Prenatal Screening For Cystic Fibrosis Research Articles

Noninvasive prenatal screening for cystic fibrosis using circulating trophoblasts: Detection of the 50 most common disease-causing variants.

Cystic fibrosis (CF) is one of the most common severe autosomal recessive disorders. Prenatal or preconception CF screening is offered in some countries. A maternal blood sample in early pregnancy can provide circulating trophoblasts and offers a DNA source for genetic analysis of both the mother and the fetus. This study aimed to develop a cell-based noninvasive prenatal test (NIPT) to screen for the 50 most common CF variants. Blood samples were collected from 30 pregnancies undergoing invasive diagnostics and circulating trophoblasts were harvested in 27. Cystic fibrosis testing was conducted using two different methods: by fragment length analysis and by our newly developed NGS-based CF analysis. In all 27 cases, cell-based NIPT provided a result using both methods in agreement with the invasive test result. This study shows that cell-based NIPT for CF screening provides a reliable result without the need for partner- and proband samples.

An Expanded Carrier Screening Tool Enhances Preconception Cystic Fibrosis Screening in Infertile Couples

The American College of Obstetricians and Gynecologists recommends offering preconception and prenatal screening for cystic fibrosis (CF) while the American College of Medical Genetics also recommends screening for spinal muscular atrophy (SMA) to all couples. Both groups suggest specific screening if there is a family or personal history of a genetic disease or if the individual is from a high risk ethnic group. The purpose of this study was to determine whether availability of a more comprehensive, affordable genetic screening tool increased the number of infertility patients choosing to be screened for CF and other genetic diseases. This was a retrospective chart review of new infertility patients evaluated between May 2010 and May 2013. Sixteen hundred seventy-five new infertility couples were offered CounsylTM expanded carrier screening. The carrier frequency for CF was 6.8% with 0% of the couples concordant heterozygotes. The carrier frequency for SMA was 2.51% with 0% of the couples concordant heterozygotes. With availability of the CounsylTM screening test, the percentage of new infertility patients choosing to have preconception genetic screening increased from 2% to 8% in this population. The largest increase (17.5% of new patients) in screening followed the reduction in out-of-pocket expense in May 2013. Infertility patients are in a unique position to investigate their family history, discuss appropriate preconception genetic screening, and, if discovered to be at high risk of a genetic illness, to review their reproductive options.

Presenting life with cystic fibrosis: a Q-methodological approach to developing balanced, experience-based prenatal screening information.

Cystic fibrosis (CF) is one of the most common life-threatening genetically inherited conditions and prenatal screening for CF is available in many countries. Genetic counsellors and other health professionals are expected to provide information about the condition in a way that facilitates personal decision making. Knowing what information to deliver about complex genetic conditions to support informed screening decisions can be challenging for health professionals. To solicit views from those with personal experience with CF on which aspects of the condition they consider most important to include in prenatal screening materials. Q-methodology; an approach to systematically explore variations in viewpoint that combines factor analytic techniques with qualitative approaches to pattern interpretation. Twelve adults with CF and 18 parents of affected children were recruited from a regional centre in the UK. Five distinct viewpoints on the items most and least important to include in screening information were identified: Factor 1 the normality of life with CF and increasing life expectancy; Factor 2 the hardships and reduced lifespan. Factor 3 medical interventions and the importance of societal support. Factor 4 longer-term consequences of CF. Factor 5 the ability to adjust to the condition. The identification of five different views on what represented the most and least important information to include about CF highlights the challenge of portraying a complex genetic condition in a balanced and accurate manner. Novel ways in which Q-methodology findings can be used to meet this challenge are presented.

Genética y formación científica : resultados de un proyecto de investigación y sus implicaciones sobre los programas escolares y la enseñanza

This paper discusses the place of genetics in thecontext of scientific literacy and the school science curriculum. It then goes on to report on the work of a three year research project which seeks to document the understanding of genetics, and of modern genetic technologies, and opinions of these technologies among 15-16 years olds in England. Four aspects of the work will be reported on here. These are concerned with understanding the genetics of cells, the universality of genetic information among living things, and gene technology, and with opinions on the advisability of prenatal screening for cystic fibrosis. The implications for the school curriculum and for teaching are then discussed. The authors are grateful to the Wellcome Trust for their support in enabling this research.

P-510: Cystic fibrosis screening: A case report and discussion of a screening algorithm

Preconception and prenatal screening for cystic fibrosis (CF) was recommended in 2001 by ACOG and physicians are increasingly ordering CF testing and interpreting results. CF mutations are relatively common, with about 1 in 29 Caucasians being carriers of a CF mutation. CF carrier screening during the preconception and prenatal period presents exciting new opportunities and challenges for physicians and patients. This paper reviews the guidelines for screening and provides an algorithm for carrier screening for CF in specific situations, utilizing a case example.

Implementing prenatal screening for cystic fibrosis in routine obstetric practice

The purpose of this study was to assess the outcome of the type of prescreening counseling on choices for prenatal cystic fibrosis screening. 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. 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 mutation-positive patients were available and consented to be tested. To date, no infants have been born with cystic fibrosis. 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.

Cystic Fibrosis Prenatal Screening in Genetic Counseling Practice: Recommendations of the National Society of Genetic Counselors

For over a decade, prenatal screening for cystic fibrosis (CF) has been considered a model for the integration of genetic testing into routine medical practice. Data from pilot studies and public policy discourse have led to recommendations by some professional organizations that CF screening should be offered or made available to pregnant women and their partners, and to couples planning a pregnancy. It is crucial that genetic counselors gain thorough understanding of the complexities of CF and the implications of positive test results, so that they may serve as a reliable, educated referral base and resource for health care providers and their patients. While not all pregnant women will be referred for genetic counseling prior to CF carrier testing, genetic counselors often will be asked to counsel clients after they have a positive test result, or who are found to be at increased risk. Genetic counselors can play an important role in providing accurate and current information as well as support for patients' informed decisions. These recommendations were created by a multicenter working group of genetic counselors with expertise in CF and are based on personal clinical experience, review of pertinent English language medical articles, and reports of expert committees. The recommendations should not be construed as dictating an exclusive course of management, nor does the use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a particular client.

Premarital and prenatal screening for cystic fibrosis: Experience in the Ashkenazi Jewish population

Purpose: Since the early 1990s, Dor Yeshorim (DY) and the Mount Sinai School of Medicine (MSSM) have conducted premarital and prenatal carrier screening for cystic fibrosis (CF) in the Ashkenazi Jewish (AJ) population as part of their genetic testing programs, respectively. Together, over 170,000 screenees have been tested. In this study, we report the CF mutation frequencies in over 110,000 screenees who reportedly were of 100% AJ descent from the DY program and MSSM. In addition, the CF mutation frequencies in a group of > 7,000 screenees for AJ diseases who were of < 100% AJ descent are reported.Methods: Testing for CF mutations was performed by either PCR and restriction digestion or ASO hybridization analyses at MSSM or sent to various academic and commercial laboratories by DY.Results: The overall (and individual) carrier frequency for the five common AJ mutations, W1282X (0.020), ΔF508 (0.012), G542X (0.0024), 3849+10kb C>T (0.0020), and N1303K (0.0016), among screenees who were 100% AJ was 1 in 26; when D1152H and the rare 1717-1G>A were included, the overall carrier frequency increased to ≈1 in 23. In four families with D1152H, five compound heterozygotes for D1152H and W1282X (n = 2), ΔF508 (1) or 3849+10kb C>T (1) were identified. In contrast, the carrier frequency for screenees reporting < 100% AJ descent was ≈1 in 30 for the seven mutations.Conclusions: The carrier frequency for five common CF mutations in a large 100% AJ sample increased from 1 in 26 to 1 in 23 when D1152H was included in the panel. Addition of D1152H to mutation panels when screening the AJ population should be considered because compound heterozygosity is associated with a variable disease phenotype. Further studies to delineate the phenotype of CF patients with this mutation are needed.

Clinical sensitivity of prenatal screening for cystic fibrosis via CFTR carrier testing in a United States panethnic population

Purpose: To estimate CFTR mutation frequencies, clinical sensitivities (proportions of carrier couples or affected fetuses detected), and birth prevalence estimates for broad racial/ethnic groups and for a panethnic U.S. population.Methods: Published sources of information were identified, corrected when appropriate, and summarized. Combining racial/ethnic-specific mutation frequencies and birth prevalence estimates allowed the computation of panethnic estimates.Results: Two of the 25 recommended mutations do not meet the 0.1% threshold in a panethnic population set by the American College of Medical Genetics. The clinical sensitivities are estimated to be 71.9%, 51.7%, 41.6%, 88.6%, and 23.4% for non-Hispanic Caucasians, Hispanic Caucasian, African American, Ashkenazi Jewish Caucasian, and Asian American couples, respectively. Birth prevalence estimates are 1:2,500, 1:13,500, 1:15,100, 1:2,270, and 1:35,100, whereas the number of couples needed to screen to detect an affected fetus are about 3,200, 26,120; 36,040; 2,600, and 129,600, respectively, for the same racial/ethnic groups.Conclusions: Overall, the panethnic estimates for CFTR mutation frequencies are similar to those for non-Hispanic Caucasians. However, large differences in both clinical sensitivity and birth prevalence exist between the broad racial/ethnic groups examined. Whether and how the differences in the numbers of couples needed to screen to detect an affected fetus are to be included in prenatal screening for cystic fibrosis needs to be more explicitly addressed.

Practice patterns of obstetrician-gynecologists regarding preconception and prenatal screening for cystic fibrosis

Objective: To assess practices of obstetrician-gynecologists regarding carrier screening for cystic fibrosis (CF).Methods: A questionnaire investigating practice patterns and opinions pertaining to CF screening was mailed to 1165 members of the American College of Obstetricians and Gynecologists (ACOG), of whom 565 participate in the Collaborative Ambulatory Research Network (CARN) and 600 were randomly selected.Results: Of the questionnaires, 64% were returned. Statistical analyses were limited to the 632 respondents whose primary medical specialty was gynecology (Gyn Only) or obstetrics and gynecology (ObGyn). CARN membership was not a significant factor on any nondemographic measure. Almost one-half of physicians do not ask nonpregnant patients their family history of CF or provide them with information about CF screening. The majority of ObGyns (88.7%) ask obstetric patients their family history of CF, and offer CF carrier screening. Almost two-thirds (65.8%) offer screening to all prenatal patients. Among those ObGyns who selectively offer CF screening to pregnant patients, only 27.4% utilized all of the selection criteria in the guidelines. Liability for not offering screening, familiarity with CF, and the ability to interpret a positive screening test were important physician concerns.Conclusion: The results indicate a need for minimizing the complexity of clinical guidelines for population-based genetic screening, prospective assessment of implementation and focused continuing education for providers.

Newborn screening for cystic fibrosis: ensuring more good than harm

Newborn screening for cystic fibrosis: ensuring more good than harm

Prenatal Screening for Cystic Fibrosis in the United States – Time to Re-Evaluate Implementation Policies

Prenatal Screening for Cystic Fibrosis in the United States – Time to Re-Evaluate Implementation Policies

Prenatal screening for cystic fibrosis in the United States – time to re-evaluate implementation policies

Prenatal screening for cystic fibrosis in the United States – time to re-evaluate implementation policies

Prenatal cystic fibrosis screening in Mexican Americans: An economic analysis

Objective We evaluated the cost benefit of cystic fibrosis screening in Mexican American gravid women. Study design With the use of decisions analysis techniques, a cost-benefit analysis was performed. Baseline assumptions were based on published references. Sensitivity analyses were performed. Results Under the baseline assumptions, screening was not cost beneficial. Threshold analysis showed that, if the test was priced under $53.00, screening became cost beneficial. Sensitivity analysis demonstrated that lower acceptance rates of amniocentesis or termination made the screening strategy less attractive. If the test sensitivity was raised to 90%, which required testing of >60 mutations, the cost of screening would need to be <$100.00 for the program to be cost beneficial. Conclusion Cystic fibrosis screening is not cost beneficial in Mexican American women over a wide range of assumptions. This is principally due to the poor sensitivity of the test in this population. Cultural factors, such as lower acceptance of amniocentesis and pregnancy termination of affected fetuses, further lower the cost-benefit ratio of screening.

Cystic fibrosis: selecting the prenatal screening strategy of choice.

Cystic fibrosis is a serious disorder. Research into the treatment of affected individuals is in progress, but a cure is not expected in the near future. In this review, we demonstrate that prenatal screening for cystic fibrosis meets the requirements for a worthwhile screening programme. We explain the reasons that have led us to conclude that one approach ('couple screening') is the method of choice. The couple-based approach calls for reporting results to the couple as a unit. Only if both parents are found to be carriers is the result designated screen-positive and an amniocentesis or chorionic villus sampling offered. This offers a substantial reduction in the proportion of women with unaffected pregnancies with positive results (the false-positive rate) compared with other methods without reducing the detection of affected pregnancies. It also avoids creating a screen-positive group for which no definitive diagnosis is available. This is a problem with other screening methods. The couple method can achieve a 72% detection rate for a 0.1% false-positive rate. The screening method is simple, non-invasive, reliable, safe and reasonably cost effective. Existing programmes have shown that screening using this method is acceptable to health care professionals and patients. Setting up a national prenatal screening programme for cystic fibrosis is timely and should be implemented using the couple screening method.

The impact of cystic fibrosis on neonatal intestinal obstruction: the need for prenatal/neonatal screening.

To determine the incidence of cystic fibrosis (CF) in neonates with intestinal obstruction (NIO) secondary to meconium ileus (MI), jejunoileal atresia (JA), meconium plug syndrome (MPS), volvulus (V), and meconium peritonitis (MP) and analyze the correlation of ultrasonographic (US) signs with CF in NIO with a prenatal diagnosis of intestinal anomaly, a prospective analysis of different types of NIO from 1990 to 1998 was undertaken. Immunoreactive trypsin measurement, genetic studies, and sweat tests were performed to confirm or rule out CF. Cases with prenatal diagnosis were analyzed for gestational age, dilated bowel, ascites, hyperechoic bowel, and calcifications. Of 80 neonates, 19 (24%) had CF: 2/33 (6%) JA, 6/14 (43%) MPS, 1/14 (7.1%) MP, 10/10 (100%) MI, and 0/9 V. Thirty (37.5%) had a prenatal diagnosis of an intestinal anomaly. The overall incidence of CF in NIO with a prenatal diagnosis of intestinal anomaly was 4/30 (13%), or 333 times the estimated risk of CF in the general population. A hyperechoic pattern with dilated bowel was associated with higher specificity for CF: 3/3 cases (100%), followed by hyperechoic bowel with ascites: 3/4 cases (75%). All babies with any type of NIO should thus be screened for CF. Prenatal screening for CF should be indicated in all pregnancies with US patterns of specific intestinal disorders.

Prenatal screening for cystic fibrosis: Where are we now?

CF is a life-threatening, autosomal recessive disease that results from a chloride channel defect that is attributable to mutations in the CFTR gene. Approximately 1000 mutations have been discovered since 1989 when collaborating investigators from Toronto and Michigan described the most common CFTR allele, known as ∆F508.5 The incidence of CF varies depending on region, ancestry, and CFTR allele prevalence in reproducing populations. In the United States, the most accurate data available6 reveal that the incidence is one CF homozygote or compound heterozygote patient for every 3500 live births, reflecting a predicted CF-heterozygote frequency of 1 in 30; this approximates the mean CF carrier frequency actually determined (1 in 31; 95% CI = 1 in 24 to 1 in 43) in the Wisconsin newborn population (reflecting actively reproducing adults7), as well

Prenatal screening for cystic fibrosis: an economic analysis.

Cystic fibrosis (CF) is the most common life-shortening genetically transmitted disease in Denmark with a birth prevalence of 1 in 4700, resulting in 12-15 new cases of cystic fibroses annually. The aim of this study is to disclose the societal resource implications of introducing a population wide prenatal screening programme for cystic fibrosis in Denmark. The present analysis is limited to the monetary consequences of introducing a screening programme, where costs of screening are compared to the potential benefits measured in cost savings involved if births of CF patients are avoided. Screening costs in a Danish setting were estimated at DKK 2 771 262 ( pound sterlings 231 438) per aborted affected fetus in the first screening round, stabilising at DKK 1 864 594 ( pound sterlings 155 383) per aborted affected fetus at subsequent screening rounds. Comparing this figure with the estimated benefits of avoiding a CF case (DKK 2.1-4.4 million; pound sterlings 175 000-366 667) suggests that introducing a screening programme for cystic fibrosis will be net cost saving irrespective of the perspective of the analysis, assumptions on replacement children and method of estimating long-term production gains/losses.

Eliciting patients' values by use of 'willingness to pay': letting the theory drive the method.

To describe the three different ways in which 'willingness to pay' (WTP) has been used to elicit patients' values of alternative interventions. For each of the three approaches a survey of patients or the public was undertaken. SETTING, PARTICIPANTS AND INTERVENTIONS: studied For two surveys, the setting was Aberdeen Maternity Hospital, where pregnant women were asked about their WTP for different methods of prenatal screening for cystic fibrosis. In the third survey, parents of primary and secondary schoolchildren were asked about their WTP for different ways of providing child health services. Ability of WTP to discriminate between options (i.e. to say whether one option is 'better' than another) and the consistency of WTP with stated preferences. Experience with some methods shows that, despite the apparent logic of the technique, it is difficult to elicit consistent responses whereby WTP values derived match the rankings of interventions compared. The most promising technique, the 'marginal approach', happens to conform more with economic theory than other approaches. Potential limitations of WTP, such as its association with ability to pay, are discussed, as are approaches to dealing with such problems. Finally, if patients prefer an intervention that is more costly than the status quo, logic dictates that those extra resources will have to be obtained from another health-care programme. In such contexts, to aid decision-making, values derived from members of the community for different programmes may be more relevant than values derived from patients. Initial studies in the use of WTP in this broader context of eliciting community values are also outlined. WTP has potential, but its application, and interpretation, are not straightforward. More testing of the 'marginal approach' is required and greater use of qualitative research, to assess the validity of the approach, should be made in this area.

Issues in implementing prenatal screening for cystic fibrosis: results of a working conference.

To summarise a conference convened to examine how cystic fibrosis screening might appropriately be introduced into routine prenatal practice. Participants included experts from various relevant disciplines. Systematic reviews and data from individual trials were presented; issues were identified and discussed. Judged by published criteria, prenatal cystic fibrosis screening is suitable for introduction. Screening can be performed cost effectively by identifying racial/ethnic groups at sufficient risk and then using either of two models for delivering laboratory services. Validated educational materials exist. Ethical issues are not unique. Once adequate facilities for patient and provider education, testing, counselling, quality control, and monitoring are in place, individual programmes can begin prenatal screening for cystic fibrosis.