- Email: [email protected]
Implementing prenatal screening for cystic fibrosis in routine obstetric practice
American Journal of Obstetrics and Gynecology (2005) 192, 527e34
www.ajog.org
Implementing prenatal screening for cystic fibrosis in routine obstetric practice Melissa H. Fries, Col, USAF MC,a,* Michael Bashford, Lt Col, USAF MC,b Mark Nunes, MDc Uniformed Services University of the Health Sciences, Bethesda, Md,a Air Force Medical Genetics Center, Keesler AFB, Miss,b and INOVA Medical Center, Fairfax, Vac Received for publication April 9, 2004; revised June 29, 2004; accepted July 15, 2004
KEY WORDS Prenatal screening Cystic fibrosis Genetic counseling
Objective: The purpose of this study was to assess the outcome of the type of prescreening counseling on choices for prenatal cystic fibrosis screening. Study design: From October 2001 to November 2002, regardless of ethnicity, all prenatal patients (n = 855) at the Air Force Medical Genetics Center, Biloxi, Miss, received education on prenatal screening for cystic fibrosis by group genetic counseling either by a presentation by a genetics professional (430 patients) or by a similar audiovisual presentation only (425 patients). A combination pretest/posttest document was used to evaluate learning and served as the consent. Partner testing was recommended for mutation-positive patients. Results: Fifty-eight percent patients requested screening, of whom 68% were white. Regardless of the type of counseling, patients showed an improvement in knowledge based on pre- and posttest scores. There was no significant difference in choices to undergo screening on the basis of counseling method. Fifteen mutation carriers were identified. Only 6 partners of mutationpositive patients were available and consented to be tested. To date, no infants have been born with cystic fibrosis. Conclusion: Audio-visual counseling is an effective means to educate patients about genetic screening and does not require a trained genetics professional to administer. Partner testing in mobile populations may prove problematic. Ó 2005 Elsevier Inc. All rights reserved.
Presented as a poster at the Armed Forces District Meeting, American College of Obstetricians and Gynecologists, October 19-22, 2002, Honolulu, Hawaii, and at the American College of Medical Genetics Annual Meeting, March 13-16, 2003, San Diego, Calif. The opinions expressed in this article are those of the authors and are not intended to represent the opinions or policies of the United States Air Force or the Department of Defense. * Reprint requests: Col Melissa H. Fries, Director, Medical Genetics, Dept. APG, 4301 Jones Bridge Road, Bethesda, MD 20814. E-mail: [email protected] 0002-9378/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.07.028
Cystic fibrosis (CF) is the most common lifeshortening autosomal recessive disease among the European white population, with an incidence of 1 in 3300 live births. The condition is caused by mutations in the CF transmembrane conductance regulator gene on chromosome 7, which encodes a cyclic adenosine monophosphateeregulated chloride channel in epithelial cells. Patients with CF have chronic pulmonary disease and infections, gastrointestinal and nutritional abnormalities, salt loss, and male infertility related to obstructive
528 azoospermia.1 In the past, the condition was largely fatal. Improvements in care, particularly antibiotic therapy, have resulted in substantially increased survival; recent analyses have shown that the probability of a child born after 1989 living O45 years was 80.4%.2 To date, O1200 mutations in the gene have been identified, although a single mutation, DF508, accounts for approximately 70% of the mutations in European white patients.3 The disease incidence varies with ethnic group. In populations of European white patients or Ashkenazi Jewish patients, the incidence is 1 in 3000 live births, with a carrier rate of 1 in 29 live births. The incidence is less in the Hispanic population in the United States (1/8500 live births; carrier rate, 1/46 live births); the black population in the United States (1/17,000 live births; carrier rate, 1/65 live births); and the Asian population in the United States (1/%32,400 live births; carrier rate, 1/90 live births).4,5 The probability of the detection of mutations also varies with ethnicity. Using the standard recommended mutation panel, 97% of the mutations can be identified in the Ashkenazi Jewish population, 92 % of which are in the European white population. Only 81% of the mutations can be identified in the black population, and 72% of the mutation scan be identified in the Hispanic population.5-8 Because of the high CF carrier frequency and mutation detection rate in certain ethnic groups, carrier screening by genetic testing is now considered a reasonable option to provide information to at-risk couples. In April 1997, a consensus statement that was issued by the National Institutes of Health recommended CF carrier screening be offered to adults with a family history of CF, partners of individuals with CF, couples planning a pregnancy, and couples seeking prenatal testing.9 A preliminary economic evaluation of such a screening program indicated that the averted medical-care cost for affected infants would offset approximately 74% to 78% of the costs of the screening.10 However, before implementation of these recommendations in the obstetrics and gynecology community, practice guidelines, educational materials, informed consent protocols, and laboratory standards for testing were needed.11 In October 2001, the American College of Obstetricians and Gynecologists (ACOG), in support of recommendations from the American College of Medical Genetics, advised CF screening to be offered to individuals with a family history of CF, reproductive partners of individuals with CF, or couples in whom 1 or both partners were Ashkenazi Jewish or white and were planning a pregnancy or seeking prenatal care and be made available to all patients as desired.12 This statement was accompanied by patient education pamphlets and general information for providers. A specific implementation strategy was not detailed, although sequential testing (testing the female patient first, followed by her partner if she were found to be a carrier)
Fries, Bashford, and Nunes was suggested. Our study details the outcome of a prenatal screening program for CF that was initiated at a large military medical facility with an ethnically diverse population. We studied the benefits of differing patient education protocols and identified a significant problem that arose while we were implementing our CF screening program.
Methods The Air Force Medical Genetics Center at Keesler Air Force Base, Miss, initiated a pilot program for prenatal CF screening in antepartum patients on October 17, 2001, in response to the ACOG recommendations. Because this was a clinical program to implement a new recommendation, institutional review board approval was not indicated. A sequential testing strategy was implemented, with screening offered to pregnant women at their new mothers’ orientation class. This class provided information about the process of antepartum care and general health during pregnancy and was held at the first obstetrics visit. All patients, regardless of ethnicity, received group genetic counseling about CF carrier screening and its implications and were given a combined demographic form and pretest on CF knowledge, which they completed before counseling (Figure 1). Questions regarding the demographics on the pre/posttest were answered before the patients received the group counseling. During the first 7 months of the project, the counseling was accomplished by a slide presentation that was given by a genetics professional (M.H.F.), followed by a posttest (on the reverse of their pretest) that then became part of their formal consent. Although the posttest questions were slightly different in their wording from the pretest questions, their content was largely matched question for question. The genetics professional explained the slides and answered questions. After May 2002, group counseling was provided only by the slide show made by the Air Force Medical Genetics Center, with cued narration for each slide, which was administered by a Women’s Health nurse practitioner. The practitioner did not provide any supplemental counseling regarding the testing nor answer any questions; patients completed the posttest and signed their consent forms as previously accomplished. Patients were given the ACOG pamphlet regarding prenatal screening for CF to take home for further review, although their decision for or against testing was made at the time of the group counseling. The decision to counsel all patients regardless of ethnicity was made to provide the greatest possibility for patient education and nondirective decision-making. The group format also enhanced educational efficiency. Although this approach differs somewhat from the recommendations, we felt it was most appropriate in
Fries, Bashford, and Nunes
529
Figure 1
Pre/posttest consent form for CF screening.
530
Fries, Bashford, and Nunes
Figure 1
(Continued).
Fries, Bashford, and Nunes Table I
531
Ethnicity of patients who accepted screening, stratified by counseling type Acceptance by counseling type (n)
Ethnicity
Patients counseled (n)
Patients accepting screening (n)
Professional (total counseled, 430)
Audio-visual (total counseled, 425)
SD in acceptance by counseling type
All patients White Black Hispanic Asian Ashkenazi Jewish Other/not specified
855 576 164 64 20 2 29
506 390 57 35 8 1 15
263 202 25 21 3 1 11
243 188 32 14 5 0 4
NS NS NS NS NS NS NS
(69%)* (20%)* (8%)* (2%)* (0.2%)* (3%)*
(68%)y (35%)y (55%)y (40%)y (50%)y (50%)y
NS, Not significant. * Percentage of the total group. y Percentage of each ethnic group.
Table II First pregnancy status of total patients and patients who accepted CF screening (731 responders = 85% response rate to question)
Pregnancy status
All patients (n)*
Patients accepting testing (n)y
P value
First pregnancy Not first pregnancy
289 (40%) 442 (60%)
176 (60.9%) 245 (55%)
! .03 NS
ded. Patients had been informed of this recommendation during their initial counseling process. Patients did not receive formal genetic counseling at this point, with the plan to offer formal genetic counseling and prenatal diagnosis if both parents were identified as carriers. Statistical comparison of groups on the basis of acceptance or declination of CF screening was performed using chi-squared evaluation of 2 by 2 contingency tables and 2-tailed Z test.
NS, Not significant. * N = 731. y N = 421.
Results meeting the needs of the particular ethnic mix of obstetric patients in our community. All testing was accomplished at the Air Force Medical Genetics Center at Keesler AFB. DNA was extracted from specimens in a standard fashion, and screening was accomplished with multiplex polymerase chain reaction and allele-specific oligonucleotide reverse dot blot scored by chemiluminescence. Twenty mutations were tested initially. In September 2002, the panel was expanded to include the recommended American College of Medical Genetics 25 mutation panel, which added I148T, 711C 1G>T, G85E, 3120C1G>A, 1898C1G>A, 3659delC, 2184delA, and 1078delT to the group of other mutations that were tested. Test completion time was approximately 2 weeks. If no mutations were identified, a report was generated by the genetics center and sent to the computer laboratory data system and to the patients’ obstetric files. The report indicated the patients’ postgenetic testing risk based on their ethnic background and was discussed by their obstetrics provider at the patients’ next obstetric visit. If a mutation were identified, the patient was contacted by telephone by a provider from the Air Force Medical Genetics Center laboratory, and testing from the father of the pregnancy was recommen-
In the time period of October 2001 to November 2002, a total of 855 patients were counseled, of whom 827 completed pre/posttests and 489 requested CF screening (58.2%). Mean age of those patients who requested screening was 24.6 years and of those patients who declined screening was 25.2 years. Sixty-nine percent of the counseled patients were white, of whom 68% requested testing. Table I details the ethnic background of the total number of patients, those accepting testing, and their decision to accept testing on the basis of the type of counseling and ethnicity. There was no significant difference in overall acceptance of screening when those who were counseled by audiovisual means were compared with professional counseling, which was reconfirmed when the group was stratified by ethnicity. Forty percent of the counseled patients (289/731 patients who indicated pregnancy status) were in their first pregnancy, with 60.5% of this group electing to have testing regardless of ethnic background (Table II). This was a significant increase (P !.03) in the choice for testing among those who were in their first pregnancy when compared with those patients who were not in their first pregnancy. In the group of 506 tested patients, based on their ethnic mix, a total of 15.23 mutations would have been
532 Table III
Fries, Bashford, and Nunes Pre- and postcounseling test scores Audio visual counseling (%)y
Genetics professional counseling (%)* Patients
Pretest
Posttest
P value
Pretest
Posttest
P value
Acceptors (n = 481) Decliners (n = 336)
68.3 G 17.5 64.5 G 20
86.5 G 14.8 84.4 G 14.9
.01 .01
72.0 G 20 68.7 G 22.1
80.2 G 16.0 81.8 G 14.0
.01 .01
Data are given as mean percentage of correct responses to questions G SD. * N = 418. y N = 399.
expected. Fifteen mutations were identified, of which 13 were DF508 mutations with 1 G5551D mutation and 1 DI507 mutation. All patients, regardless of their choice for genetic testing or the method of counseling, showed a significant improvement in knowledge on the basis of the results of the 9-question pre- and posttests (P !.01; Table III). Preand posttest scores were not significantly different between the groups who accepted and declined screening. In the group who accepted screening, there was a significant difference (P !.05) between the pre- and posttest scores of those who were counseled by genetics professional versus audio-visual counseling groups, with the audio-visual group having a slightly higher mean pretest score and a slightly lower posttest score. In the group who declined testing, there was no significant difference in mean pre- or posttest scores on the basis of the type of counseling. Both groups, regardless of counseling method, however, did have a significant improvement in posttest scores compared with pretest scores. The 15 patients with mutations that were identified by genetic screening were contacted by telephone by a genetics professional who discussed the significance of the test result and the importance of obtaining a blood specimen from the father of the pregnancy. Although all 15 patients were contacted multiple times, only 6 fathers ultimately consented to testing. No mutations were found in this group. The principal predictor of the success of obtaining paternal testing was marital status. Of the 9 married patients, 5 fathers submitted specimens. Of the 6 unmarried patients, only 1 father submitted a specimen. No prenatal CF diagnosis procedures were performed, because no maternal/paternal mutation couples were identified, and no carrier mothers elected to have amniocentesis in the absence of paternal testing. No infants who were born to the group of mutation-positive mothers have been diagnosed with CF either on newborn testing or by disease symptoms in the first 6 months of their lives.
Comment This pilot program was well received by patients who, from their improved posttest scores, appeared to un-
derstand the concepts and materials that were presented. The acceptance rate for testing (58%) was in alignment with other genetic screening programs for CF, which had reported a 57% to 60% test uptake rate.9 Our data show a significant increase in choice for screening in primigravid women, which indicates that populations who have a higher number of primigravid women may have a higher screen uptake rate. In addition, because of the greater likelihood that patients in the decliner group may have had other children, it is possible that the previous birth of a healthy child may alter patients’ perceptions of their risk. Pretest counseling was provided for all patients regardless of ethnicity. This was in accord with the ACOG recommendations that the test be made available to all populations.12 Not all patients in the high-risk population wished to have screening (only 68% of white patients chose screening) and some patients in lower-risk populations (approximately 35%-55% in black and Hispanic populations) desired screening. A higher proportion of Hispanic patients than was anticipated requested screening; the reasons for this are not clear and may warrant further investigation into CF screening attitudes in different ethnic groups, particularly because a cost-benefit review of prenatal CF screening in Hispanic patients anticipated a low screen uptake rate.13 Preliminary counseling placed the choice for testing with the patient. Given the increasing difficulty in the determination of ethnic background in some populations, allowing patients autonomy to determine whether they feel that screening has applicability for them eliminates the unintended exclusion of potential high-risk patients on the basis of the presumption of their ethnicity. Clearly, however, it is incumbent on counseling to advise patients on the limitations in risk reductions on the basis of their designation of ethnicity. We encountered substantial difficulty in obtaining paternal blood specimens after diagnosis of a maternal mutation. Although this is not unexpected, given the mobile military population, it is likely to be a concern in nonmilitary clinical settings as well and may be confounded by the difficulty of obtaining medical insurance coverage for the cost of paternal testing. For this reason, the timing of formal genetic counseling was changed to offering this at the point of the identification of maternal
Fries, Bashford, and Nunes carrier status alone. The counseling focused on the nature of CF, population-based risk for affected infants, the need for partner testing, and the option of amniocentesis for fetal evaluation if paternal testing were not feasible or if such testing showed a paternal mutation. For a mutation-positive mother, if the ethnicity of the unavailable partner were white (carrier risk, 1:29, with 92% likelihood for identification of carrier status), the fetal risk to be affected would be 7.9 of 1000 live births, which would justify the 5 in 1000 live birth risk of amniocentesis without even testing the father. Couple screening, rather than sequential screening, could preclude the difficulty of obtaining paternal testing subsequent to maternal testing but may be cost prohibitive as a general screening policy or may be perceived as a limitation to patients whose partners are unavailable. If the partner were able to anticipate that he might not be available for future testing, couple screening rather than sequential screening might be valuable on a case-by-case basis. Obtaining paternal specimens continues to be preferable at our institution instead of moving a priori to prenatal diagnosis on the basis of maternal carrier status information alone. However, the option of amniocentesis for maternal carriers with unobtainable paternal testing may be an unexpected, but necessary, additional factor in the overall screening process. Use of trained genetics professionals (such as genetic counselors, geneticists, maternal fetal medicine specialists, or genetic nurse specialists) is felt to be optimal for genetic counseling, but such providers are rare and may be unavailable at many facilities. A 2000 to 2001 survey of 190 family physicians from around the United States indicated that 23% of the physicians found it ‘‘very difficult or impossible’’ for their patients to get a consultation with a genetics professional (personal communication, Dr Louise Acheson, Case Western Reserve University, September 1, 2003). This difficulty, in association with an expanding potential for future genetic testing, will require innovative education strategies beyond increasing the numbers of formal genetic counselors and clinical geneticists who are trained annually. Our study, which was based on pre- and posttest studies, found that patients were counseled effectively about the risks and benefits of CF screening in a group setting that used either a dedicated genetic counselor or an audio-visual presentation. The difference in pre- and posttest scores of those patients who accepted testing compared by type of counseling did show a slightly higher pretest score in those who received audio-visual counseling, with a slightly lower posttest score; this difference was not seen when the group who declined testing was compared. The explanation for this finding is unclear, and its clinical relevance is uncertain, given that both counseled groups showed a significant increase in knowledge by scores. We did observe that, for those
533 patients who received counseling from a genetics professional, sufficient time was allotted before the slide presentation for patients to complete their pretest. This time was not always included when the audiovisual counseling was given, and patients were observed to be completing their pretest while they were watching the slide show, thus potentially increasing their pretest scores. After this observation, more time was allowed for the completion of the pretest before the audiovisual presentation was started. The choice to have a genetic test does not always reflect an understanding of the significance of the test, and each counseling method may have benefits to different patients, on the basis of learning style. It is possible that an audiovisual presentation may provide greater clarity to some patients and enable them to understand better the implications of testing, particularly if decisions made by face-to-face counseling could be influenced positively or negatively by the personality of the counselor. Use of audio-visual programs could reduce the cost of counseling as part of CF screening programs as well. The process of panethnic education by audio-visual counseling would be amenable to web-based patient education methods, either in a group or an individual computer or kiosk educational process. Computerized educational programs have the advantage of self-pacing but do require language and computer literacy. The continued use of the CF screening audio-visual materials in a variety of settings will allow the further assessment of the value of this counseling approach.
References 1. Rosenstein BJ, Zeitlin PL. Cystic fibrosis. Lancet 1998;375:277-80. 2. Frederiksen B, Lanng S, Koch C, Hoiby N. Improved survival in the Danish center-treated cystic fibrosis patients: results of aggressive treatment. Pediatr Pulmonol 1996;21:153-8. 3. NIH Consensus Development Conference Statement on Genetic Testing for Cystic Fibrosis. Genetic testing for cystic fibrosis. Arch Intern Med 1999;159:1529-39. 4. Heim RA, Sugarman EA, Allitto BA. Improved detection of cystic fibrosis mutations in the heterogeneous US population using an expanded, pan-ethnic mutation panel. Genet Med 2001;3:168-76. 5. Richards CS, Bradley LA, Amos J, Allitto B, Grody WW, Maddalena A, et al. Standards and guidelines for CFTR mutation testing. Genet Med 2002;4:379-91. 6. Macek M Jr, Mackova A, Hamosh A, Hilman BC, Selden RF, Lucotte G, et al. Identification of common cystic fibrosis mutations in African-Americans with cystic fibrosis increases the detection rate to 75%. Am J Hum Genet 1997;60:1122-7. 7. The Cystic Fibrosis Genetic Analysis Consortium. Population variation of common cystic fibrosis mutations. Hum Mutat 1994;4:167-77. 8. Strom CM, Huang D, Buller A, Redman J, Crossley B, Anderson B, et al. Cystic fibrosis screening using the college panel: platform comparison and lessons learned from the first 20,000 samples. Genet Med 2002;4:289-96.
534 9. Genetic testing for cystic fibrosis. NIH consensus statement. 1997;15:1-37. 10. Rowley PT, Loader S, Kaplan RM. Prenatal screening for cystic fibrosis carriers: an economic evaluation. Am J Hum Genet 1998;63:1160-74. 11. Mennuti MT, Thomson E, Press N. Screening for cystic fibrosis carrier state. Obstet Gynecol 1999;93:456-61.
Fries, Bashford, and Nunes 12. American College of Obstetricians and Gynecologists; American College of Medical Genetics. Preconception and prenatal carrier screening for cystic fibrosis: clinical and laboratory guidelines. 2001. 13. Doyle NM, Gardner MO. Prenatal cystic fibrosis screening in Mexican Americans: an economic analysis. Am J Obstet Gynecol 2003;189:769-74.
www.ajog.org
Implementing prenatal screening for cystic fibrosis in routine obstetric practice Melissa H. Fries, Col, USAF MC,a,* Michael Bashford, Lt Col, USAF MC,b Mark Nunes, MDc Uniformed Services University of the Health Sciences, Bethesda, Md,a Air Force Medical Genetics Center, Keesler AFB, Miss,b and INOVA Medical Center, Fairfax, Vac Received for publication April 9, 2004; revised June 29, 2004; accepted July 15, 2004
KEY WORDS Prenatal screening Cystic fibrosis Genetic counseling
Objective: The purpose of this study was to assess the outcome of the type of prescreening counseling on choices for prenatal cystic fibrosis screening. Study design: From October 2001 to November 2002, regardless of ethnicity, all prenatal patients (n = 855) at the Air Force Medical Genetics Center, Biloxi, Miss, received education on prenatal screening for cystic fibrosis by group genetic counseling either by a presentation by a genetics professional (430 patients) or by a similar audiovisual presentation only (425 patients). A combination pretest/posttest document was used to evaluate learning and served as the consent. Partner testing was recommended for mutation-positive patients. Results: Fifty-eight percent patients requested screening, of whom 68% were white. Regardless of the type of counseling, patients showed an improvement in knowledge based on pre- and posttest scores. There was no significant difference in choices to undergo screening on the basis of counseling method. Fifteen mutation carriers were identified. Only 6 partners of mutationpositive patients were available and consented to be tested. To date, no infants have been born with cystic fibrosis. Conclusion: Audio-visual counseling is an effective means to educate patients about genetic screening and does not require a trained genetics professional to administer. Partner testing in mobile populations may prove problematic. Ó 2005 Elsevier Inc. All rights reserved.
Presented as a poster at the Armed Forces District Meeting, American College of Obstetricians and Gynecologists, October 19-22, 2002, Honolulu, Hawaii, and at the American College of Medical Genetics Annual Meeting, March 13-16, 2003, San Diego, Calif. The opinions expressed in this article are those of the authors and are not intended to represent the opinions or policies of the United States Air Force or the Department of Defense. * Reprint requests: Col Melissa H. Fries, Director, Medical Genetics, Dept. APG, 4301 Jones Bridge Road, Bethesda, MD 20814. E-mail: [email protected] 0002-9378/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.07.028
Cystic fibrosis (CF) is the most common lifeshortening autosomal recessive disease among the European white population, with an incidence of 1 in 3300 live births. The condition is caused by mutations in the CF transmembrane conductance regulator gene on chromosome 7, which encodes a cyclic adenosine monophosphateeregulated chloride channel in epithelial cells. Patients with CF have chronic pulmonary disease and infections, gastrointestinal and nutritional abnormalities, salt loss, and male infertility related to obstructive
528 azoospermia.1 In the past, the condition was largely fatal. Improvements in care, particularly antibiotic therapy, have resulted in substantially increased survival; recent analyses have shown that the probability of a child born after 1989 living O45 years was 80.4%.2 To date, O1200 mutations in the gene have been identified, although a single mutation, DF508, accounts for approximately 70% of the mutations in European white patients.3 The disease incidence varies with ethnic group. In populations of European white patients or Ashkenazi Jewish patients, the incidence is 1 in 3000 live births, with a carrier rate of 1 in 29 live births. The incidence is less in the Hispanic population in the United States (1/8500 live births; carrier rate, 1/46 live births); the black population in the United States (1/17,000 live births; carrier rate, 1/65 live births); and the Asian population in the United States (1/%32,400 live births; carrier rate, 1/90 live births).4,5 The probability of the detection of mutations also varies with ethnicity. Using the standard recommended mutation panel, 97% of the mutations can be identified in the Ashkenazi Jewish population, 92 % of which are in the European white population. Only 81% of the mutations can be identified in the black population, and 72% of the mutation scan be identified in the Hispanic population.5-8 Because of the high CF carrier frequency and mutation detection rate in certain ethnic groups, carrier screening by genetic testing is now considered a reasonable option to provide information to at-risk couples. In April 1997, a consensus statement that was issued by the National Institutes of Health recommended CF carrier screening be offered to adults with a family history of CF, partners of individuals with CF, couples planning a pregnancy, and couples seeking prenatal testing.9 A preliminary economic evaluation of such a screening program indicated that the averted medical-care cost for affected infants would offset approximately 74% to 78% of the costs of the screening.10 However, before implementation of these recommendations in the obstetrics and gynecology community, practice guidelines, educational materials, informed consent protocols, and laboratory standards for testing were needed.11 In October 2001, the American College of Obstetricians and Gynecologists (ACOG), in support of recommendations from the American College of Medical Genetics, advised CF screening to be offered to individuals with a family history of CF, reproductive partners of individuals with CF, or couples in whom 1 or both partners were Ashkenazi Jewish or white and were planning a pregnancy or seeking prenatal care and be made available to all patients as desired.12 This statement was accompanied by patient education pamphlets and general information for providers. A specific implementation strategy was not detailed, although sequential testing (testing the female patient first, followed by her partner if she were found to be a carrier)
Fries, Bashford, and Nunes was suggested. Our study details the outcome of a prenatal screening program for CF that was initiated at a large military medical facility with an ethnically diverse population. We studied the benefits of differing patient education protocols and identified a significant problem that arose while we were implementing our CF screening program.
Methods The Air Force Medical Genetics Center at Keesler Air Force Base, Miss, initiated a pilot program for prenatal CF screening in antepartum patients on October 17, 2001, in response to the ACOG recommendations. Because this was a clinical program to implement a new recommendation, institutional review board approval was not indicated. A sequential testing strategy was implemented, with screening offered to pregnant women at their new mothers’ orientation class. This class provided information about the process of antepartum care and general health during pregnancy and was held at the first obstetrics visit. All patients, regardless of ethnicity, received group genetic counseling about CF carrier screening and its implications and were given a combined demographic form and pretest on CF knowledge, which they completed before counseling (Figure 1). Questions regarding the demographics on the pre/posttest were answered before the patients received the group counseling. During the first 7 months of the project, the counseling was accomplished by a slide presentation that was given by a genetics professional (M.H.F.), followed by a posttest (on the reverse of their pretest) that then became part of their formal consent. Although the posttest questions were slightly different in their wording from the pretest questions, their content was largely matched question for question. The genetics professional explained the slides and answered questions. After May 2002, group counseling was provided only by the slide show made by the Air Force Medical Genetics Center, with cued narration for each slide, which was administered by a Women’s Health nurse practitioner. The practitioner did not provide any supplemental counseling regarding the testing nor answer any questions; patients completed the posttest and signed their consent forms as previously accomplished. Patients were given the ACOG pamphlet regarding prenatal screening for CF to take home for further review, although their decision for or against testing was made at the time of the group counseling. The decision to counsel all patients regardless of ethnicity was made to provide the greatest possibility for patient education and nondirective decision-making. The group format also enhanced educational efficiency. Although this approach differs somewhat from the recommendations, we felt it was most appropriate in
Fries, Bashford, and Nunes
529
Figure 1
Pre/posttest consent form for CF screening.
530
Fries, Bashford, and Nunes
Figure 1
(Continued).
Fries, Bashford, and Nunes Table I
531
Ethnicity of patients who accepted screening, stratified by counseling type Acceptance by counseling type (n)
Ethnicity
Patients counseled (n)
Patients accepting screening (n)
Professional (total counseled, 430)
Audio-visual (total counseled, 425)
SD in acceptance by counseling type
All patients White Black Hispanic Asian Ashkenazi Jewish Other/not specified
855 576 164 64 20 2 29
506 390 57 35 8 1 15
263 202 25 21 3 1 11
243 188 32 14 5 0 4
NS NS NS NS NS NS NS
(69%)* (20%)* (8%)* (2%)* (0.2%)* (3%)*
(68%)y (35%)y (55%)y (40%)y (50%)y (50%)y
NS, Not significant. * Percentage of the total group. y Percentage of each ethnic group.
Table II First pregnancy status of total patients and patients who accepted CF screening (731 responders = 85% response rate to question)
Pregnancy status
All patients (n)*
Patients accepting testing (n)y
P value
First pregnancy Not first pregnancy
289 (40%) 442 (60%)
176 (60.9%) 245 (55%)
! .03 NS
ded. Patients had been informed of this recommendation during their initial counseling process. Patients did not receive formal genetic counseling at this point, with the plan to offer formal genetic counseling and prenatal diagnosis if both parents were identified as carriers. Statistical comparison of groups on the basis of acceptance or declination of CF screening was performed using chi-squared evaluation of 2 by 2 contingency tables and 2-tailed Z test.
NS, Not significant. * N = 731. y N = 421.
Results meeting the needs of the particular ethnic mix of obstetric patients in our community. All testing was accomplished at the Air Force Medical Genetics Center at Keesler AFB. DNA was extracted from specimens in a standard fashion, and screening was accomplished with multiplex polymerase chain reaction and allele-specific oligonucleotide reverse dot blot scored by chemiluminescence. Twenty mutations were tested initially. In September 2002, the panel was expanded to include the recommended American College of Medical Genetics 25 mutation panel, which added I148T, 711C 1G>T, G85E, 3120C1G>A, 1898C1G>A, 3659delC, 2184delA, and 1078delT to the group of other mutations that were tested. Test completion time was approximately 2 weeks. If no mutations were identified, a report was generated by the genetics center and sent to the computer laboratory data system and to the patients’ obstetric files. The report indicated the patients’ postgenetic testing risk based on their ethnic background and was discussed by their obstetrics provider at the patients’ next obstetric visit. If a mutation were identified, the patient was contacted by telephone by a provider from the Air Force Medical Genetics Center laboratory, and testing from the father of the pregnancy was recommen-
In the time period of October 2001 to November 2002, a total of 855 patients were counseled, of whom 827 completed pre/posttests and 489 requested CF screening (58.2%). Mean age of those patients who requested screening was 24.6 years and of those patients who declined screening was 25.2 years. Sixty-nine percent of the counseled patients were white, of whom 68% requested testing. Table I details the ethnic background of the total number of patients, those accepting testing, and their decision to accept testing on the basis of the type of counseling and ethnicity. There was no significant difference in overall acceptance of screening when those who were counseled by audiovisual means were compared with professional counseling, which was reconfirmed when the group was stratified by ethnicity. Forty percent of the counseled patients (289/731 patients who indicated pregnancy status) were in their first pregnancy, with 60.5% of this group electing to have testing regardless of ethnic background (Table II). This was a significant increase (P !.03) in the choice for testing among those who were in their first pregnancy when compared with those patients who were not in their first pregnancy. In the group of 506 tested patients, based on their ethnic mix, a total of 15.23 mutations would have been
532 Table III
Fries, Bashford, and Nunes Pre- and postcounseling test scores Audio visual counseling (%)y
Genetics professional counseling (%)* Patients
Pretest
Posttest
P value
Pretest
Posttest
P value
Acceptors (n = 481) Decliners (n = 336)
68.3 G 17.5 64.5 G 20
86.5 G 14.8 84.4 G 14.9
.01 .01
72.0 G 20 68.7 G 22.1
80.2 G 16.0 81.8 G 14.0
.01 .01
Data are given as mean percentage of correct responses to questions G SD. * N = 418. y N = 399.
expected. Fifteen mutations were identified, of which 13 were DF508 mutations with 1 G5551D mutation and 1 DI507 mutation. All patients, regardless of their choice for genetic testing or the method of counseling, showed a significant improvement in knowledge on the basis of the results of the 9-question pre- and posttests (P !.01; Table III). Preand posttest scores were not significantly different between the groups who accepted and declined screening. In the group who accepted screening, there was a significant difference (P !.05) between the pre- and posttest scores of those who were counseled by genetics professional versus audio-visual counseling groups, with the audio-visual group having a slightly higher mean pretest score and a slightly lower posttest score. In the group who declined testing, there was no significant difference in mean pre- or posttest scores on the basis of the type of counseling. Both groups, regardless of counseling method, however, did have a significant improvement in posttest scores compared with pretest scores. The 15 patients with mutations that were identified by genetic screening were contacted by telephone by a genetics professional who discussed the significance of the test result and the importance of obtaining a blood specimen from the father of the pregnancy. Although all 15 patients were contacted multiple times, only 6 fathers ultimately consented to testing. No mutations were found in this group. The principal predictor of the success of obtaining paternal testing was marital status. Of the 9 married patients, 5 fathers submitted specimens. Of the 6 unmarried patients, only 1 father submitted a specimen. No prenatal CF diagnosis procedures were performed, because no maternal/paternal mutation couples were identified, and no carrier mothers elected to have amniocentesis in the absence of paternal testing. No infants who were born to the group of mutation-positive mothers have been diagnosed with CF either on newborn testing or by disease symptoms in the first 6 months of their lives.
Comment This pilot program was well received by patients who, from their improved posttest scores, appeared to un-
derstand the concepts and materials that were presented. The acceptance rate for testing (58%) was in alignment with other genetic screening programs for CF, which had reported a 57% to 60% test uptake rate.9 Our data show a significant increase in choice for screening in primigravid women, which indicates that populations who have a higher number of primigravid women may have a higher screen uptake rate. In addition, because of the greater likelihood that patients in the decliner group may have had other children, it is possible that the previous birth of a healthy child may alter patients’ perceptions of their risk. Pretest counseling was provided for all patients regardless of ethnicity. This was in accord with the ACOG recommendations that the test be made available to all populations.12 Not all patients in the high-risk population wished to have screening (only 68% of white patients chose screening) and some patients in lower-risk populations (approximately 35%-55% in black and Hispanic populations) desired screening. A higher proportion of Hispanic patients than was anticipated requested screening; the reasons for this are not clear and may warrant further investigation into CF screening attitudes in different ethnic groups, particularly because a cost-benefit review of prenatal CF screening in Hispanic patients anticipated a low screen uptake rate.13 Preliminary counseling placed the choice for testing with the patient. Given the increasing difficulty in the determination of ethnic background in some populations, allowing patients autonomy to determine whether they feel that screening has applicability for them eliminates the unintended exclusion of potential high-risk patients on the basis of the presumption of their ethnicity. Clearly, however, it is incumbent on counseling to advise patients on the limitations in risk reductions on the basis of their designation of ethnicity. We encountered substantial difficulty in obtaining paternal blood specimens after diagnosis of a maternal mutation. Although this is not unexpected, given the mobile military population, it is likely to be a concern in nonmilitary clinical settings as well and may be confounded by the difficulty of obtaining medical insurance coverage for the cost of paternal testing. For this reason, the timing of formal genetic counseling was changed to offering this at the point of the identification of maternal
Fries, Bashford, and Nunes carrier status alone. The counseling focused on the nature of CF, population-based risk for affected infants, the need for partner testing, and the option of amniocentesis for fetal evaluation if paternal testing were not feasible or if such testing showed a paternal mutation. For a mutation-positive mother, if the ethnicity of the unavailable partner were white (carrier risk, 1:29, with 92% likelihood for identification of carrier status), the fetal risk to be affected would be 7.9 of 1000 live births, which would justify the 5 in 1000 live birth risk of amniocentesis without even testing the father. Couple screening, rather than sequential screening, could preclude the difficulty of obtaining paternal testing subsequent to maternal testing but may be cost prohibitive as a general screening policy or may be perceived as a limitation to patients whose partners are unavailable. If the partner were able to anticipate that he might not be available for future testing, couple screening rather than sequential screening might be valuable on a case-by-case basis. Obtaining paternal specimens continues to be preferable at our institution instead of moving a priori to prenatal diagnosis on the basis of maternal carrier status information alone. However, the option of amniocentesis for maternal carriers with unobtainable paternal testing may be an unexpected, but necessary, additional factor in the overall screening process. Use of trained genetics professionals (such as genetic counselors, geneticists, maternal fetal medicine specialists, or genetic nurse specialists) is felt to be optimal for genetic counseling, but such providers are rare and may be unavailable at many facilities. A 2000 to 2001 survey of 190 family physicians from around the United States indicated that 23% of the physicians found it ‘‘very difficult or impossible’’ for their patients to get a consultation with a genetics professional (personal communication, Dr Louise Acheson, Case Western Reserve University, September 1, 2003). This difficulty, in association with an expanding potential for future genetic testing, will require innovative education strategies beyond increasing the numbers of formal genetic counselors and clinical geneticists who are trained annually. Our study, which was based on pre- and posttest studies, found that patients were counseled effectively about the risks and benefits of CF screening in a group setting that used either a dedicated genetic counselor or an audio-visual presentation. The difference in pre- and posttest scores of those patients who accepted testing compared by type of counseling did show a slightly higher pretest score in those who received audio-visual counseling, with a slightly lower posttest score; this difference was not seen when the group who declined testing was compared. The explanation for this finding is unclear, and its clinical relevance is uncertain, given that both counseled groups showed a significant increase in knowledge by scores. We did observe that, for those
533 patients who received counseling from a genetics professional, sufficient time was allotted before the slide presentation for patients to complete their pretest. This time was not always included when the audiovisual counseling was given, and patients were observed to be completing their pretest while they were watching the slide show, thus potentially increasing their pretest scores. After this observation, more time was allowed for the completion of the pretest before the audiovisual presentation was started. The choice to have a genetic test does not always reflect an understanding of the significance of the test, and each counseling method may have benefits to different patients, on the basis of learning style. It is possible that an audiovisual presentation may provide greater clarity to some patients and enable them to understand better the implications of testing, particularly if decisions made by face-to-face counseling could be influenced positively or negatively by the personality of the counselor. Use of audio-visual programs could reduce the cost of counseling as part of CF screening programs as well. The process of panethnic education by audio-visual counseling would be amenable to web-based patient education methods, either in a group or an individual computer or kiosk educational process. Computerized educational programs have the advantage of self-pacing but do require language and computer literacy. The continued use of the CF screening audio-visual materials in a variety of settings will allow the further assessment of the value of this counseling approach.
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