Peri-Conceptional Biomonitoring

描述(由申请人提供)：这项建议将涉及1)准确评估人类发育早期阶段的环境暴露，以及2)在一个由300对试图怀孕的夫妇组成的社区队列中，这些暴露与精液质量和怀孕时间的关联。选定用于测量的污染物，消毒副产物(DBP)和双酚A(BPA)，在动物模型和有限的流行病学研究中与不利的生殖结果有关。这些污染物和其他环境污染物的暴露不能通过传统的流行病学方法很好地衡量，例如参与者使用问卷回忆，或在怀孕早期进行环境监测，例如在第一次产前探视时，或通过生态措施，如分配饮用水系统监测报告的污染物水平。生物标记物可以更准确地估计体内剂量，但对于瞬时暴露和半衰期短的化学品，必须在正确的时间收集生物标本，以便根据关键发育窗口对个人暴露进行适当分类。如果暴露是短暂的，或者相关化学物质的半衰期很短，在怀孕早期收集的生物标记物可能太晚了，无法检测到围产期暴露。在这种类型的设计中，也会错过影响受孕概率的排卵期暴露，因为没有怀孕的夫妇将不会进入产前护理。具体目标1.使用一种新的策略对人类先入为主的队列中的消毒副产物(DBP)和双酚A(BPA)进行前瞻性、排卵期生物监测，该策略通过观察社区居住人口的生育迹象而触发环境和生物样本的自我收集。2.评估预期测量的男性和女性暴露与精液质量和怀孕时间的生殖结果之间的关联。3.量化常用的回溯性暴露评估方法(参与者使用回忆问卷和/或档案环境监测数据对过去暴露的自我报告)与预期的排卵期生物监测和采样所产生的错误分类偏差的程度。该建议是招募一个受孕前队列，通过生物标记物和问卷进行前瞻性暴露评估，评估暴露与怀孕时间的关联，并将前瞻性测量的暴露与回顾估计的暴露进行比较。收集到的生物样本将作为未来分析的储存库。这个队列和样本库的创建将开启首席调查员(早期)Porucznik的独立职业生涯。 公共卫生相关性：以前关于环境暴露和生殖结果的研究依赖于参与者关于怀孕前后夫妇或已经分娩的夫妇的暴露报告。这个拟议的项目将在夫妇怀孕之前招募他们，教他们识别何时可能怀孕(多产或生育窗口)，并在估计的每个排卵日前后进行前瞻性暴露评估，以进行真正的排卵期(如果怀孕发生，则为围产期)暴露评估。参与者稍后将被要求报告围排卵期的召回暴露，并将比较预期值和回顾值，以确定常用的召回暴露评估引入的误差。

DESCRIPTION (provided by applicant): This proposal will address 1) accurate assessment of environmental exposures during the earliest phases of human development, and 2) association of these exposures with semen quality and time to pregnancy in a community-dwelling cohort of 300 couples trying to conceive. The contaminants selected for measurement, disinfection by-products (DBP) and bisphenol-A (BPA), have been associated with adverse reproductive outcomes in animal models and in limited epidemiologic studies. Exposure to these and other environmental contaminants is not well measured via traditional epidemiologic means such as participant recall using questionnaires or environmental monitoring in early pregnancy, such as at the time of the first prenatal visit, or ecologic measures such as assignment of contaminant levels reported from drinking water system monitoring. Biomarkers can allow for more precise estimates of internal dose, but for transient exposures and chemicals with short half-lives, the biological specimen must be collected at the right time in order to properly classify individual exposure in relation to critical developmental windows. Biomarkers collected in early pregnancy may be too late to detect peri-conceptional exposure if the exposure was transient or if the relevant chemical had a short half-life. Peri-ovulational exposures that affect probability of conception would also be missed in this type of design, as couples who fail to conceive will not enter into prenatal care. SPECIFIC AIMS 1. Conduct prospective, peri-ovulational biomonitoring for disinfection by-products (DBP) and bis-phenol-A (BPA) in a human preconception cohort using a novel strategy of self-collection of environmental and biological specimens triggered by observation of fertility signs in a community-dwelling population. 2. Evaluate the association between prospectively measured exposures in the male and the female and the reproductive outcomes of semen quality and time to pregnancy. 3. Quantify the degree of misclassification bias generated by retrospective exposure assessment methods in common use (participant self-report of past exposure using a recall questionnaire and/or archival environmental monitoring data) compared to prospective peri-ovulational biomonitoring and sampling. The proposal is to recruit a pre-conception cohort, conduct prospective exposure assessment via biomarkers and questionnaires, evaluate the association of exposure with time to pregnancy, and compare prospectively measured exposures with retrospectively estimated exposures. Collected biospecimens will be banked as a repository for future analyses. Creation of this cohort and specimen bank will launch the independent career of Principal Investigator (Early Stage) Porucznik. PUBLIC HEALTH RELEVANCE: Previous studies of environmental exposures and reproductive outcomes have relied on participant report of exposure around the time of conception from already pregnant couples or couples who have already delivered. This proposed project will recruit couples before they conceive, teach them to identify when pregnancy is likely (the fecund or fertile window) and conduct prospective exposure assessment around each estimated day of ovulation for true, peri-ovulational (peri-conceptional if conception occurs) exposure assessment. Participants will be asked later to report recalled exposures for the peri-ovulational period, and the prospective and retrospective values will be compared to determine the error introduced by recalled exposure assessment in common use.