Animal studies and human case reports suggest that bone stores of lead accumulated from environmental exposures can serve as a source of significant lead exposure to fetuses and infants during pregnancy and lactation. However, without an in vivo measure of bone lead stores, it has not been possible either to test this hypothesis directly in epidemiological studies or to quantitate the risk that bone stores of lead pose to fetal and infant development. We propose to use our state-of-the-art K x-ray fluorescence (K-XRF) instrument that is already located in mexico City to measure in vivo bone lead level in a new longitudinal study of lead exposure and reproduction among married women and men. We have already demonstrated that lactating mexican women have bone lead levels three times as high as lactating women of comparable age in Boston, and that lead in the patella (a highly trabecular bone) is a main determinant of blood lead. In Phase i of our research plan, we will recruit mexican couples who are planning to conceive within 18 months of marriage. A baseline evaluation of women will include medical, environmental, occupational, dietary, and reproductive histories, blood lead measurements, and K-XRF bone lead measurements. Follow-up will occur in women with either relatively high or low bone lead levels. For these women, we will perform in-depth home assessments to estimate lead exposure, administer follow-up questionnaires, repeat the blood lead measurements, and measure urinary B-hCG on a monthly basis. We will also perform a baseline evaluation and collect a semen specimen for a sub-study of their husbands. Phase II begins if a woman becomes pregnant, at which time exposure assessment, follow-up questionnaires, and blood lead measurements, will be repeated at each trimester and during lactation, with additional K-XRF bone lead determinations added during the post-partum period. Our major statistical analyses will focus on (1) the relative contributions of bone lead vs. environmental lead exposure to blood lead and change in blood lead during pregnancy and lactation, and (2) bone lead as a predictor of adverse pregnancy outcomes (e.g. miscarriage/spontaneous abortion). In addition, we will examine secondary hypotheses regarding the modifying influence of dietary calcium and polymorphism of the ALA-D gene on these relationships, and the association between bone lead, blood lead, and sperm abnormalities among men.
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