Harmonizing Newborn Screening Laboratory Proficiency Test Results Using the CDC NSQAP Reference Materials

Pickens, C. Austin; Sternberg, Maya; Seeterlin, Mary; Jesús, Víctor R. De; Morrissey, Mark A.; Manning, Adrienne; Bhakta, Sonal; Held, Patrice K.; Mei, Joanne V.; Cuthbert, Carla; Pétritis, Konstantinos

doi:10.3390/ijns6030075

Cited by 11 publications

(13 citation statements)

References 29 publications

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“…NBS using MS/MS is generally regarded a semi-quantitative assay as some analytes are isobaric and QC materials are not available for certain analytes, which is another reason for the discrepancy in the quantitative results and cutoffs among laboratories [ 30 ]. To reduce assay-related biases, harmonization of quantitative results, allowing head-to-head comparison among laboratories, would be ideal [ 31 ]. In the qualitative accuracy evaluation using KEQAS PT materials, there was only one sample for each analyte with disagreement.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Evaluation of the NeoBase 2 Non-derivatized MSMS Assay and Exploration of Analytes With Significantly Different Concentrations Between Term and Preterm Neonates

et al. 2022

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Background: Despite the popularity of the NeoBase 2 Non-derivatized MSMS assay (Perki-nElmer, Turku, Finland), there are no reports of its comprehensive evaluation, including the ability to distinguish transient tyrosinemia of the newborn (TTN) from tyrosinemia type 1 (TYR 1) using succinylacetone (SUAC). No newborn screening (NBS) cutoffs for preterm neonates in the Korean population have been suggested. We evaluated the NeoBase 2 assay and identified analytes requiring different cutoffs in preterm neonates.Methods: Residual NBS dried blood spot samples and proficiency testing (PT) materials of the Newborn Screening Quality Assurance Program and the Korean Association of External Quality Assessment Service were used. Precision, accuracy, limit of detection (LOD), lower limit of quantification (LLOQ), linearity, recovery, carryover, and performance of SUAC were evaluated. Cutoffs were determined, and analytes requiring different cutoffs in preterm neonates were investigated.Results: Mean CVs for within-run and between-day precision were within 15%. Accuracy analysis indicated high agreement with in-house derivatized assay results and results of other PT participants. All analytes demonstrated acceptable LOD, LLOQ, and linearity. Recoveries were acceptable, except for SUAC. Carryover was negligible. Cutoffs were established for all analytes; Tyr, adenosine, and C20:0-lysophosphatidylcholine required different cutoffs in preterm neonates. Differential diagnosis of TYR 1 and TTN was successful with simultaneous Tyr and SUAC measurement. Conclusions:The NeoBase 2 assay demonstrated satisfactory performance. The additional analytes provide a wider diagnostic coverage, and the simultaneous measurement of Tyr and SUAC is efficient in excluding TYR 1. The new cutoffs for preterm neonates may decrease false-positive rates, without compromising diagnostic sensitivity.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Evaluation of the NeoBase 2 Non-derivatized MSMS Assay and Exploration of Analytes With Significantly Different Concentrations Between Term and Preterm Neonates

et al. 2022

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“…Data harmonization is also suggested to reduce false-negative and false-positive results, correct for method differences, and achieve greater uniformity of results and clinical conclusions [ 3 , 4 , 6 , 24 , 25 ]. Harmonization, considered to be a “holy grail” [ 25 ], facilitates scaled comparisons and is “the process of recognizing, understanding, and explaining differences while taking steps to achieve uniformity of results, or at minimum, a means of conversion of results such that different groups can use the data obtained from assays interchangeably” [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…Some NBS labs have successfully used multiples of the median (MoM) to harmonize results for MPS I [ 27 , 28 ], TREC [ 29 ], and in a large study involving homocystinuria results from 32 NBS programs covering 18 countries [ 17 ]. Other methods have also been employed, such as using quality control materials and regression equations to harmonize NBS proficiency testing (PT) results for amino acids and acylcarnitines [ 24 ]. Barriers to harmonization efforts have been attributed to differences in instrumentation, methods used, analyte recovery, reagents, cutoffs, and populations screened, which can make result comparisons problematic [ 10 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…Other methods have also been employed, such as using quality control materials and regression equations to harmonize NBS proficiency testing (PT) results for amino acids and acylcarnitines [ 24 ]. Barriers to harmonization efforts have been attributed to differences in instrumentation, methods used, analyte recovery, reagents, cutoffs, and populations screened, which can make result comparisons problematic [ 10 , 24 ]. However, these differences are the reason harmonization is needed.…”

Section: Introductionmentioning

confidence: 99%

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Harmonization of Newborn Screening Results for Pompe Disease and Mucopolysaccharidosis Type I

Dorley

Dizikes

Pickens

et al. 2023

IJNS

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In newborn screening, false-negative results can be disastrous, leading to disability and death, while false-positive results contribute to parental anxiety and unnecessary follow-ups. Cutoffs are set conservatively to prevent missed cases for Pompe and MPS I, resulting in increased falsepositive results and lower positive predictive values. Harmonization has been proposed as a way to minimize false-negative and false-positive results and correct for method differences, so we harmonized enzyme activities for Pompe and MPS I across laboratories and testing methods (Tandem Mass Spectrometry (MS/MS) or Digital Microfluidics (DMF)). Participating states analyzed proofof- concept calibrators, blanks, and contrived specimens and reported enzyme activities, cutoffs, and other testing parameters to Tennessee. Regression and multiples of the median were used to harmonize the data. We observed varied cutoffs and results. Six of seven MS/MS labs reported enzyme activities for one specimen for MPS I marginally above their respective cutoffs with results classified as negative, whereas all DMF labs reported this specimen’s enzyme activity below their respective cutoffs with results classified as positive. Reasonable agreement in enzyme activities and cutoffs was achieved with harmonization; however, harmonization does not change how a value would be reported as this is dependent on the placement of cutoffs.

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“…A recent study demonstrated that interlaboratory variation can be substantially reduced by the use of common stable isotope IS (4), and another study has shown that retrospectively harmonizing screening results to the CDC's Newborn Screening Quality Assurance Program internal quality control (IQC) material reduced interlaboratory variation in a set of proficiency testing samples (5).…”

Section: Introductionmentioning

confidence: 99%

Improving Harmonization and Standardization of Expanded Newborn Screening Results by Optimization of the Legacy Flow Injection Analysis Tandem Mass Spectrometry Methods and Application of a Standardized Calibration Approach

Carling

Whyte

John³

et al. 2022

Clinical Chemistry

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Background Newborn screening (NBS) laboratories in the United Kingdom adhere to common protocols based on single analyte cutoff values (COVs); therefore, interlaboratory harmonization is of paramount importance. Interlaboratory variation for screening analytes in UK NBS laboratories ranges from 17% to 59%. While using common stable isotope internal standards has been shown to significantly reduce interlaboratory variation, instrument set-up, sample extraction, and calibration approach are also key factors. Methods Dried blood spot (DBS) extraction processes, instrument set-up, mobile-phase composition, sample introduction technique, and calibration approach of flow injection analysis–tandem mass spectrometry (FIA-MS/MS) methods were optimized. Inter- and intralaboratory variation of methionine, leucine, phenylalanine, tyrosine, isovaleryl-carnitine, glutaryl-carnitine, octanoyl-carnitine, and decanoyl-carnitine were determined pre- and postoptimization, using 3 different calibration approaches. Results Optimal recovery of analytes from DBS was achieved with a 35-min extraction time and 80% methanol (150 μL). Optimized methodology decreased the mean intralaboratory percentage relative SD (%RSD) for the 8 analytes from 20.7% (range 4.1–46.0) to 5.4% (range 3.0–8.5). The alternative calibration approach reduced the mean interlaboratory %RSD for all analytes from 16.8% (range 4.1–25.0) to 7.1% (range 4.1–11.0). Nuclear magnetic resonance analysis of the calibration material highlighted the need for standardization. The purities of isovaleryl-carnitine and glutaryl-carnitine were 85.13% and 69.94% respectively, below the manufacturer’s stated values of ≥98%. Conclusions For NBS programs provided by multiple laboratories using single analyte COVs, harmonization and standardization of results can be achieved by optimizing legacy FIA-MS/MS methods, adopting a common analytical protocol, and using standardized calibration material rather than internal calibration.

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Harmonizing Newborn Screening Laboratory Proficiency Test Results Using the CDC NSQAP Reference Materials

Cited by 11 publications

References 29 publications

Comprehensive Evaluation of the NeoBase 2 Non-derivatized MSMS Assay and Exploration of Analytes With Significantly Different Concentrations Between Term and Preterm Neonates

Comprehensive Evaluation of the NeoBase 2 Non-derivatized MSMS Assay and Exploration of Analytes With Significantly Different Concentrations Between Term and Preterm Neonates

Harmonization of Newborn Screening Results for Pompe Disease and Mucopolysaccharidosis Type I

Improving Harmonization and Standardization of Expanded Newborn Screening Results by Optimization of the Legacy Flow Injection Analysis Tandem Mass Spectrometry Methods and Application of a Standardized Calibration Approach

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