The promise of fetal cells in maternal blood

Abstract

Delaying childbirth increases the proportion of advanced maternal age pregnancies. This increases the number of pregnancies requiring invasive prenatal testing. Prenatal diagnosis of chromosomal aneuploidies and monogenic disorders requires fetal cells obtained through invasive procedures (i.e. chorionic villus sampling and amniocentesis). These procedures carry a risk of fetal loss, which causes anxiety to at-risk couples. Intact fetal cells entering maternal circulation have raised the possibility of non-invasive prenatal diagnosis. Rarity of fetal cells, however, has made it challenging. Fetal nucleated red blood cells are ideal candidate target cells because they have limited lifespan, contain true representation of fetal genotype, contain specific fetal cell identifiers (embryonic and fetal globins), and allow interrogation with chromosomal fluorescence in-situ hybridisation and possibly with array comparative genomic hybridisation. The utility of fetal nucleated red blood cells in non-invasive prenatal diagnosis has not reached clinical application because of the inconsistencies in enrichment strategies and rarity of cells.