title: The influence of sex, gestational age, birth weight, blood transfusion, and timing of the heel prick on the pancreatitis-associated protein concentration in newborn screening for cystic fibrosis.
abstract: BACKGROUND
  Pancreatitis-associated protein (PAP) is currently discussed as a marker in newborn screening (NBS) for cystic fibrosis (CF). However, it is not known if PAP concentrations are influenced by sex, gestational age, birth weight, blood transfusion or time of collection and what this would mean for NBS for CF.
  
  
  METHODS
  In 2008 all newborns in part of the Netherlands were screened for CF by an IRT/PAP protocol. PAP concentration was determined by the MucoPAP ELISA (DynaBio), which was modified to a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) method following a protocol of PerkinElmer.
  
  
  RESULTS
  In healthy newborns, the median PAP concentration was 0.5 μg/l (Interquartile range (IQR 0.3-0.8) whereas this was 3.2 μg/l (IQR 2.0-12.5) in CF infants. PAP concentrations were lower in premature infants 0.94 and 0.91 times for 25 to 31 + 6 weeks GA and 32 to 36 + 6 weeks respectively. A higher PAP concentration was observed in low-birth-weight infants (<2500 gram)(p = 0.001), per 100 gram birth weight gained the PAP concentration decreased with 0.1 %. PAP levels were higher after a blood transfusion, the 95th percentile increased from 1.3 to 3.6 μg/l leading to a higher false-positive rate. The PAP concentration increased when newborn screening was performed more than 168 hours (day 7) after birth (β = 1.63), the 95th percentile increased from 1.3-1.6 μg/l to 4.0 μg/l after 168 hours (72,874 newborns were screened).
  
  
  CONCLUSIONS
  Sex, birth weight, and gestational age lead to small differences in PAP concentrations without consequences for the screening algorithm. However, blood transfusion as well as performance of the heel prick after 168 hours (7 days) lead to clinically significant higher PAP levels and to a higher risk on a false-positive screening test result.
authors: Department of Research and Innovation, Atrium Medical Center, PO box 4446, 6401 CX Heerlen, The Netherlands. amm.vernooij+chopin@gmail.com
authors: Annette M M
authors: AM
authors: Vernooij-van Langen
authors: J Gerard
authors: JG
authors: Loeber
authors: Bert
authors: B
authors: Elvers
authors: Ralf H
authors: RH
authors: Triepels
authors: Jos
authors: J
authors: Roefs
authors: Johan J
authors: JJ
authors: Gille
authors: Sandra
authors: S
authors: Reijntjens
authors: Edward
authors: E
authors: Dompeling
authors: Jeannette E
authors: JE
authors: Dankert-Roelse
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001724:Birth Weight; D001803:Blood Transfusion; D003550:Cystic Fibrosis / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D006365:Heel / Q000098:blood supply; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D008297:Male; D015997:Neonatal Screening / Q000379:methods; D000073718:Pancreatitis-Associated Proteins; D012737:Sex Factors
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human