A drop of mum鈥檚 blood could soon be all it takes to tell whether an unborn baby has Down鈥檚 syndrome. This should reduce, and possibly eliminate, the need for invasive tests that can cause miscarriage.
Women deemed at high risk of giving birth to a child with Down鈥檚 currently face the agonising decision of whether to have an invasive test such as chorionic villus sampling (CVS) or amniocentesis.
Although the tests allow mothers to abort if they don鈥檛 want a child with Down鈥檚, they carry at least a 1% risk of miscarriage. 鈥淚 can鈥檛 tell you how much parents struggle with that decision,鈥� says Jane Fisher of the UK charity .
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A child with Down鈥檚 inherits an extra copy of chromosome 21 from their mother or father. Now two research teams have devised a simple blood test 鈥� that they say carries no risk of miscarriage 鈥� to detect this extra copy by analysing fetal genetic material shed into a mother鈥檚 blood.
Though the findings are still preliminary, of the Chinese University in Hong Kong, who first proposed fetal DNA testing in 1997, is optimistic that far fewer women will need invasive tests for Down鈥檚. 鈥淭his problem really appears to be solvable,鈥� he says.
Geographical limits
Lo鈥檚 method, developed in 2007, is now being commercialised by of San Diego, California.
The approach focuses on a stretch of chromosome 21 that is only expressed in fetuses. Sequenom detects this RNA and determines which parent it comes from by identifying differences between the individuals in single-letter variations called single nucleotide polymorphisms (SNPs).
If the amount of chromosome 21 from each parent is about the same, the fetus is healthy, but if one is about double the other, the fetus probably has Down鈥檚.
So far the company has tested the method in two small groups of women, of which 13 out of more than 400 turned out to have fetuses with Down鈥檚. However, the RNA test picked up every case, and did not incorrectly flag any 鈥渇alse positives鈥�.
One disadvantage of Sequenom鈥檚 technology, though, is that SNPs vary between populations. The current test is optimised for the US population, which has a different ethnic structure to other countries, so the current test may not work as effectively outside the US. 鈥淭his is not ready for use in the UK,鈥� says , who studies fetal medicine at University College London. Sequenom is currently working on a test for Asia.
Universal test
Meanwhile, Stephen Quake and colleagues at Stanford University in California have developed a Down鈥檚 test that doesn鈥檛 depend on SNPs.
鈥淥ur approach works on 100% of the population, independent of ethnicity,鈥� says Quake.
The team uses 鈥渟hotgun sequencing鈥� to sequence short DNA fragments in the mother鈥檚 blood. They then map each fragment to specific chromosomes and calculate the proportion from chromosome 21.
The team analysed blood samples from 18 pregnant women, half of which had fetuses with Down鈥檚. They found that these mothers had 11% more chromosome-21 fragments in their blood than the mum鈥檚 with healthy fetuses.
Both teams believe their methods have enormous potential. Sequenom plans to start offering its test to US doctors in mid-2009 after further testing.
Less risk
Though Lo鈥檚 test won鈥檛 replace invasive testing initially, it should vastly reduce the number of women who need to consider it, says Betty Dragon of Sequenom. 鈥淵ou are putting less normal children at risk for the invasive procedure,鈥� she says.
Quake meanwhile expects their approach 鈥渨ill make invasive testing obsolete鈥�.
Chitty thinks both methods are exciting, but she cautions against raising pregnant women鈥檚 hopes just yet. For one thing, she says, the techniques need to be studied in much larger numbers.
Lo and other researchers say CVS and amniocentesis may trigger the release of fetal DNA into the bloodstream. So, because Quake鈥檚 team drew their blood samples after the women had undergone these tests, their blood tests鈥� accuracy may have unintentionally raised. But Quake鈥檚 team say the proportion of fetal DNA found in their study (about 10%) falls within the range normally found in a mother鈥檚 blood.鈥�
At the very least, the tests seem likely to be another way of flagging up women at high risk of having a baby with Down鈥檚 鈥� and so reducing the number who need CVS and amniocentesis.
Whether they could be used diagnostically to replace invasive tests altogether remains to be seen, says , at Tufts University School of Medicine in Boston, Massachusetts.
Journal references: Stephen Quake 鈥� (); Dennis Lo 鈥� ()
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