Novel strategies in newborn screening for cystic fibrosis: a prospective controlled study. Issue 4 (23rd January 2012)

• Record Type: Journal Article
• Authors: Vernooij-van Langen, Annette M M; Loeber, J Gerard; Elvers, Bert; Triepels, Ralf H; Gille, Johan J P; Van der Ploeg, Catharina P B; Reijntjens, Sandra; Dompeling, Edward; Dankert-Roelse, Jeannette E
• Is Part Of: Thorax. Volume 67:Issue 4(2012)
• Page Start: 289
• Page End: 295
• Publication Date: 2012-01-23
• Subjects: Cystic fibrosis newborn screening -- immunoreactive trypsinogen -- pancreatitis-associated protein -- mutation analysis -- sequencing -- sensitivity -- specificity -- clinical epidemiology -- cystic fibrosis -- infection control -- alpha1 antitrypsin deficiency -- lung cancer -- lung proteases -- macrophage biology -- respiratory infection -- cystic fibrosis -- oxidative stress -- asthma -- exhaled airway markers -- paediatric asthma -- paediatric physician -- respiratory infection; Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thoraxjnl-2011-200730
• Languages: English
• ISSNs: 0040-6376

Abstract

Abstract : Context: Newborn screening for cystic fibrosis (CF) is included in many routine programmes but current strategies have considerable drawbacks, such as false-positive tests, equivocal diagnosis and detection of carriers. Objective: To assess the test performance of two newborn screening strategies for CF. Design, setting and participants: In 2008 and 2009, CF screening was added to the routine screening programme as a prospective study in part of the Netherlands. Interventions: Two strategies were performed in all newborns. In the first strategy, concentrations of immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) were measured. In the second method, samples with IRT ≥60 μg/litre were analysed for 36 CFTR mutations, followed by sequencing when a single mutation was detected. Tests were positive only with two identified CFTR mutations. Main outcome: Sensitivity, specificity and positive predictive value (PPV) of both screening strategies. Results: 145 499 infants were screened. The IRT/PAP approach showed a sensitivity of 95.0%, a specificity of 99.897% and a PPV of 12.3%. Test properties for the IRT/DNA/sequencing strategy were respectively 100%, 100% and 64.9%. Combining both strategies (IRT/PAP/DNA/sequencing) led to a sensitivity of 95.0%, a specificity of 100% and a PPV of 87.5%. Conclusion: In conclusion, all strategies performed well. Although there was no statistically significant difference in test performance, the IRT/DNA/sequencing strategy detected one infant that was missed by IRT/PAP (/DNA/sequencing). IRT/PAP may be the optimal choice if the use of DNA technology must be avoided. If identification of carriers and equivocal diagnosis is considered an important disadvantage, IRT/PAP/DNA/sequencing may be the best choice.