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

动物研究和人类病例报告表明， 从环境中积累的暴露可以作为一个来源， 怀孕期间胎儿和婴儿大量接触铅， 哺乳期 然而，如果没有体内骨铅储存的测量， 也不可能直接测试这个假设， 流行病学研究或定量骨储存铅的风险 对胎儿和婴儿的发育构成影响。 我们建议使用我们最先进的K X射线荧光（K-XRF） 一种已经在墨西哥城安装的测量体内骨骼的仪器 一项新铅暴露与生殖纵向研究中的铅水平 在已婚妇女和男子中。 我们已经证明了哺乳期 墨西哥妇女骨铅含量是哺乳期妇女的三倍 在波士顿，年龄相当，髌骨的铅（一个高度 骨小梁）是血铅的主要决定因素。 在第一阶段， 研究计划，我们将招募墨西哥夫妇谁是计划怀孕， 结婚18个月内。 对妇女的基线评估将包括 病史、环境史、职业史、饮食史和生殖史， 血铅测量和K-XRF骨铅测量。 后续将 发生在骨铅水平相对较高或较低的女性中。 为 这些妇女，我们将进行深入的家庭评估， 暴露，管理随访问卷，重复血铅 测量，并每月测量尿B-hCG。 我们还将 进行基线评估并采集精液样本用于子研究 他们的丈夫。 第二阶段开始于妇女怀孕， 时间暴露评估、随访问卷和血铅 测量，将在每三个月和哺乳期重复， 在产后增加额外的K-XRF骨铅测定 期 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 妊娠期和哺乳期血铅的变化;（2）骨铅 作为不良妊娠结局（例如流产/自发性流产）的预测因子 堕胎）。 此外，我们还将研究关于 钙对ALA-D基因多态性的调节作用 以及骨铅、血铅 男性精子异常的原因

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.