x Abu Dhabi, UAEWednesday 21 February 2018

New test for Down syndrome reduces risks for babies

A new non-invasive screening test is available that reduces the number of pregnant women who need to undergo amniocentesis or CVS - and so could save the lives of countless babies.

Down syndrome is more common in the UAE and, indeed, the entire Middle East, than in some other countries. iStock Photo
Down syndrome is more common in the UAE and, indeed, the entire Middle East, than in some other countries. iStock Photo
It is the dark flicker of doubt that threatens to overshadow the joy of every pregnancy - the question that, sooner or later, creeps into the mind of every mother-to-be - will my baby be all right?

Coming up with an answer can be a stressful and even traumatic affair.

The current "gold standard" procedure throughout the developed world is for all pregnant women to undergo screening for abnormalities, especially Down syndrome, between 11th and 14th week of pregnancy.

This is known as the "combined test". It involves a blood sample, taken to look for the presence of two hormones associated with pregnancy, and an ultrasound scan, during which the thickness of the nuchal transparency - a pocket of fluid at the back of the baby's neck - is measured.

Analysed together with other information, such as the mother's age, the result predicts the likelihood that the woman is carrying a baby with Down syndrome.

If she is categorised as being at high risk, one chance in 150 or greater, she is offered an invasive diagnostic test - amniocentesis, or chorionic villus sampling (CVS), in which a needle is inserted through her abdomen and into the womb and a sample is taken from the fluid around the baby or from the placenta.

These tests are conclusive, and can also detect a range of other chromosomal abnormalities - but they come with a terrible risk.

About one in every 200 amniocentesis procedures causes miscarriage, as does one in every 100 CVS tests, with the result that many babies are lost that are not suffering from Down syndrome.

Now, though, a new non-invasive screening test is available that can be carried out as early as the ninth week of pregnancy and is so accurate it radically reduces the number of pregnant women who need to undergo amniocentesis or CVS - and so could save the lives of countless babies.

PrenaTest, launched in August last year by a German company, LifeCodexx, is one of four similar tests available around the world, known collectively as NIPTs, or non-invasive prenatal tests.

NIPTs have been available privately in America and Germany since last year, and in Britain for the past six months. In the UAE it is available from Genpharm Services in Dubai.

Genpharm, which sends samples to LifeCodexx's labs in Konstanz, Germany, has just celebrated carrying out its 1,000th test in the Middle East.

The cost of PrenaTest varies. In Germany, LifeCodexx charges about ?1,000 (Dh4,900) for its express, one-week service. The cost in Dubai - without the need for an expensive flight to Europe - is ?1,200.

Like all such NIPTs, PrenaTest works by harvesting fragments of foetal genetic material circulating in the mother's bloodstream and then using the latest DNA sequencing technology to detect three specific "trisomies" - incidents of chromosomes that have generated three copies instead of the normal pair.

These are trisomies 21 (Down syndrome) and the much rarer 13 (a marker for Patau syndrome) and 18 (Edwards syndrome).

The accuracy of the tests is impressive. A European validation study looked at the results of 808 tests and found that 806 had been classified correctly. Of the two errors, one gave a false positive result for trisomy 18, and the other a false negative for 21.

This compares with a detection rate for the standard "combined test" of 75 per cent.

Down syndrome is more common in the UAE and, indeed, the entire Middle East, than in some other countries. The incidence in the UK is one in every 1,000 live births, and one in 800 births in the US. But research published in the journal Medical Principles and Practice in 2007 found that the incidence of Down syndrome in Dubai was one in 449 births.

Among non-UAE nationals the rate was one in 602 but among Emiratis it rose to one in 319. This, wrote the authors, from the Department of Genetics at Al Wasl Hospital, was "comparable to incidences reported for other Arab populations in the Middle Eastern region".

The main cause, they concluded, was "advanced maternal age, with mothers bearing children until their 50s". The mean age of UAE mothers was 33.48, with 41 per cent older than 35.

In a measure of the significance of this new test, the UK's National Health Service is developing a version of its own, although mothers there will have to wait for at least two years before NIPT is likely to become available free on the NHS.

"The good news from a UK perspective is that for the past two years a laboratory at Great Ormond Street Hospital has been undertaking a validation study based on UK technology," says Basky Thilaganathan, consultant obstetrician and professor of foetal medicine at St George's, University of London.

"That test has validated that we can do it in the UK and from next month five hospitals will be doing this for NHS patients as part of a trial to see how this test would work within the NHS system. So we may well be the first country in the world to introduce this into a healthcare system."

NIPT, he says, is not a substitute for the existing "combined test" screening, but is for women deemed at higher risk of having a child with Down syndrome, to determine whether a subsequent and potentially dangerous invasive test is really necessary.

Prof Thilaganathan says: "This test will enable us to maintain diagnostic accuracy and pick up a lot of cases of Down syndrome, but reduce by about three or fourfold the number of invasive tests that need to be done, and therefore reduce by three or fourfold the number of miscarriages that may occur as a consequence of these unnecessary invasive tests."

The current combined-test screening gives the woman a precise, if somewhat arbitrary, risk, "anywhere from one in two up to one in several thousand, and it's rather artificial" Prof Thilaganathan says.

"We say, well, if your risk is 1 in 150 or greater you're at high risk and you should consider having an amniocentesis or a CVS.

"But at the risk of 1 in 151 you suddenly magically become low risk and nothing needs to be done. It is quite difficult for women to understand that."

Whereas risk is presented on a sliding scale, with an arbitrary cut-off point between high and low, NIPT "gives a dichotomous risk, so the risk you will get is either one in two or greater - it will say your risk of a trisomy is 50 per cent or 90 per cent, which is really quite high - or it will tell you your risk is one in 10,000 or less, which is terribly low. It dichotomises the risk, it doesn't give you gradations".

As a result, "one would go ahead with amniocentesis only if one was in the high-risk category, because it doesn't make sense to have an invasive test, with a 1 in 200 risk of miscarriage, if your risk of having the original problem is less than one in 10,000".

In short, says Prof Thilaganathan, NIPT "makes the decision-making process about testing much simpler. Every day as obstetricians we see women agonising over whether to have a test at one in 149, or one in 130 risk, or asking, 'Why am I low risk at one in 151? Surely I should be able to have a test?' It's very difficult for them.

"But if you get a result that says the chances of you having a trisomy are extremely low, then that's great. You can walk away happy. And, if it comes back one in two, then it makes sense to have amniocentesis or CVS."