Preconception cystic fibrosis carrier screening: costs and consequences

The objective of the study was to determine net costs of four potential preconception cystic fibrosis (CF) carrier screening strategies, and to identify the most important cost-related parameters. An estimate was made of the costs of screening carried out during general practitioner (GP) consultations, and screening carried out during group educational sessions. Two test strategies were evaluated: single-entry two-step (SETS) and double- entry two-step (DETS). Several sensitivity analyses were performed. Under the baseline assumptions, SETS screening during GP consultations was the least expensive (net costs US dollar 1,111,354 per year). The sensitivity analysis showed that the costs depend greatly on the estimated lifetime costs of care for a CF patient and the strategy used to inform the target population. Adaptations could be made to the screening program, resulting in economic savings while the primary goal of the screening--to enable participants to make an autonomous informed choice--is guaranteed.     

Lack of interest by nonpregnant couples in population-based cystic fibrosis carrier screening.

We used signs and letters to offer free cystic fibrosis (CF) carrier screening to nonpregnant adults in stable relationships who visited numerous clinical and nonclinical sites in Nashville. A total of 179 individuals (<<1% of those eligible) elected to be tested. To understand this observation, we used questionnaires to assess individuals' attitudes about genetic testing in general and about CF carrier screening in particular (n=873). Participants expressed conflicting views about carrier screening. More than 90% of people thought that genetic testing should at least be available. Most respondents said that the views of their partners and physicians were important in their decision making, and most believed that these others favored genetic testing. Yet, more than two-thirds indicated that such factors as insurability, being "at risk," what they would need to learn, abortion, and religious beliefs were important in their decision making, opinions that mitigated against genetic testing. In particular, one-third feared that carriers would lose their health insurance, one-quarter said that they would have been more interested had they been able to provide DNA by buccal swab rather than by finger stick, and less than one-sixth believed that genetic testing was meddling in God's plan. In the face of both the low level of use of free CF carrier screening by nonpregnant couples when it was not offered in person by health-care professionals and the wide variety of concerns demonstrated, we believe that clinicians should not routinely offer carrier screening to nonpregnant individuals who do not have a family history of CF.     

PCR-based screening for cystic fibrosis carrier mutations in an ethnically diverse pregnant population.

As the most common lethal autosomal recessive disorder in North America, cystic fibrosis (CF) is an obvious candidate for general population carrier screening. Although the identification of the causative gene has made detection of asymptomatic carriers possible, the extreme heterogeneity of its mutations has limited the sensitivity of the available DNA screening tests and has called into question their utility when they are applied to patients with no family history of the disease. The purpose of this study was to determine the technical feasibility, patient acceptance and understanding, and psychosocial impact of large-scale CF carrier screening in an ethnically diverse pregnant population. A total of 4,739 pregnant women attending prenatal clinics located in both an academic medical center and a large HMO were invited in person to participate. Of this group, 3,543 received CF instruction and assessments of knowledge and mood, and 3,192 underwent DNA testing for the six most common CF mutations, by means of a noninvasive PCR-based reverse-dot-blot method. Overall participation rates (ranging from 53% at the HMO to 77% at the academic center) and consent rates for DNA testing after CF instruction (>98%) exceeded those of most other American studies. The PCR-based screening method worked efficiently on large numbers of samples, and 55 carriers and one at-risk couple were identified. Understanding of residual risk, anxiety levels, and overall satisfaction with the program were acceptable across all ethnic groups. Our strategy of approaching a motivated pregnant population in person with a rapid and noninvasive testing method may provide a practical model for developing a larger CF screening program targeting appropriate high-risk groups at the national level, and may also serve as a paradigm for population-based screening of other genetically heterogeneous disorders in the future.     

Preconception cystic fibrosis carrier couple screening: impact,understanding, and satisfaction

The impact, understanding of test-results, and satisfaction among participating couples in a preconception cystic fibrosis (CF) carrier screening project were assessed 6 months after testing. Questionnaire data were obtained from 17/18 identified carriers, 15 partners of carriers with negative test results, and 794 (73%) other participants. None of the carriers changed their reproductive plans because of their test results. Eight participants were worried about their results, including four carriers. Those who attended a general practitioner (GP) consultation for pretest education were less worried than those who attended an educational session. Seven carriers felt less healthy. Predictors of a correct understanding of test results (correct in 62% of participants) were: positive test results, high level of knowledge of CF, high level of education, attending an educational session, and previously heard of CF. All participants who reported that they were worried, all carriers, and 95% of the other participants said that they would make the same decision to be tested again. Although couples who were educated during a GP consultation were less worried, the results of the study suggest that understanding is more correct in couples attending an educational session. The results further suggest that since satisfaction with the screening was high, worries and feeling less healthy due to the test results are probably not a great burden.     

Preconceptional cystic fibrosis carrier screening: attitudes and intentions of the target population

The aim of this study was to assess the attitudes and intentions of individuals planning a pregnancy with regard to preconceptional cystic fibrosis (CF) carrier screening and to determine factors associated with a positive and negative/neutral intention to have the test. A survey, based on a questionnaire, was conducted among a stratified random sample of 303 recently married couples (606 individuals). Of the eligible individuals, 70% (n = 380) participated. Of the respondents, 73% had a positive attitude toward a routine offer of preconceptional CF carrier screening, and 56% had the intention to participate in a screening program. A positive intention to have the test was associated with high perceived anticipation of regret, intended preconceptional behavior, high perceived pressure from experts, high perceived consequences of the test results, low perceived barriers, and low perceived negative consequences for family members. These results suggest that the offer of routine preconceptional CF carrier screening would lead to substantial acceptance among couples planning a pregnancy. Several variables related with intention were identified.     

Offering cystic fibrosis carrier screening to an HMO population: factors associated with utilization.

We offered cystic fibrosis (CF) carrier testing to reproductive-age enrollees in an HMO, in order to determine factors associated with test utilization in a primarily nonpregnant population. Male and female enrollees either were mailed an invitation to have the test after attending an educational session (N = 2,713) or were approached in waiting rooms at the HMO sites and given the opportunity to have the test without making an additional visit (N = 608). Uptake was considerably higher when testing could be obtained without making an additional visit (23.5%) than when attendance at an educational session was required as a prerequisite for having the test (3.7%). Utilization was higher among respondents who were planning children. Caucasians, and those with higher educational attainment. Among respondents planning to have children, individuals with higher tolerance for test uncertainty, lower fear of stigma, and higher perceived risk of being a carrier were significantly more likely to have the test. Testing decisions were not associated with the perceived burden of a child with CF or with the likelihood of aborting for CF. Although utilization of CF carrier testing is relatively low among nonpregnant individuals, uptake is significantly higher when testing can be obtained with minimal effort. Factors associated with the decision to be tested had more to do with implications of being a carrier per se than with the concerns of having a child with CF.     

Involving consumers in the development of an educational program for cystic fibrosis carrier screening.

Input from consumers of health care was sought in developing an educational program to be provided to individuals who are considering carrier testing for cystic fibrosis (CF). In addition, we assessed the ability of health professionals to predict consumers' priorities with regard to such information. A focus group of six middle school teachers formulated questions that they would ask in trying to decide whether they wanted carrier screening for CF. Then, other adults with (n = 39) and without (n = 60) a family history of CF were presented with the questions and were asked to select the questions in the order in which they would want them answered if offered the carrier test. After each question was answered, they were asked whether they would want the carrier test if it were offered to them. CF clinic staff, clinical geneticists, and genetic counselors (n = 31) were asked to select the questions in the order in which they believed that an adult from the general population would want them answered. There were no differences in the order in which adults with and without a family history of CF would want questions answered. Consumers would want to learn about the carrier test as well as their risk of being a carrier and of having a child with CF, before receiving information on reproductive options and the effect that a child with CF would have on the family. Of the 44% of consumers who changed their mind about wanting screening during the course of selecting questions, 52% did so after the first question that they selected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acceptability of carrier screening for cystic fibrosis during pregnancy in a German population

A pilot project offering voluntary heterozygote screening for the F508 mutation causing cystic fibrosis (CF) to 638 pregnant women attending two antenatal clinics in the eastern part of Berlin was carried out from 1990–1993. Participation was invited using an information leaflet and inclusion in the study was conditional on written informed consent. Of those invited to participate, only one refused to be tested, on the grounds of non-acceptance of prenatal diagnosis. Eighteen pregnant women were identified as carriers of the F508 mutation. All of them and their male partners accepted counselling in which the genetics of CF, its prognosis and treatment were explained, with emphasis on the meaning of heterozygosity, the fact that carriers are healthy, and the risk of an affected fetus when only one parent is identified as a heterozygote. All partners agreed to be tested for the F508 R553X and G551D mutations and a second counselling session was carried out after this test result was available. No problems were observed during initial testing but, as in other studies, we found considerable anxiety on being given the result in all couples where the woman tested positive; this was reduced substantially by counselling and when the partner tested negative. All probands found to be carriers stated that they found screening acceptable. In contrast to the cautious statement by the German Berufsverband Medizinische Genetik and the hostile reaction from a representative of the CF self-support organisation towards community-based heterozygote screening for CF, this study shows that CF screening is generally acceptable in this German population and that it is actively taken up by most pregnant women when offered.     

Detection of multiple cystic fibrosis mutations by reverse dot blot hybridization: a technology for carrier screening

Summary We describe the implementation of a modified version of the reverse dot blot hybridization technology to detect eight cystic fibrosis mutations. The method is simple, quick, reliable, inexpensive, and nonradioactive and utilizes the sensitivity of the polymerase chain reaction coupled with colored or chemiluminescent substrates for mutation detection. We have used this system in a clinical laboratory to identify the F508, G542X, G551D, R553X, 621 + 1GT, W1282X, N1303K, and 1717GA mutations. The technique is practical for genotyping individuals at many potential mutation sites, as in cystic fibrosis and -thalassemia, in which over 95 mutations can cause disease. This technology appears to be the method of choice for the widespread carrier screening of multiple cystic fibrosis mutations.