Diagnosing cystic fibrosis in newborn screening in Poland - 15 years of experience

Abstract

Early diagnosis of cystic fibrosis (CF) made by the introduction of CF NBS (Cystic Fibrosis Newborn Screening) provides the opportunity to undertake preventive measures and provide treatment before the development of irreversible changes in the respiratory tract and other complications. CF NBS was conducted as a pilot programme in four Polish districts in the period 1999-2003. In 2006 CF NBS started again and was gradually extended across the country. The aim of this study was to show the evolution of the Polish CF NBS strategies and assess the diagnostic consequences of this programme.

Material and methods: The study involved children diagnosed and treated only in the IMiD Centre. The strategy in Polish CF NBS was modified over time. Firstly, the model IRT/IRT and IRT/IRT/DNA with one mutation was implemented, which was followed by IRT/DNA with a gradually expanding number of CFTR mutations (tab. I). Newborns with positive results of CF NBS were called to the CF IMiD Centre, and sweat tests were performed. The children diagnosed and children with mutations in both alleles of the CFTR gene even if at least one of them had undefined pathogenicity) were taken under IMiD Centre care. Sensitivity, specificity and positive predictive values during subsequent stages of CF NBS were calculated (tab. III).

Results: During the 1999-2003 pilot study 444 063 newborns underwent CF NBS and in 74 cases CF was diagnosed. 582 693 newborns were screened from September 2006 to December 2011 in four regions and 100 children were diagnosed with CF. The frequencies of CF in the Polish population in both screening periods were 1:5767 and 1:5712 respectively. Firstly, the IRT/IRT model was implemented, but the number of newborns called to the CF Centre was high - the PPV was 7.6%. In the next step CF NBS DNA analysis was used. Here sensitivity and specificity were high - nearly 100%. In the following years the number of mutations detected was expanded (including 16 most common ones in the Polish population). Due to the panel changes, the number of calls declined and the PPV (predictive positive value) improved (to 26.1%) after the application of expanded genetic analysis. Expanding the panel of mutations resulted in an increased number of carriers and observational subjects.

Conclusions: IRT/DNA strategy with expanded DNA analysis provides the opportunity for earlier CF diagnosis even in children with normal sweat test values. However, this model caused frequent carrier detection and inconclusive diagnosis in comparison to IRT/IRT or IRT/IRT/DNA with a limited number of mutations. Further research and changes in Polish CF NBS are needed to increase the PPV, while preserving high sensitivity and specificity..