August 9, 2011

Fetal sex can be determined reliably with a non-invasive genetic test as early as 7 weeks into a pregnancy, according to a new meta-analysis published this week in the Journal of the American Medical Association. The results of the NIH-funded analysis have important implications for early diagnosis of genetic diseases linked to genes on the X chromosome, since those diseases only affect males. In most cases today, doctors diagnose X-linked diseases prenatally with invasive tests, such as chorionic villus sampling or amniocentesis, which carry a small risk of miscarriage. The fetal gender test cannot diagnose X-linked diseases but can determine whether a fetus is male before conducting more invasive testing. The ability to determine the sex of a fetus accurately and early in pregnancy could reduce the number of invasive tests for sex-specific diseases by 50%.

In 1997, a research group led by Dennis Lo showed, through the presence of Y chromosome markers, that fetal DNA is detectable in maternal blood very early in pregnancy. Many research groups have since replicated these findings at different gestational ages, using various DNA markers and techniques and different sample types. However, until this week, no single study had analyzed the ability of the test to correctly identify fetal sex across all published reports. The new research provides the strongest evidence to date of the overall ability of the test to correctly identify fetal sex, and identifies variables that affect the test’s performance. It was conducted by Diana Bianchi of the Mother Infant Research Institute at Tufts Medical Center, along with Joan Scott and Stephanie Devaney, formerly of the Genetics & Public Policy Center at the Berman Institute of Bioethics at Johns Hopkins University, and Glenn Palomaki of the Women & Infants Hospital.

Across 68 published data sets, the authors found that testing for fetal DNA in maternal blood correctly identified male fetuses 95.4% of the time and female fetuses 98.6% of the time. Of the test characteristics analyzed (year of publication, DNA amplification method, Y chromosome sequence, sample type, and gestational age), amplification method and gestational age had the largest effects on test performance. Tests done after 20 weeks’ gestation using a quantitative DNA amplification method (RTQ-PCR) had the best performance. However, testing can be done reliably any time after 7 weeks. Tests using urine and those done prior to 7 weeks’ gestation were not reliable.

Non-invasive fetal sex determination is currently offered as early as 5 weeks gestation directly to consumers over the Internet, through a handful of companies that claim accuracies as high as 99%. It is not yet used in clinical practice in the United States, although it is offered more widely in Europe. Clinical practices that adopt this test to identify fetuses at risk for a sex-specific condition should develop a protocol to validate the presence of fetal DNA in cases of negative results (the absence of Y chromosome). This will ensure that a negative result correlates with the presence of a female fetus and is not simply due to the absence of detectable DNA .


Media contact:
Tufts University, Julie Jette,

Link to Article on JAMA website


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