Role of CPM among Infants with Fetal Growth Restriction (PDF - 109.03 KB)
Dr. Louise Wilkins-Haug, Department of Obstetrics & Gynecology, Division of Reproductive Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
CPM, the coexistence chromosomally normal and abnormal placental cell lines, occurs in 1 percent to 2 percent of first trimester pregnancies. CPM can arise from different etiologies and similarly has variable effects on placental development and clinical outcomes. Further contributors to the clinical outcomes include variable persistence throughout gestation, the specific aneuploidy or polyploidy involved, and the influence of UPD. Analyses of pregnancy cohorts with a first trimester diagnosis of CPM indicate an increased frequency of fetal growth restriction in most but not all studies. Relatively uninvestigated, however, is the frequency of CPM among infants who deliver with IUGR. Several small series of IGUR infants (< 20 infants) suggest CPM may occur in 10 percent to 20 percent of such growth-restricted newborns. A single larger study suggests CPM is not apparent in mildly growth-restricted infants in whom neither antepartum identification nor fetal compromise is a factor.
Unanswered questions remain concerning the absolute frequency of CPM among a large series of antenatally identified fetuses with IUGR, the role of aneuploidy as opposed to polyploidy and the contribution of UPD. We have undertaken a case control analysis of 75 pregnancies with a fetal diagnosis of IUGR (<10%) without recognized risk factors matched by maternal age to 75 appropriately grown infants. Multiple site placental biopsies for conventional and molecular cytogenetic studies were obtained in addition to fetal and parental DNA extracted. Karyotype analyses of long-term cultures from placental biopsies identified CPM among 7/75 (9.3 %) of the IUGR cases and 1/75 (1.3%) controls. Among the IUGR cases, the majority of CPM involved considerable levels of polyploidy, which could be confirmed in uncultured placental cells by FISH technology. To search for additional instances of CPM not detected by the current biopsies due either to variation in gestational age presence or geographic location within the placenta, fluorescent genotyping of dinucleotide alleles was performed. In 16 infant-mother-father sets in which CPM was not identified by long term culture, one to three polymorphic markers per chromosome assessed biparental inheritance. Two instances of UPD were identified: maternal heterodisomy for chromosome 14, and paternal isodisomy for chromosome 9.
This large, case control series in conjunction with the earlier smaller series, establishes CPM as occurring in approximately 10 percent of infants with antenatally diagnosed growth restriction in whom recognized risk factors are absent. Polyploidy represents a major contributor though whether a primary etiologic factor or reflective of other etiologies of IUGR remains unclear. Intricate searches for uniparental disomy suggest that UPD may contribute to an additional 10 percent to 15 percent of cases of fetal growth restriction either directly, or as a marker for preexisting CPM. Further study of placental aneuploidy is expected to contribute further to our growing knowledge of genetic control of fetal growth.