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Licensed Unlicensed Requires Authentication Published by De Gruyter October 26, 2020

Development of a pregnancy-specific reference material for thyroid biomarkers, vitamin D, and nutritional trace elements in serum

  • Ashley S. P. Boggs ORCID logo EMAIL logo , Lisa E. Kilpatrick , Carolyn Q. Burdette , Denise S. Tevis , Zachary A. Fultz , Michael A. Nelson , Jeffery M. Jarrett , Jennifer V. Kemp , Ravinder J. Singh , Stefan K. G. Grebe , Stephen A. Wise , Brittany L. Kassim and Stephen E. Long

Abstract

Objectives

Matrix differences among serum samples from non-pregnant and pregnant patients could bias measurements. Standard Reference Material 1949, Frozen Human Prenatal Serum, was developed to provide a quality assurance material for the measurement of hormones and nutritional elements throughout pregnancy.

Methods

Serum from non-pregnant women and women in each trimester were bottled into four levels based on pregnancy status and trimester. Liquid chromatography tandem mass spectrometry (LC-MS/MS) methods were developed and applied to the measurement of thyroid hormones, vitamin D metabolites, and vitamin D-binding protein (VDBP). Copper, selenium, and zinc measurements were conducted by inductively coupled plasma dynamic reaction cell MS. Thyroid stimulating hormone (TSH), thyroglobulin (Tg), and thyroglobulin antibody concentrations were analyzed using immunoassays and LC-MS/MS (Tg only).

Results

Certified values for thyroxine and triiodothyronine, reference values for vitamin D metabolites, VDBP, selenium, copper, and zinc, and information values for reverse triiodothyronine, TSH, Tg, and Tg antibodies were assigned. Significant differences in serum concentrations were evident for all analytes across the four levels (p≤0.003).

TSH measurements were significantly different (p<0.0001) among research-only immunoassays. Tg concentrations were elevated in research-only immunoassays vs. Federal Drug Administration-approved automated immunoassay and LC-MS/MS. Presence of Tg antibodies increased differences between automated immunoassay and LC-MS/MS.

Conclusions

The analyte concentrations’ changes consistent with the literature and the demonstration of matrix interferences in immunoassay Tg measurements indicate the functionality of this material by providing a relevant matrix-matched reference material for the different stages of pregnancy.


Corresponding author: Ashley S. P. Boggs, PhD, Research Biologist, National Institute of Standards and Technology, 331 Fort Johnson Rd, Charleston, SC 29412, USA, Phone: 843 460 9789, Fax: 843 998 6940, E-mail:

Acknowledgments

We thank the National Institute of Health and the Office of Dietary Supplements for funding and support of the development of this material.

  1. Research funding: National Institute of Health and the Office of Dietary Supplements and the National Institute of Standards and Technology.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The authors declare that they have no competing interests in the publication of this manuscript.

  4. Disclaimer: Commercial equipment, instruments, or materials are identified to specify adequately the experimental procedure. Such identification does not imply recommendation or endorsement by NIST nor the CDC, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose. According to NIST’s Order 1801.00, “NIST does not evaluate commercial products unless such an evaluation is part of a formal agreement, usually with the manufacturer of the product.” “NIST does not endorse commercial products or services; commercial products shall be neither promoted nor disparaged by NIST.” Therefore, manufacturer names of commercially available ELISA kits were redacted to comply with federal regulations. This analysis was conducted not to assess manufacturer’s products, but to assess the measurement technique compared to other techniques.

  5. Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and was approved by the Institutional Review Board and NIST Human Subjects Protection Office (MML-17-0013).

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2020-0977).


Received: 2020-06-24
Accepted: 2020-10-06
Published Online: 2020-10-26
Published in Print: 2021-03-26

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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