Existing Technique Can Detect Fetal Genetic Abnormalities in Maternal Blood

Team found that MLPA assay can identify fetal DNA without invasive sampling.

Netherlands-based researchers suggest that a technique currently used to detect fetal chromosomal abnormalities in maternal amniotic fluid or chorionic villi samples is sensitive enough to detect the same abnormalities in a maternal blood. Maastricht University Medical Centre clinical geneticist, Suzanna Frints, Ph.D., and colleagues are using multiplex ligation-dependent probe amplification (MLPA) to detect fetal DNA in the blood of women who were at least 6–8 weeks pregnant. They report on their findings at the 26^th annual meeting of the European Society of Human Reproduction and Embryology in Rome.

The MLPA assay is part of an existing kit used with samples of amniotic fluid or chorionic villi, which have to be obtained invasively. It has just not previously been tested on maternal blood, Dr. Frints points out. The Maastricht team say they have already used the MLPA approach to identify DNA from the fetal Y chromosome in maternal blood and are now progressing to evaluate the technology’s ability to detect trisomy 21 Down syndrome, trisomy 13 Patau syndrome, and trisomy 18 Edward syndrome.

“Although we need to test and refine this MLPA technique further, our results so far are promising,” Dr. Frints claims. “This is innovative translational research, and when we succeed in developing the MLPA procedure for use in maternal blood, we will be able to offer a safe, cheap, fast, reliable, and accurate noninvasive test, which will be of immediate benefit to pregnant women.”

The Maastricht team’s work to validate the use of MLPA on maternal blood samples started in 2009 and is expected to continue until at least 2012, they point out. They are evaluating the test in women undergoing pregnancy terminations due to invasively diagnosed trisomy 13, 18, or 21 in comparison with women who have undergone noninvasive prenatal screening and those who have had invasive screening procedures because they were at least 36 years of age on becoming pregnant. The control cohort includes nonpregnant women who have had up to three children each.

Dr. Frints claims the early results are very promising. “The MLPA tests results obtained in 2009 were compared with the results of amniocentesis, chorionic villus sampling, and pregnancy outcome. All but one sample correlated with the noninvasive MLPA test results, detecting fetal Y-chromosome sequences.” They admit that at present the test is only about 80% reliable due to false negatives, but work is ongoing to improve the accuracy of the probe.

Dr. Frints believes MLPA could change the way fetal diagnosis is carried out worldwide. “Blood samples can be taken at routine antenatal visits. It is inexpensive compared to the costs of invasive prenatal diagnosis and could easily be implemented at low cost, between €30–150 (about $36–184) per kit per person, with a small apparatus in every hospital in the world.”