The Generation R cohort study as an NIEHS resource

需要更多的流行病学数据，以了解背景水平暴露于半衰期短的人造化学品与胎儿和儿童发育的关系。胚胎和胎儿发育阶段是对外源性物质影响的敏感性提高的时期。对于半衰期较短的外源性物质，过去很好地描述接触情况一直是一个挑战。多个尿液样本是评估此类制剂暴露的首选方法。 最近的数据表明，孕妇接触非持久性农药的背景水平可能导致后代神经发育受损。我们力求提高我们的能力，以研究本底水平接触半衰期短的化学品与怀孕结果和儿童发育的关系。 为了实现这一目标，我们支持在R代研究中采集妊娠期间的多份尿液标本（如下所述）。该计划旨在支持队列中2 500名儿童的母亲在怀孕期间收集3次尿液。 Generation R是一项正在进行的前瞻性研究，将对10，000名儿童进行从胎儿早期到成年早期的跟踪，旨在研究怀孕和幼儿期的因素和事件如何影响以后的生长，发育和健康。鹿特丹某个特定区域的所有孕妇，凡在2002年6月至2006年6月期间分娩的，都被邀请与其伴侣一起参加。这项研究是由伊拉斯谟医学中心发起的。 从怀孕早期开始，对这一群体进行多学科定性，建立了一个数据库，其中载有生物、医学、遗传、心理和与社区有关的数据，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。 研究这一群体的优势，例如，与挪威母子队列研究相比，我们将有多个尿液样本，包括前三个月的一个样本，这增强了我们评估暴露的能力，特别是在器官形成期间。此外，R世代队列的结果评估比挪威更加密集和标准化。 2004年2月，NIEHS的支持使得从每个孕妇收集的尿液样本数量从1个增加到3个（妊娠12周、20周和30周）。 当每个孕妇对她的胎儿进行超声检查时，她提供了一个现场尿液样本，该样本被分成三个20毫升的等分试样，并在-20摄氏度下冷冻在聚丙烯容器中。 其中两份等分试样保留用于与NIEHS的合作研究。 我们主要关注的是有三个完整尿液的女性。 登记现已完成。 我们为2,025名女性提供了一套完整的3个尿液，为970名女性提供了2个尿液，为356名女性提供了1个尿液。 我们将100份妊娠晚期尿液样本送到实验室，以检查这一人群的暴露水平。 实验室结果在前几年发表。 除了少数例外，邻苯二甲酸酯、非持久性农药和双酚A的水平与发达国家其他人群中报告的水平相似。 总二甲基烷基代谢物（有机磷农药）的水平高于CHAMACOS研究（萨利纳斯，加州）;总二乙基代谢物相似。 双酚A的水平与卡拉法特等人2005年的NHANES报告中的水平大致相同。 因此，与这些污染物有关的健康结果的检查将是值得的。 为了研究有机磷农药代谢物浓度与神经发育的关系，分析了尿液样本（800名妇女的三份尿液样本，每个儿童一份尿液样本）。今年，我们完成了两项分析，检查1）化学混合物，包括邻苯二甲酸酯，双酚和有机磷农药，与胎儿至幼儿生长轨迹相关; 2）产前有机磷农药暴露与儿童心脏终点相关。这些文件正在编写中。此外，在一个合作项目中，我们研究了有机磷农药代谢物对10岁儿童肥胖指标的影响（PMID：37606291）。

More epidemiologic data are needed on the relation of background-level exposure to man-made chemicals with short half-lives to fetal and child development. The embryonic and fetal stages of development are periods of heightened susceptibility to effects of xenobiotics. For xenobiotics with short half-lives, characterizing exposure well has been a challenge in the past. Multiple urine specimens are the approach of choice for assessing exposure to such agents. Recent data suggest 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 a specific section of Rotterdam who gave birth between June 2002 and June 2006 were invited to participate, together with their partner. This study was set up by the Erasmus Medical Center. The multidisciplinary characterization of the cohort, starting in early pregnancy, has produced 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. Our primary interest is in women with a complete set of three urines. 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 were published in previous years. With a few exceptions, the levels of phthalates, nonpersistent pesticides, and bisphenol A were similar to those reported in other populations in developed countries. 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 will be worthwhile. To study organophosphate pesticide metabolite concentration in relation to neurodevelopment, urine specimens were analyzed (three urine specimens from 800 women, and one urine specimen per child). This year, we completed two analyses examining 1) chemical mixtures, including phthalates, bisphenols, and organophosphate pesticides, in association with trajectories of fetal to early childhood growth; and 2) prenatal organophosphate pesticide exposure in association with child cardiac endpoints. These papers are in preparation. Additionally, in a collaborative project, we examined the impact of organophosphate pesticide metabolites on child adiposity measures at age 10 (PMID: 37606291).