Test Screens Maternal Blood for Fetal Aneuploidies

A routine maternal blood cell-free (cf) DNA test is being used to detect three specific chromosomal abnormalities, called trisomies, early in pregnancy.

In trisomies, fetuses carry all or part of an extra chromosome 21, called trisomy 21 or Down’s syndrome, or chromosome 18, called trisomy 18 or Edwards’ syndrome, or chromosome 13, called trisomy 13 or Patau syndrome.


Scientists at King’s College Hospital (London, UK) and University College Hospital (London, UK) enrolled 1,005 pregnant women attending their clinic. Women in the study were between 20 and 49 years old and 85.7% had conceived naturally, 11.6% having conceived by in vitro fertilization (IVF) and 2.7% having conceived after taking drugs to promote ovulation. Blood samples were taken from the women at 10 weeks into their pregnancy to perform the DNA-based screening test and part of the existing screening test, called the combined test, and at 12 weeks the women had the ultrasound needed as part of the combined test.

The cfDNA screening was performed using the Harmony Prenatal Test (Ariosa Diagnostics; San Jose, CA, USA), which is based on directed analysis, where specific cfDNA fragments from maternal blood are uniformly analyzed across all samples. This is approximately a tenth the number required for massively parallel shotgun sequencing, thereby reducing variability and making it easier to optimize assay conditions and informatics requirements.

The results of the screening test that among the 984 women, 967 had very low risk for all three trisomies, 11 were at high risk for trisomy 21 only, 5 were at high risk for trisomy 18 only, and 1 had an increased risk for trisomy 13 only. Overall, the combined screening test identified 49 women (5%) to be at increased risk of trisomy 21 with over 1% risk. Sixteen of these women were found to have a trisomy pregnancy on diagnostic testing.

The authors concluded that routine use of the Harmony Prenatal Test for trisomies 21, 18, and 13 at 10 weeks into pregnancy is feasible, and gives fewer false positive results than the existing screening test for trisomy 21. The results of the screening test still needed to be confirmed by invasive diagnostic testing. The study has highlighted the advantages of cfDNA testing compared with the combined test, in terms of substantial reduction in false positive rates and clear separation of high- and low-risk results, but has also demonstrated the problem of the failure of cfDNA testing in providing results and the need to investigate abnormal results by invasive testing. The study was published on June 7, 2013, in the journal Ultrasound in Obstetrics & Gynecology.

Related Links:
King’s College Hospital
University College Hospital
Ariosa Diagnostics