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Review
. 2020 Mar 30;6(2):28.
doi: 10.3390/ijns6020028. eCollection 2020 Jun.

Pancreatitis-Associated Protein in Neonatal Screening for Cystic Fibrosis: Strengths and Weaknesses

Olaf Sommerburg  1   2 , Jutta Hammermann  3
Affiliations
Review

Pancreatitis-Associated Protein in Neonatal Screening for Cystic Fibrosis: Strengths and Weaknesses

Olaf Sommerburg et al. Int J Neonatal Screen. .

Abstract

There are currently four countries and one local region in Europe that use PAP in their newborn screening programme. The first country to employ PAP at a national level was the Netherlands, which started using IRT/PAP/DNA/EGA in 2011. Germany followed in 2016 with a slightly different IRT/PAP/DNA strategy. Portugal also started in 2016, but with an IRT/PAP/IRT programme, and in 2017, Austria changed its IRT/IRT protocol to an IRT/PAP/IRT program. In 2018, Catalonia started to use an IRT/PAP/IRT/DNA strategy. The strengths of PAP are the avoidance of carrier detection and a lower detection rate of CFSPID. PAP seems to have advantages in detecting CF in ethnically-diverse populations, as it is a biochemical approach to screening, which looks for pancreatic injury. Compared to an IRT/IRT protocol, an IRT/PAP protocol leads to earlier diagnoses. While PAP can be assessed with the same screening card as the first IRT, the second IRT in an IRT/IRT protocol requires a second heel prick around the 21st day of the patient's life. However, IRT/PAP has two main weaknesses. First, an IRT/PAP protocol seems to have a lower sensitivity compared to a well-functioning IRT/DNA protocol, and second, IRT/PAP that is performed as a purely biochemical protocol has a very low positive predictive value. However, if the advantages of PAP are to be exploited, a combination of IRT/PAP with genetic screening or a second IRT as a third tier could be an alternative for a sufficiently performing CF-NBS protocol.

Keywords: biochemical screening; cystic fibrosis; immunoreactive trypsinogen; newborn screening; pancreatitis associated protein.

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Conflict of interest statement

Conflicts of InterestThe authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schemes of the two main variants of the pure biochemical IRT/PAP protocol: (A) IRT/PAP protocol published by Sarles et al. 2005 [8] and (B) the IRT/PAP-SN protocol with IRT-dependent safety net modified by Sommerburg et al. [11]. Values in parenthesis show the PAP cut-off values as given before correction of the dilution factor by the manufacturer (see explanation in the main Text).
Figure 2
Figure 2
Simplified schemes of three selected PAP-based CF NBS protocols currently used: (A) The Netherlands: IRT/PAP/DNA(35)/EGA protocol including last modifications from 2016, (B) Germany: IRT/PAP-SN/DNA(31) protocol, (C) Portugal: IRT/PAP-SN/IRT protocol.
See this image and copyright information in PMC

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