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Down's Syndrome screening: where to now?
British Journal of Obstetrics and Gynaecology June 2001, Vol. 108, pp. 559±561
COMMENTARY
Down's Syndrome screening: where to now? Introduction There can be little doubt that antenatal screening services in the UK, especially for Down's Syndrome and anomaly screening, are generally in a poor state of health. At the moment women in different parts of the UK requesting Down's Syndrome screening may be offered a variety of tests or sometimes nothing at all. Information from the Department of Health shows that about 71% of women have access to serum screening, about 8% to nuchal translucency and 21% have only age-restricted access. So why have things turned out so unsatisfactorily? Screening for Down's Syndrome was introduced in the late 1980s on the back of alpha-fetoprotein screening for open neural tube defects by measurement of alphafetoprotein. The observation that alpha-fetoprotein levels were lower in women with a Down's Syndrome fetus led to its introduction as a method of screening for this condition. This was regretable and disappointingly, when it was shown that the use of a second (b human chorionic gonadotrophin) and even a third analyte (oestriol) improved detection, implementation was again only patchy. Not only were there technical problems in the measurement and interpretation of these analytes, but the dif®culties of ensuring adequate counselling before the woman underwent the test were not satisfactorily addressed. Indeed, counselling is largely unfunded and is often undertaken by midwives with no special training or support. Obstetricians tend to take a backseat as regards counselling, apart from those with particular interest in prenatal diagnosis, although the British Journal of Obstetricians and Gynaecologists (RCOG) did establish a Working Party which reported in 1993 1. Some of their most important recommendations have still to be put in place. For example, the need for counselling before testing, the need for co-ordinators, the fact that screening should only be undertaken with the knowledge and consent of the women, and the need for quality control and audit. Here was the guidance needed to establish a satisfactory screening service for Down's Syndrome. So what has gone wrong? As far as serum screening is concerned there has never been general agreement about whether two, three or, more recently, four analytes should be used. The cutoff to be used, whether 1 in 250, 1 in 300 or whatever, has not been settled. Uniformity in the way the tests have been performed and the software used in their interpretation have never been decided. Some q RCOG 2001 British Journal of Obstetrics and Gynaecology PII: S 0306-545 6(00)00129-7
laboratories do only a few thousand tests a year making quality assurance problematic. The introduction of new methods of screening has produced even more confusion. Thus screening in the ®rst trimester either biochemically or by ultrasound using nuchal translucency (NT) has opened up further areas of uncertainty. Nuchal translucency seems a good method, but it is operator-dependent and needs to be performed in early pregnancy. This raises other issues because although some women may have decided on their preferred method of screening before their booking, many women have not and may receive information about nuchal translucency only when they ®rst attend the maternity unit. The use of nuchal translucency currently is being assessed in the United States 2, while in the UK we await the outcome of the SURUSS study which should be known sometime in 2001. The report of another study undertaken in Scotland which addresses the use of nuchal translucency is also awaited. First trimester screening by both serum testing and ultrasound formed the basis of a further RCOG Study Group which reported in 1997 3. Not all of the recommendations were agreed unanimously, but it was considered that in appropriate circumstances NT may be preferable to serum testing but only in with a high level of competence in ultrasound and using equipment of high quality. Clearly these caveats have important resource implications, and three members expressed uncertainty that the case had been made satisfactorily for nuchal translucency. However, important recommendations of this study group included the need for improved education and training for family doctors, midwives, obstetricians and health visitors. These recommendations seem to have been overlooked. Our understanding of the problems are not, in my view, helped by papers extolling the virtues of a one-stop approach 4. On the face of it this method seems to answer all the problems of organisation, being quick and convenient for the woman, to the extent that in this study 97.6% of the women agreed to take part. Women were seen in the community for counselling before visiting the clinic, a practice which certainly must be developed if screening in the ®rst trimester is to be contemplated. However, what sort of population has a virtually 100% acceptance of a test which, if positive will place the pregnancy at risk if an invasive procedure is to be performed or, if the fetus is affected, will result in a termination? Unfortunately, the authors give us no description of the population and its ethnic mix. The ethical issues which underlie such a high www.bjog-elsevier.com
560 COMMENTARY
acceptance rate are not debated in the paper and as far as one can tell, ethics approval for the study was not considered necessary. So what can be done to improve antenatal screening for Down's Syndrome in the UK? Although there was nothing speci®cally in the NHS Plan about screening for Down's Syndrome, there was a recommendation to improve antenatal screening services generally and especially screening for haemoglobinopathies. However, the problem of poor organisation applies to all types of screening in the antenatal period and following advice from the UK National Screening Committee, Government ministers have agreed a programme which should lead to a properly structured, organised and audited system. The plan is to establish eight regional co-ordinators in England; Wales, Scotland and Northern Ireland will make separate but similar arrangements. The regional co-ordinators will establish and support a network of Health Authority and Trust local co-ordinators and provide direction to them in setting up, running and monitoring antenatal screening programmes. They will be responsible for the organisation of their local counsellors who should be situated at individual Trusts, although despite previous recommendations local counsellors do not yet exist in all Trusts. They also will be responsible for the training and continuing education of all doctors, midwives and all health visitors involved in antenatal screening in their area. It should be possible with such an organisation to implement a national policy on antenatal screening and to monitor its effect. Local de®ciencies will be identi®ed and dealt with by the regional co-ordinators. One way to improve matters immediately would be to establish screening around an accepted standard rather than speci®c methods. Exactly what that standard should be has yet to be agreed, but a detection rate of about 65% for a false positive rate (intervention rate) of no greater than 7% may be appropriate. Obviously, some other combination of tests may be more effective, but they have to be deliverable nationally. Once a suitable infrastructure to provide screening has been established, the introduction of preferred methods of screening should be relatively easy and at least will allow an even distribution of an accepted standard over the whole of the UK. Of course this is a considerable challenge. Signi®cantly, some real money has been fed into the system, and it is important that all of us act responsibly to ensure that our patients get the best deal for the money available. Even more importantly, it is vital that women understand clearly the implications of the test, something which is dif®cult to achieve when the health professionals are themselves sometimes confused and often divided about what to do for the best. The ideal screening test is not clear. Nuchal translu-
cency performs well but there are considerable resource implications. Perhaps the most important resource is people. As is the case for other NHS personnel, radiographers are not in abundant supply and yet nuchal translucency depends on them. In addition, nuchal translucency requires the backing of chorionic villus sampling for de®nite diagnosis if the goal of an early diagnosis is to be achieved. But chorionic villus sampling is not generally available and has higher rate of miscarriage than amniocentesis; the concept of the obstetrician doing an occasional one or two would not be acceptable practice. Screening by nuchal translucency requires skillful counselling very early in pregnancy which at present rarely occurs. Although it is not possible without data to tell whether ®rst or second trimester counselling would incur the greater expense, the problems of women being able to obtain information before attending the clinic could be signi®cant. Ideally, what is required is a reliable and simple test, probably a biochemical test, which will have a reasonable detection rate (70 to 80%) but with a very low false positive rate (less than 2%). Are we anywhere near this? Certainly not at the moment. The combination of ®rst trimester nuchal translucency plus biochemistry in the ®rst and second trimester could be the preferred test but would be costly and has yet to be proved. However, although the two-stage approach looks cumbersome, it solves the problem of counselling immediately, as soon as the woman books. She can take her time to decide whether she wishes to go to the next stage. It also deals with the natural wastage of aneuploidy fetuses from the ®rst trimester and reduces unnecessary intervention. When the second trimester results are available the ®rst trimester result can be combined for an overall risk calculation. However, there is still the disadvantage of the need for someone to do the nuchal translucency. Screening for Down's Syndrome has suffered from the phenomenon of creeping technology occurring in the context of poor organisational arrangements. We now have the opportunity to rectify these problems, supported by reasonable investment. Had the recommendations of the two RCOG working parties on Down's Syndrome screening been heeded, screening services in the UK would not be in their current state of disorganisation. We must not fail again. Martin Whittle Department of Obstetrics and Gynaecology, Birmingham Women's Hospital, Birmingham, UK References 1. Report of the RCOG Working Party on Biochemical Markers and the Detection of Down's Syndrome. London: RCOG Press 1993. 2. Malone FD, Berkowitz RL, Carrick JA, D'Alton ME. First trimester
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 559±561
COMMENTARY 561 screening for aneuploidy: research or standard of care? Am J Obstet Gynecol 2000;182:490±496. 3. Grudzinskas JG, Ward HT. Screening for Down Syndrome in the First Trimester. London: RCOG Press, 1997.
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 559±561
4. Spencer K, Spencer CE, Power M, Moakes A, Nicolaides KH. One stop clinic for assessment of risk for fetal anomalies: a report of the ®rst year of prospective screening for chromosome anomalies in the ®rst trimester. Br J Obstet Gynaecol 2000;107:1271±1275.
COMMENTARY
Down's Syndrome screening: where to now? Introduction There can be little doubt that antenatal screening services in the UK, especially for Down's Syndrome and anomaly screening, are generally in a poor state of health. At the moment women in different parts of the UK requesting Down's Syndrome screening may be offered a variety of tests or sometimes nothing at all. Information from the Department of Health shows that about 71% of women have access to serum screening, about 8% to nuchal translucency and 21% have only age-restricted access. So why have things turned out so unsatisfactorily? Screening for Down's Syndrome was introduced in the late 1980s on the back of alpha-fetoprotein screening for open neural tube defects by measurement of alphafetoprotein. The observation that alpha-fetoprotein levels were lower in women with a Down's Syndrome fetus led to its introduction as a method of screening for this condition. This was regretable and disappointingly, when it was shown that the use of a second (b human chorionic gonadotrophin) and even a third analyte (oestriol) improved detection, implementation was again only patchy. Not only were there technical problems in the measurement and interpretation of these analytes, but the dif®culties of ensuring adequate counselling before the woman underwent the test were not satisfactorily addressed. Indeed, counselling is largely unfunded and is often undertaken by midwives with no special training or support. Obstetricians tend to take a backseat as regards counselling, apart from those with particular interest in prenatal diagnosis, although the British Journal of Obstetricians and Gynaecologists (RCOG) did establish a Working Party which reported in 1993 1. Some of their most important recommendations have still to be put in place. For example, the need for counselling before testing, the need for co-ordinators, the fact that screening should only be undertaken with the knowledge and consent of the women, and the need for quality control and audit. Here was the guidance needed to establish a satisfactory screening service for Down's Syndrome. So what has gone wrong? As far as serum screening is concerned there has never been general agreement about whether two, three or, more recently, four analytes should be used. The cutoff to be used, whether 1 in 250, 1 in 300 or whatever, has not been settled. Uniformity in the way the tests have been performed and the software used in their interpretation have never been decided. Some q RCOG 2001 British Journal of Obstetrics and Gynaecology PII: S 0306-545 6(00)00129-7
laboratories do only a few thousand tests a year making quality assurance problematic. The introduction of new methods of screening has produced even more confusion. Thus screening in the ®rst trimester either biochemically or by ultrasound using nuchal translucency (NT) has opened up further areas of uncertainty. Nuchal translucency seems a good method, but it is operator-dependent and needs to be performed in early pregnancy. This raises other issues because although some women may have decided on their preferred method of screening before their booking, many women have not and may receive information about nuchal translucency only when they ®rst attend the maternity unit. The use of nuchal translucency currently is being assessed in the United States 2, while in the UK we await the outcome of the SURUSS study which should be known sometime in 2001. The report of another study undertaken in Scotland which addresses the use of nuchal translucency is also awaited. First trimester screening by both serum testing and ultrasound formed the basis of a further RCOG Study Group which reported in 1997 3. Not all of the recommendations were agreed unanimously, but it was considered that in appropriate circumstances NT may be preferable to serum testing but only in with a high level of competence in ultrasound and using equipment of high quality. Clearly these caveats have important resource implications, and three members expressed uncertainty that the case had been made satisfactorily for nuchal translucency. However, important recommendations of this study group included the need for improved education and training for family doctors, midwives, obstetricians and health visitors. These recommendations seem to have been overlooked. Our understanding of the problems are not, in my view, helped by papers extolling the virtues of a one-stop approach 4. On the face of it this method seems to answer all the problems of organisation, being quick and convenient for the woman, to the extent that in this study 97.6% of the women agreed to take part. Women were seen in the community for counselling before visiting the clinic, a practice which certainly must be developed if screening in the ®rst trimester is to be contemplated. However, what sort of population has a virtually 100% acceptance of a test which, if positive will place the pregnancy at risk if an invasive procedure is to be performed or, if the fetus is affected, will result in a termination? Unfortunately, the authors give us no description of the population and its ethnic mix. The ethical issues which underlie such a high www.bjog-elsevier.com
560 COMMENTARY
acceptance rate are not debated in the paper and as far as one can tell, ethics approval for the study was not considered necessary. So what can be done to improve antenatal screening for Down's Syndrome in the UK? Although there was nothing speci®cally in the NHS Plan about screening for Down's Syndrome, there was a recommendation to improve antenatal screening services generally and especially screening for haemoglobinopathies. However, the problem of poor organisation applies to all types of screening in the antenatal period and following advice from the UK National Screening Committee, Government ministers have agreed a programme which should lead to a properly structured, organised and audited system. The plan is to establish eight regional co-ordinators in England; Wales, Scotland and Northern Ireland will make separate but similar arrangements. The regional co-ordinators will establish and support a network of Health Authority and Trust local co-ordinators and provide direction to them in setting up, running and monitoring antenatal screening programmes. They will be responsible for the organisation of their local counsellors who should be situated at individual Trusts, although despite previous recommendations local counsellors do not yet exist in all Trusts. They also will be responsible for the training and continuing education of all doctors, midwives and all health visitors involved in antenatal screening in their area. It should be possible with such an organisation to implement a national policy on antenatal screening and to monitor its effect. Local de®ciencies will be identi®ed and dealt with by the regional co-ordinators. One way to improve matters immediately would be to establish screening around an accepted standard rather than speci®c methods. Exactly what that standard should be has yet to be agreed, but a detection rate of about 65% for a false positive rate (intervention rate) of no greater than 7% may be appropriate. Obviously, some other combination of tests may be more effective, but they have to be deliverable nationally. Once a suitable infrastructure to provide screening has been established, the introduction of preferred methods of screening should be relatively easy and at least will allow an even distribution of an accepted standard over the whole of the UK. Of course this is a considerable challenge. Signi®cantly, some real money has been fed into the system, and it is important that all of us act responsibly to ensure that our patients get the best deal for the money available. Even more importantly, it is vital that women understand clearly the implications of the test, something which is dif®cult to achieve when the health professionals are themselves sometimes confused and often divided about what to do for the best. The ideal screening test is not clear. Nuchal translu-
cency performs well but there are considerable resource implications. Perhaps the most important resource is people. As is the case for other NHS personnel, radiographers are not in abundant supply and yet nuchal translucency depends on them. In addition, nuchal translucency requires the backing of chorionic villus sampling for de®nite diagnosis if the goal of an early diagnosis is to be achieved. But chorionic villus sampling is not generally available and has higher rate of miscarriage than amniocentesis; the concept of the obstetrician doing an occasional one or two would not be acceptable practice. Screening by nuchal translucency requires skillful counselling very early in pregnancy which at present rarely occurs. Although it is not possible without data to tell whether ®rst or second trimester counselling would incur the greater expense, the problems of women being able to obtain information before attending the clinic could be signi®cant. Ideally, what is required is a reliable and simple test, probably a biochemical test, which will have a reasonable detection rate (70 to 80%) but with a very low false positive rate (less than 2%). Are we anywhere near this? Certainly not at the moment. The combination of ®rst trimester nuchal translucency plus biochemistry in the ®rst and second trimester could be the preferred test but would be costly and has yet to be proved. However, although the two-stage approach looks cumbersome, it solves the problem of counselling immediately, as soon as the woman books. She can take her time to decide whether she wishes to go to the next stage. It also deals with the natural wastage of aneuploidy fetuses from the ®rst trimester and reduces unnecessary intervention. When the second trimester results are available the ®rst trimester result can be combined for an overall risk calculation. However, there is still the disadvantage of the need for someone to do the nuchal translucency. Screening for Down's Syndrome has suffered from the phenomenon of creeping technology occurring in the context of poor organisational arrangements. We now have the opportunity to rectify these problems, supported by reasonable investment. Had the recommendations of the two RCOG working parties on Down's Syndrome screening been heeded, screening services in the UK would not be in their current state of disorganisation. We must not fail again. Martin Whittle Department of Obstetrics and Gynaecology, Birmingham Women's Hospital, Birmingham, UK References 1. Report of the RCOG Working Party on Biochemical Markers and the Detection of Down's Syndrome. London: RCOG Press 1993. 2. Malone FD, Berkowitz RL, Carrick JA, D'Alton ME. First trimester
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 559±561
COMMENTARY 561 screening for aneuploidy: research or standard of care? Am J Obstet Gynecol 2000;182:490±496. 3. Grudzinskas JG, Ward HT. Screening for Down Syndrome in the First Trimester. London: RCOG Press, 1997.
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 559±561
4. Spencer K, Spencer CE, Power M, Moakes A, Nicolaides KH. One stop clinic for assessment of risk for fetal anomalies: a report of the ®rst year of prospective screening for chromosome anomalies in the ®rst trimester. Br J Obstet Gynaecol 2000;107:1271±1275.