Improving the Sensitivity and Positive Predictive Value in a Cystic Fibrosis Newborn Screening Program Using a Repeat Immunoreactive Trypsinogen and Genetic Analysis - 26/07/16
, Rachel Lee, PhD 2, 3, Daniel Wright, BS 3, Debra Freedenberg, MD, PhD 2, Scott D. Sagel, MD, PhD 4Abstract |
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.
Study design |
A retrospective review of the IRT/IRT/DNA algorithm implemented in Colorado, Wyoming, and Texas.
Results |
A total of 1 520 079 newborns were screened, 32 557 (2.1%) had abnormal first IRT; 8794 (0.54%) on second. Furthermore, 14 653 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 1:2.5, and newborns with CF to newborns with CFTR-related metabolic syndrome was 10.8:1. 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 (∼97 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.
Le texte complet de cet article est disponible en PDF.Keywords : neonatal screening, accuracy, carriers, cystic fibrosis-related metabolic syndrome
Abbreviations : CF, CFFNPR, CRMS, DBS, IRT, NBS, PPV
Plan
| Supported by the Cystic Fibrosis Foundation (Sontag07AO) and collaborations established in the Mountain States Regional Genetics Collaborative, a grant from the United States Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Bureau, Genetic Services Branch (H46MC24095). The authors declare no conflicts of interest. |
Vol 175
P. 150 - août 2016 Retour au numéro
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