Jan. 12, 2011— -- Lynn Harris, pregnant for the first time and in her late 30s, faced a decision many older women at higher risk for Down syndrome babies are asked to make: choose a form of prenatal testing.
"Such a brutally tough call," wrote Harris, a New York City journalist, in an article on the topic on Babble.
"I talked to friends, I spread-sheeted statistics, I lay awake."
Instead of amniocentesis, which would require her to wait until 18 to 20 weeks, she chose chorionic villus sampling (CVS) -- an invasive test which, like amniocentesis, carries a risk of miscarriage.
Right after the procedure, Harris lost most of her amniotic fluid and lost an otherwise healthy baby at 12 weeks. "I am still not over it," she said.
Pre-natal screening for Down syndrome, which affects 1 pregnancy in 691, is fraught with unclear test results, risks to the unborn baby and profound anxiety for expectant mothers and their partners.
But now, a new maternal blood test has the potential to reduce the number of women referred for invasive testing for Down syndrome by 98 percent.
A study, led by researchers at Li Ka Shing Institute of Health Sciences at The Chinese University of Hong Kong (CHUHK) and published this week in the Journal of British Medicine (BMJ) looked at the new technology, which uses the latest tools in gene sequencing to detect abnormalities in the fetus.
This technology was developed in 2008, but this is the first large-scale study, including more than 750 blood samples from pregnant women in Hong Kong, Britain and the Netherlands -- 86 from those who were carrying a child with Down syndrome.
The most robust version of the new blood test tested on 314 pregnancies detected Down syndrome in 100 percent of the cases, with only a 2.1 percent false positive rate.
"Over the years, several versions of the test have been developed, but this test is one of the most promising in terms of diagnostic performance," said Dr. Rossa Chiu, first author of the study and a clinical chemist at CUHK.
"The availability of the safe DNA blood test could therefore greatly reduce the number of pregnant couples having to bear the emotional burden of going through a potentially risky and daunting procedure, like amniocentesis."
The study is being hailed as a breakthrough.
"This paper is a proof of concept that fine-tunes the nitty-gritty science behind these upcoming prenatal noninvasive diagnostic testing," said Dr. Brian Skotko, a clinical fellow in genetics at Children's Hospital Boston and an expert in Down syndrome.
"In short, the science is getting even better, but the controversies and the overall conceptual frameworks are the same: One day soon, expectant mothers will have the option of knowing in the first trimester whether or not they have a fetus with Down syndrome without any risk to the pregnancy."
Prenatal Invasive Tests Carry Miscarriage Risk
Harris, now 41 and co-creator of the website BreakupGirl, went on to have two healthy children and said that had doctors been able to rule out Down syndrome early in her pregnancy, she might not have ever had CVS.
"Nothing adds any definitive answers, but it's another tool a woman can put in the decision-o-matic to figure out what course of testing or not testing feels right for them," she said.
Until now, maternal blood tests have only been able to detect hormone markers that may show an increased risk for Down syndrome. Those who are determined to be at higher risk are advised to undergo CVS or an amniocentesis for a definitive diagnosis.
Both invasive procedures carry a 1 percent risk of miscarriage.
In 1997, Dr. Dennis Lo and his co-researchers at CHUHK discovered that during pregnancy a fetus releases its DNA into the mother's blood plasma. Now they know that the entire fetal genome is present in the mother's blood.
Down syndrome is the most common genetic condition in the United States, causing an array of physical and mental challenges for both child and parents.
Children with the genetic disorder, also known as trisomy 21, have three copies of chromosome 21.
With new sequencing technology, scientists can analyze millions of DNA fragments from each blood sample, looking for abnormalities of chromosome 21.
For decades, amniocentesis has been the gold standard of prenatal testing, performed on 430,000 to 600,000 women a year. The procedure is usually performed at 18 weeks gestation when termination can be traumatic. Doctors insert a needle into the uterus and withdraw amniotic fluid, which can cause fetal injury or miscarriage in 1 out of 200 patients.
Chorionic villus sampling -- is also invasive, but can be done earlier -- at 10 to 13 weeks -- and entails getting a sample of placental tissue. It carries a 1 in 100 miscarriage risk and fetal injury.
Nuchal translucency screening, a type of ultrasound that's done at 11 to 13 weeks in conjunction with blood tests, is safe, but yields an unclear diagnosis.
Existing tests can detect 90 to 95 percent of cases of Down syndrome, but have a 5 percent false positive rate. Each year about 40,000 of the 3 million who take the blood test are directed toward amniocentesis for follow-up.
"The ideal is to aim for 100 percent detection," said Chui, but until new technologies are perfected, new blood tests could supplement current screening.
For example, Hong Kong has 40,000 births a year and about 50 children with Down syndrome, according to Chiu. "But we don't know which 50 they are."
If all 40,000 went through the existing ultrasound and hormone blood test protocols, about 2,000 would be flagged as high risk and sent for invasive testing even though "the majority are normal," she said.
New Down Syndrome Test Saves Healthy Babies
And of those, 1 percent, or about 20, would miscarry.
But with the new DNA blood test, only about 40 of those 2,000 women would be labeled "positive" for Down syndrome and .4 percent would miscarry.
"We are saving babies," said Chui. "And just because we know the results doesn't mean women have to terminate. We are saving women from losing normal children just because of a procedure."
Chui said labs need to be upgraded to handle the sophisticated testing and right now the cost -- $2,000 a test -- is prohibitive.
But American geneticists say the science of sequencing is moving so fast that these blood tests should soon be available.
"Within a year, you are going to be able to buy this off the shelf, way cheaper," said Dr. Laird G Jackson, a geneticist and obstetrician at Drexel University College of Medicine. "What you have here is a wedge opening so what this is demonstrating here is that it could [be available] relatively soon and for a reasonable price."
Expectant mothers are also excited, even though it might mean just one more test to get worked up about.
"If I had the opportunity to take a blood test instead of amniocentesis, I would take the blood test hands down," said Amy Ball, 45, who is 20 weeks pregnant with her first child.
Fortunately, as a high-risk mother, she has passed all the initial genetic screening -- blood tests, ultrasounds and even an "organ inventory" - with no problems. She was offered CVS but declined.
"You get poked a million times anyway when you are pregnant," said the marketing manager from Sebastapol, Calif. "Another blood test is no big deal. But a needle going in the amniotic sac and potentially harming the baby is scary, particularly at an older age. You are a little more paranoid."