Ayşe Şenay ŞAŞİHÜSEYİNOĞLU, Derya Ufuk ALTINTAŞ, Atıl BİŞGİN, Dilek DOĞRUEL, Mustafa YILMAZ, Mahir SERBES

Two years of newborn screening for cystic fibrosis in Turkey: Çukurova experience

The severity of cystic fibrosis (CF) depends on the type of cystic fibrosistransmembrane conductance regulator (CFTR) mutation. The primary goal ofnewborn screening (NBS) is to decrease morbidity, mortality and associateddisabilities. The National NBS for CF programme was initiated in Turkey since01.01.2015. The aim of this study was to present two years of experience ofour CF center which is located in the south of Turkey. The study populationcomprised of infants who were born in Adana between 1 January 2015 - 31December 2016, referred to our CF center as part of NBS for CF and performedCFTR gene analysis. The infants were divided into three groups according tolaboratory tests and symptoms as CF, CRMS (cystic fibrosis transmembraneconductance regulator-related metabolic syndrome) and false positive NBS.Between January 1, 2015 and December 31, 2016, NBS was performed in77,437 newborns in Adana. Two hundred seven (0.26%) newborns screenedwere positive for CF. A total of 184 infants were included to the study. Wereported 12 babies as CF with an incidence of 1:6,452. The babies diagnosed asCF constituted 6.5% of positive CF NBS. Rest of study group diagnosed withCRMS/CFSPID (54/184, 29.5%) and false positive (118/184, 64%). Positivepredictive value (PPV) of NBS was 6.5%. The most common CFTR mutationswere 508del, p.F1052L and p.L997 F. The implementation of CF-NBS programhas been successful in Turkey. But it is too early to determine the specificityand sensitivity of the program.

PDF

___

1. Radivojevic D, Sovtic A, Minic P, et al. Newborn screening for cystic fibrosis in Serbia: A pilot study. Pediatr Int 2013; 55: 181-184.

2. Gürson CT, Sertel H, Gürkan M, Pala S. Newborn screening for cystic fibrosis with the chloride electrode and neutron activation analysis. Helv Paediatr Acta 1973; 28: 165-174.

3. Lilley M, Christian S, Hume S, et al. Newborn screening for cystic fibrosis in Alberta: Two years of experience. Paediatr Child Health 2010; 15: 590-594.

4. Cantin AM, Hartl D, Konstan MW, Chmiel JF. Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy. J Cyst Fibros 2015; 14: 419-430.

5. Schaefer JF, Hector A, Schmidt K, et al. A semiquantitative MRI-Score can predict loss of lung function in patients with cystic fibrosis: Preliminary results. Eur Radiol 2018; 28: 74-84.

6. Sosnay PR, White TB, Farrell PM, et al. Diagnosis of cystic fibrosis in nonscreened populations. J Pediatr 2017; 181: S52-S57. e2.

7. Farriaux JP, Vidailhet M, Briard ML, Belot V, Dhondt JL. Neonatal screening for cystic fibrosis: France rises to the challenge J. Inherit Metab Dis 2003; 26: 729- 744. 8. Levy H, Nugent M, Schneck K, et al. Refining the continuum of CFTR-associated disorders in the era of newborn screening. Clin Genet 2016; 89: 539-549. 9. Ren CL, Borowitz DS, Gonska T, et al. Cystic fibrosis transmembrane conductance regulator-related metabolic syndrome and cystic fibrosis screen positive, inconclusive diagnosis. J Pediatr 2017; 181: S45-S51.e1. 10. Doğum istatistikleri. Available at: www.tuik.gov.tr (Accesed on 05.11.2017). 11. World Medical Association (WMA). World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 2000; 284: 3043-3045. 12. Cinel G, Doğru D, Yalçın E, Özçelik U, Gürcan N, Kiper N. Sweat conductivity test: Can it replace chloride titration for cystic fibrosis diagnosis? Turk J Pediatr 2012; 54: 576-582. 13. Ersu R, Çakır E. Kistik Fibrozis Yenidoğan Tarama Testi ile Tanı Alan Hastaları İzleme Rehberi.T.C. Sağlık Bakanlığı Türkiye Halk Sağlığı Kurumu, 2015. Available at:http://www.kistikfibrozisturkiye. org/files/admin/KF_yenidogan_tarama_rehberi.pdf (Accesed on 22.04.2016). 14. Farrell PM, Rosenstein BJ, White TB, et al; Cystic Fibrosis Foundation. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report. J Pediatr 2008; 153: S4-S14. 15. Farrell PM, White TB, Howenstine MS, et al. Diagnosis of cystic fibrosis in screened populations. J Pediatr 2017; 181S: S33-S44. e2. 16. Rock MJ, Mischler EH, Farrell PM, Bruns WT, Hassemer DJ, Laessig RH. Immunoreactive trypsinogen screening for cystic fibrosis: Characterization of infants with a false-positive screening test. Pediatr. Pulmonol 1989; 6: 42-48. 17. Rueegg CS, Kuehni CE, Gallati S, et al; Swiss CF Screening Task Force. One-year evaluation of a neonatal screening program for cystic fibrosis in Switzerland. Dtsch Arztebl Int 2013; 110: 356-363. 18. Sands D, Zybert K, Mierzejewska E, Ołtarzewski M. Diagnosing cystic fibrosis in newborn screening in Poland - 15 years of experience. Dev Period Med 2015; 19: 16-24. 19. Kloosterboer M, Hoffman G, Rock M, et al. Clarification of laboratory and clinical variables that influence cystic fibrosis newborn screening with initial analysis of immunoreactive trypsinogen. Pediatrics 2009; 123: e338-e346. 20. Sanders DB1, Lai HJ, Rock MJ, Farrell PM. Comparing age of cystic fibrosis diagnosis and treatment initiation after newborn screening with two common strategies. J Cyst Fibros 2012; 11: 150-153. 21. Padoan R, Genoni S, Moretti E, Seia M, Giunta A, Corbetta C. Genetic and clinical features of falsenegative infants in a neonatal screening programme for cystic fibrosis. Acta Paediatr 2002; 91: 82-87. 22. Wilcken B, Wiley V, Sherry G, Bayliss U. Neonatal screening for cystic fibrosis: A comparison of two strategies for case detection in 1.2 million babies. J Pediatr 1995; 127: 965-970. 23. Sontag MK, Hammond KB, Zielenski J, Wagener JS, Accurso FJ. Two-tiered immunoreactive trypsinogenbased newborn screening for cystic fibrosis in Colorado: Screening efficacy and diagnostic outcomes. J Pediatr 2005; 147(Suppl 3): S83-S88. 24. NCCLS. Sweat Testing: Sample Collection and Quantitative Analysis; Approved Guideline (2nd edition). NCCLS document C34-A2. NCCLS, Pennsylvania USA, 2000. 25. Laguna TA, Lin N, Wang Q, Holme B, McNamara J, Regelmann WE. Comparison of quantitative sweat chloride methods after positive newborn screen for cystic fibrosis. Pediatr Pulmonol 2012; 47: 736-742. 26. Desax MC, Ammann R, Hammer J, Schoeni MH, Barben J; Swiss Paediatric Respiratory Research Group. Nanoduct sweat testing for rapid diagnosis in newborns, infants and children with cystic fibrosis. Eur J Pediatr 2008; 167: 299-304. 27. Borowitz D, Parad RB, Sharp JK, et al. Cystic Fibrosis Foundation practice guidelines for the management of infants with cystic fibrosis transmembrane conductance regülatör-related metabolic syndrome during the first two years of life and beyond. J Pediatr 2009; 155(Suppl 6): 106-116. 28. Sosnay PR, Siklosi KR, Van Goor F, et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet 2013; 45: 1160-1167. 29. Rock MJ, Levy H, Zaleski C, Farrell PM. Factors accounting for a missed diagnosis of cystic fibrosis after newborn screening. Pediatr Pulmonol 2011; 46: 1166-1174. 30. Mayell SJ, Munck A, Craig JV, et al; European Cystic Fibrosis Society Neonatal Screening Working Group. A European consensus for the evaluation and management of infants with an equivocal diagnosis following newborn screening for cystic fibrosis. J Cyst Fibros 2009; 8: 71-78. 31. Munck A, Mayell SJ, Winters V, et al. Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID): A new designation and management recommendations for infants with an inconclusive diagnosis following newborn screening. J Cyst Fibros 2015; 14: 706-713. 32. Kharrazi M, Yang J, Bishop T, et al; California Cystic Fibrosis Newborn Screening Consortium. Newborn screening for cystic fibrosis in California. Pediatrics 2015; 136: 1062-1072. 33. Ooi CY, Castellani C, Keenan K, et al. Inconclusive diagnosis of cystic fibrosis after newborn screening. Pediatrics 2015; 135: e1377-e1385. 34. Groves T, Robinson P, Wiley V, Fitzgerald DA. Longterm outcomes of children with intermediate sweat chloride values in infancy. J Pediatr 2015; 166: 1469- 1474.