News in Science

Blood test takes risk out of prenatal testing

The days of pregnant women having an eight-centimetre-long hollow needle jabbed into their abdomens may be numbered.

In this week's Nature journal, scientists show a simple blood test, rather than invasive tests such as amniocentesis, can determine a foetus's genetic make-up, identifying mutations causing any of about 3,000 inherited disorders, such as cystic fibrosis.

Unlike a procedure unveiled last month, the one announced this week can be done without knowing who the father is, much less obtaining a sample of his DNA.

Since paternity is unknown or incorrect in an estimated 3% to 10% of births in the US, the father-free method promises to make foetal DNA sequencing possible in every pregnancy, if hurdles including cost and accuracy are overcome.

Last month, scientists led by Associate Professor Jay Shendure of the University of Washington in Seattle announced a similar foetal-genome technique using DNA from the pregnant woman's blood. It determined the foetus's genome more directly, by comparing it to the mother's and father's.

Prenatal treatment

Determining a foetus's genome might give women more reasons to end a pregnancy. But it would also let physicians identify conditions that can be treated before birth or immediately after, says Professor Stephen Quake of Stanford University in California, who led the new study.

"The way it's done now, parents wait until a newborn gets sick and suffers in the first weeks of life, and only then does the doctor start figuring out the baby has a metabolic or immune disorder," he says.

With prenatal genetic testing, in contrast, the parents would know by the end of the first trimester (12 to 13 weeks) if the foetus has a genetic or chromosomal defect. That way, they can be ready if the baby has special needs, which can be as simple as a certain diet.

Knowing so early that something has gone wrong might also allow physicians to treat a foetus.

"Now we can challenge our colleagues in surgery and pharmacology," says Quake. "We'll soon be able to diagnose all these genetic disorders; what are you going to do about them?"

Today, most prenatal genetic tests are done through amniocentesis or chorionic villus sampling (CVS). For an amnio, done at 15 to 18 weeks gestation, a physician uses a hollow needle to remove a small sample of amniotic fluid; a lab then analyses the foetal cells in it. In CVS, done at 10 to 12 weeks, a needle through the abdomen or cervix harvests cells from the placenta.

Drawbacks

Both procedures have significant drawbacks, experts say. Amnio poses a 1-in-400 risk of miscarriage. And both amnio and CVS can be used for only a couple of genetic tests, says Stanford bioethicist Professor Hank Greely. About 1% to 2% of pregnant women in the United States have amnio or CVS.

Because the new foetal genome test requires only a blood sample, not a needle into the uterus, it poses no risk of miscarriage. Sequencing the medically relevant regions of the foetal genome would cost about $2000, but that will drop as sequencing costs plummet.

But only if the tests become more accurate. The version unveiled in June by scientists at the University of Washington, as well as the Stanford procedure, miss some mutations and mistakenly identified some healthy genes as abnormal.

The new study is based on the fact a pregnant woman's blood contains millions of DNA fragments. Most are from her own cells. But early in pregnancy, 5% to 10% are from her foetus. Unfortunately, it's not possible to tell directly which is the mother's DNA and which is the baby's.

Using sequencing machines, Quake and his team deduced the foetal genome sequence by counting the relative proportions of different DNA variants, knowing that the most common ones had to be mum's because the mix of DNA contained her own as well as that the foetus inherited from her.

The Stanford study is a proof of principle, not hard evidence the technique will work outside the lab. The scientists determined the gene sequences of only two foetuses.

In one, however, the mother has a chromosomal deletion that can cause DiGeorge syndrome, which is marked by heart, neuromuscular and cognitive problems. The study determined, correctly, that the foetus had the condition, too.

In 2008, Quake's team discovered that foetal DNA from the mother's blood can be used to detect Down syndrome. Last year, the test - more accurate than what obstetricians had used for decades - went on the market.