How does learning false positive results through newborn screening for cystic fibrosis influence cascade testing and family planning?

2014 ◽  
Vol 47 (15) ◽  
pp. 134-135
Author(s):  
Yvonne Bombard ◽  
Fiona A. Miller ◽  
Robin Z. Hayeems ◽  
Carolyn J. Barg ◽  
Sarah J. Patton ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Family Planning ◽  
Newborn Screening ◽  
False Positive ◽  
Cascade Testing ◽  
Positive Results

scholarly journals Psychological Impact of NBS for CF

2020 ◽  
Vol 6 (2) ◽  
pp. 27 ◽  
Author(s):  
Jane Chudleigh ◽  
Holly Chinnery
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Health Professionals ◽  
False Positive ◽  
Psychological Impact ◽  
Confirmatory Test ◽  
Test Results ◽  
Burden Of Care ◽  
Positive Results ◽  
Screening Result

Newborn screening for cystic fibrosis has resulted in diagnosis often before symptoms are recognised, leading to benefits including reduced disease severity, decreased burden of care, and lower costs. The psychological impact of this often unsought diagnosis on the parents of seemingly well children is less well understood. The time during which the screening result is communicated to families but before the confirmatory test results are available is recognised as a period of uncertainty and it is this uncertainty that can impact most on parents. Evidence suggests this may be mitigated against by ensuring the time between communication and confirmatory testing is minimized and health professionals involved in communicating positive newborn screening results and diagnostic results for cystic fibrosis to families are knowledgeable and able to provide appropriate reassurance. This is particularly important in the case of false positive results or when the child is given a Cystic Fibrosis Screen Positive, Inconclusive Diagnosis designation. However, to date, there are no formal mechanisms in place to support health professionals undertaking this challenging role, which would enable them to meet the expectations set out in specific guidance.

Psychological Effects of False-Positive Results in Cystic Fibrosis Newborn Screening: A Two-Year Follow-Up

2010 ◽  
Vol 156 (5) ◽  
pp. 771-776.e1 ◽  
Author(s):  
Julie Beucher ◽  
Emmanuelle Leray ◽  
Eric Deneuville ◽  
Monique Roblin ◽  
Isabelle Pin ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
False Positive ◽  
Psychological Effects ◽  
Positive Results

scholarly journals Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT Versus IRT/PAP/IRT

2019 ◽  
Vol 5 (3) ◽  
pp. 32
Author(s):  
Sadik ◽  
Algaba ◽  
Jiménez ◽  
Benito ◽  
Blasco-Alonso ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
False Positive ◽  
Good Alternative ◽  
Safety Net ◽  
Strategy Versus ◽  
Second Tier ◽  
Post Hoc ◽  
Positive Results ◽  
Immunoreactive Trypsinogen

Identifying newborns at risk for cystic fibrosis (CF) by newborn screening (NBS) using dried blood spot (DBS) specimens provides an opportunity for presymptomatic detection. All NBS strategies for CF begin with measuring immunoreactive trypsinogen (IRT). Pancreatitis-associated protein (PAP) has been suggested as second-tier testing. The main objective of this study was to evaluate the analytical performance of an IRT/PAP/IRT strategy versus the current IRT/IRT strategy over a two-year pilot study including 68,502 newborns. The design of the study, carried out in a prospective and parallel manner, allowed us to compare four different CF-NBS protocols after performing a post hoc analysis. The best PAP cutoff point and the potential sources of PAP false positive results in our non-CF newborn population were also studied. 14 CF newborns were detected, resulting in an overall CF prevalence of 1/4, 893 newborns. The IRT/IRT algorithm detected all CF cases, but the IRT/PAP/IRT algorithm failed to detect one case of CF. The IRT/PAP/IRT with an IRT-dependent safety net protocol was a good alternative to improve sensitivity to 100%. The IRT × PAP/IRT strategy clearly performed better, with a sensitivity of 100% and a positive predictive value (PPV) of 39%. Our calculated optimal cutoffs were 2.31 µg/L for PAP and 167.4 µg2/L2 for IRT × PAP. PAP levels were higher in females and newborns with low birth weight. PAP false positive results were found mainly in newborns with conditions such as prematurity, sepsis, and hypoxic-ischemic encephalopathy.

scholarly journals 33 High rate of false-positive results in cystic fibrosis newborn screening among a Spanish population of Maghribian origin

2013 ◽  
Vol 12 ◽  
pp. S56
Author(s):  
P. Mondejar-Lopez ◽  
M.D. Pastor-Vivero ◽  
A. Mula-Anton ◽  
J.M. Olmos-García ◽  
E. Fiot ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
False Positive ◽  
High Rate ◽  
Spanish Population ◽  
Positive Results

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.

False-positive results of genetic testing in cystic fibrosis

1997 ◽  
Vol 130 (4) ◽  
pp. 658-660 ◽  
Author(s):  
W.Stuart Warren ◽  
Ada Hamosh ◽  
Michelle Egan ◽  
Beryl J. Rosenstein
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Testing ◽  
False Positive ◽  
Positive Results

scholarly journals NeoSeq: a new method of genomic sequencing for newborn screening

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Huaiyan Wang ◽  
Yuqi Yang ◽  
Lingna Zhou ◽  
Yu Wang ◽  
Wei Long ◽  
...  
Keyword(s):  
Newborn Screening ◽  
False Positive ◽  
Disease Risk ◽  
Amplicon Sequencing ◽  
Dried Blood Spots ◽  
Inborn Errors ◽  
Screening Cost ◽  
Diagnostic Time ◽  
Significant Difference ◽  
Positive Results

Abstract Objective To explore the clinical application of NeoSeq in newborn screening. Methods Based on the results obtained from traditional newborn screening (NBS) with tandem mass spectrometry (TMS), three cohorts were recruited into the present study: 36 true positive cases (TPC), 60 false-positive cases (FPC), and 100 negative cases. The dried blood spots of the infants were analyzed with NeoSeq, which is based on multiplex PCR amplicon sequencing. Results Overall, the sensitivity of NeoSeq was 55.6% (20/36) in the detection of TPC. NeoSeq detected disease-related genes in 20 of 36 TPC infants, while it could not identify these genes in eight children. Five cases (3.1%) with disease risk were additionally found in the FPC and NC cohorts. There was a significant difference in the diagnostic time between the two methods—10 days for NeoSeq vs. 43 days for traditional NBS. Conclusions NeoSeq is an economic genomic screening test for newborn screening. It can detect most inborn errors of metabolism, reduce the rate of false positive results, shorten the porting cycles, and reduce the screening cost. However, it is still necessary to further optimize the panel design and add more clinically relevant genomic variants to increase its sensitivity.

scholarly journals Rapid 2nd-Tier Test for Measurement of 3-OH-Propionic and Methylmalonic Acids on Dried Blood Spots: Reducing the False-Positive Rate for Propionylcarnitine during Expanded Newborn Screening by Liquid Chromatography–Tandem Mass Spectrometry

2007 ◽  
Vol 53 (7) ◽  
pp. 1364-1369 ◽  
Author(s):  
Giancarlo la Marca ◽  
Sabrina Malvagia ◽  
Elisabetta Pasquini ◽  
Marzia Innocenti ◽  
Maria Alice Donati ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
False Positive ◽  
Tandem Mass ◽  
Blood Spots ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Positive Results

Abstract Background: The expansion of newborn screening programs has increased the number of newborns diagnosed with inborn errors of metabolism in the presymptomatic phase, but it has also increased the number of costly, stress-producing false-positive results. Because propionylcarnitine (C3) is one of the analytes most frequently responsible for false-positive results, we aimed to develop a rapid liquid chromatography–tandem mass spectrometry (LC-MS/MS) method to identify free methylmalonic (MMA) and 3-OH propionic (3OH-PA) acids in blood spots. Methods: We studied newborn screening spots from 250 healthy controls; 124 from infants with abnormal C3, of whom only 5 (4%) were truly affected; 124 from infants with altered isolated methylmalonylcarnitine; and 4 from clinically diagnosed patients. Whole blood was eluted from a 3.2-mm dried blood spot by a CH3CN/H2O 7:3 and 5 mL/L formic. This extract was injected into a LC-MS/MS equipped with pneumatically assisted electrospray without derivatization. Total analysis time was 5 min per sample. Results: The assays were linear up to 3300 nmol/L for both metabolites. Intra- and interassay imprecision data were 3.6%–8% and 3.1%–6%, respectively, for MMA and 5.2%–20% and 3.6%–17% for 3OH-PA. Limit of detection and limit of quantitation were 1.95 and 4.2 μmol/L, respectively, for MMA and 8 and 10 μmol/L for 3OH-PA. The recoveries were 92.9%–106.1%. No deterioration was noted on the columns after 500 chromatographic runs. If the new method had been used as a 2nd-tier test for the 124 samples, only the 5 true positives would have been recalled for additional samples, and the positive predictive value would have been 100%. Conclusions: This method has the potential to markedly reduce false-positive results and the associated costs and anxiety. It may also be suitable for diagnosing and routinely monitoring blood spots for methylmalonic aciduria and propionic acidemia.

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