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Optimising prenatal diagnosis of Down's syndrome

BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7539.433 (Published 23 February 2006) Cite this as: BMJ 2006;332:433

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Optimising prenatal diagnosis of Down's syndrome - full karyotyping contra-indicated for women referred solely for risk of Down's syndrome.

Dear Sirs,

We welcome the paper by Chitty et al (1), which proposes a strategy
for Down syndrome detection based on QF-PCR testing alone for fetuses with
NT<_4mm and="and" qf-pcr="qf-pcr" plus="plus" full="full" karyotyping="karyotyping" for="for" fetuses="fetuses" with="with" nt="nt"/>4mm.
This is in line with the recommendations put forward in our publication
last year (2) following a London-wide audit of chromosome abnormalities in
patients referred for increased risk of Down’s syndrome.

The commentary by Professors Neilson and Alfirevic (3), however,
contains some errors and omissions that we would like to address. They
state that full karyotyping will pick up “more truly positive cases of
Down's syndrome”. In fact, QF-PCR will detect all true cases of Down’s
syndrome; other chromosome abnormalities that may be detected by full
karyotype analysis are not ‘truly positive cases of Down’s syndrome’, but
incidental findings. Many of these findings will be of unknown clinical
significance. In the above paper on this subject (2), we suggest that
full karyotype analysis, when the referral is for raised risk of Down’s
syndrome, is actually contra-indicated, so this is not simply an economic
argument. The WHO guidelines on screening tests state that these should
have a specified aim and a clear treatment pathway (4). Many of the
unexpected karyotype abnormalities detected by full karyotyping will not
have clear treatment pathways, as their clinical significance is unknown.
Much parental anxiety is generated by the discovery of these chromosome
abnormalities, and pregnancies that are most likely to result in a normal
phenotype may be terminated unnecessarily.

The suggestion made by Professors Neilson and Alfirevic that patients
could be counselled prior to choosing whether or not to have full
karyotype testing is unrealistic, when the professionals themselves do not
understand the significance of the test. The authors have assumed that
more information is always better, but this is not always true if some of
the additional information is of uncertain value or cannot be interpreted.

The reality is that, had the technology been available in the late
sixties, targeted testing for Down’s syndrome by QF-PCR would have been
the gold standard test for those at risk of Down’s. However, full
karyotyping was the only available option then; the time has now come to
recognize it as inappropriate for these patients, and to withdraw testing
from the NHS. This is not only for economic reasons, but also in the
interests of good clinical practice.

Caroline Ogilvie, Principal Scientist

Alison Lashwood, Consultant Genetic Counsellor

Frances Flinter, Consultant Clinical Geneticist; Clinical Director,

Women’s and Children’s Services
Genetics Centre,
Guy’s & St Thomas’ NHS Foundation Trust, 5th Floor, Guy’s Tower, St Thomas St,
London, SE1 9RT,
UK.

1. Chitty LS, Kagan KO, Molina FS, Waters JJ, Nicolaides KH. Fetal
nuchal translucency scan and early diagnosis of chromosomal abnormalities
by rapid aneuploidy screening: observational study. BMJ (2006);332: 452-4.

2. Mackie Ogilvie C, Lashwood A, Chitty L, Waters JJ, Scriven PN,
Flinter F. The future of prenatal diagnosis: rapid testing or full
karyotype? An audit of chromosome abnormalities and pregnancy outcomes for
women referred for Down's Syndrome testing.
BJOG: An International Journal of Obstetrics & Gynaecology (2005) 112:
1369-1375.

3. Neilson JP, Alfirevic Z. Optimising prenatal diagnosis of Down's
syndrome. BMJ (2006);332:433-434.

4. Wilson J, Jungner G. Principles and Practice of Screening for
Disease. Geneva: World Health Organization; 1968.

Competing interests:
None declared

Competing interests: No competing interests

02 March 2006
Caroline Ogilvie
Principal Scientist
Alison Lashwood, and Frances Flinter
Guy's & St Thomas NHS Foundation Trust, London SE9 4RQ