The Generation R cohort study as an NIEHS resource

关于半衰期短的人造化学品的本底暴露水平与儿童发育的关系，需要更多的流行病学数据。胚胎和胎儿发育阶段是对外源物质影响高度敏感的时期。对于半衰期短的外源生物来说，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。多份尿样通常是评估接触这类药物的选择媒介。 最近的数据表明：a)孕妇暴露于背景水平的双酚A会导致女性后代更早进入月经初潮，b)背景水平的孕妇暴露于非持久性杀虫剂会导致新生儿体重减轻并损害后代的神经发育，c)背景水平的邻苯二甲酸酯暴露可能会对生殖产生不利影响。 我们试图提高我们的能力，研究半衰期短的本底水平接触化学品与儿童发育的关系。为了实现这一目标，我们建议支持在新开始的队列中收集怀孕期间的多个尿样，R代研究(如下所述)。还将购买用于长期储存标本的冰柜。我的计划是支持从队列中3000名儿童的孕妇那里收集尿液。 研究这一队列的好处是，与挪威出生队列相比，我们将有多个尿样，包括一份怀孕前三个月的尿样，这增强了我们评估接触的能力，特别是在器官发生期间。此外，新队列中的结果评估比挪威更加密集和标准化。 R世代是一项正在进行的前瞻性研究，对10,000名儿童进行跟踪，从早期胎儿生活到年轻成年，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月期间分娩的孕妇都被邀请与她们的伴侣一起参加。这项研究是由伊拉斯谟医学中心建立的。从怀孕早期开始对该队列进行多学科描述，将产生一个数据库，其中包含与生物、医学、遗传、心理和社区有关的数据，可用于解决广泛的研究问题。研究问题被细分为生长和身体发育、认知和行为、疾病和事故以及卫生保健资源的利用。 我们对R世代研究队列的附加项目是一个新的小项目，但如果合作成功，它可能会带来一些非常令人兴奋和重要的工作。 去年的进展： 2004年2月，NIEHS的支持使从每个孕妇身上收集的尿样数量从1个增加到3个(怀孕12周、20周和30周)。当每名孕妇对胎儿进行超声波检查时，她会提供一份现场尿样，分成3份20毫升的等量尿液，并将其冷冻在-20摄氏度的聚丙烯容器中。这些等分中的两个是为与NIEHS的合作研究保留的。虽然我们的主要兴趣是拥有一套三个尿液的妇女(计划中的1/3个月，n=3000)，但出于后勤原因，所有提出超声检查的妇女都提供了储存的尿样。目前，R世代妇女接受超声波检查的比率为每月500人。目前到位的资金只提供到2004年年底的样本收集，但R世代的总体登记现在计划持续到2006年或更晚。我们现在正在准备分析100个晚期妊娠尿样，以检查这一人群的暴露水平，并继续支持尿液收集，直到登记结束。

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 earlier age at menarche among female offspring, b) that background-level of exposure of pregnant women to nonpersistent pesticides can result in reduced birthweight and impaired neurodevelopment in offspring, and c) that background-level exposure to phthalates may be having adverse reproductive effects. We seek to increase our capacity to study the relation of background-level exposure to chemicals with short half-lives to child development. To achieve this goal we propose to support collection multiple urine specimens during pregnancy in a newly begun cohort, the Generation R study (described below). Freezers for long-term storage of the specimens will also be purchased. My plan is to support collection of urine from the pregnant mothers of 3,000 children in the cohort. The advantage to studying this cohort, e.g., over the Norwegian birth cohort, 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 new cohort is more intensive and standardized than in Norway. 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. Our add-on to the Generation R study cohort is a small new project, but if the collaboration is successful, it could lead to some very exciting and important work. Last year's progress: 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 3 20ml aliquots and frozen at -20o C in polypropylene containers. Two of these aliquots are reserved for collaborative studies with NIEHS. Although our primary interest is in women with a complete set of three urines (1/trimester, n=3000 planned), for logistic reasons all women presenting for ultrasound provide a urine specimen that is stored. The current rate of Gen R women receiving an ultrasound examination is 500 per month. Funding currently in place provides only for specimen collection through the end of calendar year 2004, yet overall Generation R enrollment is now scheduled to continue to 2006 or later. We are now making preparations to analyze 100 third trimester urine specimens to check the levels of exposure in this population, and to continue support for urine collection to the end of enrollment.