European best practice guidelines for cystic fibrosis neonatal screening  Carlo Castellani, Kevin W. Southern, Keith Brownlee, Jeannette Dankert Roelse, Alistair Duff, Michael Farrell, Anil Mehta, Anne Munck, Rodney Pollitt, Isabelle Sermet-Gaudelus, Bridget Wilcken, Manfred Ballmann, Carlo Corbetta, Isabelle de Monestrol, Philip Farrell, Maria Feilcke, Claude Férec, Silvia Gartner, Kevin Gaskin, Jutta Hammermann, Nataliya Kashirskaya, Gerard Loeber, Milan Macek, Gita Mehta, Andreas Reiman, Paolo Rizzotti, Alec Sammon, Dorota Sands, Alan Smyth, Olaf Sommerburg, Toni Torresani, Georges Travert, Annette Vernooij, Stuart Elborn  Journal of Cystic Fibrosis  Volume 8, Issue 3, Pages 153-173 (May 2009) DOI: 10.1016/j.jcf.2009.01.004 Copyright © 2009 European Cystic Fibrosis Society Terms and Conditions

Fig. 1 Therapeutic costs in infants diagnosed by neonatal screening (NBS) and presenting clinically (CD). The apparent paucity of dots on the left is an illusion because the ‘missing’ data points lie on top of each other in the lower cost categories. Reproduced with permission from [33]. Journal of Cystic Fibrosis 2009 8, 153-173DOI: (10.1016/j.jcf.2009.01.004) Copyright © 2009 European Cystic Fibrosis Society Terms and Conditions

Fig. 2 Accumulation of nebulised drugs in cohorts of infants with CF. Screened (NBS) cohorts accumulate compared to either those presenting with symptoms within the same time period as NBS (early-CD, first two months of life) or those presenting clinically after two months of age (late-CD). Reproduced with permission from [30]. Journal of Cystic Fibrosis 2009 8, 153-173DOI: (10.1016/j.jcf.2009.01.004) Copyright © 2009 European Cystic Fibrosis Society Terms and Conditions

Fig. 3 Standard CF NBS procedure. ⁎Some mutations like 3849+10 Kb C>T or R117H may be associated with sweat chloride <30 mmol/L. Journal of Cystic Fibrosis 2009 8, 153-173DOI: (10.1016/j.jcf.2009.01.004) Copyright © 2009 European Cystic Fibrosis Society Terms and Conditions

Fig. 4 Three examples of intermediate tier strategies. ⁎ the cut-off for resampled IRT is lower than the cut-off for IRT at birth. ⁎⁎ if IRT at birth exceeds a cut-off higher than the one used to start the procedure, the protocol proceeds to resampling even though no mutations were detected. Journal of Cystic Fibrosis 2009 8, 153-173DOI: (10.1016/j.jcf.2009.01.004) Copyright © 2009 European Cystic Fibrosis Society Terms and Conditions

Fig. 5 Effect of CFTR mutation coverage on yields. The data shown are calculated using the Hardy–Weinberg equation for a population where 0.5% of the initial screening samples are sent for a single-stage mutation analysis. It is assumed that carriers for all the mutations examined are over-represented to the same extent as carriers of F508del. Journal of Cystic Fibrosis 2009 8, 153-173DOI: (10.1016/j.jcf.2009.01.004) Copyright © 2009 European Cystic Fibrosis Society Terms and Conditions

Fig. 6 Diagnostic algorithm for inconclusive diagnoses following CF NBS. Reproduced from [48]. Journal of Cystic Fibrosis 2009 8, 153-173DOI: (10.1016/j.jcf.2009.01.004) Copyright © 2009 European Cystic Fibrosis Society Terms and Conditions

Fig. 7 Time periods common to all CF NBS protocols. Journal of Cystic Fibrosis 2009 8, 153-173DOI: (10.1016/j.jcf.2009.01.004) Copyright © 2009 European Cystic Fibrosis Society Terms and Conditions