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| Journal of the New Zealand Medical Association,
24-June-2005, Vol 118 No 1217
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Prenatal testing for aneuploidy in New Zealand: time for
action
BackgroundScreening for aneuploidy and
particularly Down Syndrome (Trisomy 21) is inevitably becoming part of early
antenatal care due to increasing knowledge and expectations by women and the
availability of methods of risk prediction. Since the first description of the
association between low maternal serum alpha fetoprotein and fetal chromosomal
abnormalities1 the possibility of detecting
women at risk of having a baby with aneuploidy has become available. At present
in New Zealand this is available in some centres by the ultrasound measurement
of fetal nuchal translucency (NT) in the first trimester of pregnancy.
A system of maternal serum screening in the second trimester
of pregnancy was developed, but some time ago funding was withdrawn and the
patient is now required to pay $75.00 for the testing. The ultrasound scan on
which the first trimester risk prediction is based is funded in part or full by
the Health Benefits subsidy provided for early pregnancy scanning services. It
is therefore a reasonable deduction for women to make that as funding is
available, the funder must believe that the procedure is worth doing.
The funder and the Ministry of Health must then take some
responsibility for the situation in New Zealand whereby women are using the
result of the NT scan to decide on the advisability of further testing for
aneuploidy in their fetus.
The further testing performed after nuchal translucency
scanning usually involves invasive procedures such as amniocentesis or chorionic
villus sampling. Both these tests, whilst being considered diagnostic do have
their own risks including loss of the pregnancy.
Implications of current situationFurther screening prior to invasive
diagnostic testing, such as first trimester maternal serum testing is either
unavailable or, in the case of second trimester serum screening, has had
Government funding withdrawn, thus creating a disincentive for patients and
clinicians to use this approach. The fact that second trimester maternal serum
screening is no longer funded is not only a disincentive for this type of
testing but also implies that the Ministry of Health does not consider it to be
a valuable part of antenatal care provision.
Evidence detailing the efficacy of an integrated approach to
prenatal screening for trisomy 21 using a combination of ultrasound and
biochemistry in the first2 and second
trimesters,3 the so called “Integrated
test” has been presented over 5 years ago. In the United Kingdom, the
National Screening Committee has already commenced a process of introducing
nationwide screening with defined targets both for programme outcomes in terms
of detection rates and national coverage. An indepth description of the process
can be found on the website: http://www.nelh.nhs.uk/screening/dssp/home.htm
Current evidenceThe SURUSS
trial4 has shown that for a 3% false positive
rate, a test programme with ultrasound and first and second trimester
biochemistry can achieve a detection rate for Trisomy 21 of 92%. This contrasts
with a detection rate of 67% for ultrasound (NT) alone at the 3% false positive
rate. Higher false positive rates such as 5% only increase the ultrasound
detection rate to 73% but with an increase in invasive testing with its
attendant risks of procedure related pregnancy loss. Of interest, offering
second trimester maternal serum alone (as was formerly the case in New Zealand)
achieved a detection rate of 77% for a 3% false positive rate. Combined first
and second trimester serum testing which avoids the problems of having
sufficient well trained sonographers available will achieve an 82% detection
rate for a 3% false positive rate. It would seem that there is little evidence
to support the use of nuchal translucency scanning alone as is the widespread
practice in New Zealand at present. Other outcomes of nuchal translucency
scanning such as determining accurate gestation or detecting obvious fetal
anomalies fall outside the concepts of a screening programme for fetal
chromosomal abnormality.
The current situation in New Zealand can be described as an
ad hoc arrangement where individual women may avail themselves of screening but
not within the framework of a properly designed screening programme and all that
this involves. A screening programme as distinct from opportunistic testing,
includes pre and post test counselling, quality assurance procedures around the
actual testing and audit of the performance of the programme with changes as new
knowledge becomes available. The purpose of such an approach would be to offer
the best possible tests for the minimal harm to woman and fetus. This is a
fundamental principle of any screening procedure.
There is a very real likelihood, based on data from
SURUSS4 and FASTER (the First and Second
Trimester Evaluation of
Risk
trial, presented in abstract form at the Society of Maternal-Fetal
Medicine 24th Annual Clinical Meeting in the USA in 2004) that the current
approaches here have led to a high invasive testing rate for a relatively low
detection rate. This implies that more chromosomally normal pregnancies are
being lost than is necessary for a barely acceptable detection rate.
The principal reason for prenatal testing for aneuploidy in
New Zealand remains maternal age. Maternal age related risk effectively just
states the prevalence in the population. Using maternal age alone as the screen
for aneuploidy has been shown to be an inefficient and indeed a crude form of
screening leading to high numbers of invasive tests for low detection rates.
This is not only because most women having babies are under the age of 35 years
at delivery but also because at any age, most babies are likely to be normal.
Experience in France evaluating the impact of antenatal screening showed that
offering amniocentesis to women >38 years of age resulted in a detection rate
of only 59.1% in that age group.5 At present on
the data that is available from the cytogenetics services in New Zealand
(personal communication, LabPlus, Auckland District Health Board) and the loss
rates after invasive testing, it is apparent that using age and /or age combined
with NT, more unaffected pregnancies are likely to be being lost that abnormal
ones are being detected. This must surely be an unsustainable and undesirable
situation. The median age of the pregnant population and the demography of this
population are changing and the demands for prenatal testing for aneuploidy will
continue to increase. The problem of providing the best form of screening based
on the best current evidence will remain and will require resolution.
There are a number of misconceptions that have been used to
oppose an integrated first and second trimester approach including that women
prefer the earliest screening possible irrespective of the likelihood that
earlier testing may be “slightly” less
efficient.6 In fact, for a detection rate of
Trisomy 21 of 85%, the first trimester combined scan and blood has a false
positive rate of 4.2% as opposed to the first and second trimester integrated
test with a false positive rate 5 times lower at 0.9%.
Also, it is well recognised that around 20% of Trisomy 21
fetuses miscarry between the first and second trimesters and should all of these
have been detected, then women would have had to go through a medical procedure
when nature would have effected a spontaneous miscarriage. There is considerable
evidence that at least in the first half of pregnancy, the decision to terminate
a wanted but affected pregnancy is very traumatic regardless of gestation and it
may be the doctors rather than the women who perceive advantages of ending the
affected pregnancy as soon as
possible.7–9 Even in the study by
Wapner,10 only half of the women who elected to
terminate the pregnancy did so before 16 weeks Recent data also suggests that
health care professionals place a higher value on earlier tests than pregnant
women do.9
The way forwardThe two recent studies(SURUSS and
FASTER) provide good evidence about the performances of a number of screening
procedures and give us an opportunity to establish a system in New Zealand which
would satisfy the prerequisites of a screening programme. The introduction of
such a programme requires a commitment on the part of government in the first
instance, not the least because equity of access is an important criterion of
any programme. Other criteria require participation by caregivers including
training in counselling and accreditation for the scanning and laboratory
procedures. These latter criteria would be best met by a staged introduction of
a programme with performance goals to be achieved over an agreed period of
time.
Of greatest importance is the decision to commence a
programme. There are many details which would require discussion and resolution
but these are secondary to the commitment to move from the current
unsatisfactory situation. For example, first and second trimester maternal serum
testing has a higher detection rate of trisomy 21 than NT alone and could be
introduced almost immediately. Once all sonography services participating in a
future programme were accredited, a coordinated serum and ultrasound programme
would be feasible with very high detection rates for low false positive rates
and an achievable target of one case of trisomy 21 detected for every six
amniocenteses (16%) examined by the cytogenetics laboratories. This would be a
huge reduction on the current workloads where 1.2% of the amniotic fluids
examined test positive when done after screening. The actual components of
prenatal screening such as the inclusion of fetal nasal bone findings on
ultrasound11 remain to be validated within a
screening programme. Differing approaches to serum testing such as repeated
measures screening12 can be decided upon based
on current evidence once the programme is agreed in principle.
The need for action nowThe screening for and detection of
aneuploidy is a health issue. For many women, it is an important part of
prenatal care. International evidence shows that the current New Zealand
situation can be dramatically improved and at present it is probable more harm
than good is being done. The key question is not when or why but how will New
Zealand resolve this issue. In fact, the National Screening Unit in the Ministry
of Health has an opportunity to develop a uniquely New Zealand solution which
could be a model for elsewhere. Few countries actually have properly constructed
screening programmes as opposed to screening testing. There should be few
impediments to proceeding with this now. The test costs are modest and most of
the personnel and the ultrasound services are in place already. There is little
doubt from informal surveys conducted by the author that clinicians would
welcome progress on the issue. It would be prudent for the Ministry of Health to
act to limit any further potential adverse effects due to the lack of a
programme. Failure to do so risks the further development of ad hoc testing
lacking all the quality assurance and other vital features of a coordinated
national screening programme.
Peter Stone
Professor Maternal Fetal Medicine, Head of Department of Obstetrics and Gynaecology Faculty of Medical and Health Sciences, University of Auckland Auckland References:
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