Parents usually have to wait until nearly the end of the first trimester of pregnancy, or even into the second, to find out whether they're expecting a boy or a girl. But a new technique done with a simple blood draw from the expectant mother can reveal the gender of a developing fetus as early as five weeks into a pregnancy.
Most importantly, it appears to be 100 percent accurate, say Dutch researchers whose findings were reported in Monday’s edition of the journal Obstetrics and Gynecology.
The Dutch study took place over the course of five years, from 2003 to 2009 and included 201 expectant mothers referred by geneticists or gynecologists in the Netherlands. Of 201 women tested, the researchers were able to issue a conclusion 189 times. They were correct every time.
The technique is less a breakthrough than a continuation of successful research and trials that have brought such non-invasive fetal testing to the brink of wide commercialization, said Dr. Diana Bianchi, the Natalie V. Zucker professor of pediatrics, obstetrics and gynecology at Tufts University. Bianchi is not affiliated with the Dutch study.
While such testing is sure to raise concerns over its possible use to select the gender of a baby based simply on parental preference, non-invasive gender tests are already used in the United Kingdom and some European countries as a screen for very real medical conditions.
X-linked disorders, for example, are gene-based diseases such as hemophilia and Duchenne muscular dystrophy carried by the X chromosome that almost always occurs in males. Congenital adrenal hyperplasia, or CAH, is a condition in females that leads to the virilization of sex organs. CAH can be treated in utero if it’s discovered.
Current invasive fetal diagnostic tests, like amniocentesis and chorionic villus sampling, carry small but real risks to the fetus and cannot be performed as early as the new non-invasive procedures. So ultimately, the potential market for such testing could be every pregnant woman on earth.
With the 100 percent accuracy rate in his team’s study, Dr. Peter Scheffer of Sanquin Research Amsterdam, part of the University of Amsterdam where the study was conducted, has no doubts the system for gender testing should be applied in clinics around the world right now.
“It eliminates the dangers associated with invasive testing,” he said. “With regard to fetal sex determination, it would allow for definitive sex determination earlier in pregnancy, sparing most female fetuses from unnecessary invasive testing” when there is fear of X-linked disorders, “or guiding clinical management. It can also help reduce parental anxiety.”
'Fraught with ethical problems'
University of Pennsylvania bioethicist and msnbc.com contributor Arthur Caplan, Ph.D., calls the techonology "very useful,” but points out that for most inherited disorders there are few therapies, which means “elective abortion is just about the only option in response to fetal testing.” While most doctors would discourage its use merely to select gender, its increasing availability "puts physicians in the position of offering testing that may lead to abortions for non-medical reasons," making the test "fraught with ethical problems."
In the Dutch study, blood was drawn from the mothers and, when possible, the fathers. DNA was extracted from the maternal blood and tested for the presence of SRY (sex-determining region Y gene) found only on the Y chromosome. Partway through the study, the researchers began looking for a second Y chromosome-only bit of DNA, the DYS-14 gene. Since women do not normally possess either of these sequences, if the researchers found them in the mother’s blood, they concluded that she was carrying a male fetus.
These steps mirror those of other well-established protocols, Bianchi explained. But one problem with such testing is what to do if the maternal blood is negative for these telltale signs of maleness; a negative result does not necessarily mean the woman carries a female fetus.
So Scheffer and colleagues looked for the presence of slight genetic alterations called polymorphisms that were unique to the father.
“A [polymorphism] can only be used as a fetal marker if it is absent from the maternal genome,” Scheffer explained. “If it is then found in the maternal plasma, its origin has to be fetal” and inherited from the father. If polymorphisms matched the father, and there were no Y-linked gene sequences, the fetus was a female.
While the tests confirmed gender, they weren’t diagnostic, a gender test cannot tell if a fetus has a disease, only if further testing is warranted.
In all, 65 mothers in the Dutch study avoided invasive procedures, and 27 were able to stop taking drugs for suspected cases of cortical adrenal hyperplasia. Test results were available in two to four days.
The race for a definitive diagnosis
Companies are in a scramble to create similar non-invasive tests for actual diagnoses of syndromes and diseases. One strategy would use whole fetal cells.
Over 100 years ago a German doctor named Georg Schmorl studied eclampsia, seizures that can afflict some pregnant women. Schmorl performed autopsies on eclampsia victims and discovered unusual cells had accumulated in their lungs. Those cells turned out to be fetal cells.
Finding such cells would enable labs to perform an entire genome analysis on a fetus, conceivably diagnosing everything from Down Syndrome to a predisposition to late-life breast cancer. Finding circulating fetal cells, however, is extremely difficult.
In 1997, Hong Kong scientist Dennis Lo discovered that fetal DNA and RNA could also be found in mother’s blood. While these nucleic acids cannot provide as much information as a whole cell, they are easier to isolate.
Scandal in the industry
With so much money at stake, the rush to create diagnostic products by finding these nucleic acids has led to scandals. Some commercial outfits already offer direct-to-consumer gender tests, but the tests have proven to be of questionable reliability.
Last spring Harry Stylli, then the CEO of San Diego-based Sequenom, announced that his company would introduce a non-invasive test for Down Syndrome by September with more diagnostic tests to follow quickly. Less than two weeks later, the company announced that the data backing up its claims of reliability had been cooked. Stylli and others were fired, the FBI and U.S. attorney’s office investigated, and shareholder lawsuits were filed.
Despite such setbacks, Bianchi — who works on the scientific advisory of another testing company, San Carlos, California-based Artemis Health — said data from research groups like the Dutch scientists is accumulating rapidly. While no company has yet gone commercial with a diagnostic test, she said, “it looks promising.”