be fully explored. OBJECTIVES: We aimed to examine associations between mid-pregnancy blood lead (BPb) and concomitant measures of thyroid function among participants in the Yugoslavia Prospective Study of Environmental Lead Exposure. METHODS: As part of a population-based prospective study of two towns in Kosovo-one with high levels of environmental lead and one with low-women were recruited during the second trimester of pregnancy, at which time blood samples and questionnaire data were collected. We measured concentrations of BPb, free thyroxine (FT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibodies (TPOAb) in archived serum samples. RESULTS: Compared with women from the unexposed town, women from the exposed town had lower mean FT4 (0.91 ± 0.17 vs. 1.03 ± 0.16 ng/dL), higher mean TPOAb (15.45 ± 33.08 vs. 5.12 ± 6.38 IU/mL), and higher mean BPb (20.00 ± 6.99 vs. 5.57 ± 2.01 µg/dL). No differences in TSH levels were found. After adjustment for potential confounders, for each natural log unit increase in BPb, FT4 decreased by 0.074 ng/dL (95% CI: -0.10, -0.046 ng/dL), and the odds ratio for testing positive to TPOAb was 2.41 (95% CI: 1.53, 3.82). We found no association between BPb and TSH. CONCLUSIONS: Prolonged lead exposure may contribute to maternal thyroid dysfunction by stimulating autoimmunity to the thyroid gland.