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.

需要更多流行病学数据来了解半衰期短的人造化学品的背景水平暴露与儿童发育的关系。胚胎和胎儿发育阶段是对异生素影响高度敏感的时期。对于半衰期短的外源物质，测量在过去一直是一个挑战，但新技术现在支持更好的暴露评估。多个尿液样本通常是评估此类物质暴露情况的首选媒介。 最近的数据表明：a) 孕妇接触背景水平的双酚 A 会导致流产风险增加、对神经发育产生不利影响以及女性后代初潮年龄提前，以及 b) 接触背景水平的双酚 A孕妇接触非持久性农药可能会导致后代神经发育受损。 我们寻求提高研究短半衰期化学品背景水平暴露与妊娠结局和儿童发育之间关系的能力。 为了实现这一目标，我们支持在 R 代研究中收集怀孕期间的多个尿液样本（如下所述）。该计划旨在支持该队列中 2,500 名儿童的母亲在怀孕期间收集 3 次尿液。 R 世代是一项持续进行的前瞻性研究，对 10,000 名儿童进行从胎儿早期到成年早期的跟踪研究，旨在研究怀孕和儿童早期的因素和事件如何影响以后的生长、发育和健康。鹿特丹所有预计在 2002 年 6 月至 2006 年 6 月期间分娩的孕妇及其伴侣均受邀参加。这项研究是由伊拉斯谟医学中心发起的。 该队列的多学科特征从怀孕早期开始，将产生一个包含生物、医学、遗传、心理和社区相关数据的数据库，可用于解决广泛的研究问题。研究问题已细分为生长和身体发育、认知和行为、疾病和事故以及医疗保健资源的利用。 研究这一队列的优势（例如，相对于挪威母婴队列研究），是我们将拥有多个尿液样本，其中包括妊娠早期的一个，从而增强我们评估暴露的能力，特别是在器官形成期间。此外，R 一代群体的结果评估比挪威更加密集和标准化。 2004 年 2 月，在 NIEHS 的支持下，每位孕妇采集的尿液样本数量从 1 个增加到 3 个（妊娠 12、20 和 30 周时）。 当每位孕妇对其胎儿进行超声检查时，她会提供一份尿液样本，将其分为三份 20 毫升等份，并在聚丙烯容器中冷冻于 -20 摄氏度。 其中两份保留用于与 NIEHS 的合作研究。 尽管我们的主要兴趣是具有完整的三次尿液的女性（每三个月一次，计划 n=2,500），但出于后勤原因，所有接受超声检查的女性都提供了储存的尿液样本。 报名现已完成。 我们有 2,025 名女性的 3 份尿液、970 名女性的 2 份尿液以及 356 名女性的 1 份尿液。 我们将 100 份妊娠晚期尿液样本送往实验室，以检查该人群的暴露水平。 目前实验室结果已经出来。 除少数例外，邻苯二甲酸盐、非持久性农药和双酚 A 的含量与发达国家其他人群中报告的含量相似。 两种抗雄激素邻苯二甲酸盐（MEHP 和 MnBP）的水平高于 Swans 研究中的水平，在 Swans 研究中，肛门生殖器距离缩短与邻苯二甲酸盐暴露有关。 总二甲基烷基代谢物（有机磷酸酯农药）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 等人的水平大致相同。 NHANES 2005 年的报告。因此，检查与这些污染物相关的健康结果可能是值得的。 未来的研究将取决于 R 代研究中受试者的随访是否成功（其结果在队列中确定），以及其他研究人员未来对健康影响的报告。 去年的进展： 我们一直在与荷兰的同事合作进行一项研究，以评估在怀孕期间不同时间测量的尿液中双酚 A 和有机磷农药代谢物浓度的重现性。 R 世代队列研究的样本被运送到德国的一个实验室，用于分析双酚 A 和有机磷农药代谢物。 我们现在正在分析双酚 A 的结果并准备手稿；有机磷农药的数据仍有待实验室提供。 重现性研究的结果将支持项目的开发，这些项目将实现我们项目的总体目标，以检查与儿童健康结果相关的暴露水平。 开发这项工作的合同已于去年准备完毕，招标将于 2012 年进行。