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Rapid response to:


Optimising prenatal diagnosis of Down's syndrome

BMJ 2006; 332 doi: (Published 23 February 2006) Cite this as: BMJ 2006;332:433

Rapid Response:

Risk-free prenatal diagnosis of Down's syndrome

Following an editorial in the BMJ on optimising prenatal diagnosis of
Down’s syndrome (1), a recent report by Dhallan et al (2) on the potential
for risk-free prenatal diagnosis of Down’s syndrome (DS) by the use of
maternal blood samples alone has attracted much media attention. There
have also recently been a number of other reports (3,4) indicating that
this might soon become a viable alternative to current prenatal diagnosis,
where unfortunately amniocentesis and chorionic villus sampling (CVS) are
associated with a fetal loss rate of around 0.5-1%.

The outstanding question is then how best to introduce such new non-
invasive prenatal diagnosis (NIPD) for DS in relation to currently
available maternal DS screening programmes. These schemes include in
particular serum screening and ultrasound for fetal nuchal translucency
(NT). Might the best option be to adopt NIPD as an adjunct to current
screening tests? Or would it make more sense to introduce NIPD as a
replacement for the NT part of the screening, which is the most expensive
and labour intensive? Or indeed, would the best solution be to simply
replace current screening with the new NIPD test? Many people seem to a
priori find this latter option the most logical.

The situation in the UK as regards maternal DS screening is quite
different to that in many other countries. On the one hand the first
trimester screening facilities and the one-stop-clinics in London are the
most advanced world wide. In this clinical setting, the sensitivity of
screening for DS is 92.6% and the specificity 94.8% (5). Yet again, many
Obstetric Units up and down the country still rely on either second
trimester screening alone or a combination of first and second trimester
screening with much lower detection rates.

It is obvious that the best way forward will require consideration of
the economic as well as social implications of NIPD. We would argue
therefore that there is now no time to lose in looking at these. This
notion is of special importance considering the potentially very high
uptake by pregnant women of a new risk-free diagnostic test compared to
current schemes requiring CVS or amniocentesis, with their inherent fetal
loss rates.

Any policy for introducing a new non-invasive prenatal DS diagnosis
programme is likely to become the responsibility of the UK National
Screening Committee (6). We hope that a timely and careful analysis by
researchers of the options, along with supporting evidence and an
effective national planning strategy, will assist in providing a coherent
and clear policy for the future. The continued debate around existing
screening and diagnostic DS tests, including molecular ones, should
hopefully dissipate with the obvious advantages that these new
developments can bring.

Maj Hultén, Professor Medical Genetics, Department of Biological

Ala Szczepura, Professor Health Services Research, Warwick Medical School
University of Warwick, Coventry CV4 7AL


1. Editorial: James P Neilson and Zarko Alfirevic. Optimising prenatal
diagnosis of Down's syndrome. BMJ 2006; 332: 433-434

2. Dhallan R, Guo X, Emche S, Damewood M, Bayliss P, Cronin M, Barry
J, Betz J, Franz K, Gold K, Vallecillo B, Varney J. A non-invasive test
for prenatal diagnosis based on fetal DNA present in maternal blood: a
preliminary study. Lancet. Published Online February 2, 2007.

3. Lo YM Fetal DNA in maternal plasma: progress through epigenetics.
Ann N Y Acad Sci. 2006 Sep;1075:74-80

4. Lo YM, Tsui NB, Chiu RW, Lau TK, Leung TN, Heung MM, Gerovassili
A, Jin Y, Nicolaides KH, Cantor CR, Ding C. Plasma placental RNA allelic
ratio permits noninvasive prenatal chromosomal aneuploidy detection. Nat
Med. 2007 Jan 7; [Epub ahead of print]

5. Nicolaides KH et al. Multicenter study of first-trimester
screening for trisomy 21 in 75 821 pregnancies: results and estimation of
the potential impact of individual risk-orientated two-stage first-
trimester screening. Ultrasound Obstet Gynecol. 2005 Mar;25(3):221-6.

6. National Screening Committee (

Conflicts of interest
MH is the Director of Simeg Ltd and has filed patents on NIPD technology

Competing interests:
MH is the director of Simeg Ltd and has filed patents on technology for non-invasive prenatal diagnosis

Competing interests: No competing interests

09 February 2007
Maj A Hulten
Professor of Medical Genetics
Maj A Hulten, Ala Szczepura
Department of Biological Sciences, University of Warwick, Coventry CV$ 7AL