The Generation R cohort study as an NIEHS resource

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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.