In Singapore, 1 in 5 pregnancies occur in mothers >35 years old and genetic diseases, such as thalassaemia, are common. Current methods for the diagnosis of aneuploidy and monogenic disorders require invasive testing by amniocentesis, chorion villus biopsy or fetal blood sampling. These tests carry a procedure-related risk of miscarriage that is unacceptable to many couples. Development of non-invasive methods for obtaining intact fetal cells would allow accurate prenatal diagnosis for aneuploidy and single gene disorders, without the attendant risks associated with invasive testing, and would increase the uptake of prenatal diagnosis by women at risk. Isolation of fetal erythroblasts from maternal blood should allow accurate non-invasive prenatal diagnosis of both aneuploidies and monogenic disorders. Expression of γ-globin in maternal erythroblasts and the inability to locate fetal erythroblasts reliably in all pregnancies have prevented its clinical application. In the absence of a highly specific fetal cell marker, enrichment, identification and diagnosis – the 3 components of non-invasive prenatal diagnosis – have clearly defined objectives. Since fetal cells are rare in maternal blood, the sole purpose of enrichment is yield – to recover as many fetal cells as possible – even if purity is compromised at this stage. In contrast, the primary goal of identification is specificity; absolute certainty of fetal origin is required at this stage if the ultimate objective of diagnosis, accuracy, is to be achieved. This review summarises the current state of the art of non-invasive prenatal diagnosis using fetal erythroblasts enriched from maternal blood.
Without prenatal diagnosis, 1 in 50 babies are born with serious physical or mental handicap, and as many as 1 in 30 with some form of congenital malformation. These may be due to structural or chromosomal abnormalities, or single gene disorders.
This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.