Peri-Conceptional Biomonitoring

描述（由申请人提供）：本提案将解决1)在人类发育早期阶段环境暴露的准确评估，以及2)在300对试图怀孕的社区居住队列中，这些暴露与精液质量和怀孕时间的关联。在动物模型和有限的流行病学研究中，选择用于测量的污染物，消毒副产物（DBP）和双酚a (BPA)，与不利的生殖结果有关。通过传统的流行病学手段，如使用问卷的参与者回忆或怀孕早期（如第一次产前检查时）的环境监测，或诸如饮用水系统监测报告的污染物水平分配等生态措施，无法很好地测量暴露于这些和其他环境污染物的情况。生物标志物可以提供更精确的内剂量估计，但对于短暂暴露和半衰期短的化学品，必须在适当的时间收集生物标本，以便根据关键发育窗口对个体暴露进行适当分类。如果暴露是短暂的，或者相关化学物质的半衰期很短，那么在怀孕早期收集的生物标志物可能来不及检测出怀孕前后的暴露。在这种类型的设计中，也会忽略影响受孕概率的排卵期暴露，因为未能怀孕的夫妇不会进入产前护理。1.具体目标通过观察社区居民的生育体征，采用一种新颖的自我收集环境和生物标本的策略，对人类孕前队列中的消毒副产物（DBP）和双酚a （BPA）进行前瞻性、围排卵期生物监测。2. 评估男性和女性前瞻性测量暴露与生殖结果（精液质量和怀孕时间）之间的关系。3. 量化常用的回顾性暴露评估方法（参与者使用召回问卷和/或存档环境监测数据自我报告过去暴露）与前瞻性围排卵期生物监测和抽样所产生的误分类偏差程度。建议招募孕前队列，通过生物标志物和问卷进行前瞻性暴露评估，评估暴露与妊娠时间的关系，并比较前瞻性测量暴露与回顾性估计暴露。收集的生物标本将作为将来分析的储存库。这个队列和标本库的创建将启动首席研究员（早期）Porucznik的独立职业生涯。

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.