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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
Author(s) -
Vernooijvan Langen Annette M. M.,
Loeber J. Gerard,
Elvers Bert,
Triepels Ralf H.,
Roefs Jos,
Gille Johan J.,
Reijntjens Sandra,
Dompeling Edward,
DankertRoelse Jeannette E.
Publication year - 2013
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-012-9498-6
Subject(s) - medicine , cystic fibrosis , gestational age , newborn screening , birth weight , interquartile range , obstetrics , gastroenterology , bronchopulmonary dysplasia , blood transfusion , low birth weight , pediatrics , pregnancy , genetics , biology
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). Conclusion 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.