Screening Strategies For Cystic Fibrosis Research Articles

Comparison between two newborn screening strategies for cystic fibrosis in Argentina: IRT/IRT versus IRT/PAP.

The benefits of early cystic fibrosis (CF) detection using newborn screening (NBS) has led to widespread use in NBS programs. Since 2002, a two-stage immunoreactive trypsinogen (IRT/IRT) screening strategy has been used as a CFNBS method in all public maternity units in the City of Buenos Aires, Argentina. However, novel screening strategies may be more efficient. The aim of this study is to prospectively compare two CFNBS strategies: IRT/IRT and IRT/PAP (pancreatitis-associated protein). A two-year prospective study was performed. IRT was measured in dried blood samples collected 48-72 h after birth. When an IRT value was abnormal, PAP was determined, and a second visit was scheduled to obtain another sample for IRT before 25 days of life. Newborns with a positive CFNBS were referred for a confirmatory sweat test. There were 69,827 births in the City of Buenos Aires during the period studied; 918 (1.31%) had an abnormal IRT. A total of 207 children (22.5%) failed to return for the second IRT, but only two PAP (0.2%) were not performed. IRT/IRT was more likely to lead to a referral for sweat testing than IRT/PAP (odds ratio 2.3 [95% confidence interval 1.8-2.9], p < .001). Sensitivity and specificity were: 80% and 100% and 86.5% and 82.6% for IRT/IRT and IRT/PAP strategies, respectively. The IRT/PAP strategy is more sensitive than IRT/IRT and has similar specificity; it avoids a second visit and unnecessary sweat testing, and it reduces loss to follow-up in our population.

A model-based economic evaluation of four newborn screening strategies for cystic fibrosis in Flanders, Belgium

ABSTRACTObjectives: The most cost-effective newborn screening strategy for cystic fibrosis (CF) for Flanders, Belgium, is unknown. The aim of this study was to assess the cost-effectiveness of four existing newborn screening strategies for CF: IRT-DNA (immunoreactive trypsinogen, cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation analysis), IRT-PAP (pancreatitis-associated protein), IRT-PAP-DNA, and IRT-PAP-DNA-EGA (extended CFTR gene analysis).Methods: Using data from published literature, the cost-effectiveness of the screening strategies was calculated for a hypothetical cohort of 65,606 newborns in Flanders, Belgium. A healthcare payer perspective was used, and the direct medical costs associated with screening were taken into account. The robustness of the model outcomes was assessed in sensitivity analyses.Results: The IRT-PAP strategy was the most cost-effective strategy in terms of costs per CF case detected (€9314 per CF case detected). The IRT-DNA strategy was more costly (€13,966 per CF case detected), but with an expected sensitivity of 93.4% also the most effective strategy, and was expected to detect 2.2 more cases of CF than the IRT-PAP strategy. The incremental cost-effectiveness ratio of IRT-DNA vs. IRT-PAP was €54,180/extra CF case detected. The IRT-PAP-DNA strategy and the IRT-PAP-DNA-EGA strategy were both strongly dominated by the IRT-PAP strategy.Conclusion: The IRT-PAP strategy was the most cost-effective strategy in terms of costs per CF case detected. However, the strategy did not fulfil the European Cystic Fibrosis Society guidelines for sensitivity and positive predictive value. Therefore, the more costly and more effective IRT-DNA strategy may be the most appropriate newborn screening strategy for Flanders.

Assessing the improvements in the newborn screening strategy for cystic fibrosis in the Balearic Islands

ObjectivesNewborn screening strategies for cystic fibrosis (CF) are run worldwide, and aim at the early detection of the disorder to significantly improve the quality of life. Elevated levels of immunoreactive trypsinogen (IRT) represent a high likelihood for the screened child to be affected with CF. However, the specificity of IRT is low. The objective of this study was to assess the screening program in the Balearic Islands during the past 14years. Design & methodsWe evaluated all results of the screening program after 14years, by considering all changes in the protocol and assessing the number of positive samples, the mutations detected, the number of sweat tests performed, the incidence of CF and the presence of false-negative cases. ResultsDespite a great variability among the different Balearic Islands, the global incidence of CF was 1:6059 for the 14years assessed. The incidence in the smaller islands is about 5 times higher than in Majorca (1:2376 versus 1:10,613). After different changes in the protocol, an IRT cut-off value of 60ng/mL was established. The two most common mutations are ΔF508 and G542X, in accordance with other geographical regions. ConclusionsThe changes in the protocol helped reduce the number of sweat tests performed without any increase in the false-negative rate.

PND14 Comparing Expected Costs associated with Three Screening Strategies for Cystic Fibrosis Along Spain

Cystic fibrosis (CF) is the most frequent hereditary (autosomal-recessive) and childhood-onset health problem of more devastating consequences, among Caucasians. Its incidence is between 0.027% and 0.036% in Spain, so CF is included among the rare diseases (however about 25-30% of the population may be asymptomatic carrier of the disease). Neonatal screening of CF can detect between 90-99% of affected infants in their first two months of life. In the absence of screening, the age of clinical diagnosis is variable, because some patients have suggestive symptoms in the first few hours or days after birth (meconium ileus) while others patients expressed their symptoms in the weeks of age (stunting) and, in milder cases, in adult life (recurrent respiratory infections).

Cost-effectiveness of 4 Neonatal Screening Strategies for Cystic Fibrosis

The purpose of this work was to assess the costs of 4 neonatal screening strategies for cystic fibrosis in relation to health effects. In each strategy, the first test was the measurement of serum concentration of immunoreactive trypsin. The second step consisted of either a second immunoreactive trypsin test (strategy 1) or a multiple mutation analysis (strategy 2). In strategies 3 and 4, a third step was added to strategy 2: a second immunoreactive trypsin test (strategy 3) or an extended mutation analysis of the cystic fibrosis gene, that is, a denaturing gradient gel electrophoresis analysis (strategy 4). We conducted an economic-modeling exercise in the Netherlands based on published data and expert opinions. Subjects were a hypothetical cohort of 200 000 neonates, the approximate number of children born annually in the Netherlands, and we assessed the costs and number of life-years gained as a result of neonatal screening for cystic fibrosis. The costs and effects of changes in reproductive decisions because of neonatal screening were also assessed. Immunoreactive trypsin + immunoreactive trypsin had the most favorable cost-effectiveness ratio of 24,800 euro per life-year gained. Immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis achieved more health effects than immunoreactive trypsin + DNA + immunoreactive trypsin at lower cost. The incremental costs per life-year gained of the immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis strategy compared with the immunoreactive trypsin + immunoreactive trypsin strategy were 130,700 euro, whereas the incremental costs of the immunoreactive trypsin + DNA strategy compared with the immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis strategy were 2,154,300 euro. When changes in reproductive decisions as a result of neonatal screening are also taken into account, neonatal screening for cystic fibrosis may lead to financial savings of approximately 1.8 million euro annually, depending on the screening strategy used. Cystic fibrosis screening for neonates is a good economic option, and positive health effects can also be expected. Immunoreactive trypsin + immunoreactive trypsin and immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis are the most cost-effective strategies.

Étude du gène CFTR chez 207 patients du Sud-Ouest de la France atteints de mucoviscidose : fréquence élevéedes mutations N1303K et 1811+1,6kbA>G

The large molecular heterogeneity in cystic fibrosis (CF) represents the main difficulty for the genotype characterization. Moreover, numerous studies have reported considerable variations in frequencies of cystic fibrosis transmembrane conductance regulator ( CFTR) mutations in different populations. Material and methods. – We analyzed the genotype of 207 CF children living in southwest France. Results. – Among 50 identified mutations, we report for some of them a widely modified incidence compared with those observed in other regions of France. These differences were more significant in the subset of the CF chromosomes originating in southwest France. Thus, the 1811 +1.6kbA >G mutation, rarely observed in the other French regions (< 0.5% ), proved to be, with a frequency of 8.8%, the most frequent mutation after the F508 deletion (57%). The frequencies of N1303K, 1811 +1.6kbA >G and R334W mutations were also clearly increased: 7.9 and 2.6%, respectively. Conclusion. – We show that the southwest of France is characterized by a specific mutational spectrum. We consider that these regional data on the spectrum of CF mutations are crucial to develop more accurate and less expensive molecular screening strategies for cystic fibrosis in France.