Title: Long-term consequences of environmental lead exposure in Kosovo
Description: Between May 1985 and December 1986, a cohort of 1,502 pregnant women was recruited at two government clinics in Kosovo (formerly a province of Yugoslavia) for a study of the relationship between environmental lead (Pb) exposure and birth outcomes. Subsequently, a representative group of 541 of their children were selected for long-term follow up. The children were followed longitudinally at six-month intervals for 12 years to examine the effects of environmental Pb exposure on a variety of health outcomes including cognitive and motor function, anemia, endocrine function and growth. This work produced numerous landmark publications (Popovac et al, 1982; Graziano et al., 1990, 1991, 2004; Murphy et al., 1990; Factor-Litvak et al, 1993, 1996, 1998, 1999; Wasserman et al,. 1992, 1994, 1997, 1998, 2000) that contributed to the modification of environmental policies to reduce Pb exposure worldwide. The long-term study ultimately linked environmental Pb exposure from the Trepca mining and smelting operations in Mitrovica to adverse effects on intelligence, motor function, blood pressure, renal, endocrine and hematological functioning.

Follow up rates over time were excellent in that 70% of the total cohort was evaluated at 6 years of age, and 65% were evaluated at 12 years of age, at which point the study was - until now - concluded. For the present study, we located 101 members of the original study cohort and requested their participation in a follow-up study in which participants were evaluated to assess their current blood lead (BPb) levels and health outcomes as follows: a) blood pressure; b) biomarkers of endothelial cell function that are associated with cardiovascular disease; c) and measurements of erythropoietin, a glycoprotein hormone produced in the kidney that regulates the production of red blood cells in the bone marrow. The participants, whose environmental exposure history is very well documented from 12 weeks of gestation through 12 years of age, were between 25-26 years of age during the follow-up study. We found a statistically significant association between BPb and systolic blood pressure (sBP), and a marginally significant association between BPb and diastolic blood pressure (dBP), which is consistent with a multitude of studies and meta-analyses referenced in this dissertation.

These results provide further evidence that recent circulating dose, as estimated by BPb, or as estimated by lifetime cumulative exposure, is associated with slight increase in sBP. Furthermore, we detected a suggestive relationship between BPb and levels of circulating serum intercellular adhesion molecules (sICAM-1) and serum intravascular adhesion molecules (sVCAM-1), possibly a mechanism by which Pb may lead to increased BP. These findings support the hypothesis that the exposure to Pb either prenatally or in early adulthood, may lead to increased BP and increased circulating levels of sICAM-1 and sVCAM-1 later in life. Lastly, the results regarding the serum erythropoietin (EPO) production presented here resemble the findings reported in this cohort at 4.5 and 6.5 years of age and in contrast with the findings in this cohort when the study participants were 9.5 and 12 years of age (Graziano et al., 2004). In addition, they also contrast the findings reported in the anemic mothers of this study cohort (Graziano et al., 1991) where serum-EPO levels were lower in those with higher BPb levels.