490 47 Med Genet 1992; 29: 490-491
Attitudes towards prenatal diagnosis and carrier screening for cystic fibrosis among the parents of patients in a paediatric cystic fibrosis clinic Eila K Watson, Joanna Marchant, Andrew Bush, Bob Williamson Abstract The parents of all children attending the Royal Brompton National Heart and Lung Hospital cystic fibrosis paediatric clinic were asked to complete an anonymous postal questionnaire addressing attitudes towards prenatal diagnosis and population carrier screening for cystic fibrosis (CF); 65% (170/261) of parents responded. Of the respondents, 92% would support the introduction of a population screening test to detect carriers of CF and 19% felt such a test should be mandatory. A total of 64% of CF parents felt they would choose not to have any further children in the knowledge that they were both carriers, 74% would choose to have a prenatal test if they became pregnant, 44% would consider terminating an affected pregnancy, 33% would not, and 23% were unsure. Overall, 72% of respondents indicated they would choose to avoid having a further child with CF either by not having further children or by terminating an affected pregnancy.
London SW3. J Marchant A Bush
Cystic fibrosis is the most common serious recessively inherited disorder in Britain affecting around 1 in every 2500 live births and with a carrier incidence of approximately 1 in 25. The disorder is characterised by abnormal secretions of the exocrine glands causing chronic pulmonary disease and pancreatic insuffliciency. The gene responsible for cystic fibrosis (cystic fibrosis transmembrane regulator) was isolated in 1989.' Characterisation of the gene has shown one major mutation (AF508) and numerous rarer mutations, many of which have been reported in only one or two families worldwide. The AF508 mutation accounts for approximately 70% of CF chromosomes throughout northern European populations. In Britain, the AF508 mutation accounts for between 75 to 80% of CF chromosomes.2 Three additional mutations (G551D, G542X, and 621 + 1 G-*T) together account for a further 5 to 7% of British CF chromosomes (unpublished data from this laboratory). It is therefore possible to detect approximately 85% of all CF carriers in Britain and the test can be done simply by applying the polymer-
Correspondence
ase
Regional DNA Laboratory, Department of Biochemistry and Molecular Genetics, St Mary's Hospital Medical School, Norfolk Place, London W2 1PG. E K Watson R Williamson
Royal Brompton National Heart and Lung Hospital,
Sydney Street,
to
chain reaction to either a small blood or a mouthwash sample.3 The advantages and disadvantages of intro-
Ms Watson. Received 14 October 1991.
sample
Revised version accepted 5 December 1991.
ducing
a
general population screening
test to
identify CF carriers have been discussed elsewhere.4 The aim of such a programme would be to identify carrier couples before the birth of an affected child and to provide such couples with maximum reproductive choice. Currently, several pilot projects, including our own,4 are running to assess the laboratory, educational, and counselling requirements of a carrier screening programme. It is also important to investigate the extent to which the reproductive decisions of CF parents are influenced by their knowledge of genetic risk. This survey, which expands upon a previous report in 1989,5 considers the attitudes of those most involved with cystic fibrosis to give an indication of the issues which must be considered when the possibility of a national CF screening programme is discussed. Methods Questionnaires (appendix) with a covering letter were sent to 135 addresses comprising the home addresses of every patient attending the clinic. (The questionnaire was first approved by the Royal Brompton National Heart and Lung hospital ethical committee.) A questionnaire for both parents was sent to 126 addresses and for single parents to nine addresses (eight mothers, one father). A total of 134 females and 127 males was contacted. A reminder letter and second questionnaire were sent to households where neither parent had responded within eight weeks.
Results After the initial contact, at least one parent from 79 households responded. A further 18 households responded to the reminder letter. Overall, 72% of households (97/135) and 65% of subjects (170/261) responded. The female response rate was 69% (92/134) and the male response rate 61% (77/127). In the analysis which follows, the responses of individual persons rather than families are considered. Responders were characterised in terms of social class (classified according to OCPCS classification system), religion, and number of children with and without CF (table 1). A total of 92% of subjects (156/169) indicated they would support the introduction of a population screening test to detect carriers of CF, 2% (four persons) would not (one of whom reasoned that the money used for screening purposes would detract from research into treatments for CF sufferers), and 6% (nine) were unsure. The responses to the
Attitudes towards prenatal diagnosis and carrier screening for cystic fibrosis among the parents of patients in a paediatric cystic fibrosis clinic
491
Table 1 Characteristics of the survey population.
Three in every four of this group of parents would request prenatal diagnosis in a future Social class (83% responses classified) 27% (38/141) I pregnancy. After the diagnosis of an affected 24% (34/141) II pregnancy almost one half would consider a 11% (15/141) IIInm 29% (41/141) IIIm termination, one third would not, and the 9% (13/141) IV remainder were unsure. Similar attitudes toReligion prenatal diagnosis and abortion were wards 55% (93/169) C/E 28% (47/169) Roman Catholic reported in a study involving CF parents in 1% (2/169) Jewish Wales/West Midlands.6 Overall, 72% (122/ 3% (5/169) Hindu Muslim 169) of respondents in this survey would 4% (6/169) Other to avoid having a further child with CF choose 9% (16/169) None not having more children or by by either No of affected children 1 CF child opting for prenatal diagnosis and selective ter89% (148/1167) > 1 CF child 11% (19/167) mination. The large majority of this group No of unaffected children believes that the introduction of a population 0 unaffected 35% (59/170) screening test to detect CF carriers would be 1 unaffected 39% (66/170) > 1 unaffected 26% (45/170) desirable. The attitudes of CF families should be considered along with the outcome of pilot carrier screening programmes when the issues of questions regarding reproductive decisions are screening are discussed. There is clearly suppresented in table 2. Overall, 64% (98) of port for community approaches to genetic testparents felt that they might not have any ing and education among the families of those further children knowing the risk of CF, 74% with the disease and it is unlikely that they (118) would request prenatal diagnosis in a would feel disadvantaged were there to be an future pregnancy, and 44% (70) indicated they active and widely based programme of CF would consider terminating an affected preg- carrier testing. nancy. Of the 26 respondents planning a 1 Kerem BS, Rommens JM, Buchanan JA, et al. Identification further pregnancy, 54% (14) would consider of the cystic fibrosis gene: genetic analysis. Science 1989;245: 1073-80. terminating an affected pregnancy as comEK, Mayall ES, Simova L, et al. The incidence of pared to 41% (54) of the group who were 2 Watson AF508 CF mutation and associated haplotypes in a sample of English families. Hum Genet 1990;85:435-6. either not planning further children or did not N, Stanier P, Williamson R. A unique non-invasive know, although this difference does not reach 3 Lench method to obtain DNA for single gene analysis. Lancet 1988;ii: 1356-8. significance (X2= 1 48, p=0 224) (table 2). EK, Mayall E, Chapple J, et al. Screening for Similarly, a higher proportion of the group 4 Watson carriers of cystic fibrosis through primary health care BMJ 1991 ;303:504-7. to services. compared children who have no unaffected EK, Williamson R, Chapple J. Attitudes to carrier those who have at least one unaffected child 5 Watson screening for cystic fibrosis. Br J Gen Pract 1991;41:23740. would consider terminating an affected pregLN, Goodchild MC, Ryley HC, Harper PS. Attinancy (51% (27) v 40% (43)) although again 6 Al-Jader tudes of parents of cystic fibrosis children towards neonatal screening and antenatal diagnosis. Clin Genet 1990;38:460this difference does not reach significance 5.
(X2= 1-67, p=0 197) (table 2). Discussion These data represent the views on prenatal diagnosis and population carrier screening for CF of a group of subjects who have direct experience of CF. More than one half of the respondents felt they would choose not to have any further children in the knowledge that both they and their partner are CF carriers.
Table 2 Reproductive attitudes of CF parents. Yes Do you think you may choose not to have any more children because you know both you and your partner are 64% (98/153) CF carriers? Would you choose to have a prenatal test to determine whether or not a future pregnancy is affected 74% (118/159) by CF? Would you consider terminating an affected pregnancy? 44% (70/160) 1 Overall response (96% response) 54% (14/26) 2 (a) If planning more children (b) If unsure or not planning more 41% (54/132) children 3 (a) If have one or more child who 40% (43/107) does not have CF (b) If have no children without 51% (27/53) CF
No
Don't know
29% (45/153)
6% (10/153)
17% (27/159)
9% (14/159)
33% (53/160)
23% (37/160)
27% (7/26)
19% (5/26)
35% (46/132)
24% (32/132)
36% (39/107)
23% (25/107)
26% (14/53)
23% (12/53)
Appendix-Questionnaire. (Please tick the appropriate boxes) (1) Sex: Male ( ) Female( ) Roman Catholic (2) Religion: C of E/Protestant ( ) None Hindu ( ) Muslim ( ) Jewish ( ) Others-please specify. (3) What is your occupation? (4) What relationship are you to the person in your family with cystic fibrosis? Other (please specify) Father ( ) Mother ( ) (5) How many children do you have? have with CF? do How children you many (6) (7) What age is/are your affected child(ren)? (8) Are you planning to have any more children? Don't know( ) No ( ) Yes( ) (10) Do you consider the 1 in 4 risk of carrier couples having a CF child to be high? Don't know( ) No ( ) Yes( ) (11) Do you think that for carrier couples a 3 in 4 chance of having a normal child is acceptable? Don't know( ) No ( ) Yes( ) (12) Do you think a population carrier screening test should be voluntary? Don't know( ) No( ) Yes( ) (13) Do you think you may choose not to have any more children because you know both you and your partner are CF carriers? Don't know( ) No( ) Yes( ) (14) Would you choose to have a prenatal test to determine whether or not a future pregnancy is affected by CF? Don't know( ) No ( ) Yes( ) (15) Would you consider terminating an affected pregnancy? No ( ) Don't know( ) Yes( ) (16) When do you think might be the most suitable time for testing? Before marriage At school ( ) At birth ( ) When pregnant When planning a family ( ) ( ) Not at all( ) (17) Please add any additional comments you would like to make in the space below.
Attitudes towards prenatal diagnosis and carrier screening for cystic fibrosis among the parents of patients in a paediatric cystic fibrosis clinic Eila K Watson, Joanna Marchant, Andrew Bush, Bob Williamson Abstract The parents of all children attending the Royal Brompton National Heart and Lung Hospital cystic fibrosis paediatric clinic were asked to complete an anonymous postal questionnaire addressing attitudes towards prenatal diagnosis and population carrier screening for cystic fibrosis (CF); 65% (170/261) of parents responded. Of the respondents, 92% would support the introduction of a population screening test to detect carriers of CF and 19% felt such a test should be mandatory. A total of 64% of CF parents felt they would choose not to have any further children in the knowledge that they were both carriers, 74% would choose to have a prenatal test if they became pregnant, 44% would consider terminating an affected pregnancy, 33% would not, and 23% were unsure. Overall, 72% of respondents indicated they would choose to avoid having a further child with CF either by not having further children or by terminating an affected pregnancy.
London SW3. J Marchant A Bush
Cystic fibrosis is the most common serious recessively inherited disorder in Britain affecting around 1 in every 2500 live births and with a carrier incidence of approximately 1 in 25. The disorder is characterised by abnormal secretions of the exocrine glands causing chronic pulmonary disease and pancreatic insuffliciency. The gene responsible for cystic fibrosis (cystic fibrosis transmembrane regulator) was isolated in 1989.' Characterisation of the gene has shown one major mutation (AF508) and numerous rarer mutations, many of which have been reported in only one or two families worldwide. The AF508 mutation accounts for approximately 70% of CF chromosomes throughout northern European populations. In Britain, the AF508 mutation accounts for between 75 to 80% of CF chromosomes.2 Three additional mutations (G551D, G542X, and 621 + 1 G-*T) together account for a further 5 to 7% of British CF chromosomes (unpublished data from this laboratory). It is therefore possible to detect approximately 85% of all CF carriers in Britain and the test can be done simply by applying the polymer-
Correspondence
ase
Regional DNA Laboratory, Department of Biochemistry and Molecular Genetics, St Mary's Hospital Medical School, Norfolk Place, London W2 1PG. E K Watson R Williamson
Royal Brompton National Heart and Lung Hospital,
Sydney Street,
to
chain reaction to either a small blood or a mouthwash sample.3 The advantages and disadvantages of intro-
Ms Watson. Received 14 October 1991.
sample
Revised version accepted 5 December 1991.
ducing
a
general population screening
test to
identify CF carriers have been discussed elsewhere.4 The aim of such a programme would be to identify carrier couples before the birth of an affected child and to provide such couples with maximum reproductive choice. Currently, several pilot projects, including our own,4 are running to assess the laboratory, educational, and counselling requirements of a carrier screening programme. It is also important to investigate the extent to which the reproductive decisions of CF parents are influenced by their knowledge of genetic risk. This survey, which expands upon a previous report in 1989,5 considers the attitudes of those most involved with cystic fibrosis to give an indication of the issues which must be considered when the possibility of a national CF screening programme is discussed. Methods Questionnaires (appendix) with a covering letter were sent to 135 addresses comprising the home addresses of every patient attending the clinic. (The questionnaire was first approved by the Royal Brompton National Heart and Lung hospital ethical committee.) A questionnaire for both parents was sent to 126 addresses and for single parents to nine addresses (eight mothers, one father). A total of 134 females and 127 males was contacted. A reminder letter and second questionnaire were sent to households where neither parent had responded within eight weeks.
Results After the initial contact, at least one parent from 79 households responded. A further 18 households responded to the reminder letter. Overall, 72% of households (97/135) and 65% of subjects (170/261) responded. The female response rate was 69% (92/134) and the male response rate 61% (77/127). In the analysis which follows, the responses of individual persons rather than families are considered. Responders were characterised in terms of social class (classified according to OCPCS classification system), religion, and number of children with and without CF (table 1). A total of 92% of subjects (156/169) indicated they would support the introduction of a population screening test to detect carriers of CF, 2% (four persons) would not (one of whom reasoned that the money used for screening purposes would detract from research into treatments for CF sufferers), and 6% (nine) were unsure. The responses to the
Attitudes towards prenatal diagnosis and carrier screening for cystic fibrosis among the parents of patients in a paediatric cystic fibrosis clinic
491
Table 1 Characteristics of the survey population.
Three in every four of this group of parents would request prenatal diagnosis in a future Social class (83% responses classified) 27% (38/141) I pregnancy. After the diagnosis of an affected 24% (34/141) II pregnancy almost one half would consider a 11% (15/141) IIInm 29% (41/141) IIIm termination, one third would not, and the 9% (13/141) IV remainder were unsure. Similar attitudes toReligion prenatal diagnosis and abortion were wards 55% (93/169) C/E 28% (47/169) Roman Catholic reported in a study involving CF parents in 1% (2/169) Jewish Wales/West Midlands.6 Overall, 72% (122/ 3% (5/169) Hindu Muslim 169) of respondents in this survey would 4% (6/169) Other to avoid having a further child with CF choose 9% (16/169) None not having more children or by by either No of affected children 1 CF child opting for prenatal diagnosis and selective ter89% (148/1167) > 1 CF child 11% (19/167) mination. The large majority of this group No of unaffected children believes that the introduction of a population 0 unaffected 35% (59/170) screening test to detect CF carriers would be 1 unaffected 39% (66/170) > 1 unaffected 26% (45/170) desirable. The attitudes of CF families should be considered along with the outcome of pilot carrier screening programmes when the issues of questions regarding reproductive decisions are screening are discussed. There is clearly suppresented in table 2. Overall, 64% (98) of port for community approaches to genetic testparents felt that they might not have any ing and education among the families of those further children knowing the risk of CF, 74% with the disease and it is unlikely that they (118) would request prenatal diagnosis in a would feel disadvantaged were there to be an future pregnancy, and 44% (70) indicated they active and widely based programme of CF would consider terminating an affected preg- carrier testing. nancy. Of the 26 respondents planning a 1 Kerem BS, Rommens JM, Buchanan JA, et al. Identification further pregnancy, 54% (14) would consider of the cystic fibrosis gene: genetic analysis. Science 1989;245: 1073-80. terminating an affected pregnancy as comEK, Mayall ES, Simova L, et al. The incidence of pared to 41% (54) of the group who were 2 Watson AF508 CF mutation and associated haplotypes in a sample of English families. Hum Genet 1990;85:435-6. either not planning further children or did not N, Stanier P, Williamson R. A unique non-invasive know, although this difference does not reach 3 Lench method to obtain DNA for single gene analysis. Lancet 1988;ii: 1356-8. significance (X2= 1 48, p=0 224) (table 2). EK, Mayall E, Chapple J, et al. Screening for Similarly, a higher proportion of the group 4 Watson carriers of cystic fibrosis through primary health care BMJ 1991 ;303:504-7. to services. compared children who have no unaffected EK, Williamson R, Chapple J. Attitudes to carrier those who have at least one unaffected child 5 Watson screening for cystic fibrosis. Br J Gen Pract 1991;41:23740. would consider terminating an affected pregLN, Goodchild MC, Ryley HC, Harper PS. Attinancy (51% (27) v 40% (43)) although again 6 Al-Jader tudes of parents of cystic fibrosis children towards neonatal screening and antenatal diagnosis. Clin Genet 1990;38:460this difference does not reach significance 5.
(X2= 1-67, p=0 197) (table 2). Discussion These data represent the views on prenatal diagnosis and population carrier screening for CF of a group of subjects who have direct experience of CF. More than one half of the respondents felt they would choose not to have any further children in the knowledge that both they and their partner are CF carriers.
Table 2 Reproductive attitudes of CF parents. Yes Do you think you may choose not to have any more children because you know both you and your partner are 64% (98/153) CF carriers? Would you choose to have a prenatal test to determine whether or not a future pregnancy is affected 74% (118/159) by CF? Would you consider terminating an affected pregnancy? 44% (70/160) 1 Overall response (96% response) 54% (14/26) 2 (a) If planning more children (b) If unsure or not planning more 41% (54/132) children 3 (a) If have one or more child who 40% (43/107) does not have CF (b) If have no children without 51% (27/53) CF
No
Don't know
29% (45/153)
6% (10/153)
17% (27/159)
9% (14/159)
33% (53/160)
23% (37/160)
27% (7/26)
19% (5/26)
35% (46/132)
24% (32/132)
36% (39/107)
23% (25/107)
26% (14/53)
23% (12/53)
Appendix-Questionnaire. (Please tick the appropriate boxes) (1) Sex: Male ( ) Female( ) Roman Catholic (2) Religion: C of E/Protestant ( ) None Hindu ( ) Muslim ( ) Jewish ( ) Others-please specify. (3) What is your occupation? (4) What relationship are you to the person in your family with cystic fibrosis? Other (please specify) Father ( ) Mother ( ) (5) How many children do you have? have with CF? do How children you many (6) (7) What age is/are your affected child(ren)? (8) Are you planning to have any more children? Don't know( ) No ( ) Yes( ) (10) Do you consider the 1 in 4 risk of carrier couples having a CF child to be high? Don't know( ) No ( ) Yes( ) (11) Do you think that for carrier couples a 3 in 4 chance of having a normal child is acceptable? Don't know( ) No ( ) Yes( ) (12) Do you think a population carrier screening test should be voluntary? Don't know( ) No( ) Yes( ) (13) Do you think you may choose not to have any more children because you know both you and your partner are CF carriers? Don't know( ) No( ) Yes( ) (14) Would you choose to have a prenatal test to determine whether or not a future pregnancy is affected by CF? Don't know( ) No ( ) Yes( ) (15) Would you consider terminating an affected pregnancy? No ( ) Don't know( ) Yes( ) (16) When do you think might be the most suitable time for testing? Before marriage At school ( ) At birth ( ) When pregnant When planning a family ( ) ( ) Not at all( ) (17) Please add any additional comments you would like to make in the space below.
