Non‐invasive fetal cell isolation from maternal blood

Each year in this country there are about 800,000 deliveries'. Forty thousand will be born to women over the age of 35 years to whom prenatal diagnosis will usually be offered because of their age. If all accepted invasive testing, there would be 400 procedure-related miscarriages per annum, most of them normal fetuses. This does not take account of the number of invasive tests performed for other indications, such as previous abnormality, family history and anomalies detected by routine ultrasound. Not all women will accept invasive tests, with around 20% declining the offer2. Nonetheless, these figures represent a significant emotional burden, a situation that is likely to worsen as women are leaving childbirth until later in life'. Of secondary importance is the considerable financial cost to the health service. Current methods of antenatal diagnosis for fetal genetic or chromosomal abnormality include amniocentesis, chorion villus sampling and cordocentesis. All are very accurate with failed diagnosis occurring in less than 1% of cases3, but unfortunately there is a procedure-related miscarriage risk of between 0.5%) and 2% depending on the technique employed and the experience of the ~pera top . ~ . In order to minimise these risks, various methods of screening for abnormalities have been developed. These aim to identify a high risk population and thus target invasive tests more effectively. Maternal age is an example, with women over 35-37 years of age being considered high risk. These women have the highest rate of trisomy, but 80% of children with trisomies are born to wbmen younger than 35 years6. A good screening test should encompass the whole at risk population. Biochemical screening tests and nuchal translucency scanning fulfil this criterion, but may only identify between 75% and 85% of affected women7. *, at the cost of a 5% false positive rate. Women in the high risk group still require invasive testing for definitive diagnosis. Furthermore, women who screen negative may be falsely reassured, and still have a baby with Down's syndrome. There is no ideal test for antenatal screening or diagnosis in current obstetric practice. In an effort to address this problem and develop a test with high diagnostic accuracy but not risk of miscarriage there has been considerable interest in developing a noninvasive method of fetal cell isolation from maternal blood samples. There is now a large body of evidence supporting the existence of fetomaternal cell traffic. Fetal cells, such as nucleated red blood cells and trophoblasts, can be isolated by a variety of methods and have been used to diagnose fetal aneuploidy antenatally, as described in isolated reports. Both chorion villus sampling and amniocentesis have a sensitivity and specificity in excess of 99? h3v9. Any replacement diagnostic test must be equal to, or better than this. A screening test however, does not have to achieve such accuracy, with current tests achieving detection rates of 75% to 85% as mentioned above. The extent to which either diagnosis or screening may become possible using current noninvasive cell isolation techniques is the subject of this review.