Inconclusive diagnosis of cystic fibrosis after newborn screening

To prospectively study infants with an inconclusive diagnosis of cystic fibrosis (CF) identified by newborn screening (NBS; "CF screen positive, inconclusive diagnosis" [CFSPID]) for disease manifestations. Infants with CFSPID and CF based on NBS from 8 CF centers were prospectively evalua...

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Published in:Pediatrics (Evanston) 2015-06, Vol.135 (6), p.e1377-e1385
Main Authors: Ooi, Chee Y, Castellani, Carlo, Keenan, Katherine, Avolio, Julie, Volpi, Sonia, Boland, Margaret, Kovesi, Tom, Bjornson, Candice, Chilvers, Mark A, Morgan, Lenna, van Wylick, Richard, Kent, Steven, Price, April, Solomon, Melinda, Tam, Karen, Taylor, Louise, Malitt, Kylie-Ann, Ratjen, Felix, Durie, Peter R, Gonska, Tanja
Format: Article
Language:English
Subjects:
Babies
Care and treatment
Cystic fibrosis
Cystic Fibrosis - diagnosis
Cystic Fibrosis - genetics
Diagnosis
Female
Genotype & phenotype
Health aspects
Humans
Infant, Newborn
Infants
Infants (Newborn)
Male
Medical diagnosis
Medical examination
Medical screening
Mutation
Neonatal Screening
Pediatrics
Predictive Value of Tests
Prospective Studies
Reproducibility of Results
Sweat tests
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Summary:To prospectively study infants with an inconclusive diagnosis of cystic fibrosis (CF) identified by newborn screening (NBS; "CF screen positive, inconclusive diagnosis" [CFSPID]) for disease manifestations. Infants with CFSPID and CF based on NBS from 8 CF centers were prospectively evaluated and monitored. Genotype, phenotype, repeat sweat test, serum trypsinogen, and microbiology data were compared between subjects with CF and CFSPID and between subjects with CFSPID who did (CFSPID→CF) and did not (CFSPID→CFSPID) fulfill the criteria for CF during the first 3 years of life. Eighty-two subjects with CFSPID and 80 subjects with CF were enrolled. The ratio of CFSPID to CF ranged from 1:1.4 to 1:2.9 in different centers. CFTR mutation rates did not differ between groups; 96% of subjects with CFSPID and 93% of subjects with CF had 2 mutations. Subjects with CFSPID had significantly lower NBS immunoreactive trypsinogen (median [interquartile range]:77 [61-106] vs 144 [105-199] μg/L; P < .0001) than did subjects with CF. Pseudomonas aeruginosa and Stenotrophomonas maltophilia were isolated in 12% and 5%, respectively, of subjects with CFSPID. CF was diagnosed in 9 of 82 (11%) subjects with CFSPID (genotype and abnormal sweat chloride = 3; genotype alone = 4; abnormal sweat chloride only = 2). Sweat chloride was abnormal in CFSPID→CF patients at a mean (SD) age of 21.3 (13.8) months. CFSPID→CF patients had significantly higher serial sweat chloride (P < .0001) and serum trypsinogen (P = .009) levels than did CFSPID→CFSPID patients. A proportion of infants with CFSPID will be diagnosed with CF within the first 3 years. These findings underscore the need for clinical monitoring, repeat sweat testing at age 2 to 3 years, and extensive genotyping.
ISSN:0031-4005
1098-4275
DOI:10.1542/peds.2014-2081