Letters

Screening for cystic fibrosis Screening before pregnancy is preferred

Firstly, the authors suggest (in table II) that a majority of women, whether entering the trial or not, preferred screening during pregnancy. This is not borne out by the results they present since, although small numbers are involved, 60.5% of the non-participants preferred screening before pregnancy, compared with 46% of the participants. A previous survey of pregnant women found that 98% preferred screening before pregnancy and 69% would accept carrier screening during pregnancy.² There is actually substantial interest in prepregnancy screening. This is signficant because the acceptability of screening to the general population is likely to alter with the improving clinical picture for cystic fibrosis³ as well as gene therapy.

Secondly, the authors conclude that although prepregnancy screening "permits some reproductive choice" those choices are unlikely to be pursued. The experience from screening programmes for Tay-Sachs disease and thalassaemia are given as evidence. We doubt this for two reasons: the evidence, particularly from Tay-Sachs carrier screening, that carriers exercise reproductive choice by their choice of partner, and also because the examples quoted are particular to ethnic minority groups that were well informed and highly motivated so that genetic information was understood and used in making decisions. Cystic fibrosis is the first recessive gene that can be screened for in the white population, in which the knowledge of the disease and the motivation to avoid it are limited. The models are very different and one should be careful about generalising from one disease to another, especially when there are different social and cultural influences.⁴

The model of cystic fibrosis screening proposed by Livingstone and colleagues may be feasible but it limits reproductive choice for couples. Prepregnancy screening should not be dismissed since reproductive choice is preserved and there is evidence that it is preferred. If any lesson is to be taken from the successful ethnic minority screening programmes it is that population awareness and motivation are achieved only with appropriate public education programmes. The model for cystic fibrosis population screening, if that is what we want, needs wide debate since it may well provide a blueprint for subsequent genetic screening programmes.

J D A Cooper, A J Franks

Wakefield Healthcare, Wakefield WF1 1LT University of Leeds, Leeds

1. Livingstone L, Axon R A, Gilfillan A, Mennie M, Compton M, Liston W A, et al. Antenatal screening for cystic fibrosis: a trial of the couple model. BMJ 1994;308:1459-62. (4 June.) [Abstract/Free Full Text]
2. Botkin J R, Alemagno S. Carrier screening for cystic fibrosis: a pilot study of the attitudes of pregnant women. Am J Public Health 1992;82:723-5. [Abstract/Free Full Text]
3. Britton J, Knox A J. Screening for cystic fibrosis. Lancet 1991;338:1524.
4. Green J M. Practicalities of carrier screening: attitudes of recent parents. J Med Genet 1992;29:313-9. [Abstract]

Antenatal testing has higher yield

EDITOR, - Genetic centres offer testing for cystic fibrosis heterozygosity to relatives of affected individuals. Usually such programmes respond to consultants' requests. Super and colleagues proposed a proactive approach, taking screening into the population to the relatives of index cases.¹ In their trial they tested 1563 relatives and partners of subjects in 129 index families and identified 15 heterozygous couples (1%). By extrapolation to 10 000 relatives and partners, 100 heterozygous couples would be detected and 25 affected fetuses found. It was claimed that this is equal to the number of children with cystic fibrosis born annually in their region.

Inspection of the data shows the fallacy of the argument. Among relatives tested no fewer than 427/1122 (38%) were carriers. Thus the study concentrated predominantly on close relatives. In the next phase, as the cascade moves to more distant relatives, the proportion of carriers detected will inevitably drop. It is misleading to extrapolate the figure of 1% for heterozygous couples found in the easy part of the programme to more difficult parts.

Furthermore, it cannot be assumed that all heterozygous couples would be planning pregnancies or would seek prenatal diagnosis and act on the results. Of the 15 heterozygous couples reported by Super and colleagues, one had completed their family and another five did not request parental diagnosis. This contrasts with the 12 heterozygous couples detected through our antenatal screening programmes,^2,3 all of whom have requested prenatal diagnosis.

It is impossible to measure the theoretical effectiveness of cascade testing by simple extrapolation. It is necessary to create models with family size distributions and alternative testing strategies. Our projections, using such modelling, suggest that less than 25% of heterozygous couples be detected by cascading to the second cousin level.⁴ In contrast, we have already shown that over 50% of heterozygous couples can be detected by either of the two major forms of antenatal screening.^2,3

D J H Brock

Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU

1. Super M, Schwarz MJ, Malone G, Roberts T, Haworth A, Dermody G. Active cascade testing for carriers of cystic fibrosis. BMJ 1994;308:1462- 8. (4 June.) [Abstract/Free Full Text]
2. Livingstone J, Axton RA, Gilfillan A, Mennie M, Compton M, Liston WA, et al. Antenatal screening for cystic fibrosis: a trial of the couple model. BMJ 1994;308:1459-62. (4 June.)
3. Mennie M, Gilfillan A, Compton M, Curtis L, Liston WA, Pullen I, et al. Prenatal screening for cystic fibrosis. Lancet 1992;340:214-6. [Medline]
4. Holloway SH, Brock DJH. Cascade testing for carriers of cystic fibrosis. Journal of Medical Screening (in press).

General practitioners should be involved

EDITOR, - Cascade screening for carriers of the cystic fibrous gene has the tempting appeal, particularly when done before conception, of detecting clusters of carriers in particular families.¹ Unfortunately, couple screening, in which couples of whom only one partner is a carrier are identified as being at low risk,² would undermine any cascade screening programme. Reasonably, in her commentary on the study of cascade screening¹ Theresa Marteau has brought to light various concerns about a cascade approach to screening. Other concerns exist - for instance, the impact on family and kinship networks of introducing the possibility of "family illness" through a cascade of possibility of "family illness" through a cascade. In other settings more distant relatives have been shown to be disinclined to undergo, or are uninformed about, carrier testing.³

The alternative situation, in which a carrier index subject blocks dissemination of genetic information to the extended family, also needs to be considered. This could later give rise to friction within the family - for instance, if a sibling later discovered her carrier status after the birth of an affected child. Other members of the family could be contacted without the confidentiality of the index subject being broken only if there was a complementary population screening programme based in general practice.

For an effective preconceptional programme the primary care team needs to be informed and involved. M Super and colleagues and Jean Livingstone and colleagues do not elaborate on the role of the primary care teams in their screening programmes.^1,2 Unless the health professionals themselves appreciate the issues they are not able to help patients make an informed choice. Even when adequately informed, patients could take days, months, or even years to decide whether to be screened.

Screening programmes based in secondary care are unlikely to offer carrier screening at the time when patients feel able actively to seek it.⁴ This reinforces the argument that population based genetic screening and counselling should be easily available in general practice.⁵ This cannot happen, however, without adequate assessment of the information and skills needed by the primary care team.

N Quereshi 

Department of General Practice, Medical School, Queen's Medical Centre, Nottingham NG7 2UH.

1. Super M, Schwarz MJ, Malone G, Roberts T, Haworth A, Dermody G. Active cascade testing for carriers of cystic fibrosis gene. BMJ 1994;308:1462-8. (4 June.)
2. Livingstone J, Axton RA, Gilfillan A, Mennie M, Compton M, Liston WA, et al. Antenatal screening for cystic fibrosis: a trial of the couple model. BMJ 1994;308:1459-62. (4 June.)
3. Varekamp I, Suurmeijer TPBM, Brocker-Vriends AHJT, van Dijck H, Smit C, Rosendaal FR, et al. Carrier testing and prenatal diagnosis for haemophilia: experiences and attitudes of 549 potential and obligate carrier. Am J Med Genet 1990;37:147-54. [Medline]
4. Raeburn S. Screening for carriers of cystic fibrosis. BMJ 1994;308:1451-2. (4 June.) [Free Full Text]
5. Qureshi N, Raeburn JA. Clinical genetics meets primary care. BMJ 1993;307:816-7.

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Related Article

Antenatal screening for cystic fibrosis: a trial of the couple model

J Livingstone, R A Axton, A Gilfillan, M Mennie, M Compton, W A Liston, A A Calder, A J Gordon, and D J H Brock
BMJ 1994 308: 1459-1462. [Abstract] [Full Text]

This article has been cited by other articles:

• Super, M, Schwarz, M J, Malone, G, Roberts, T, Haworth, A, Dermody, G, Brun, J, Magnay, D (1994). Screening for cystic fibrosis Should begin with cascade screening. BMJ 309: 877c-878 [Full text]