title: Screening for cystic fibrosis in New York State: considerations for algorithm improvements.
abstract: Newborn screening for cystic fibrosis (CF), a chronic progressive disease affecting mucus viscosity, has been beneficial in both improving life expectancy and the quality of life for individuals with CF. In New York State from 2007 to 2012 screening for CF involved measuring immunoreactive trypsinogen (IRT) levels in dried blood spots from newborns using the IMMUCHEM(™) Blood Spot Trypsin-MW ELISA kit. Any specimen in the top 5% IRT level underwent DNA analysis using the InPlex(®) CF Molecular Test. Of the 1.48 million newborns screened during the 6-year time period, 7631 babies were referred for follow-up. CF was confirmed in 251 cases, and 94 cases were diagnosed with CF transmembrane conductance regulated-related metabolic syndrome or possible CF. Nine reports of false negatives were made to the program. Variation in daily average IRT was observed depending on the season (4-6 ng/ml) and kit lot (<3 ng/ml), supporting the use of a floating cutoff. The screening method had a sensitivity of 96.5%, specificity of 99.6%, positive predictive value of 4.5%, and negative predictive value of 99.5%.
  
  
  CONCLUSIONS
  Considerations for CF screening algorithms should include IRT variations resulting from age at specimen collection, sex, race/ethnicity, season, and manufacturer kit lots.
  
  
  BACKGROUND
  Measuring IRT level in dried blood spots is the first-tier screen for CF. Current algorithms for CF screening lead to substantial false-positive referral rates.
  
  
  BACKGROUND
  IRT values were affected by age of infant when specimen is collected, race/ethnicity and sex of infant, and changes in seasons and manufacturer kit lots The prevalence of CF in NYS is 1 in 4200 with the highest prevalence in White infants (1 in 2600) and the lowest in Black infants (1 in 15,400).
authors: Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120, New Scotland Ave., Albany, NY, 12208, USA. denise.kay@health.ny.gov.
authors: Denise M
authors: DM
authors: Kay
authors: Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120, New Scotland Ave., Albany, NY, 12208, USA. breanne.maloney@health.ny.gov.
authors: Breanne
authors: B
authors: Maloney
authors: Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120, New Scotland Ave., Albany, NY, 12208, USA. rhonda.hamel@health.ny.gov.
authors: Rhonda
authors: R
authors: Hamel
authors: Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120, New Scotland Ave., Albany, NY, 12208, USA. melissa.pearce@health.ny.gov.
authors: Melissa
authors: M
authors: Pearce
authors: Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120, New Scotland Ave., Albany, NY, 12208, USA. lenore.demartino@health.ny.gov.
authors: Lenore
authors: L
authors: DeMartino
authors: Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120, New Scotland Ave., Albany, NY, 12208, USA. rebecca.mcmahon@health.ny.gov.
authors: Rebecca
authors: R
authors: McMahon
authors: Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120, New Scotland Ave., Albany, NY, 12208, USA. emily.mcgrath@health.ny.gov.
authors: Emily
authors: E
authors: McGrath
authors: Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120, New Scotland Ave., Albany, NY, 12208, USA. lea.krein@health.ny.gov.
authors: Lea
authors: L
authors: Krein
authors: Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120, New Scotland Ave., Albany, NY, 12208, USA. beth.vogel@health.ny.gov.
authors: Beth
authors: B
authors: Vogel
authors: Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120, New Scotland Ave., Albany, NY, 12208, USA. carlos.saavedra@health.ny.gov.
authors: Carlos A
authors: CA
authors: Saavedra-Matiz
authors: Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120, New Scotland Ave., Albany, NY, 12208, USA. michele.caggana@health.ny.gov.
authors: Michele
authors: M
authors: Caggana
authors: Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120, New Scotland Ave., Albany, NY, 12208, USA. norma.tavakoli@health.ny.gov.|Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, NY, USA. norma.tavakoli@health.ny.gov.
authors: Norma P
authors: NP
authors: Tavakoli
mesh_terms: D000465:Algorithms; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000453:epidemiology; 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*; D009518:New York / Q000453:epidemiology; D015995:Prevalence; D012680:Sensitivity and Specificity; D014362:Trypsinogen / Q000097:blood*
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014362:Trypsinogen
keywords: CFTR; Cystic fibrosis; Immunoreactive trypsinogen; Mutation analysis; Newborn screening