Format

Send to

Choose Destination
J Pediatr. 2016 Aug;175:150-158.e1. doi: 10.1016/j.jpeds.2016.03.046. Epub 2016 Apr 27.

Improving the Sensitivity and Positive Predictive Value in a Cystic Fibrosis Newborn Screening Program Using a Repeat Immunoreactive Trypsinogen and Genetic Analysis.

Author information

1
Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO. Electronic address: marci.sontag@ucdenver.edu.
2
Laboratory Services Section, Texas Department of State Health Services, Austin, TX; Laboratory Services Division, Colorado Department of Public Health and Environment, Denver, CO.
3
Laboratory Services Division, Colorado Department of Public Health and Environment, Denver, CO.
4
Laboratory Services Section, Texas Department of State Health Services, Austin, TX.
5
Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO.

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.

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.

KEYWORDS:

accuracy; carriers; cystic fibrosis-related metabolic syndrome; neonatal screening

PMID:
27131402
DOI:
10.1016/j.jpeds.2016.03.046
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science Icon for University of Colorado, Strauss Health Sciences Library
Loading ...
Support Center