A systematic review of the outcomes of false‐positive results on newborn screening for congenital hypothyroidism

2021 ◽  
Author(s):  
Kerri R. Rosettenstein ◽  
Samantha J. Lain ◽  
Nicola Wormleaton ◽  
Michelle M. Jack
Keyword(s):  
Systematic Review ◽  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
False Positive ◽  
Positive Results

Thyroid Screening for Early Discharged Infants

PEDIATRICS ◽  
1996 ◽  
Vol 98 (1) ◽  
pp. 41-44
Author(s):  
Judy G. Saslow ◽  
Ernest M. Post ◽  
Carol A. Southard
Keyword(s):  
New Jersey ◽  
Congenital Hypothyroidism ◽  
False Positive ◽  
False Negative ◽  
Negative Results ◽  
Thyroid Screening ◽  
False Negative Results ◽  
Positive Results

Objective. As neonatal discharge before 24 hours of life becomes commonplace, the rejection of congenital hypothyroidism (CH) screening specimens obtained too early has created the need for numerous additional tests. We sought to determine whether the specimens obtained before 24 hours could be used safely. Methods. During a 31-day period we measured thyrotropin in all thyroid-screening specimens that had been obtained before 24 hours. We also examined the early specimens from every infant diagnosed in New Jersey with CH during 1993 or 1994. Results. Among the 663 specimens, those obtained at or before 12 hours and those from infants with birth weights less than 2500 g had too many low thyroxine results to be useful. Among the 515 specimens obtained at more than 12 to 24 hours from newborns weighing 2500 g or more, 37 (7%) had low thyroxine levels and 12 (2.3%) had thyrotropin levels of 20 µIU/mL (mU/L) or higher. Four hundred seventy-one of the 515 infants had subsequent specimens obtained at more than 24 hours, and none of the results were abnormal. There was no child weighing more than or equal to 2500 g who was diagnosed with CH in 1993 and 1994 whose specimen obtained at 24 hours or less was normal. Conclusions. Accepting specimens obtained at more than 12 to 24 hours from infants weighing 2500 g or more would have resulted in more than the usual number of false-positive results but no false-negative results. This would have decreased the requests for additional specimens by more than 90%.

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.

State Newborn Screening in the Tandem Mass Spectrometry Era: More Tests, More False-Positive Results

PEDIATRICS ◽  
2006 ◽  
Vol 118 (2) ◽  
pp. 448-456 ◽  
Author(s):  
B. A. Tarini ◽  
D. A. Christakis ◽  
H. G. Welch
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
False Positive ◽  
Tandem Mass ◽  
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.

scholarly journals Second Tier Molecular Genetic Testing in Newborn Screening for Pompe Disease: Landscape and Challenges

2020 ◽  
Vol 6 (2) ◽  
pp. 32 ◽  
Author(s):  
Laurie D. Smith ◽  
Matthew N. Bainbridge ◽  
Richard B. Parad ◽  
Arindam Bhattacharjee
Keyword(s):  
Genetic Testing ◽  
Newborn Screening ◽  
Pompe Disease ◽  
False Positive ◽  
Clinical Decision Making ◽  
Molecular Genetic ◽  
Screening Tests ◽  
Molecular Genetic Testing ◽  
Second Tier ◽  
Positive Results

Pompe disease (PD) is screened by a two tier newborn screening (NBS) algorithm, the first tier of which is an enzymatic assay performed on newborn dried blood spots (DBS). As first tier enzymatic screening tests have false positive results, an immediate second tier test on the same sample is critical in resolving newborn health status. Two methodologies have been proposed for second tier testing: (a) measurement of enzymatic activities such as of Creatine/Creatinine over alpha-glucosidase ratio, and (b) DNA sequencing (a molecular genetics approach), such as targeted next generation sequencing. (tNGS). In this review, we discuss the tNGS approach, as well as the challenges in providing second tier screening and follow-up care. While tNGS can predict genotype-phenotype effects when known, these advantages may be diminished when the variants are novel, of unknown significance or not discoverable by current test methodologies. Due to the fact that criticisms of screening algorithms that utilize tNGS are based on perceived complexities, including variant detection and interpretation, we clarify the actual limitations and present the rationale that supports optimizing a molecular genetic testing approach with tNGS. Second tier tNGS can benefit clinical decision-making through the use of the initial NBS DBS punch and rapid turn-around time methodology for tNGS, that includes copy number variant analysis, variant effect prediction, and variant ‘cut-off’ tools for the reduction of false positive results. The availability of DNA sequence data will contribute to the improved understanding of genotype-phenotype associations and application of treatment. The ultimate goal of second tier testing should enable the earliest possible diagnosis for the earliest initiation of the most effective clinical interventions in infants with PD.

scholarly journals Reduction in newborn screening metabolic false-positive results following a new collection protocol

2013 ◽  
Vol 16 (6) ◽  
pp. 477-483 ◽  
Author(s):  
Mindy Morris ◽  
Kristin Fischer ◽  
Karen Leydiker ◽  
Lisa Elliott ◽  
Joan Newby ◽  
...  
Keyword(s):  
Newborn Screening ◽  
False Positive ◽  
Positive Results

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

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 Improving the Dutch Newborn Screening for Central Congenital Hypothyroidism by Using 95% Reference Intervals for Thyroxine-Binding Globulin

2021 ◽  
pp. 1-8
Author(s):  
Kevin Stroek ◽  
Annemieke C. Heijboer ◽  
Marja van Veen-Sijne ◽  
Annet M. Bosch ◽  
Catharina P.B. van der Ploeg ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
False Positive ◽  
Reference Population ◽  
Total Sample ◽  
Reference Intervals ◽  
Thyroid Stimulating Hormone ◽  
Published Data ◽  
Free T4 ◽  
Indirect Measure

Introduction: Newborn screening (NBS) for congenital hypothyroidism (CH) in the Netherlands consists of thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin (TBG) measurements to detect thyroidal CH and central CH (CH-C). CH-C is detected by T4 or a calculated T4/TBG ratio, which serves as an indirect measure of free T4. TSH and TBG are only measured in the lowest 20 and 5% of daily T4 values, respectively. A recent evaluation of the Dutch NBS for CH showed that the T4 and T4/TBG ratio contribute to the detection of CH-C but also lead to a low positive predictive value (PPV). Dried blood spot (DBS) reference intervals (RIs) are currently unknown and may contribute to improvement of our NBS algorithm. Materials and Methods: RIs of T4, TSH, TBG, and the T4/TBG ratio were determined according to Clinical &amp; Laboratory Standards Institute guidelines in heel puncture cards from routine NBS in both sexes and at the common NBS sampling ages. Scatter plots were used to compare the healthy reference population to previously published data of CH-C patients and false positives. Results: Analyses of 1,670 heel puncture cards showed small differences between subgroups and led to the formulation of total sample DBS RIs for T4 (56–118 nmol/L), TSH (<2.6 mIU/L), TBG (116–271 nmol/L), and the T4/TBG ratio (>20). 46% of false-positive referrals based on T4 alone had a TBG below the RI, indicating preventable referral due to partial TBG deficiency. One case of CH-C also had partial TBG deficiency (TBG 59 and T4 12 nmol/L blood). Discussion/Conclusion: Established DBS RIs provided possibilities to improve the PPV of the Dutch CH NBS algorithm. We conclude that by taking partial TBG deficiency into account, approximately half of T4 false-positive referrals may be prevented while maintaining NBS sensitivity at the current level.

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