A report in the August 10 issue of JAMA states, that reviews and analysis of previous studies have revealed that a noninvasive method of determining the sex of a fetus by using cell-free fetal DNA obtained from the mother’s blood 7 weeks after gestation performed well compared with urine-based tests, which seem to be unreliable.

Although invasive cytogenetic determination is the most popular current procedure for determining sex and single-gene disorders, the noninvasive prenatal determination of fetal sex could provide an important alternative. According to background information in the article, Amniocentesis has small but measurable rates of procedure-related pregnancy loss while sonographies can be performed as early as 11 weeks’ gestation to determine fetal sex, however, this method is not reliable. The authors comment,

“The availability of a reliable noninvasive alternative to determine fetal sex would reduce unintended fetal losses and would presumably be welcomed by pregnant women carrying fetuses at risk for disorders.”

The noninvasive method of using cell-free DNA for prenatal determination of fetal sex also provides an alternative to invasive techniques for various heritable disorders. The transition to routine clinical care has already been integrated in some countries, such as the Netherlands, United Kingdom, France and Spain despite the absence of formal performance assessments.

Background information in the article reads,

“More recently, companies have begun offering this technology directly to the consumer over the Internet. The tests are marketed for nonmedical use to curious parents-to-be with promises in some cases of accuracy as high as 95 percent to 99 percent at as early as 5 to 7 weeks’ gestation.”

A systematic review and meta-analysis of previous research to examine the analytic validity of cell-free fetal DNA testing describing the test’s ability to detect Y chromosome sequences within maternal samples, as well as the clinical validity of the test, as indicated by its ability to correctly identify fetal sex was researched by Stephanie A. Devaney, Ph.D., of the National Institutes of Health, Bethesda, Md., and her fellow researchers. The investigation analysis included 57 studies comprising of 80 data sets representing 3,524 male-bearing pregnancies and 3,017 female-bearing pregnancies. The overall test performance revealed a high performance using maternal blood with a sensitivity of 95.4 percent, specificity of 98.6 percent, positive predictive value, 98.8 percent, and negative predictive value of 94.8 percent.

The biggest effect on test performance was by DNA methodology and gestational age, with real-time quantitative polymerase chain reaction (RTQ-PCR) outperforming conventional PCR.

High test performance was achieved by using RTQ-PCR on a blood sample taken at 7 weeks’ gestation or later, a time during pregnancy when sufficient cell-free fetal DNA was present, with ultimate performance levels after 20 weeks’ gestation. Tests carried out using blood and all urine tests before 7 weeks’ gestation were found to be unreliable.

The authors comment,

“The improved performance with later gestation is likely attributable to the increased concentration of cell-free fetal DNA within maternal blood as the fetus and placenta develop. This would explain the poor performance of the test prior to 7 weeks’ gestation and the near-perfect performance in the third trimester.”

The research concludes,

“This technology can be useful in clinical settings for early detection of fetuses at risk for sex-linked disorders requiring follow-up testing.”

Written by Petra Rattue