Optimization of the French cystic fibrosis newborn screening programme by a centralized tracking process

Munck, À.; Delmas, Dominique; Audrézet, Marie-Pierre; Lemonnier, Lydie; Cheillan, David; Roussey, M.

doi:10.1177/0969141317692611

Cited by 20 publications

(21 citation statements)

References 26 publications

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“…In the present study, only two of our 80 CF-SPID patients (i.e., 2.5%) evolved to CF, differently by other studies that report 3% to 20% of CF-SPID evolved to CF during a three-years follow-up [ 8 , 23 , 24 ]. This may depend in part by the use of gene sequencing during NBS, considering that also among our patients diagnosed as CF, four cases had an intermediate ST and the second causing variant was identified by the sequencing, allowing to classify such cases as CF and not as CF-SPID.…”

Section: Discussioncontrasting

confidence: 99%

Cystic Fibrosis-Screening Positive Inconclusive Diagnosis: Newborn Screening and Long-Term Follow-Up Permits to Early Identify Patients with CFTR-Related Disorders

et al. 2020

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Background: Newborn screening (NBS) early-identifies cystic fibrosis (CF), but in CF-screening positive inconclusive diagnosis (CF-SPID) the results of immunoreactive trypsinogen (IRT), molecular analysis and sweat test (ST) are discordant. A percentage of CF-SPID evolves to CF, but data on long-term monitoring are lacking. We describe the follow-up of all CF and CF-SPID identified between 2008 and 2019. Methods: NBS was performed by IRT followed by molecular analysis and ST between 2008 and 2014; double IRT followed by molecular analysis and ST after 2014. Results: NBS revealed 47 CF and 99 CF-SPID newborn, a ratio 1:2.1—the highest reported so far. This depends on the identification by gene sequencing of the second variant with undefined effect in 40 CF-SPID that otherwise would have been defined as carriers. Clinical complications and pulmonary infections occurred more frequently among CF patients than among CF-SPID. Two CF-SPID cases evolved to CF (at two years), while eight evolved to CFTR-related disorders (CFTR-RD), between one and eight years, with bronchiectasis (two), recurrent pneumonia (four, two with sinonasal complications), recurrent pancreatitis (two). No clinical, biochemical or imaging data predicted the evolution. Conclusion: Gene sequencing within the NBS reveals a higher number of CF-SPID and we first describe an approach to early identify CFTR-RD, with relevant impact on their outcome.

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Section: Discussioncontrasting

confidence: 99%

Cystic Fibrosis-Screening Positive Inconclusive Diagnosis: Newborn Screening and Long-Term Follow-Up Permits to Early Identify Patients with CFTR-Related Disorders

et al. 2020

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“…A total of six CF cases and three individuals with an inconclusive diagnosis (the screen negative equivalent of CFSPID) were missed by the screening program and diagnosed clinically, representing a false negative rate of 7.8% for CF (8.8% for CF+CFSPID). This rate is higher than reported by other screening programs, with false negative rates ranging from 2-8% in the literature, depending on the jurisdiction and approach to screening [20][21][22]. This higher false negative rate may reflect the centralized service for CF in BC and a corresponding likelihood of a clinically ascertained diagnoses being communicated back to the screening program.…”

Section: False Negativesmentioning

confidence: 62%

Performance of a Three-Tier (IRT-DNA-IRT) Cystic Fibrosis Screening Algorithm in British Columbia

Sinclair

McMahon

Schellenberg

et al. 2020

IJNS

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Newborn screening for Cystic Fibrosis has been implemented in most programs worldwide, but the approach used varies, including combinations of immunoreactive trypsinogen (IRT) and CFTR mutation analysis on one or more specimens. The British Columbia (BC) newborn screening program tests ~45,000 infants per year in BC and the Yukon Territory, covering almost 1.5 million km2 in western Canada. CF screening was initiated using an IRT-DNA-IRT approach with a second bloodspot card at 21 days of age for all CFTR mutation heterozygotes and any non-carriers in the top 0.1% for IRT. This second IRT was implemented to avoid sweat testing of infants without persistent hypertrypsinemia, reducing the burden of travel for families. Over nine years (2010–2018), 401,977 infants were screened and CF was confirmed in 76, and a further 28 were deemed CF screen positive inconclusive diagnosis (CFSPID). Day 21 IRT was normal in 880 CFTR mutation carriers who were quoted a very low CF risk and offered optional sweat testing. Only 13% of families opted for sweat testing and a total of 1036 sweat tests were avoided. There were six false negative CF cases (and three CFSPID) due to a low initial IRT or no CFTR mutations. Although one CFSPID case had a normal repeat IRT result, the addition of the day 21 IRT did not contribute to any CF false negatives.

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“…Therefore, the significant risk reported for neonates with an inconclusive diagnosis to develop a CF disease [58] might be considerably lowered as many more cases are detected through EGA before sweat testing. By contrast, removal of R117H from the variant panel of the French NBS program led to dramatically improved performance, with the PPV increasing from 16% to 34% and the ratio CF:CFSPID from 6.3:1 to 9:1 [32].…”

Section: Discussionmentioning

confidence: 90%

The Role of Extended CFTR Gene Sequencing in Newborn Screening for Cystic Fibrosis

Bergougnoux

Lopez

Girodon

2020

IJNS

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There has been considerable progress in the implementation of newborn screening (NBS) programs for cystic fibrosis (CF), with DNA analysis being part of an increasing number of strategies. Thanks to advances in genomic sequencing technologies, CFTR-extended genetic analysis (EGA) by sequencing its coding regions has become affordable and has already been included as part of a limited number of core NBS programs, to the benefit of admixed populations. Based on results analysis of existing programs, the values and challenges of EGA are reviewed in the perspective of its implementation on a larger scale. Sensitivity would be increased at best by using EGA as a second tier, but this could be at the expense of positive predictive value, which improves, however, if EGA is applied after testing a variant panel. The increased detection of babies with an inconclusive diagnosis has proved to be a major drawback in programs using EGA. The lack of knowledge on pathogenicity and penetrance associated with numerous variants hinders the introduction of EGA as a second tier, but EGA with filtering for all known CF variants with full penetrance could be a solution. The issue of incomplete knowledge is a real challenge in terms of the implemention of NBS extended to many genetic diseases.

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Optimization of the French cystic fibrosis newborn screening programme by a centralized tracking process

Cited by 20 publications

References 26 publications

Cystic Fibrosis-Screening Positive Inconclusive Diagnosis: Newborn Screening and Long-Term Follow-Up Permits to Early Identify Patients with CFTR-Related Disorders

Cystic Fibrosis-Screening Positive Inconclusive Diagnosis: Newborn Screening and Long-Term Follow-Up Permits to Early Identify Patients with CFTR-Related Disorders

Performance of a Three-Tier (IRT-DNA-IRT) Cystic Fibrosis Screening Algorithm in British Columbia

The Role of Extended CFTR Gene Sequencing in Newborn Screening for Cystic Fibrosis

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