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

2020 ◽  
Vol 6 (2) ◽  
pp. 46
Author(s):  
Graham Sinclair ◽  
Vanessa McMahon ◽  
Amy Schellenberg ◽  
Tanya N. Nelson ◽  
Mark Chilvers ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
British Columbia ◽  
Newborn Screening ◽  
Screening Program ◽  
False Negative ◽  
Yukon Territory ◽  
Screening Algorithm ◽  
Sweat Testing ◽  
Cftr Mutations ◽  
Cystic Fibrosis Screening

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.

scholarly journals The first five-year evaluation of cystic fibrosis neonatal screening program in São Paulo State, Brazil

2020 ◽  
Vol 36 (10) ◽  
Author(s):  
Léa Maria Zanini Maciel ◽  
Patrícia Künzle Ribeiro Magalhães ◽  
Ieda Regina Lopes Del Ciampo ◽  
Maria Luísa Barato de Sousa ◽  
Maria Inez Machado Fernandes ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Screening Program ◽  
False Negative ◽  
Clinical Manifestations ◽  
Sao Paulo ◽  
São Paulo ◽  
Court Order ◽  
Paulo State ◽  
São Paulo State

The Hospital of the Ribeirão Preto Medical School, University of São Paulo is one of the three screening centers in São Paulo State, Brazil, and has included a test for cystic fibrosis (CF) since February 6, 2010, by a court order. We evaluated the first five years of this CF-newborn screening program. The original immunoreactive trypsinogen (IRT)/IRT screening protocol was adopted in Brazil. A total of 173,571 newborns were screened, 1,922 (1.1%) of whom showed IRT1 ≥ 70ng/mL. Of these, 1,795 (93.4%) collected IRT2, with elevated results (IRT2 ≥ 70ng/mL) in 102 of them (5.2%). We identified a total of 26 CF cases during this period, including three CF cases that were not detected by the CF-newborn screening. The incidence of the disease among the screened babies was 1:6,675 newborns screened. Median age at the initial evaluation was 42 days, comparable to that of neonates screened with the IRT/DNA protocol. Almost all infants with CF already exhibited some manifestations of the disease during the neonatal period. The mutation most frequently detected in the CF cases was F508del. These findings suggest the early age at the beginning of treatment at our center was due to the effort of the persons involved in the program regarding an effective active search. Considering the false negative results of CF-newborn screening and the early onset of clinical manifestations of the disease in this study, pediatricians should be aware of the diagnosis of CF even in children with negative test.

scholarly journals Clinical and Genotypical Features of False-Negative Patients in 26 Years of Cystic Fibrosis Neonatal Screening in Tuscany, Italy

Diagnostics ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 446 ◽  
Author(s):  
Giovanni Taccetti ◽  
Matteo Botti ◽  
Vito Terlizzi ◽  
Maria Chiara Cavicchi ◽  
Anna Silvia Neri ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Dna Analysis ◽  
Screening Program ◽  
Genetic Disorder ◽  
False Negative ◽  
Clinical Manifestations ◽  
Primary Care Providers ◽  
Developed Countries ◽  
Care Providers

Cystic fibrosis (CF) is a life-threatening and common genetic disorder. Cystic fibrosis newborn screening (CF NBS) has been implemented in many countries over the last 30 years, becoming a widely accepted public health strategy in economically developed countries. False-negative (FN) cases can occur after CF NBS, with the number depending on the method. We evaluated the delayed diagnosis of CF, identifying the patients who had false-negative CF NBS results over 26 years (1992–2018) in Tuscany, Italy. The introduction of DNA analysis to the newborn screening protocol improved the sensitivity of the test and reduced the FNs. Our experience showed that, overall, at least 8.7% of cases of CF received FNs (18 cases) and were diagnosed later, with an average age of 6.6 years (range: 4 months to 22 years). Respiratory symptoms and salt-loss syndrome (metabolic hypochloremic alkalosis) are suggestive symptoms of CF and were commons events in FN patients. In Tuscany, a region with a high CFTR allelic heterogeneity, the salt-loss syndrome was a common event in FNs. Therefore, we provided evidence to support the claim that the FN patients had CFTR mutations rarer compared with the true-positive cases. We underline the importance of vigilance toward clinical manifestations suggestive of CF on the part of the primary care providers and hospital physicians in a region with an efficient newborn screening program.

Neonatal cystic fibrosis screening program in the state of Paraná: evaluation 30 months after implementation

10.2223/1345 ◽  
2005 ◽  
Vol 81 (3) ◽  
pp. 240-244
Author(s):  
Grégor P. Chermikoski Santos ◽  
Mouseline T. Domingos ◽  
Ehrenfried O. Wittig ◽  
Carlos A. Riedi ◽  
Nelson A. Rosário
Keyword(s):  
Cystic Fibrosis ◽  
Screening Program ◽  
The State ◽  
Cystic Fibrosis Screening

scholarly journals Massachusetts’ Findings from Statewide Newborn Screening for Spinal Muscular Atrophy

2021 ◽  
Vol 7 (2) ◽  
pp. 26
Author(s):  
Jaime E. Hale ◽  
Basil T. Darras ◽  
Kathryn J. Swoboda ◽  
Elicia Estrella ◽  
Jin Yun Helen Chen ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Newborn Screening ◽  
New England ◽  
Screening Program ◽  
Muscular Atrophy ◽  
Treatment Options ◽  
Newborn Screening Program ◽  
Treatment Protocols ◽  
Screening Algorithm ◽  
New Treatment

Massachusetts began newborn screening (NBS) for Spinal Muscular Atrophy (SMA) following the availability of new treatment options. The New England Newborn Screening Program developed, validated, and implemented a screening algorithm for the detection of SMA-affected infants who show absent SMN1 Exon 7 by Real-Time™ quantitative PCR (qPCR). We screened 179,467 neonates and identified 9 SMA-affected infants, all of whom were referred to a specialist by day of life 6 (average and median 4 days of life). Another ten SMN1 hybrids were observed but never referred. The nine referred infants who were confirmed to have SMA were entered into treatment protocols. Early data show that some SMA-affected children have remained asymptomatic and are meeting developmental milestones and some have mild to moderate delays. The Massachusetts experience demonstrates that SMA NBS is feasible, can be implemented on a population basis, and helps engage infants for early treatment to maximize benefit.

Challenges in Implementing a Successful Newborn Cystic Fibrosis Screening Program

2005 ◽  
Vol 147 (3) ◽  
pp. S89-S93 ◽  
Author(s):  
Anne Marie Comeau ◽  
Richard Parad ◽  
Robert Gerstle ◽  
Brian P. O'Sullivan ◽  
Henry L. Dorkin ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Screening Program ◽  
Cystic Fibrosis Screening

P016 First results from national newborn screening program for cystic fibrosis in the Republic of North Macedonia

2020 ◽  
Vol 19 ◽  
pp. S59
Author(s):  
S. Fustikj ◽  
V. Anastasovska ◽  
D. Plaseska Karanfilska ◽  
L. Spirevska ◽  
M. Pesevska ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Screening Program ◽  
Newborn Screening Program ◽  
First Results ◽  
The Republic

scholarly journals Evaluation of Technical Issues in a Pilot Multicenter Newborn Screening Program for Sickle Cell Disease

2018 ◽  
Vol 5 (1) ◽  
pp. 2
Author(s):  
Maddalena Martella ◽  
Giampietro Viola ◽  
Silvia Azzena ◽  
Sara Schiavon ◽  
Andrea Biondi ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Newborn Screening ◽  
Molecular Analysis ◽  
Sickle Cell ◽  
Screening Program ◽  
Globin Gene ◽  
False Negative ◽  
Confirmatory Test ◽  
Cell Disease ◽  
Technical Issues

A multicenter pilot program for universal newborn screening of Sickle cell disease (SCD) was conducted in two centres of Northern Italy (Padova and Monza). High Performance Liquid Chromatography (HPLC) was performed as the first test on samples collected on Guthrie cards and molecular analysis of the β-globin gene (HBB) was the confirmatory test performed on the HPLC-positive or indeterminate samples. 5466 samples of newborns were evaluated. Of these, 5439/5466 were submitted to HPLC analysis and the molecular analysis always confirmed in all the alteration detected in HPLC (62/5439 newborns); 4/5439 (0.07%) were SCD affected, 37/5439 (0.68%) were HbAS carriers and 21/5439 (0.40%) showed other hemoglobinopathies. Stored dried blood spots were adequate for HPLC and β-globin gene molecular analysis. Samples were suitable for analysis until sixteen months old. A cut-off of A1 percentage, in order to avoid false negative or unnecessary confirmation tests, was identified. Our experience showed that several technical issues need to be addressed and resolved while developing a multicenter NBS program for SCD in a country where there is no national neonatal screening (NBS) program for SCD and NBS programs occur on a regional basis.

scholarly journals Newborn Screening for Cystic Fibrosis by Use of a Multiplex Immunoassay

2010 ◽  
Vol 56 (3) ◽  
pp. 445-450 ◽  
Author(s):  
Barbara A Lindau-Shepard ◽  
Kenneth A Pass
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Screening Program ◽  
Pancreatic Disease ◽  
High Rate ◽  
Dna Testing ◽  
Second Tier ◽  
Sample Set ◽  
Positive Results ◽  
Immunoreactive Trypsinogen

Abstract Background: Since its beginnings, newborn screening for cystic fibrosis (CF) using an assay for immunoreactive trypsinogen (IRT) has been plagued by a high rate of false-positive results (screen positive, diagnosis negative), despite attempts to reduce this rate by use of altered cutoffs and second-tier DNA testing. IRT exists as 2 isoforms: IRT1 and IRT2, with IRT2 being more closely aligned with pancreatic disease, including CF. Assay standardization between programs is a continuing problem because the IRT assays currently in use variously recognize either 1 or both isoforms. Here we report the development of a multiplexed assay for both forms of IRT simultaneously. Methods: Using 2 different Luminex bead sets, we developed assays for each IRT isoform separately and then combined them. Using the sum of IRT1 and IRT2 values (IRT1+IRT2), we compared the results with a CF kit currently in use. Results: In a sample set consisting of 16 cases confirmed positive for CF, we established a cutoff at >97 μg/L total IRT. Seven of 8 carriers with 1 CF mutation screen-positive by the standard method were also screen-positive by IRT1+IRT2. Of 32 cases screen-positive by standard IRT, 11 were screen-negative by IRT1+IRT2. None of these 11 cases had CF mutations identified by the screening program. Conclusions: These data indicate that the multiplex method with specificity for 2 isoforms of IRT has performance comparable to that of a standard IRT method and the advantage of improved standardization by detection of the 2 isoforms.

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