Reference intervals and longitudinal changes in copeptin and MR-proADM concentrations during pregnancy

Annemiek M.C.P. Joosen; Ivon J.M. van der Linden; Lianne Schrauwen; Alisia Theeuwes; Monique J.M. de Groot; Antonius A.M. Ermens

doi:10.1515/cclm-2017-0110

Article

Reference intervals and longitudinal changes in copeptin and MR-proADM concentrations during pregnancy

Annemiek M.C.P. Joosen , Ivon J.M. van der Linden , Lianne Schrauwen , Alisia Theeuwes , Monique J.M. de Groot and Antonius A.M. Ermens

Published/Copyright: June 16, 2017

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 56 Issue 1

Abstract

Background:

Vasopressin and adrenomedullin and their stable by-products copeptin and midregional part of proadrenomedullin (MR-proADM) are promising biomarkers for the development of preeclampsia. However, clinical use is hampered by the lack of trimester-specific reference intervals. We therefore estimated reference intervals for copeptin and MR-proADM in disease-free Dutch women throughout pregnancy.

Methods:

Apparently healthy low risk pregnant women were recruited. Exclusion criteria included current or past history of endocrine disease, multiple pregnancy, use of medication known to influence thyroid function and current pregnancy as a result of hormonal stimulation. Women who miscarried, developed hyperemesis gravidarum, hypertension, pre-eclampsia, hemolysis elevated liver enzymes and low platelets, diabetes or other disease, delivered prematurely or had a small for gestational age neonate were excluded from analyses. Blood samples were collected at 9–13 weeks (n=98), 27–29 weeks (n=94) and 36–39 weeks (n=91) of gestation and at 4–13 weeks post-partum (PP) (n=89). Sixty-two women had complete data during pregnancy and PP. All analyses were performed on a Kryptor compact plus.

Results:

Copeptin increases during pregnancy, but 97.5th percentiles remain below the non-pregnant upper reference limit (URL) provided by the manufacturer. MR-proADM concentrations increase as well during pregnancy. In trimesters 2 and 3 the 97.5th percentiles are over three times the non-pregnant URL provided by the manufacturer.

Conclusions:

Trimester- and assay-specific reference intervals for copeptin and MR-proADM should be used. In addition, consecutive measurements and the time frame between measurements should be considered as the differences seen with or in advance of preeclampsia can be expected to be relatively small compared to the reference intervals.

Keywords: copeptin; CT-proAVP; midregional part of proadrenomedullin (MR-proADM); pregnancy

Corresponding author: Dr. Annemiek M.C.P. Joosen, Laboratory of Clinical Chemistry and Haematology, Franciscus Gasthuis and Vlietland, Kleiweg 500, 3045 PM Rotterdam, The Netherlands

Acknowledgments

We gratefully acknowledge the primary midwife practices of Verloskundigen Etten-Leur, Trivia, De Moriaen, Doortje Uil, Verloskundig Centrum Breda, Het Zomerhuis, Prinsenbeemden, Het Klavertje, Luna, Vita and De Ooievaar and the Origine birth centre for recruitment of the volunteers. We thank ThermoFisher Scientific for providing the test kits.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2017-2-6

Accepted: 2017-4-25

Published Online: 2017-6-16

Published in Print: 2017-11-27

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Articles in the same Issue

https://doi.org/10.1515/cclm-2017-0110

Keywords for this article

copeptin; CT-proAVP; midregional part of proadrenomedullin (MR-proADM); pregnancy