CPM and Pregnancy Outcome: What We Know and What We Need to Know (PDF - 121.83 KB)
Dr. John Wolstenholme, Institute of Human Genetics, Newcastle Upon Tyne, United Kingdom
The phenomenon of CPM was recognized prior to the use of CVS for prenatal diagnosis, but it has only been since the introduction of this technique in 1984 that we have been aware of its extent. It affects 1.5 percent to 2.0 percent of pregnancies undergoing CVS and is extremely heterogeneous in nature. Collaborative studies in the United States, United Kingdom and Europe have shaped protocols for handling the risk of misdiagnosis due to feto-placental discrepancy. Unfortunately, these studies were not set up to look at the linked problem of adverse outcomes of pregnancy, notably IUGR, in a subgroup of CPM cases, of which the corrected trisomies are the best investigated. Most cases have no details of birthweight; DNA studies were not undertaken; and in many cases, local protocols meant that only cytogenetic results from direct preparations or cultured cells were available, when it is now known that both are important for a full analysis. The Association of Clinical Cytogeneticists, United Kingdom, collaborative study on choronic villus sampling has been extended to include newer cases, with such additional data where available. This database, which will be demonstrated, can be used to better define risks of fetal cytogenetic abnormality and adverse outcomes related to placental abnormality, UPD, etc. Trisomy 18 is a CVS finding where the primary risk seems to be fetal trisomy. Conversely, trisomy 16 produces most adverse effects through the results of placental trisomy and UPD. Major gaps in the knowledge of the effects of trisomy 16 CPM arise from an almost complete lack of systematic, long-term follow up of these cases. In particular, the link between placental mosaicism and gonadal mosaicism, which undoubtedly exists, has not been investigated other than at the fetal stage. This link may also apply to other chromosomes involved in CPM and can be inferred from other family studies. The range of outcomes in corrected trisomy 2 pregnancies is extremely variable and does not correlate very well with the parent or mechanism of origin of the original abnormality, or with the abnormal cell distribution seen in the placenta. CPM for structural abnormalities is a particularly neglected area. Although most of these structural abnormalities are clearly of little clinical consequence, a minority are not. Identification of this minority is hampered by their extreme heterogeneity of presentation and apparent complex nature of origin. It is possible that CPM for structural abnormalities may also be complicated by UPD.