(Taken from application) Evidence from case reports and studies of lead isotope ratios suggest that lead stored in the skeleton is mobilized during pregnancy and lactation, placing the mother and, in particular, the developing fetus and infant at risk of lead poisoning. The placenta is fully permeable to lead, and lead is present in breast milk. Calcium intake may protect against lead absorption. To investigate the hypothesis that skeletal lead is mobilized during pregnancy, and perhaps more importantly during lactation, we propose an intervention study with repeated measures of blood and bone lead in a population of women in Morelos, Mexico with high environmental lead exposure. Women will be randomized to receive calcium and vitamin supplements, calcium without vitamin supplements, or vitamin supplements alone. We will simultaneously follow a control group of non-pregnant women. We hypothesize that as lead is mobilized during pregnancy and lactation, maternal, fetal and infant blood-lead levels will increase, and maternal bone-lead levels will decrease. We will compare bone- and whole blood-lead levels prior to pregnancy with measurements obtained from the same women at two weeks, six months and twelve months postpartum. Bone-lead levels will be measured by X-Ray Fluorescence. We will examine molecular biomarkers of bone turnover to assess whether concurrent bone remodeling and lead mobilization occurs. We hypothesize that bone-lead levels will decrease during pregnancy, and further during lactation as a result of bone-lead mobilization. The control group of non-pregnancy women will allow us to compare the natural history of bone-lead changes in the absence of pregnancy and lactation. Blood-lead levels obtained in each child at the same time as the mother s postpartum evaluations will provide information about maternal transfer of circulating lead to the child. To assess gene-environment interactions, we will examine whether polymorphisms in ALA-D, the hemochromatosis gene and the Vitamin D receptor influence lead release from bone. We hypothesize that women receiving calcium supplements will have less lead mobilization and thus less transfer to their developing child. We will also assess whether calcium plus vitamin supplements is more protective than calcium alone. This study will be undertaken in Morelos, Mexico where the population has high environmental lead exposure, predominantly through the use of lead-glazed ceramics, and where women have high rates of breast-feeding. Thus we will be able to compare bone-lead mobilization during lactation with that which occurs during pregnancy. The investigation should provide important insights into the potential health effects of chronic environmental lead exposure to pregnant and lactating women, developing fetuses, and infants through breast feeding, as well as insights into approaches for prevention.
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