It's rare that I come across a pregnant woman who doesn't already know the gender of the baby she is carrying. Ultrasound assessment of a fetus is routinely performed during pregnancy to identify fetal anomalies and, very often, gender identification is offered. After the 13th week of pregnancy, ultrasound is quite accurate in determining a baby's sex. There are circumstances, however, where knowing a fetus is a boy or a girl is important. For example, male fetuses born to women who are carriers of X-linked genetic disorders are at risk of inheriting the disorder. In such instances, knowledge of a fetus' gender before 13 weeks can be advantageous.
Today, the Journal of the American Medica Association (JAMA) published a systematic review and meta-analysis (a systematic method of evaluating statistical data based on results of several independent studies of the same problem) that sought to determine the performance of DNA tests performed on maternal blood to determine fetal sex. As a reminder, DNA from a fetus circulates in maternal blood. This cell-free fetal DNA can be detected and amplified and is the basis of other emerging diagnostic tests.
This report evaluated the results from 57 different studies that tried to determine fetal gender using a test performed on a sample of mother's blood or urine. The 57 reports contained results from 6,541 women; 54% who delivered boys and 46% who delivered girls. Because this was a meta-analysis, several different testing techniques were used in the included studies but all of them looked for the presence or absence Y chromosome-specific molecular markers. If those markers were detected, the fetus predicted to be a male. If they were not detected, the fetus was predicted to be a female.
Collectively, the tests performed very well. They correctly identified 95.4% of the male fetuses (test sensitivity) and 98.6% of the female fetuses (test specificity). The tests did not work well if maternal urine was used as the test sample which is not surprising because cell-free fetal DNA is very difficult to detect in urine. The report also noted that real-time quantitative PCR (RTQ-PCR) methods had better performance than conventional PCR techniques.
As might be expected, test performance improved along with the gestational age of the fetus. At less than 7 weeks test sensitivity (see above for definition) was 74.5% but increased to 95% after 7 weeks at was 99.6% at more than 20 weeks. That makes sense because there is more fetal DNA circulating in the mom's blood as the pregnancy progresses and the fetus increases in size.
Because of the potential clinical use of the test to identify male fetuses of mother's with X-linked genetic diseases, the authors caution that these types of sex-predicting tests should be optimized to achieve high sensitivity (detection of male fetuses) even if it compromises the specificity (detection of female fetuses). They also cautioned that any tests developed and offered by laboratories should thorough validate that a negative (i.e. female fetus) test result reflects the presence of a female fetus and not simply the inability to detect any fetal DNA (which would also give a negative (female) result).
While there are some direct-to-consumer labs that offer this type of DNA-based testing to determine fetal sex, the test is marketed as one of convenience to satisfy a mother's curiosity regarding her baby's gender. Currently, I am unaware of any clinical laboratories in the United States that offer such testing for diagnostic purposes although the tests are available for that reason in the European Union. I predict that this type of test will become more widely available in clinical labs over the next few years. There is much promise to be realized from tests based on circulating cell-free DNA!