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A screening test for Down’s syndrome could identify nearly 90 per cent
of cases. Launched last week, the test is being marketed directly at women,
who will have to pay for the service. The best test available on the NHS
detects only 30 per cent of Down’s babies. The launch has re-opened the
debate about the way screening is carried out in Britain.

The NHS’s current method of screening for Down’s syndrome is to offer
amniocentesis to pregnant women over the age of 36. Amniocentesis involves
drawing off fluid from around the fetus, culturing cells in the fluid, and
looking directly for the defect on chromosome 21 which is responsible for
Down’s syndrome.

For the new test, developed at St James’s University Hospital in Leeds,
a woman only needs to give a blood sample. The hospital sends the woman
a test tube and a microscope slide. She must then ask her family doctor
to take some blood, fill the tube and smear blood on the slide. The kit
is returned to Leeds, along with a cheque for £88.

The blood is subjected to the ‘triple’ test, a technique developed at
St Bartholomew’s Hospital in London (New Å®ÉúСÊÓƵ, Science, 15 October
1988). Women carrying a Down’s syndrome fetus have higher or lower than
normal levels of certain hormones and proteins. The triple test is an analysis
of three such substances – the hormones human chorionic gonadotrophin and
oestriol, and alpha-fetoprotein, which is produced by the fetal liver.

The combination of the levels of these three substances indicate the
degree of risk of having a Down’s baby. Women who give a positive test then
have amniocentesis for a firm diagnosis. The triple test can identify around
60 per cent of Down’s pregnancies.

The St James’s ‘triple plus’ test goes further. Blood smeared on the
slide is stained red to reveal an enzyme called urea-resistant neutrophil
alkaline phosphatase (UR-NAP), which is produced by white blood cells called
neutrophils. An analyst then scores each sample according to the amount
and depth of colour taken up by neutrophils. The activity of this enzyme
is higher than normal in Down’s sufferers. Last year, Howard Cuckle and
his colleagues at St Bartholomew’s measured levels of UR-NAP in women diagnosed
as having a Down’s pregnancy. The test identified 79 per cent of them. ‘To
our knowledge no other single blood test can identify Down’s syndrome so
effectively,’ they concluded.

According to models, when the risk measured with UR-NAP is combined
with the risk estimated from the triple test, ‘detection will go up to 80
per cent and probably near 90′, says Cuckle, who is now at St James’s Hospital,
and who developed the test.

He is unapologetic about introducing the test on a commercial basis.
‘The service hasn’t been available before,’ he says. ‘We’re offering it
in the absence of any other test.’ Cuckle says he hopes health authorities
and the entire NHS will take up the test. In the meantime, profits from
the service are being ploughed back into research into Down’s syndrome,
he says.

In an editorial in the British Medical Journal last year, Cuckle called
for a new national body to decide when new screening tests should be adopted.
‘These decisions need to be taken, otherwise good screening tests like this
take years to come in,’ he says.

At present, decisions on screening for all conditions except breast
cancer are made locally. While screening for Down’s syndrome is available
across the country for women over 36, only a few districts have adopted
the triple test.

Opinions vary on why the triple test has not been adopted nationwide.
Dulcie Coleman, professor of cytopathology and cytogenetics at St Mary’s
Hospital in London, says introducing a new screening test would be a large
investment. Even the triple test, at £45 a time, is considerably more
expensive than a cervical smear, which costs about £3. ‘There isn’t
any money coming forward,’ she says. But besides costs, new tests have to
have proven cost effectiveness, accuracy and reliability, says Coleman.

‘I would say that the triple test isn’t that widely accepted or understood,’
says Charles Rodeck, professor of obstetrics and gynaecology at University
College and Middlesex School of Medicine in London. ‘You’ve got to recognise
that you have to have good evidence to convince government and policy makers.’

Clinical trials of the triple test have not been widely performed by
groups other than the team at St Bartholomew’s. However, at least one recent
trial concluded that the triple test should replace screening based only
on maternal age.

As for the triple plus test, Rodeck points out that there is confusion
over UR-NAP’s role in the body and why the enzyme should be present at increased
concentrations in Down’s pregnancies. Without that sort of understanding,
people are bound to be wary.

A better understanding of the enzyme and of Down’s syndrome, and the
development of a test that can be performed in the first three months of
pregnancy are the priorities for research at St James’s, says Cuckle. ‘It
wouldn’t surprise me if we or another group find a single chemical which
gives a better indicator of risk than all these (tests) put together,’ he
adds.