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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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Volume 56, Issue 1


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

Annemiek M.C.P. Joosen
  • Corresponding author
  • Laboratory of Clinical Chemistry and Haematology, Franciscus Gasthuis and Vlietland, Kleiweg 500, 3045 PM Rotterdam, The Netherlands
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ivon J.M. van der Linden / Lianne Schrauwen / Alisia Theeuwes
  • Laboratory of Clinical Chemistry and Haematology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Monique J.M. de Groot
  • Laboratory of Clinical Chemistry and Haematology, Amphia Hospital, Breda, The Netherlands
  • Laboratory of Clinical Chemistry and Haematology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Antonius A.M. Ermens
Published Online: 2017-06-16 | DOI: https://doi.org/10.1515/cclm-2017-0110



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.


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.


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.


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


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About the article

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

Received: 2017-02-06

Accepted: 2017-04-25

Published Online: 2017-06-16

Published in Print: 2017-11-27

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.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 1, Pages 113–119, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0110.

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