Confined placental mosaicism (CPM), the identification of placenta aneuploidy in conjunction with a karyotypically normal fetus, occurs in 1- 2% of chorionic villus samples (CVS) obtained for prenatal diagnosis. Following identification of CVS mosaicism, increased pregnancy loss and fetal growth retardation have been noted by some but not all investigators. The overall clinical contribution of placenta aneuploidy to adverse pregnancy outcome remains unknown. Investigation of specific pregnancy outcomes for the presence of CPM will provide valuable information regarding the biologic mechanisms surrounding pregnancy survival and fetal growth. Placenta aneuploidy and its clinical presentations warrant further exploration if appropriate management decisions and therapeutic interventions to alter pregnancy outcome are to be successful. The broad objective of this proposal is to determine the frequency, clinical impact and variability of CPM in two populations with adverse pregnancy outcomes: spontaneous losses and intrauterine growth retardation. Specific aims include: 1) determination of CPM frequency in pregnancies experiencing spontaneous loss, elective termination, fetal growth retardation and appropriate birth weight, 2) quantification of the extent of placental mosaicism using molecular cytogenetic techniques, 3) determination of fetal uniparental disomy by polymorphic markers targeted to the trisomic chromosome identified in CPM cases, and 4) delineation of the clinical presentation of CPM with respect to antepartum, neonatal, histologic and pathologic variables. Each population with adverse outcome (spontaneous loss, fetal growth retardation) will have a control population (elective terminations and appropriate weight newborns, respectively) ascertained and karyotyped in a similar fashion. Proposed parameters influencing the clinical impact of CPM, such as extent of placenta involvement and uniparental chromosome inheritance, will next be addressed. Fluorescent in situ hybridization (FISH) for identification of aneuploidy at additional, uncultured placental sites will provide quantification of the extent of mosaicism. Determination of uniparental disomy will be undertaken by PCR of highly polymorphic regions. Clinical parameters will be tabulated in a consistent fashion to allow analysis of variables associated with CPM. This proposal details the ascertainment, anticipated sample sizes and scientific methodology for addressing these aims in a large obstetric population over a five year period of time.