The Generation R cohort study as an NIEHS resource

作为 NIEHS 资源的 R 世代队列研究

• 批准号: 8336616
• 负责人: Matthew Longnecker
• 金额: $ 5.75万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8336616
• 关键词: Accidents; Address; Adverse effects; Affect; Age at Menarche; Aliquot; Animals; Biological; Birth; California; Chemicals; Child; Child Development; Cognition; Cohort Studies; Collection; Communities; Contracts; Data; Databases; Developed Countries; Development; Elderly; Embryo; Enrollment; Environmental Pollution; Event; Exposure to; Female; Fetus; First Pregnancy Trimester; Freezing; Future; Generations; Germany; Goals; Growth; Growth and Development function; Health; Human; Laboratories; Life; Logistics; Manuscripts; Measurement; Measures; Medical Genetics; Medical center; Mothers; National Health and Nutrition Examination Survey; National Institute of Environmental Health Sciences; Netherlands; Norway; Organogenesis; Organophosphates; Outcome; Outcome Assessment; Pesticides; Polypropylenes; Population; Predisposition; Pregnancy; Pregnancy Outcome; Pregnancy loss; Pregnant Women; Prospective Studies; Reporting; Reproducibility; Reproducibility of Results; Research; Research Personnel; Resources; Risk; Salinum; Shipping; Ships; Sick Role; Specimen; Spottings; Staging; Testing; Third Pregnancy Trimester; Time; Ultrasonography; Urine; Woman; Work; Xenobiotics; bisphenol A; cohort; early childhood; early life exposure; epidemiologic data; fetal; follow-up; health care service utilization; interest; man; mono-(2-ethylhexyl)phthalate; multidisciplinary; neurodevelopment; new technology; offspring; phthalates; psychologic; success; young adult

More epidemiologic data are needed on the relation of background-level exposure to man-made chemicals with short half-lives to child development. The embryonic and fetal stages of development are periods of heightened susceptibility to effects of xenobiotics. For xenobiotics with short half-lives, measurement has been a challenge in the past, but new technologies now support better exposure assessment. Multiple urine specimens are frequently the medium of choice for assessing exposure to such agents. Recent data suggest: a) that exposure of pregnant women to background-levels of bisphenol A results in increased risk of pregnancy loss, adverse effects on neurodevelopment, and earlier age at menarche among female offspring, and b) that background-level of exposure of pregnant women to nonpersistent pesticides can result in impaired neurodevelopment in offspring. We seek to increase our capacity to study the relation of background-level exposure to chemicals with short half-lives to pregnancy outcomes and child development. To achieve this goal we supported collection of multiple urine specimens during pregnancy in the Generation R study (described below). The plan was to support collection of urine 3 times during pregnancy for the mothers of 2,500 children in the cohort. Generation R is an ongoing prospective study of 10,000 children who will be followed from early fetal life to young adulthood, and aims to study how factors and events during pregnancy and early childhood can affect growth, development, and health in later life. All pregnant women in Rotterdam who expect to give birth between June 2002 and June 2006 are invited to participate, together with their partner. This study has been set up by the Erasmus Medical Center. The multidisciplinary characterization of the cohort, starting in early pregnancy, will produce a database containing biological, medical, genetic, psychological and community-related data which can be used to address a wide spectrum of research questions. The research questions have been subdivided as growth and physical development, cognition and behavior, illnesses and accidents, and utilization of health care resources. The advantage to studying this cohort, e.g., over the Norway Mother and Child Cohort Study, is that we will have multiple urine specimens, including one during the first trimester, enhancing our ability assess exposures, especially during organogenesis. Furthermore, the outcome assessment in the Generation R cohort is more intensive and standardized than in Norway. In February of 2004, NIEHS support enabled an increase in the number of urine specimens collected from each pregnant woman from 1 to 3 (at 12, 20, and 30 weeks of gestation). As each pregnant woman presents for an ultrasound examination of her fetus, she provides a spot urine specimen that is divided into three 20ml aliquots and frozen at -20 degrees C in polypropylene containers. Two of these aliquots are reserved for collaborative studies with NIEHS. Although our primary interest was in women with a complete set of three urines (1/trimester, n=2,500 planned), for logistic reasons all women presenting for ultrasound provided a urine specimen that was stored. Enrollment is now complete. We have a complete set of 3 urines for 2,025 women, 2 urines for 970 women, and 1 urine for 356 women. We had 100 third trimester urine specimens sent to a laboratory to check the levels of exposure in this population. The laboratory results have now been obtained. With a few exceptions, the levels of phthalates, nonpersistent pesticides, and bisphenol A were similiar to those reported in other populations in developed countries. The levels of two antiandrogenic phthalates,MEHP and MnBP, were higher than in Swans study where reduced anogenital distance was associated with phthalate exposure. The levels of total dimethyl alkyl metabolites (of organophosphate pesticides) were higher than in the Chamacos study (Salinas, California); total diethyl metabolites were similar. Levels of bisphenol A were about the same as in the Calafat et al. NHANES report from 2005. Thus, examinations of health outcomes in relation to these contaminants may be worthwhile. Future studies will depend on the success of follow-up of subjects in the Generation R study, which outcomes are ascertained in the cohort, and future reports of health effects by other investigators. Last years progress: We have been collaborating with our colleagues in the Netherlands to conduct a study to evaluate the reproducibility of the urine concentrations of bisphenol A and organophosphate pesticide metabolites measured at different times in pregnancy. Specimens from the Generation R Cohort Study were shipped to a laboratory in Germany for analysis of bisphenol A and organophosphate pesticide metabolites. We are now analyzing the results for bisphenol A and preparing a manuscript; the data for the organophosphate pesticides are still pending from the laboratory. The results from the reproducibility study will support development of projects that will address our overall goals of the project, to examine exposure levels in relation to health outcomes in children. A contract to develop this work was prepared over the past year, and the solicitation should occur in 2012.

关于背景水平与人造化学物质的关系，需要更多的流行病学数据，其中半衰期为儿童发育。发育的胚胎和胎儿阶段是对异种生物的影响的敏感性增强的时期。对于半衰期短的异生物学，过去的测量一直是一个挑战，但是新技术现在支持更好的接触评估。多种尿液样本通常是评估暴露于此类药物的首选媒介。 最近的数据表明：a）孕妇暴露于双足酚A的背景水平A导致妊娠丧失的风险增加，对神经发育的不利影响以及女性后代中的初潮和初潮的早期年龄以及b）孕妇在孕妇中暴露于非急诊式载体的背景水平会导致神经发育受损。 我们试图提高研究背景水平接触的关系的能力，其中半衰期短于怀孕结局和儿童发育。 为了实现这一目标，我们支持在R研究中收集怀孕期间多个尿液标本（如下所述）。该计划是在同类中有2500名儿童的母亲在怀孕期间3次尿液收集。 R代是对10,000名儿童的持续前瞻性研究，这些儿童将从早期的胎儿生活到成年，旨在研究怀孕和幼儿期间的因素和事件如何影响以后生活的成长，发展和健康。希望在2002年6月至2006年6月之间分娩的鹿特丹的所有孕妇都与伴侣一起参加。这项研究是由伊拉斯mus医疗中心建立的。 从怀孕初期开始，该队列的多学科表征将产生一个包含生物学，医学，遗传，心理和社区相关数据的数据库，这些数据可用于解决广泛的研究问题。研究问题已被细分为增长，身体发展，认知和行为，疾病和事故以及医疗保健资源的利用。 研究这一队列的优点，例如，比挪威的母亲和儿童队列研究，我们将拥有多个尿液标本，其中包括一个孕期一个，增强了我们的能力评估暴露量，尤其是在器官发生过程中。此外，与挪威相比，R r群体中的结果评估更密集和标准化。 2004年2月，NIEHS支持使从1到3（妊娠12、20和30周）收集的尿液标本数量增加了。 当每位孕妇对胎儿进行超声检查时，她提供了一个尿液标本，分为三个20ml等分试样，并在聚丙烯容器中以-20摄氏度冷冻。 这些等分试样中的两个保留用于与NIEHS的协作研究。 尽管我们的主要兴趣是对三个尿液（1/孕期，n = 2,500的计划）的妇女，但出于逻辑原因，所有用于超声的女性都提供了存储的尿液标本。 注册现已完成。 我们为2,025名女性提供了一组完整的3尿液，2次尿液，970名女性，1次尿液，356名妇女的尿液。 我们有100个三个月尿液标本发送到实验室，以检查该人群的暴露水平。 现已获得实验室结果。 除少数例外，邻苯二甲酸盐，非持久性农药和双酚A的水平与发达国家其他人群中报道的水平相似。 在研究中，两个抗二元性邻苯二甲酸盐MEHP和MNBP的水平高于Swans研究，在该研究中，肛门生殖器距离降低与邻苯二甲酸酯有关。 总二甲基烷基代谢物（有机磷酸盐农药）的水平高于Chamacos研究（加利福尼亚州萨利纳斯）。总二乙基代谢物相似。 双酚A的水平与Calafat等人的水平相同。 NHANES报告从2005年开始。因此，对这些污染物的健康结果的检查可能值得。 未来的研究将取决于在R Generation研究中对受试者的随访成功，该研究在同类中确定了结果，以及其他研究人员对健康影响的未来报告。 去年进度： 我们一直在与荷兰的同事合作进行一项研究，以评估双酚A的尿液浓度和在妊娠不同时间测量的有机磷酸盐农药代谢物的可重复性。 Ren Generation R研究的标本被运送到德国的一个实验室，以分析Bisphenol A和有机磷酸盐农药代谢物。 现在，我们正在分析双酚A的结果并准备手稿；有机磷酸盐农药的数据仍在实验室中。 可重复性研究的结果将支持将解决我们项目总体目标的项目的开发，以研究与儿童健康结果有关的暴露水平。 在过去的一年中，准备了开发这项工作的合同，招标应在2012年发生。