Epidemiologic Study Of Reproductive Outcomes And Environmental Exposures

National Institute Of Environmental Health Sciences

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Abstract

Summary: In the mid-1980s we carried out a prospective study of early pregnancy in which we enrolled 221 health women who were planning to become pregnant. These women collected daily urine specimens for up to six months. We've assayed these specimens to describe the hormonal events of the menstrual cycle and early pregnancy. 155 women became clinically pregnant during the study, while 44 had pregnancies that ended so early that the pregnancies were detectable only by assay of urinary human chorionic gonadotropin. This unique study has been called a landmark, and continues to provide a rich resource for the description of the earliest stages of pregnancy. (More than 30,000 urine samples are still being stored.) We've published 50 papers from this study over the past two decades, some of which have led to new understanding of the fundamental processes of conception and early pregnancy. In addition, we have continued to make use of large population registries in order to pursue basic questions on pregnancy and maternal and infant health. We have worked especially closely with Norwegian colleagues in the analysis of the Norwegian Medical Birth Registry. Last year's progress: Exposures during pregnancy can affect future health of the child. However, collection of data on pregnancy exposures either requires the study of pregnant women followed by a long period of waiting, or information based on mothers recall some years later. In a series of papers, we assessed how well women could remember how long it took them to get pregnant (a measure of their fertility)(1) and common events during pregnancy itself (2). This information had already been recorded as much as 25 years earlier by the mothers themselves in our Early Pregnancy Study. Women had reasonable recall of the number of months it took them to get pregnant, but very poor recall of their cigarette smoking, alcohol consumption, and other exposures during pregnancy. This study emphasizes the importance of prospectively collected data for studies of exposures during pregnancy. Several studies of epigenetic patterns in newborn infants have shown epigenetic changes related to a mothers exposures during pregnancy. However, no studies had shown that a mothers age could affect the epigenetic patterns of her offspring. We were surprised, therefore, to find epigenetic changes in a little-understood gene (KLHL35) that were strongly related to the mothers age at delivery. We were skeptical of this finding, but proceeded to replicate the changes in another sample of newborn infants, and then in a sample of adult women (3). The persistence of these changes in adults suggests that a mothers age at the time they are born may have long-term effects. We are not aware of health related effects that are related to this gene. If nothing else, the findings suggest more complex mechanisms of epigenetic changes in the newborn than are currently understood. Bisphenol A (BPA) and phthalate metabolites have been associated with a range of reproductive disruptions in laboratory animals. Their effects in humans are less clear. We took advantage of urine samples and menstrual diaries collected as part of our Early Pregnancy Study to assess possible effects of these environmental contaminants on the menstrual cycle. Nearly six hundred cycles were available for analysis. We found little evidence that ambient levels of these contaminants, as measured in urine, had any effect on ovulation or development of the corpus luteum (4). The small number of positive associations need to be replicated in other studies.