Biotin-free Prenatal Screening Assays

No biotin interference: Testing on B·R·A·H·M·S PAPP-A KRYPTOR and B·R·A·H·M·S PlGF plus KRYPTOR assays

The objective of the testing was to evaluate an effect of increased biotin concentration on the performance of B·R·A·H·M·S KRYPTOR assays.

Biotin, also known as vitamin B7, is a water-soluble vitamin often found in multi-vitamins, prenatal vitamins, and dietary supplements marketed for hair, skin, and nail growth. There is increasing evidence that biotin in blood or other samples taken from patients who are ingesting high levels of biotin in dietary supplements can cause clinically significant incorrect lab test results. Screening laboratories need to be vigilant to immunoassay interference due to the significant impact of the results on patient decision outcome by biotin. In prenatal screening there is the potential for fetal loss due to an unnecessary invasive diagnostic procedure, with associated maternal stress and anxiety and further intensive pregnancy monitoring.

B·R·A·H·M·S KRYPTOR assay technology does not use biotin-streptavidin binding

  • The TRACE (Time Resolved Amplified Cryptate Emission) technology used in B·R·A·H·M·S KRYPTOR assays is independent from a biotin-streptavidin binding (What is TRACE technology?). B·R·A·H·M·S KRYPTOR instruments use a homogenous immunoassay principle which eliminates the need for washing or separation steps, thus reducing the test time.
  • Simultaneous reference reading removes risk of unspecific signals, which provides extraordinary test precision for reliable and reproducible screening results.
  • This technology has proven to ensure the highest precision and reproducibility of B·R·A·H·M·S KRYPTOR immunoassays.

Biotin interference testing on B·R·A·H·M·S KRYPTOR prenatal screening assays

B·R·A·H·M·S PAPP-A KRYPTOR and B·R·A·H·M·S PlGF plus KRYPTOR assays were used to analyse a native serum sample at low, medium and high concentration of analyteRef-1-2. The samples were also measured with PAPP-A and PlGF assays of another provider containing biotin-streptavidin bindingRef-3. On the native samples both technologies confirmed well detectable analytes.

The native samples were then spiked with different biotin concentrations (from 15 to 3510 ng/mL) and results from B·R·A·H·M·S assays and the other provider of biotin containing assays were compared.

 

Results confirm that B·R·A·H·M·S PAPP-A KRYPTOR and B·R·A·H·M·S PlGF plus KRYPTOR assays are not impacted by biotin interference

When samples were spiked with different biotin concentrations, it was shown that the assays PAPP-A and PlGF of the other provider were detecting less amounts of both analytes (see figures 1 to 4). Spiked concentration of biotin of 30 ng/mL resulted in 2-7% bias on the other provider PAPP-A assay. The higher the biotin concentration in the sample the less PAPP-A or PlGF could be detected. 

Regardless of biotin concentration measurement of PAPP-A and PlGF on the B·R·A·H·M·S KRYPTOR results in the constantly low bias of 0-2%. The data confirm that B·R·A·H·M·S PAPP-A KRYPTOR and B·R·A·H·M·S PlGF plus KRYPTOR assays are not impacted by biotin interference (see figure 1).

PNS-biotin-interferenceFigure 1: Dose response curves: Effect of biotin interference on bias of measurements of PAPP-A and PlGF assays

 

Figures 2 and 3 show the effect of different biotin concentrations expressed as % of control from unspiked serum samples. The results indicate average plus standard deviation of several repeated tests.

PAPP-A

biotin-interference-PAPP-AFigure 2: Biotin spiked samples measured with B·R·A·H·M·S PAPP-A KRYPTOR and the other provider's PAPP-A Samples 1, 2, 3 measured with different biotin concentrations: 30, 75, 150, 300, 600, 1200 ng/mL

 

PlGF

biotin-interference-PlGF-plusFigure 3: Biotin spiked samples measured with B·R·A·H·M·S PIGF plus KRYPTOR and the other provider's PlGF Samples 1, 2, 3 measured with different biotin concentrations: 15, 30, 500, 1200, 3510 ng/mL

 

Conclusion: No biotin interference detected in B·R·A·H·M·S PAPP-A KRYPTOR or B·R·A·H·M·S PlGF plus KRYPTOR assays

  • The other provider's assays PAPP-A and PlGF demonstrate strong biotin interference increasing with rising biotin concentration in sample.
  • B·R·A·H·M·S KRYPTOR prenatal screening assay results are not impacted by biotin concentration in the measured sample.

  

B·R·A·H·M·S immunoassays: Completely free of biotin >

References

Ref-1: The FDA Warns that Biotin May Interfere with Lab Tests: FDA Safety Communication.

Ref-2: McEnroe R. J., (2018) April 30, CLSI EP37: Supplemental Tables for Interference Testing in Clinical Chemistry, 1st Edition.

Ref-3: Roche Diagnostics GmbH. Roche Elecsys method sheets. Manheim: Roche Diagnostics GmbH, 2016.

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