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Prenatal diagnosis of Down’s syndrome (Trisomy 21) for the unborn baby requires an invasive test. This takes the form of an amniocentesis where fluid is taken  from around the fetus in the womb after 14 weeks of gestation. A fine needle through the abdomen is used. The alternative, available about 3 weeks earlier is CVS where a tiny piece of the afterbirth (placenta) is extracted. Until now.

Screening Tests for Down’s Syndrome
The screening tests which are non-invasive have varying degrees of detection rates from a lowly 30% for maternal age alone to a clearly impressive 85% for a combination of maternal age, fetal nuchal translucency (scan) and maternal serum biochemistry at 11-14 weeks. This is called the Integrated Test.

Research has also shown that fetuses affected by Down’s syndrome have a missing nasal bone on an ultrasound scan performed at 11-14 weeks. This test alone has been shown to identify around 70% of Down’s syndrome babies. Crucially however, it did not appear to give any advantage over the longer established nuchal translucency scan performed at the same gestation and therefore the uptake has been poor.

One of the most frustrating weaknesses of all screening tests is the fact that they also falsely detect unaffected babies, occasionally leading to unnecessary invasive diagnostic tests and always causing significant stress to prospective parents. The false positive rate of screening tests is around 5%.

Moreover, even the most sensitive screening test will still miss some babies that are affected and for all parents this means a little seed of doubt until the baby arrives.

Diagnostic Tests for Down’s Syndrome
The definitive diagnostic tests mentioned (amniocentesis and CVS) suffer from one Achilles heel: They are invasive and therefore carry the potential risk of provoking miscarriage. This can happen regardless of whether the baby is affected by Down’s syndrome or not. Because of this, there has been a lot of research activity to find a risk-free reliable diagnostic prenatal test for Down’s Syndrome. This is why the recent announcement of a development of such a test reported in the medical journal The Lancet (Feb. 3, 2007) has caused such a stir.

Maternal Blood Test for Down’s Syndrome
Dr Ravinder Dhallan of Ravgen Inc. has reported results of a study to diagnose Down’s syndrome for the unborn baby using Maternal blood and therefore practically eliminating the potential risk of miscarriage associated with the available invasive tests. What Dr Dhallan and colleagues did in this study was to collect blood from 60 mothers whose median age was 34. Eight of the mothers had their blood samples taken in the first trimester (13 weeks or below).

The breakthrough was that they managed to successfully identify and separate the small amount of fetal DNA that cross into the maternal circulation. This was analyzed via what are known as SNP (single nucleotide polymorphisms) tests to identify where there was an extra chromosome on set No. 21 (Trisomy 21).

Their tests in this study correctly identified 58 of the 60 chromosomal make up. Among the 58 correctly analyzed, two had Trisomy 21 (Down’s syndrome). The two that were not correctly analyzed included one who had Down’s but labeled as normal (false negative) and the other one was incorrectly identified to have Down’s syndrome (false positive).
 

Implication of this development
This is potentially quite a major advance. Its strength lies in the fact that it does away with an invasive procedure therefore eliminating in a stroke the spectre of miscarriage that hangs over the currently used procedures. This risk is indeed small but quite real and when it occurs, is devastating.

However, it is important to stress that this is only an early stage of this potential breakthrough. Here are the facts:

• The study had quite a small sample (60) and it is therefore crucial that it is replicated in larger  studies.                                
• There is still a lot of room for refinement. In this study, whilst the earliest sample was taken at 8 weeks gestation, the first case of Down’s was identified at just over 17 weeks. For this to be truly useful, it will have to have the ability to establish the diagnosis early, ideally in the first trimester. Also the interval between blood sample collection and getting the results need to be reasonably short, lasting no more than 2 or 3 weeks.
• The current diagnostic tests have quite a high 99% accuracy rate. This test will need to match that and ideally surpass it.

Science research thrives on this kind of challenge and there is a lot of excitement in the medical research world about this potential breakthrough.

In fact, this research work by Ravgen Inc. in the United States is not the only current development in this area. Researchers in Hong Kong are also reportedly on the verge of a similar breakthrough but employing a different method which utilises placental DNA in maternal circulation.

These methods might usher in a new era of safe and effective prenatal diagnostic tests. If the hurdles are overcome, the rough estimate is that the tests may be available for use in about three years.

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Down’s Prenatal Diagnosis

End of invasive procedures in sight?