Improving the Sensitivity and Positive Predictive Value in a Cystic Fibrosis Newborn Screening Program Using a Repeat Immunoreactive Trypsinogen and Genetic Analysis.
J Pediatr
; 175: 150-158.e1, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-27131402
ABSTRACT
OBJECTIVE:
To evaluate the performance of a new cystic fibrosis (CF) newborn screening algorithm, comprised of immunoreactive trypsinogen (IRT) in first (24-48 hours of life) and second (7-14 days of life) dried blood spot plus DNA on second dried blood spot, over existing algorithms. STUDYDESIGN:
A retrospective review of the IRT/IRT/DNA algorithm implemented in Colorado, Wyoming, and Texas.RESULTS:
A total of 1â520â079 newborns were screened, 32â557 (2.1%) had abnormal first IRT; 8794 (0.54%) on second. Furthermore, 14â653 mutation analyses were performed; 1391 newborns were referred for diagnostic testing; 274 newborns were diagnosed; and 201/274 (73%) of newborns had 2 mutations on the newborn screening CFTR panel. Sensitivity was 96.2%, compared with sensitivity of 76.1% observed with IRT/IRT (105 ng/mL cut-offs, P < .0001). The ratio of newborns with CF to heterozygote carriers was 12.5, and newborns with CF to newborns with CFTR-related metabolic syndrome was 10.81. The overall positive predictive value was 20%. The median age of diagnosis was 28, 30, and 39.5 days in the 3 states.CONCLUSIONS:
IRT/IRT/DNA is more sensitive than IRT/IRT because of lower cut-offs (â¼97 percentile or 60 ng/mL); higher cut-offs in IRT/IRT programs (>99 percentile, 105 ng/mL) would not achieve sufficient sensitivity. Carrier identification and identification of newborns with CFTR-related metabolic syndrome is less common in IRT/IRT/DNA compared with IRT/DNA. The time to diagnosis is nominally longer, but diagnosis can be achieved in the neonatal period and opportunities to further improve timeliness have been enacted. IRT/IRT/DNA algorithm should be considered by programs with 2 routine screens.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tripsinogênio
/
Testes Genéticos
/
Triagem Neonatal
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Regulador de Condutância Transmembrana em Fibrose Cística
/
Fibrose Cística
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Limite:
Female
/
Humans
/
Male
/
Newborn
País/Região como assunto:
America do norte
Idioma:
En
Revista:
J Pediatr
Ano de publicação:
2016
Tipo de documento:
Article