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Pediatrics. 2015 Jun;135(6):e1377-85. doi: 10.1542/peds.2014-2081. Epub 2015 May 11.

Inconclusive diagnosis of cystic fibrosis after newborn screening.

Author information

1
Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia; Sydney Children's Hospital Randwick, Sydney, Australia; Division of Gastroenterology, Hepatology, and Nutrition.
2
Cystic Fibrosis Centre, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy;
3
Physiology and Experimental Medicine, Research Institute.
4
Division of Gastroenterology, Hepatology, and Nutrition, and.
5
Division of Respirology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Canada;
6
Division of Respiratory Medicine, Department of Pediatrics, University of Calgary, Alberta Children's Hospital, Calgary, Alberta, Canada;
7
Division of Pediatric Respiratory Medicine, Department of Pediatrics, BC Children's Hospital, Vancouver, British Columbia, Canada;
8
Pediatric Cystic Fibrosis Clinic, Windsor Regional Hospital, Windsor, Ontario, Canada;
9
Department of Pediatrics, School of Medicine, Queen's University, Kingston, Ontario, Canada;
10
Victoria General Hospital, Victoria, British Columbia, Canada; and.
11
Children's Hospital of Western Ontario, London, Ontario, Canada.
12
Division of Clinical and Metabolic Genetics, and.
13
Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia;
14
Physiology and Experimental Medicine, Research Institute, Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada;
15
Division of Gastroenterology, Hepatology, and Nutrition, Physiology and Experimental Medicine, Research Institute.
16
Division of Gastroenterology, Hepatology, and Nutrition, Physiology and Experimental Medicine, Research Institute, tanja.gonska@sickkids.ca.

Abstract

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
25963003
DOI:
10.1542/peds.2014-2081
[Indexed for MEDLINE]
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