ORGANOPHOSPHATE PESTICIDES AND HUMAN REPRODUCTIVE HEALTH

描述：（改编自研究者摘要）本研究旨在 招募并前瞻性地跟踪一群妇女及其丈夫 评估接触有机磷（OP）农药对不良反应的影响 男性和女性农业工人的生殖结果。已婚 目前在安庆市海口镇工作的20-34岁不吸烟女性， 谁已获得生育许可，以及谁将尝试生育 在研究过程中怀孕将有资格参加该研究。 生殖终点将包括 (1) 精液参数（浓度、总量 计数、活动性、进展和形态），（2）月经失调 （月经稀发、闭经、月经过多、经间期出血、经期延长 月经出血、痛经、月经不调）； (3) 变更 激素模式，包括雌激素排泄减少 (REE)、无排卵、 女性黄体期（ALP）异常和卵泡期（AFP）异常 男性 LH、FSH、TSH、SHBG、抑制素 B 和睾酮异常； (4) 生育力； (5) 妊娠结局，包括自然流产， 早产、低出生体重和宫内发育迟缓。之后 注册后，面试官将管理一份之前经过验证的调查问卷 向妇女及其丈夫收集基线信息 社会人口、环境、职业和个人协变量。精液 样本将由经过培训的技术人员在注册时获取，并再次获取四个样本 几个月后。每个女人都会记下自己的月经信息的日记， 环境暴露和饮食摄入。每日尿液样本将 从每位女性受试者身上收集长达一年或直至怀孕 发生。将测量尿 PdG、EIC、LH、FSH 和 hCG 以识别异常 内分泌模式和亚临床妊娠。女人一旦怀孕， 她将通过跟踪调查获得妊娠结果 以及婴儿出生的医院记录。广泛的暴露评估 将在整个随访期间进行，因此，剂量反应 可以建立关系。所有参与者将保持每日曝光 日记。将测量尿液样本中选定暴露的代谢物 天。将研究一部分参与者的个人空气监测和 对尿液代谢物进行系列分析以验证暴露日记和尿液 代谢物测定。研究人员表示，拟议的研究有几个方面 优点：（1）它将在具有广泛范围的人群中进行 接触有机磷农药； (2) 暴露将得到很好的表征； (3) 每位妇女及其丈夫同时接受研究； (4) 的 前瞻性研究设计可以消除某些缺陷或潜在偏差 以前的回顾性研究； (5)受孕时间和自然流产 将使用改进的特异性 hCG 检测进行评估，该检测可以检测 植入后几天内怀孕； (6)最近开发的生物标志物， 包括尿激素测定和 FISH 方法，将应用于 学习； (7) 测试基因与环境的相互作用； (8) 现场成本 中国远低于美国； (9) 人口拥有 用于检验所提出的假设的独特特征，即稳定的 员工队伍、非吸烟团体和出色的合规率。

DESCRIPTION: (Adapted from the Investigator's Abstract) This study is designed to recruit and prospectively follow a cohort of women and their husbands to assess the effects of exposure to organophosphate (OP) pesticides on adverse reproductive outcomes in both men and women in agricultural workers. Married never-smoking women age 20-34 who currently work in Haikou Township, Anqing, who have obtained permission to have a child, and who will be attempting to become pregnant over the course of the study will be eligible for the study. Reproductive endpoints will include (1) semen parameters (concentration, total count, motility, progression and morphology), (2) menstrual disorders (oligomenorrhea, amenorrhea, polymenorrhea, intermenstrual bleeding, prolonged menstrual bleeding, dysmenorrhea, and irregular menstruation); (3) alterations in hormone patterns including reduced estrogen excretion (REE), anovulation, abnormal luteal phase (ALP), and abnormal follicular phase (AFP) in women and abnormalities of LH, FSH, TSH, SHBG, inhibin-B and testosterone in men; (4) fecundability; and (5) pregnancy outcomes including spontaneous abortion, preterm delivery, low birth weight and intrauterine growth retardation. After enrollment, interviewers will administer a previously validated questionnaire to the women and their husbands to collect baseline information on sociodemographic, environmental, occupational, and personal covariates. Semen samples will be obtained by trained technicians at enrollment and again four months later. Each woman will keep a diary of her menstrual information, environmental exposures, and dietary intake. Daily urine samples will be collected from each female subject for up to one year or until a pregnancy occurs. Urinary PdG, EIC, LH, FSH and hCG will be measured to identify abnormal endocrine patterns and subclinical pregnancy. Once a woman becomes pregnant, she will be followed for pregnancy outcomes obtained from a follow-up survey and hospital records where the baby is delivered. Extensive exposure assessment will be conducted throughout the follow-up period and, therefore, dose-response relationships can be established. All participants will keep daily exposure diaries. Urine samples will be measured for metabolites on selected exposure days. A subset of participants will be studied for personal air monitoring and serial analysis of urine metabolites to validate the exposure diary and urine metabolite assay. The investigators state that the proposed study has several strengths: (1) it will be conducted in a population with a broad range of organophosphate pesticide exposure; (2) exposure will be well-characterized; (3) each woman and her husband will be studied simultaneously; (4) the prospective study design can eliminate certain flaws or potential biases in previous retrospective studies; (5) time to conception and spontaneous abortion will be evaluated with the improved specific hCG assay, which can detect pregnancy within a few days of implantation; (6) recently-developed biomarkers, including urinary hormone assays and FISH methods, will be applied to the study; (7) gene-environment interactions will be tested; (8) the field cost in China is much lower than that in the U.S.; and (9) the population possesses unique characteristics for examining the proposed hypothesis, i.e., a stable workforce, a non-smoking group and excellent compliance rates.