Newborn Screening for CF in the UK

1. Newborn Screening for CF in the UK An Overview Kevin Southern kwsouth@liv.ac.uk

2. Content • Why we screen infants for CF • How we screen • Screening protocols in Europe • The UK protocol • Adverse effects of screening • Consensus statements on • Equivocal diagnosis • Management

3. Why we screen infants for CF • Early identification • Prevent the patient odyssey • Facilitate early treatment • Provide family reproductive options • Longer life • Doull et al (PMID: 11340682) • Healthier life • Nutritional benefits • Respiratory benefits

4. CXR scores in the Wisconsin study Farrell et al, AJRCCM, 2004 (PMID: 12917228)

5. Data from population studies • UK CF database • Cohort of 184 screened infants • Improved CXR appearances and lower rates of PsA • Able to maintain excellent condition with less treatment • Lancet , PMID: 17416263 • “Sims and Mehta”

6. Conclusionwhy screen • It is valid and ethical to screen infants for CF, providing there is a significant incidence of the condition in the region and the infrastructure exists to provide appropriate levels of care • Phil Farrell, • Is newborn screening for cystic fibrosis a basic human right? • Journal of CF, PMID: 18262856

7. How we screen • IRT measurement in first week of life • NBS protocols • Very sensitive • Second tier • DNA analysis on the same blood spot • Second IRT measurement (21-28 days) • More specific • Infants with one mutation • Infants with a very high IRT

8. Adverse effects of NBS • Processing a positive screening result • ‘the waiting period” • Recognition of carrier status • Inconclusive results • Equivocal diagnosis • Inadequate CF care services • Management consensus • Potential for discrimination

9. UK Standard Protocol Newborn Screening for CF Day 5 blood spot samples: IRT assay 10,000 9950 50 IRT < 99.5th centile IRT >99.5th centile Note: 0.25 CF infants will not be identified through screening (IRT inaccurate in meconium ileus) DNA analysis – 4 mutations Report: CF not suspected Two CF mutations No mutation detected One CF mutation 3 6 41 DNA analysis – 29 or 31 panel 0.5 One CF mutation 5.5 IRT>99.9th centile Refer with presumptive diagnosis of CF IRT on 2nd blood spot IRT on 2nd blood spot Yes 3.5 No Av. < Cut-off 2 Av. > Cut-off 2 Av. > Cut-off 2 Av. < Cut-off 2 Report: CF not suspected ‘High likelihood’Clinical referral Report: CF not suspected ‘Low likelihood’ Advice, counselling ‘High likelihood’Clinical referral 0.5 5 38 0.1 2.9 Full implementation 2007

10. What went well • Clear referral pathways • Screening Link Health Visitors • Early diagnosis • Cheshire and Merseyside, • Two mutations, median 26 days • One mutation, median 28 days • Clear information for families

11. England (April-Sept, 2007) 255,304 infants 1441 (0.59%) high first IRT

12. Compared to Wales (2000-2007) (no second IRT) High IRT, number (%) 1441 (0.59%) 1530 (0.60 %)

13. What could we do better • Equivocal cases • Guidelines (Mayell et al. JCF, 18957277) • Best Practice Document • Castellani et al. (submitted JCF) • Management consensus • Round two, Delphi process • Database • Emerging CF Registry

14. Potential for Research • Multi-centre interventional studies • Adopt a similar philosophy to the CRC • Prophylactic antibiotics • RSV prophylaxis (palivizumab) • Routine Physiotherapy • Pancreatic Enzyme Replacement Therapy • Vitamin K • Long-term surveillance studies

15. Summary • Implementation has proceeded well across the UK (and increasingly Europe) • Need to continue to examine and compare protocols and assess performance. • Need to grasp the opportunities that NBS affords to better understand CF and define ideal management.

16. Thank you • http://www.ich.ucl.ac.uk/newborn/ • The UK Newborn Screening Programme Centre • Click on • “The CF Programme” • “Information for implementation…” kwsouth@liv.ac.uk