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ORIGINAL RESEARCH |
From the Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Address reprint requests to: Jeffrey A. Kuller, MD, Reproductive Genetics and AFP Screening Program, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, 214 MacNider Building, CB# 7570, Chapel Hill, NC 27599-7570, E-mail: kuller{at}med.unc.edu
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Methods: A multiple-choice questionnaire was mailed to all active North Carolina nonfederal physicians with a primary specialty of obstetrics and gynecology. Ten questions surveyed the participants’ knowledge about cystic fibrosis.
Results: Two hundred eighty-six surveys were returned for a response rate of 30.4%. The respondents differed in their knowledge base depending on their specialty, age, and number of years of experience as a physician. The youngest physicians and the least experienced yielded the highest percentage correct. The questions most frequently answered correctly dealt primarily with clinical information about cystic fibrosis, whereas the questions most often answered incorrectly dealt with carrier frequency and testing information.
Conclusion: The obstetrics-gynecology community is not yet prepared to comply with the NIH Consensus Statement to offer cystic fibrosis carrier screening to couples preconceptionally or prenatally. Further education is necessary before obstetrician-gynecologists can counsel patients adequately.
Cystic fibrosis, the most common genetic disorder in the white population, is incurable. This autosomal recessive genetic disease has a carrier frequency of one in 25 to one in 30. Most men with classic cystic fibrosis have congenital bilateral absence of the vas deferens, causing azospermia and subsequent infertility. Women may have reduced fertility due to viscous cervical secretions.1 Most patients affected with cystic fibrosis have normal cognition and can lead productive lives. However, despite advances in treatment, the average life span remains only 30 years; pulmonary complications are the leading cause of death.2 Heterozygosity does not guarantee immunity from the effects of the mutation. Men who are carriers of specific mutations of cystic fibrosis can have congenital bilateral absence of the vas deferens but normal pancreatic and pulmonary function. Some female carriers of specific mutations of cystic fibrosis may develop bronchial and sinus abnormalities. Thus, additional difficulties arise in genetic counseling: although considered an autosomal recessive condition, cystic fibrosis can be expressed mildly in the heterozygote. Further research to develop an understanding of gene expression and variance for each cystic fibrosis mutation will help provide thorough and appropriate counseling to patients known to carry a cystic fibrosis mutation.
A mutation in the cystic fibrosis membrane conductance regulator gene causes defective chloride transport, which leads to thick mucus secretion from the lungs, pancreas, and sweat glands.2 There are more than 600 mutations of the cystic fibrosis membrane conductance regulator gene that can cause cystic fibrosis. A strong correlation exists between genotype and phenotype for pancreatic function; however, no similar correlations have been identified for pulmonary function. Approximately five to 30 mutations account for the majority of the cystic fibrosis carriers. Attempting to screen an individual for all known mutations is not cost-effective. Screening methodology involves offering a polymerase chain reaction based on DNA analysis for the common mutations. There is wide variability between laboratories with respect to the specific number of mutations evaluated. Some screen for as few as the five most common mutations, whereas others choose the 30 or even the 64 most common mutations.
No consensus has been reached regarding which mutations should be evaluated, with the exception of the 
F508 allele (the most common allele). Sensitivity of carrier detection depends on the ethnicity of the individual screened and the number of mutations evaluated. This ranges from 30% in Asians to 97% in Ashkenazi Jews. The F508 mutation is present in all populations studied thus far; however, the relative frequency varies with the particular ethnic background (Table 1
). Several other mutations have higher frequency and specificity in certain ethnic groups. Specifically, the I-19 or 3489+10kbC
T mutation commonly is seen in the Ashkenazi Jewish population, and the 3120+1GA is noted in 11.4% of the black population.
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However, ACOG and the American College of Medical Genetics expressed concern about the NIH recommendations, and ACOG subsequently issued a policy statement specifying the College’s areas of disagreement.
ACOG supports the recommendations to offer cystic fibrosis genetic testing to adults with a positive family history of cystic fibrosis and to partners of people with cystic fibrosis. ACOG does not agree with the recommendations to offer cystic fibrosis genetic testing to couples planning a pregnancy and couples seeking prenatal testing. The College will continue to evaluate scientific developments in cystic fibrosis testing and review data regarding implementation of cystic fibrosis testing as a component of preconception and prenatal care (ACOG statement on cystic fibrosis testing. ACOG Today 1998 May–June).
Other issues associated with cystic fibrosis testing include the following: who should offer screening (obstetrician-gynecologists, family practitioners, nurse specialists, genetic counselors, geneticists, maternal-fetal medicine experts), how will the patient-couple be educated, will informed consent be required, will there be insurance reimbursement, is there enough manpower to undertake this endeavor, which mutations should be offered and to whom, and what carrier detection rate is acceptable for each ethnic background?
Concern has been expressed that the obstetrics-gynecology community does not yet have the knowledge about cystic fibrosis testing to discuss it adequately with patients. To assess this issue we undertook a study to determine obstetricians-gynecologists’ knowledge about cystic fibrosis and cystic fibrosis carrier screening.
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) was mailed to all active, nonfederal physicians with a primary specialty in obstetrics and gynecology in the North Carolina (n = 936). The questionnaire was approved by the Committee on the Protection of the Rights of Human Subjects at the University of North Carolina at Chapel Hill. The questions were designed to illicit the respondents’ knowledge in several areas: clinical symptoms and course of cystic fibrosis, inheritance of cystic fibrosis, diagnostic and carrier screening methods available, and ethnic diversity of cystic fibrosis mutations (Table 2).
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The average correct score among all respondents was 66% (mean 65.7% ± 0.9 standard deviation [95% confidence interval 64.0, 67.5]). On further analysis by the type of practitioner, general obstetrician-gynecologists averaged 58% correct (58.0 ± 1.0 [56.0, 60.0]), residents 74% correct (74.4 ± 3.3 [67.4, 80.6]), maternal-fetal medicine specialists 80% correct (80.0 ± 3.0 [73.4, 85.6]) and other specialists 72% correct (71.7 ± 5.8 [58.6, 82.5]). The respondents averaged 11.5 years in practice. The mean age was 42 years (range 26–69) (Figure 1). Maternal-fetal medicine specialists had a mean of 14 years in practice and a mean age of 41 years. Other specialists had a mean of 11 years in practice and mean age of 36 years.
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The predominant trend shows that the youngest and the least experienced physicians had the greatest number of correct answers. This most likely reflects an increased focus on genetics in medical school and residency training programs. Maternal-fetal medicine specialists scored well, with an 80% correct response rate. This result may be explained by the significant focus maternal-fetal medicine fellowships and subspecialty board examinations generally have on genetics and prenatal diagnosis. Other obstetric-gynecology subspecialists also scored well, which may reflect that these physicians generally work in an academic environment with greater exposure to newer information.
The pattern of questions answered correctly was consistent among all physicians analyzed. The questions most frequently answered correctly pertained to mode of inheritance and clinical diagnosis. The questions routinely answered wrong pertained to carrier frequencies, life expectancy, prenatal diagnosis, and mutation analysis.
On the basis of the responses to our survey, we conclude that obstetrician-gynecologists are well prepared to answer questions regarding the clinical aspects related to cystic fibrosis testing (survey questions 1, 5, 6, and 7) but not questions dealing with carrier risks and testing (questions 2, 3, and 4). The most glaring example of obstetrician-gynecologists’ lack of knowledge was the 15% correct response rate to the question addressing the carrier frequency of cystic fibrosis in the black population (question 8) and the only 48% correct response to the question about which ethnic group has the highest detection rate for cystic fibrosis (question 4). The NIH consensus recommends offering cystic fibrosis carrier testing to all prenatal or preconceptional patients independent of their ethnic background. Therefore, obstetrician-gynecologists must be familiar with the carrier frequencies and detection rates for individuals of diverse ethnic backgrounds. When ordering cystic fibrosis carrier testing, care givers also must be aware of the panel of mutations used by individual laboratories to ensure that the mutations known to occur with the highest frequencies in a patient’s ethnic group are covered by the laboratory’s mutation panel.
A study by Myers et al4 evaluated the involvement of potential patients in the development of a cystic fibrosis carrier screening program. Middle-school teachers were asked to formulate questions to help patients to decide whether or not to have carrier screening for cystic fibrosis. The questions formulated were then presented to 99 adults, one-third with and two-thirds without a family history of cystic fibrosis. These adults were then asked to rank the importance of the questions in their decision making about whether or not to undergo carrier screening for cystic fibrosis. Regardless of whether or not the surveyed individuals had a family history of cystic fibrosis, the questions thought to be most important were their risk of being a carrier, risk of having a child with cystic fibrosis, and how carrier testing is performed. Of secondary concern were the course of the disease, the potential impact on the family, and reproductive and prenatal diagnostic options.
A cost-effectiveness analysis of prenatal carrier screening for cystic fibrosis was published recently.5 A cost-benefit equation was developed based on the hypothesis that the cost of prenatal diagnosis required to diagnose and prevent one case of cystic fibrosis should be equal to or less than the lifetime cost generated from the birth of a child with cystic fibrosis. However, the authors assumed that in-person genetic counseling and patient education are necessary only when both parents are found to be carriers. We think that genetic counseling is better performed before any testing. A somewhat similar test, maternal serum screening for aneuploidy and neural tube defects, generally is performed only after direct patient counseling. ACOG6 recommends that counseling emphasize that serum screening is voluntary. Only after being informed of the risks and advantages of serum screening may a patient elect to undergo testing.
If cystic fibrosis screening and testing is to be adopted in a similar fashion to maternal serum screening in the obstetrics-gynecology community, increased physician education is necessary.7,8 Before the NIH guidelines can be implemented, continuing education must occur. The use of or interaction with genetic counselors, reproductive geneticists, and maternal-fetal medicine subspecialties may need to be increased, especially upon initial implementation.
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Footnotes |
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Received May 26, 1998. Received in revised form September 9, 1998. Accepted September 24, 1998.
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References |
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2. Haan E. Screening for carriers of genetic disease: Points to consider. Med J Aust 1993;158:419–21.[Medline]
3. Genetics testing for cystic fibrosis. NIH Consensus Statement 1997 Apr 14–16; 15(4):1–37.
4. Myers MF, Bernhardt BA, Tambor ES, Holtzman NA. Involving consumers in the development of an educational program for cystic fibrosis carrier screening. Am J Hum Genet 1994;54:719–26.[Medline]
5. Vintzileos AM, Ananth CV, Fisher AJ, Smulian JC, Day-Salvatore D, Beazoglou T. An economic evaluation of first-trimester genetic sonography for prenatal detection of Down syndrome. Obstet Gynecol 1998;91:535–9.[Abstract]
6. American College of Obstetricians and Gynecologists. Maternal serum screening. ACOG educational bulletin no. 228. Washington, DC: American College of Obstetricians and Gynecologists, 1996.
7. Boulton M, Cummings C, Williamson R. The views of general practitioners on community carrier screening for cystic fibrosis. Br J Gen Pract 1996;46:299–301.[Medline]
8. Williamson R. University community carrier screening for cystic fibrosis. Nat Genet 1993;3:195–201.[Medline]
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