Cell-Free Fetal DNA in the Maternal Circulation and its Future Uses in Obstetrics

Objective: To provide an introduction to new technologies involving maternal plasma cell-free fetal DNA for non-invasive prenatal diagnosis and screening in obstetrics. Options: Limited to introductory discussion of maternal plasma cell-free fetal DNA. Evidence: MEDLINE was searched to identify publications related to the topic after 1996. This document represents an abstraction of the information. Values: This update is a consensus of the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC). Benefits, Harms, and Costs: This update educates about new technology and its future use in obstetrics. At present, there is no harm or cost (research with limited clinical application) identified. Conclusions: 1. Significant and measurable amounts of cell-free fetal DNA are present in the maternal circulation and increase throughout pregnancy. 2. Different fetal (trisomy 21, trisomy 13) and placental abnormalities can affect the levels of cell-free fetal DNA within the maternal plasma. 3. Diagnostic and screening techniques may be able to utilize this cell-free fetal DNA in the future to provide non-invasive screening and diagnosis opportunities. This DNA technique is already well established for fetal sexing in pregnancies at risk of an X-linked disorder and fetal rhesus-D evaluation. Other conditions with well-identified unique paternal mutations can also reliably apply this cell-free fetal DNA technology for prenatal diagnosis. 4. The overall use of this molecular technology is still limited and requires the identification of sex-independent DNA markers so that female fetal DNA can be distinguished from maternal DNA, allowing its use in the screening or diagnosis of fetal and placental disease in pregnancies of either fetal sex.