Mother’s blood test for Down’s syndrome DNA is more accurate than current screening methods
In a news item published on 22 October 2008 we reported that workers from Stanford University had used massive parallel sequencing of cell-free DNA (cfDNA) from mother’s blood in pregnancy to diagnose Down’s syndrome. Each of 17 women with Down’s pregnancies had more DNA fragments of chromosome 21 (from the baby’s placenta) than other pregnancies. The study's senior author, Professor Stephen Quake, said that the next step was to repeat the work in larger numbers.
Several large proof-of-principle studies of non-invasive prenatal testing (NIPT) for increased cfDNA of chromosome 21 have since shown it to be effective in women whose first trimester screen indicated a high risk of abnormality.
A new large multicentre study of women undergoing routine first trimester prenatal screening was published online in the New England Journal of Medicine on 1 April 2015. Prediction of Down’s syndrome from cfDNA testing was compared with prediction from routine screening. In the 15,841 women from 35 centres in the United States, Canada, and Europe who completed screening, cfDNA testing predicted all 38 babies with Down’s syndrome with only nine false positives (0.06%). Standard screening predicted 30 of the 38 but with 854 false positives (5.4%).
Making a firm diagnosis following a screening test that suggests the baby has a high risk of Down’s syndrome, involves offering an invasive test, either amniocentesis or chorionic villus sampling, to examine the baby’s cells directly. These tests, performed from 11 weeks’ gestation, carry about a 1% risk of miscarriage and the possibility of infection. Each year about 25,000 of the 700,000 pregnant women in the UK have an invasive test following standard screening. The new study suggests this number could be reduced substantially with cfDNA screening which is not yet provided by the NHS. (It is available privately at a cost between £400 and £900 depending on whether a scan and consultation is included.)
Lyn Chitty, Professor of Genetics and Foetal Medicine at the Institute of Child Health, University College London, is part of a research team based at Great Ormond Street Hospital that is evaluating the requirements for implementing the cfDNA test as part of the NHS Down’s syndrome screening programme. A report is expected later this year. She told the BBC that testing every pregnant woman's blood is unlikely. However, she believes it can and should be integrated into the existing screening so that high-risk women have an extra check before deciding if an invasive procedure is needed.