Chapter 2: Non-invasive prenatal diagnosis

Non-invasive prenatal diagnosis of monogenic disorders is becoming integrated into routine clinical care for many indications. This is carried out by testing cell-free DNA extracted from the plasma portion of a maternal blood sample. The cell-free DNA is low in concentration, and consists of a mixture of maternal and fetally-derived DNA which are not easy to separate. Methods used therefore need to be rapid, sensitive and specific, including real-time PCR, digital PCR and next generation sequencing with complex algorithms. Testing may be required for pregnancies with an increased chance of a monogenic disorder due to family history or carrier status, or where there are specific abnormalities identified by ultrasound scan. In these situations, testing is considered to be diagnostic and therefore does not require confirmation by invasive testing. With increased access to genomic technologies, and more diagnoses for rare disease patients, future demand for NIPD and possibilities during pregnancy will continue.