Neonatal screening for cystic fibrosis: comparing the performances of IRT/DNA and IRT/PAP
Jacques Sarles1, Roch Giorgi2, Patrice Berthézène3
1AFDPHE, 75015 Paris, France; Aix-Marseille University, Hôpital d'Enfants de la Timone, 13005 Marseille, France.
Insights
The IRT/PAP newborn screening strategy shows comparable sensitivity to IRT/DNA for cystic fibrosis (CF) detection, potentially reducing sweat tests when mild forms are not a priority.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- A large-scale study in France evaluated two newborn screening methods for cystic fibrosis (CF).
- The study compared the Immuno-reactive Trypsinogen (IRT)/DNA versus IRT/Pseudomonas aeruginosa lipase (PAP) assays.
- Over 550,000 newborns were included in this comparative performance analysis.
Purpose of the Study:
- To compare the diagnostic performance of IRT/DNA and IRT/PAP screening strategies for cystic fibrosis in newborns.
- To determine optimal PAP cutoffs for CF newborn screening.
- To assess the non-inferiority of the IRT/PAP strategy compared to IRT/DNA.
Main Methods:
- Newborns with elevated IRT levels underwent parallel IRT/DNA and PAP testing.
- Provisional PAP cutoffs were applied based on IRT values (50-100 μg/L and >100 μg/L).
- Optimal cutoffs were determined using a non-inferiority method, followed by sweat testing for positive cases.
Main Results:
- The IRT/DNA strategy identified 85 CF cases (73 classical, 12 atypical).
- Optimal PAP cutoffs identified 82 CF cases (77 classical, 5 atypical), with significantly fewer sweat tests compared to IRT/DNA.
- The IRT/PAP strategy required 1039 sweat tests versus 314 for IRT/DNA.
Conclusions:
- The IRT/PAP strategy demonstrates non-inferior sensitivity to IRT/DNA for detecting cystic fibrosis, particularly when mild forms are not the primary focus.
- Optimized PAP cutoffs can enhance the efficiency of newborn screening by reducing the number of required sweat tests.
- This suggests IRT/PAP is a viable alternative for CF newborn screening, offering potential advantages in resource utilization.
Background:
French health authorities promoted a study on 553,167 newborns comparing the performances of IRT/DNA and IRT/PAP for CF newborn screening.
Methods:
In parallel to IRT/DNA, PAP was assayed in newborns with IRT>50 μg/L. Provisional PAP cutoffs at 3.0 μg/L when 50
Results:
95 CF newborns were identified (83 classical forms (ClF), including 9 meconium ileus (MI), and 12 atypical (mild) forms (AF) Of them, IRT/DNA identified 85 (73 ClF including 5 MI and 12 AF). PAP cutoffs at 1.8 μg/L when 50< IRT<100 μg/L and 0.6 μg/L when IRT>100 μg/L would identify 82 CF: 77 ClF, including 8 MI, and 5 AF. The number of sweat tests was 314 and 1039 in the IRT/DNA and IRT/PAP strategies, respectively.
Conclusions:
Using the optimal cutoffs, the sensitivity of the IRT/PAP strategy would not be inferior to that of IRT/DNA if identification of MF is not required.
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