Pancreatitis-Associated Protein in Neonatal Screening for Cystic Fibrosis: Strengths and Weaknesses
Olaf Sommerburg1,2, Jutta Hammermann3
1Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Department of Pediatrics III, University of Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany.
Insights
Pancreatic enzyme activity (PAP) is used in newborn screening programs across Europe. While PAP offers advantages like earlier diagnosis and better detection in diverse populations, it has lower sensitivity and predictive value compared to DNA-based methods.
Area of Science:
- Biochemistry
- Genetics
- Public Health
Background:
- Newborn screening programs are crucial for early detection of genetic disorders.
- Cystic Fibrosis (CF) is a primary target for newborn screening.
- Different screening protocols, including those using Pancreatic enzyme activity (PAP), are employed globally.
Purpose of the Study:
- To review the implementation and effectiveness of PAP in European newborn screening programs.
- To compare PAP-based protocols with other screening strategies like IRT/IRT and IRT/DNA.
- To identify the strengths and weaknesses of PAP in newborn screening for Cystic Fibrosis.
Main Methods:
- Review of national newborn screening protocols in European countries and regions.
- Analysis of screening strategies including IRT/PAP/DNA/EGA, IRT/PAP/DNA, and IRT/PAP/IRT.
- Comparison of PAP-based protocols with IRT/IRT and IRT/DNA protocols regarding diagnostic capabilities and efficiency.
Main Results:
- Four European countries and one region currently utilize PAP in their newborn screening.
- PAP offers advantages such as avoiding carrier detection and reducing False Positive Screening results for CFSPID.
- IRT/PAP protocols enable earlier diagnoses than IRT/IRT, but may have lower sensitivity than IRT/DNA and a low positive predictive value if purely biochemical.
Conclusions:
- PAP-based newborn screening shows promise, particularly in ethnically diverse populations, due to its biochemical nature.
- Combining IRT/PAP with genetic screening or a second IRT (third tier) may enhance the performance of CF-NBS protocols.
- Further optimization of PAP protocols is needed to maximize its benefits in newborn screening for Cystic Fibrosis.
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.
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