title: Newborn Screening for Cystic Fibrosis in California.
abstract: OBJECTIVE
  This article describes the methods used and the program performance results for the first 5 years of newborn screening for cystic fibrosis (CF) in California.
  
  
  METHODS
  From July 16, 2007, to June 30, 2012, a total of 2,573,293 newborns were screened for CF by using a 3-step model: (1) measuring immunoreactive trypsinogen in all dried blood spot specimens; (2) testing 28 to 40 selected cystic fibrosis transmembrane conductance regulator (CFTR) mutations in specimens with immunoreactive trypsinogen values ≥62 ng/mL (top 1.6%); and (3) performing DNA sequencing on specimens found to have only 1 mutation in step 2. Infants with ≥2 mutations/variants were referred to CF care centers for diagnostic evaluation and follow-up. Infants with 1 mutation were considered carriers and their parents offered telephone genetic counseling.
  
  
  RESULTS
  Overall, 345 CF cases, 533 CFTR-related metabolic syndrome cases, and 1617 carriers were detected; 28 cases of CF were missed. Of the 345 CF cases, 20 (5.8%) infants were initially assessed as having CFTR-related metabolic syndrome, and their CF diagnosis occurred after age 6 months (median follow-up: 4.5 years). Program sensitivity was 92%, and the positive predictive value was 34%. CF prevalence was 1 in 6899 births. A total of 303 CFTR mutations were identified, including 78 novel variants. The median age at referral to a CF care center was 34 days (18 and 37 days for step 2 and 3 screening test-positive infants, respectively).
  
  
  CONCLUSIONS
  The 3-step model had high detection and low false-positive levels in this diverse population.
authors.affiliation: California Department of Public Health, Richmond, California; and marty.kharrazi@cdph.ca.gov.
authors.forename: Martin
authors.initials: M
authors.lastname: Kharrazi
authors.affiliation: California Department of Public Health, Richmond, California; and.
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.affiliation: California Department of Public Health, Richmond, California; and.
authors.forename: Tracey
authors.initials: T
authors.lastname: Bishop
authors.affiliation: California Department of Public Health, Richmond, California; and.
authors.forename: Shellye
authors.initials: S
authors.lastname: Lessing
authors.affiliation: Sequoia Foundation, La Jolla, California.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Young
authors.affiliation: California Department of Public Health, Richmond, California; and Sequoia Foundation, La Jolla, California.
authors.forename: Steven
authors.initials: S
authors.lastname: Graham
authors.affiliation: Sequoia Foundation, La Jolla, California.
authors.forename: Michelle
authors.initials: M
authors.lastname: Pearl
authors.affiliation: California Department of Public Health, Richmond, California; and.
authors.forename: Helen
authors.initials: H
authors.lastname: Chow
authors.affiliation: California Department of Public Health, Richmond, California; and.
authors.forename: Thomson
authors.initials: T
authors.lastname: Ho
authors.affiliation: California Department of Public Health, Richmond, California; and.
authors.forename: Robert
authors.initials: R
authors.lastname: Currier
authors.affiliation: California Department of Public Health, Richmond, California; and.
authors.forename: Leslie
authors.initials: L
authors.lastname: Gaffney
authors.affiliation: California Department of Public Health, Richmond, California; and.
authors.forename: Lisa
authors.initials: L
authors.lastname: Feuchtbaum
mesh_terms: D000465:Algorithms; D002140:California; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000175:diagnosis*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening / Q000379:methods*; D011237:Predictive Value of Tests; D015995:Prevalence; D012680:Sensitivity and Specificity; D014362:Trypsinogen / Q000097:blood*
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014362:Trypsinogen