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: From our study of early pregnancy, we assayed stored urine samples collected while women were trying to become pregnant to assess their exposures to phthalates and bisphenol A. We then assessed how those exposures might be related to the hormonal events of the menstrual cycle and early pregnancy. Menstrual cycle-specific estimates of urinary BPA and phthalate metabolites were not associated with detrimental changes in follicular-phase length, time to pregnancy, or early pregnancy loss. BPA and MCOP were associated with shorter luteal phase, although the clinical significance of this association is not clear (6). Our study of prenatal exposures and the subsequent risk of cerebral palsy is based within the two national birth cohorts of Norway and Denmark. This study, in collaboration with Norwegian and Danish researchers, includes 400 children with cerebral palsy whose mothers were enrolled in the two birth cohorts. This is by far the largest cohort study of cerebral palsy ever conducted, and allows biological specimens collected during pregnancy to be used to identify exposures and early biological changes (such as inflammation) that may lead to cerebral palsy. It has previously been reported that caffeine can reduce the risk of cerebral palsy among preterm infants. We therefore considered whether a mother's caffeine consumption during pregnancy was associated with reduced risk of cerebral palsy. No association was found (15). We also have collaborated with Norwegian researchers in the analysis of data from the Norwegian population-based health registries. Using linked family data, we explored the risk of a range of neurologic problems in the siblings of children diagnosed with cerebral palsy. There was in fact elevated risk of neurodevelopmental problems (including epilepsy), intellectual disability, autism spectrum disorders, attention-deficit/hyperactivity disorder, blindness, and schizophrenia. Families with children with CP also had increased risk of losing another child through stillbirth or neonatal death 17). These associations suggest that a wide range of neurologic and developmental problems share underlying causes. Using US vital statistics data, we addressed a methodological problem in the analysis of feta; mortality. Preeclampsia is associated with increased risk of stillbirth overall, but among preterm births, preeclampsia appears protective when risk is calculated as a proportion of all births at that gestational age. We demonstrated that the appropriate denominator for such risk is not births, but fetuses at the given gestational age. With proper analysis, the risk of fetal death during the preterm period is actually much higher with preeclampsia than among other pregnancies (5).
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