Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT versus IRT/PAP/IRT
Identifying newborns at risk for cystic fibrosis (CF) by newborn screening (NBS) using dried blood spot (DBS) specimens provides an opportunity for presymptomatic detection. All NBS strategies for CF begin with measuring immunoreactive trypsinogen (IRT). Pancreatitis-associated protein (PAP) has bee...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-09-01
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| Series: | International Journal of Neonatal Screening |
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| Online Access: | https://www.mdpi.com/2409-515X/5/3/32 |
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| author | Ilham Sadik Inmaculada Pérez de Algaba Rocío Jiménez Carmen Benito Javier Blasco-Alonso Pilar Caro Víctor M. Navas-López Javier Pérez-Frías Estela Pérez Juliana Serrano Raquel Yahyaoui |
| author_facet | Ilham Sadik Inmaculada Pérez de Algaba Rocío Jiménez Carmen Benito Javier Blasco-Alonso Pilar Caro Víctor M. Navas-López Javier Pérez-Frías Estela Pérez Juliana Serrano Raquel Yahyaoui |
| author_sort | Ilham Sadik |
| collection | DOAJ |
| description | Identifying newborns at risk for cystic fibrosis (CF) by newborn screening (NBS) using dried blood spot (DBS) specimens provides an opportunity for presymptomatic detection. All NBS strategies for CF begin with measuring immunoreactive trypsinogen (IRT). Pancreatitis-associated protein (PAP) has been suggested as second-tier testing. The main objective of this study was to evaluate the analytical performance of an IRT/PAP/IRT strategy versus the current IRT/IRT strategy over a two-year pilot study including 68,502 newborns. The design of the study, carried out in a prospective and parallel manner, allowed us to compare four different CF-NBS protocols after performing a post hoc analysis. The best PAP cutoff point and the potential sources of PAP false positive results in our non-CF newborn population were also studied. 14 CF newborns were detected, resulting in an overall CF prevalence of 1/4, 893 newborns. The IRT/IRT algorithm detected all CF cases, but the IRT/PAP/IRT algorithm failed to detect one case of CF. The IRT/PAP/IRT with an IRT-dependent safety net protocol was a good alternative to improve sensitivity to 100%. The IRT × PAP/IRT strategy clearly performed better, with a sensitivity of 100% and a positive predictive value (PPV) of 39%. Our calculated optimal cutoffs were 2.31 µg/L for PAP and 167.4 µg<sup>2</sup>/L<sup>2</sup> for IRT × PAP. PAP levels were higher in females and newborns with low birth weight. PAP false positive results were found mainly in newborns with conditions such as prematurity, sepsis, and hypoxic-ischemic encephalopathy. |
| first_indexed | 2024-12-12T00:10:01Z |
| format | Article |
| id | doaj.art-fdafe36004dc47d19d4b757d04a1f62a |
| institution | Directory Open Access Journal |
| issn | 2409-515X |
| language | English |
| last_indexed | 2024-12-12T00:10:01Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Neonatal Screening |
| spelling | doaj.art-fdafe36004dc47d19d4b757d04a1f62a2022-12-22T00:45:00ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2019-09-01533210.3390/ijns5030032ijns5030032Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT versus IRT/PAP/IRTIlham Sadik0Inmaculada Pérez de Algaba1Rocío Jiménez2Carmen Benito3Javier Blasco-Alonso4Pilar Caro5Víctor M. Navas-López6Javier Pérez-Frías7Estela Pérez8Juliana Serrano9Raquel Yahyaoui10Clinical Laboratory, Hospital La Línea de la Concepción, 11300 Cádiz, SpainLaboratory of Metabolic Disorders and Newborn Screening Center of Eastern Andalusia, Málaga Regional University Hospital, Avenida Arroyo de los Angeles s/n, 29011 Málaga, SpainLaboratory of Metabolic Disorders and Newborn Screening Center of Eastern Andalusia, Málaga Regional University Hospital, Avenida Arroyo de los Angeles s/n, 29011 Málaga, SpainDepartment of Genetics, Málaga Regional University Hospital, 29011 Málaga, SpainDepartment of Pediatrics, Málaga Regional University Hospital, 29011 Málaga, SpainDepartment of Pediatrics, Málaga Regional University Hospital, 29011 Málaga, SpainDepartment of Pediatrics, Málaga Regional University Hospital, 29011 Málaga, SpainDepartment of Pediatrics, Málaga Regional University Hospital, 29011 Málaga, SpainDepartment of Pediatrics, Málaga Regional University Hospital, 29011 Málaga, SpainDepartment of Pediatrics, Málaga Regional University Hospital, 29011 Málaga, SpainLaboratory of Metabolic Disorders and Newborn Screening Center of Eastern Andalusia, Málaga Regional University Hospital, Avenida Arroyo de los Angeles s/n, 29011 Málaga, SpainIdentifying newborns at risk for cystic fibrosis (CF) by newborn screening (NBS) using dried blood spot (DBS) specimens provides an opportunity for presymptomatic detection. All NBS strategies for CF begin with measuring immunoreactive trypsinogen (IRT). Pancreatitis-associated protein (PAP) has been suggested as second-tier testing. The main objective of this study was to evaluate the analytical performance of an IRT/PAP/IRT strategy versus the current IRT/IRT strategy over a two-year pilot study including 68,502 newborns. The design of the study, carried out in a prospective and parallel manner, allowed us to compare four different CF-NBS protocols after performing a post hoc analysis. The best PAP cutoff point and the potential sources of PAP false positive results in our non-CF newborn population were also studied. 14 CF newborns were detected, resulting in an overall CF prevalence of 1/4, 893 newborns. The IRT/IRT algorithm detected all CF cases, but the IRT/PAP/IRT algorithm failed to detect one case of CF. The IRT/PAP/IRT with an IRT-dependent safety net protocol was a good alternative to improve sensitivity to 100%. The IRT × PAP/IRT strategy clearly performed better, with a sensitivity of 100% and a positive predictive value (PPV) of 39%. Our calculated optimal cutoffs were 2.31 µg/L for PAP and 167.4 µg<sup>2</sup>/L<sup>2</sup> for IRT × PAP. PAP levels were higher in females and newborns with low birth weight. PAP false positive results were found mainly in newborns with conditions such as prematurity, sepsis, and hypoxic-ischemic encephalopathy.https://www.mdpi.com/2409-515X/5/3/32cystic fibrosisnewborn screening (NBS)dried blood spot (DBS)immunoreactive trypsinogen (IRT)pancreatitis-associated protein (PAP) |
| spellingShingle | Ilham Sadik Inmaculada Pérez de Algaba Rocío Jiménez Carmen Benito Javier Blasco-Alonso Pilar Caro Víctor M. Navas-López Javier Pérez-Frías Estela Pérez Juliana Serrano Raquel Yahyaoui Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT versus IRT/PAP/IRT International Journal of Neonatal Screening cystic fibrosis newborn screening (NBS) dried blood spot (DBS) immunoreactive trypsinogen (IRT) pancreatitis-associated protein (PAP) |
| title | Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT versus IRT/PAP/IRT |
| title_full | Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT versus IRT/PAP/IRT |
| title_fullStr | Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT versus IRT/PAP/IRT |
| title_full_unstemmed | Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT versus IRT/PAP/IRT |
| title_short | Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT versus IRT/PAP/IRT |
| title_sort | initial evaluation of prospective and parallel assessments of cystic fibrosis newborn screening protocols in eastern andalusia irt irt versus irt pap irt |
| topic | cystic fibrosis newborn screening (NBS) dried blood spot (DBS) immunoreactive trypsinogen (IRT) pancreatitis-associated protein (PAP) |
| url | https://www.mdpi.com/2409-515X/5/3/32 |
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