Newborn Screening Program for Cystic Fibrosis in Türkiye: Experiences from False-Negative Tests and Requirement for Optimization
Background: Since January 2015, the Cystic Fibrosis National Newborn Bloodspot Screening (CF-NBS) program has been implemented in Türkiye with two samples of immune reactive trypsinogen (IRT-1/IRT-2) testing. Aims: To evaluate the Turkish national CF screening program, which included patients refer...
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| Format: | Article |
| Language: | English |
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Galenos Publishing House
2025-01-01
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| Series: | Balkan Medical Journal |
| Online Access: | https://balkanmedicaljournal.org/text.php?lang=en&id=2655 |
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| author | Fevziye Çoksüer Gökçen Kartal Öztürk Handan Duman Şenol Meral Barlık Mehmet Mustafa Özaslan Bahar Girgin Dindar Ece Ocak Ece Halis Şükrü Atacan Öğütcü Figen Gülen Esen Demir |
| author_facet | Fevziye Çoksüer Gökçen Kartal Öztürk Handan Duman Şenol Meral Barlık Mehmet Mustafa Özaslan Bahar Girgin Dindar Ece Ocak Ece Halis Şükrü Atacan Öğütcü Figen Gülen Esen Demir |
| author_sort | Fevziye Çoksüer |
| collection | DOAJ |
| description | Background: Since January 2015, the Cystic Fibrosis National Newborn Bloodspot Screening (CF-NBS) program has been implemented in Türkiye with two samples of immune reactive trypsinogen (IRT-1/IRT-2) testing.
Aims: To evaluate the Turkish national CF screening program, which included patients referred to a tertiary pediatric pulmonology center, to ascertain the optimal cut-off values for IRT-1/IRT-2 and to identify alternative strategies for mitigating the number of late-diagnosed false-negative patients (FNPs) who initially exhibited screen negative results but were diagnosed subsequently based on clinical suspicion. The study also compared NBS-positive patients to FNPs to determine the influence of delayed diagnosis.
Study Design: A retrospective cohort study.
Methods: Screening for CF was conducted in accordance with the national CF-NBS program within 48-72 hours of birth by collecting a few drops of heel blood on Guthrie paper. A cut-off value of 90 µg/l was accepted for the first IRT, while 70 µg/l was accepted for the second sample. Infants with elevated IRT values in both samples were referred to the CF centers for a sweat test (ST). Based on the diagnosis, the NBS-positive infants referred to our CF center for ST analysis were divided into three groups: CF; cystic fibrosis-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID); and false-positive NBS. In addition, the study included NBS-negative patients who initially received negative screen results but were subsequently diagnosed with CF based on clinical suspicion.
Results: Of the 227 NBS-positive infants referred within the study period, 53 (23.34%) were diagnosed with CF (true-positive NBS), 11 were classified as CRMS/CFSPID (4.84%), and 163 were classified as false-positive NBS (71.8%). CF was diagnosed in 66 infants, 53 (80.3%) of whom were confirmed using the NBS test, while the 13 (19.7%) patients who were missed on the NBS test were diagnosed based on clinical suspicion (FNP). The study findings indicate that the IRT/IRT approach exhibited a sensitivity of 80.3% and a positive predictive value (PPV) of 23.3%.
Conclusion: The current study is the first to analyze the NBS program for CF using data from the Western Anatolian Region of Türkiye. Due to the low sensitivity and PPV of the IRT/IRT protocol and the high proportion of false-positive infants and FNPs, the current national program is not practicable for Türkiye. False-negative results significantly delay the diagnosis and invalidate the screening objectives. It is essential to establish optimal cut-off values for IRT-1/IRT-2 or revise existing strategies to reduce the number of FNPs missed by the screening program. |
| format | Article |
| id | doaj-art-ccb2b7a786a04308b69cad17e09618fa |
| institution | Kabale University |
| issn | 2146-3123 2146-3131 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Galenos Publishing House |
| record_format | Article |
| series | Balkan Medical Journal |
| spelling | doaj-art-ccb2b7a786a04308b69cad17e09618fa2025-01-07T12:50:21ZengGalenos Publishing HouseBalkan Medical Journal2146-31232146-31312025-01-01421455310.4274/balkanmedj.galenos.2024.2024-7-144Newborn Screening Program for Cystic Fibrosis in Türkiye: Experiences from False-Negative Tests and Requirement for OptimizationFevziye Çoksüer0https://orcid.org/0000-0003-1992-1603Gökçen Kartal Öztürk1https://orcid.org/0000-0002-0793-9710Handan Duman Şenol2https://orcid.org/0000-0002-7152-5053Meral Barlık3https://orcid.org/0000-0003-1640-1733Mehmet Mustafa Özaslan4https://orcid.org/0000-0003-0611-0852Bahar Girgin Dindar5https://orcid.org/0000-0002-0523-4856Ece Ocak6https://orcid.org/0000-0002-4466-0620Ece Halis7https://orcid.org/0000-0003-4859-2933Şükrü Atacan Öğütcü8https://orcid.org/0000-0001-6195-5474Figen Gülen9https://orcid.org/0000-0002-5431-3913Esen Demir10https://orcid.org/0000-0003-2736-8924Department of Pediatric Pulmonology, Ege University Faculty of Medicine, İzmir, TürkiyeDepartment of Pediatric Pulmonology, Ege University Faculty of Medicine, İzmir, TürkiyeDepartment of Pediatric Allergy and Clinical Immunology, Ege University Faculty of Medicine, İzmir, TürkiyeDepartment of Pediatric Pulmonology, Ege University Faculty of Medicine, İzmir, TürkiyeDepartment of Pediatric Pulmonology, Ege University Faculty of Medicine, İzmir, TürkiyeDepartment of Pediatric Pulmonology, Ege University Faculty of Medicine, İzmir, TürkiyeDepartment of Pediatric Pulmonology, Ege University Faculty of Medicine, İzmir, TürkiyeDepartment of Pediatric Pulmonology, Ege University Faculty of Medicine, İzmir, TürkiyeDepartment of Pediatric Pulmonology, Ege University Faculty of Medicine, İzmir, TürkiyeDepartment of Pediatric Pulmonology, Ege University Faculty of Medicine, İzmir, TürkiyeDepartment of Pediatric Pulmonology, Ege University Faculty of Medicine, İzmir, TürkiyeBackground: Since January 2015, the Cystic Fibrosis National Newborn Bloodspot Screening (CF-NBS) program has been implemented in Türkiye with two samples of immune reactive trypsinogen (IRT-1/IRT-2) testing. Aims: To evaluate the Turkish national CF screening program, which included patients referred to a tertiary pediatric pulmonology center, to ascertain the optimal cut-off values for IRT-1/IRT-2 and to identify alternative strategies for mitigating the number of late-diagnosed false-negative patients (FNPs) who initially exhibited screen negative results but were diagnosed subsequently based on clinical suspicion. The study also compared NBS-positive patients to FNPs to determine the influence of delayed diagnosis. Study Design: A retrospective cohort study. Methods: Screening for CF was conducted in accordance with the national CF-NBS program within 48-72 hours of birth by collecting a few drops of heel blood on Guthrie paper. A cut-off value of 90 µg/l was accepted for the first IRT, while 70 µg/l was accepted for the second sample. Infants with elevated IRT values in both samples were referred to the CF centers for a sweat test (ST). Based on the diagnosis, the NBS-positive infants referred to our CF center for ST analysis were divided into three groups: CF; cystic fibrosis-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID); and false-positive NBS. In addition, the study included NBS-negative patients who initially received negative screen results but were subsequently diagnosed with CF based on clinical suspicion. Results: Of the 227 NBS-positive infants referred within the study period, 53 (23.34%) were diagnosed with CF (true-positive NBS), 11 were classified as CRMS/CFSPID (4.84%), and 163 were classified as false-positive NBS (71.8%). CF was diagnosed in 66 infants, 53 (80.3%) of whom were confirmed using the NBS test, while the 13 (19.7%) patients who were missed on the NBS test were diagnosed based on clinical suspicion (FNP). The study findings indicate that the IRT/IRT approach exhibited a sensitivity of 80.3% and a positive predictive value (PPV) of 23.3%. Conclusion: The current study is the first to analyze the NBS program for CF using data from the Western Anatolian Region of Türkiye. Due to the low sensitivity and PPV of the IRT/IRT protocol and the high proportion of false-positive infants and FNPs, the current national program is not practicable for Türkiye. False-negative results significantly delay the diagnosis and invalidate the screening objectives. It is essential to establish optimal cut-off values for IRT-1/IRT-2 or revise existing strategies to reduce the number of FNPs missed by the screening program.https://balkanmedicaljournal.org/text.php?lang=en&id=2655 |
| spellingShingle | Fevziye Çoksüer Gökçen Kartal Öztürk Handan Duman Şenol Meral Barlık Mehmet Mustafa Özaslan Bahar Girgin Dindar Ece Ocak Ece Halis Şükrü Atacan Öğütcü Figen Gülen Esen Demir Newborn Screening Program for Cystic Fibrosis in Türkiye: Experiences from False-Negative Tests and Requirement for Optimization Balkan Medical Journal |
| title | Newborn Screening Program for Cystic Fibrosis in Türkiye: Experiences from False-Negative Tests and Requirement for Optimization |
| title_full | Newborn Screening Program for Cystic Fibrosis in Türkiye: Experiences from False-Negative Tests and Requirement for Optimization |
| title_fullStr | Newborn Screening Program for Cystic Fibrosis in Türkiye: Experiences from False-Negative Tests and Requirement for Optimization |
| title_full_unstemmed | Newborn Screening Program for Cystic Fibrosis in Türkiye: Experiences from False-Negative Tests and Requirement for Optimization |
| title_short | Newborn Screening Program for Cystic Fibrosis in Türkiye: Experiences from False-Negative Tests and Requirement for Optimization |
| title_sort | newborn screening program for cystic fibrosis in turkiye experiences from false negative tests and requirement for optimization |
| url | https://balkanmedicaljournal.org/text.php?lang=en&id=2655 |
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