Innovation: Early low-risk test for Down's Syndrome

A TEST that can detect Down's Syndrome as early as 12 weeks into pregnancy from a sample of the mother's blood, avoiding the dangers of amniocentesis, will be available by the end of 1995, writes Nuala Moran.

The current test involves taking a sample of amniotic fluid from around the foetus, which carries a one in 200 risk of miscarriage. To add to the anxiety, the sample cannot be taken until 16 weeks, and it takes a further three weeks to culture and analyse it. The new test will take just two hours.

The new test is being developed by an Anglo-American company called Applied Imaging, based in Sunderland, and Cytocell, a start-up company in Banbury.

Down's Syndrome is caused by an effect called trisomy, in which the foetus has three, rather than the usual two, copies of chromosome number 21. Although the mechanism that causes trisomy is not understood, its occurrence is linked to maternal age; the chance of carrying a Down's Syndrome child increases markedly over the age of 35.

Because of the risks associated with amniocentesis, the test is routinely offered only to women over 35, so most Down's Syndrome children are born to women under this age. Les Grant, president of Applied Imaging, says the new test is free of risks and cheap enough to offer to all pregnant women.

The test involves two stages: separating out the tiny number of foetal red blood cells from the mother's blood cells, and using a genetic probe, which attaches selectively to chromosome 21, to check that the foetus has only two copies of the chromosome. Mr Grant says the challenge is to find the 150 to 200 cells of foetal origin among 15 billion maternal cells in a 20ml blood sample. The sample is treated mechanically to remove maternal cells on the basis of their different physical characteristics. This reduces the sample to a more manageable 2ml, containing 10 million cells with 20 to 50 of foetal origin.

This sample is put on a slide and analysed by computerised imaging techniques that can pinpoint the foetal cells because they look different. The slide is then stained with the Cytocell genetic probe which binds specifically to chromosome 21. The probe is labelled with a fluorescent dye which glows when the probe is illuminated.

After staining, the probe is placed back in the Applied Imaging machine which inspects each of the foetal cells in turn. If the foetus has Down's Syndrome each cell will have three fluorescent spots, rather than two, indicating the presence of trisomy.

Applied Imaging is currently assessing the technique against results from amniocentesis tests. Mr Grant believes it may be possible to find enough cells to apply the test at 10 weeks, although he points out that the mechanism by which foetal blood cells enter the maternal blood stream through the umbilical cord is not understood.

The Cytocell probe for chromosome 21 is currently being tested at St George's Hospital in London to see if it can be used to analyse foetal cells in amniotic fluid without having to culture the sample, allowing results to be given on the day of the test. Bruce Savage of Cytocell says this approach is now routine in Canada.