Journal of the New Zealand Medical Association, 24-June-2005, Vol 118 No 1217
Prenatal testing for aneuploidy in New Zealand: time for action
Screening 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A system of maternal serum screening in the second trimester of pregnancy was developed, but some time ago funding was withdrawn and the patient is now required to pay $75.00 for the testing.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 situation
Further 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serum testing is either unavailable or, in the case of second trimester serum screening, has had Government funding withdrawn, thus creating a disincentive for patients and clinicians to use this approach.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
The 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 forward
The 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 now
The 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.
Professor Maternal Fetal Medicine, Head of Department of Obstetrics and Gynaecology
Faculty of Medical and Health Sciences, University of Auckland
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