LEAD EXPOSURE, ACCUMULATION IN BONE, AND REPRODUCTIVE TOXICITY IN MEXICO

动物研究和人类病例报告表明，骨骼中储存的铅 从环境暴露中积累起来的可以作为 怀孕期间胎儿和婴儿的显著铅暴露和 哺乳。然而，在没有活体测量骨骼铅储存的情况下，它 也不可能直接在 流行病学研究或量化骨储存铅的风险 对胎儿和婴儿发育的姿势。 我们计划使用我们最先进的K-x射线荧光(K-XRF) 已经位于墨西哥城的测量活体骨骼的仪器 一项新的铅暴露和生殖纵向研究中的铅水平 在已婚女性和男性中。我们已经证明了哺乳 墨西哥妇女的骨铅水平是哺乳期妇女的三倍 在波士顿年龄相当的人，而在膝盖骨中的铅(高度 骨小梁)是血铅的主要决定因素。在我们的第一阶段 研究计划，我们将招募计划怀孕的墨西哥夫妇 在结婚后18个月内。对妇女的基线评估将包括 医疗、环境、职业、饮食和生育史， 血铅测量和K-XRF骨铅测量。后续行动将 发生在骨铅水平相对较高或较低的女性身上。为 这些女性，我们将进行深入的家庭评估，以估计铅 暴露，管理跟踪调查问卷，重复血铅 每月测量一次尿β-hCG。我们还将 执行基线评估并收集精液样本以用于子研究 他们的丈夫。如果女性怀孕，第二阶段就开始了 时间暴露评估、后续调查问卷和血铅 将在每三个月和哺乳期重复测量， 产后补充K-XRF骨铅测定 句号。我们的主要统计分析将集中在(1)相对 骨铅与环境铅暴露对血铅的贡献 和血铅在妊娠和哺乳期的变化，以及(2)骨铅 作为不良妊娠结局的预测指标(例如流产/自然流产 堕胎)。此外，我们还将研究有关 膳食钙的修饰效应与ALA-D基因的多态性 这些关系，以及骨铅、血铅、 以及男性中的精子异常。

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.