Published online February 1, 2009
PEDIATRICS Vol. 123 No. 2 February 2009, pp. e338-e346 (doi:10.1542/peds.2008-1681)
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kloosterboer, M.
Right arrow Articles by Farrell, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kloosterboer, M.
Right arrow Articles by Farrell, P. M.
Related Collections
Right arrow Respiratory Tract
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

ARTICLE

Clarification of Laboratory and Clinical Variables That Influence Cystic Fibrosis Newborn Screening With Initial Analysis of Immunoreactive Trypsinogen

Molly Kloosterboer, MSa, Gary Hoffman, BSb, Michael Rock, MDc, William Gershan, MDd, Anita Laxova, BSc, Zhanhai Li, PhDe and Philip M. Farrell, MD, PhDa,b

Departments of a Population Health Sciences
c Pediatrics
e Biostatistics and Medical Informatics
b Wisconsin State Laboratory of Hygiene, University of Wisconsin, Madison, Wisconsin
d Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin

OBJECTIVES. To ensure that each newborn receives an equitable test of the highest possible sensitivity, we recognized the necessity to reassess immunoreactive trypsinogen and DNA issues in cystic fibrosis newborn screening algorithms. Our objectives included clarification of various factors that influence immunoreactive trypsinogen concentrations and resolution of long-standing questions about variations in immunoreactive trypsinogen levels among newborns.

METHODS. Immunoreactive trypsinogen data on 660443 newborns who were born between July 1, 1994, and June 30, 2004, were abstracted from the Wisconsin State Laboratory of Hygiene databases and deidentified for analysis. Using a compiled data set, we analyzed various demographic characteristics to determine their role, if any, in immunoreactive trypsinogen variation. Specifically, season of birth, reagent lot, and birth weight were examined. Sensitivities of the most common cystic fibrosis newborn screening protocols, namely immunoreactive trypsinogen/immunoreactive trypsinogen and immunoreactive trypsinogen/DNA, were also investigated.

RESULTS. Mean and 95th percentile immunoreactive trypsinogen levels were shown to vary by both season and reagent lot number and affect sensitivity of the assay. Low birth weight infants had significantly higher immunoreactive trypsinogen values than normal birth weight infants. Sensitivities were also found to vary on the basis of the algorithm used, with the highest sensitivity of 96.2% calculated for an immunoreactive trypsinogen/DNA protocol with 23 cystic fibrosis transmembrane conductance regulator mutation analyses compared with 80.2% with the immunoreactive trypsinogen/immunoreactive trypsinogen method used in 9 states.

CONCLUSIONS. Floating, rather than fixed, cutoff values for the initial immunoreactive trypsinogen portion of any cystic fibrosis newborn screening protocol are generally necessary on the basis of the seasonal and reagent lot variations observed. Because of its lower sensitivity, immunoreactive trypsinogen/immunoreactive trypsinogen does not optimize detection of patients with cystic fibrosis.

Key Words: cystic fibrosis • immunoreactive trypsinogen • newborn screening • DNA

Abbreviations: NBS—newborn screening • CF—cystic fibrosis • IRT—immunoreactive trypsinogen • CFTR—cystic fibrosis transmembrane conductance regulator • MI—meconium ileus • WSLH—Wisconsin State Laboratory of Hygiene • CI—confidence interval

Accepted Oct 28, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?