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Clinical Chemistry and Laboratory Medicine (CCLM)

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

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Volume 56, Issue 1


Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia

Carin P. De Villiers
  • Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
  • Department of Biomedical Sciences, University of Stellenbosch, Cape Town, South Africa
  • Other articles by this author:
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/ Paula L. Hedley
  • Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
  • Department of Biomedical Sciences, University of Stellenbosch, Cape Town, South Africa
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Sophie Placing / Karen R. Wøjdemann / Anne-Cathrine Shalmi
  • Department of Fetal Medicine, Copenhagen University Hospital, Copenhagen, Denmark
  • Department of Obstetrics and Gynecology, Hillerød Hospital, Hillerød, Denmark
  • Other articles by this author:
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/ Anting L. Carlsen / Line Rode / Karin Sundberg / Ann Tabor / Michael Christiansen
  • Corresponding author
  • Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
  • Department for Congenital Disorders, Statens Serum Institut, 5 Artillerivej, 2300S Copenhagen, Denmark
  • Email
  • Other articles by this author:
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Published Online: 2017-07-12 | DOI: https://doi.org/10.1515/cclm-2017-0356



Placental protein-13 (PP13) is involved in placental invasion and has been suggested as a maternal serum marker of preeclampsia (PE) development. However, the discriminatory ability of PP13 in first trimester has not been completely clarified.


PP13 was measured in first trimester (week 10+3–13+6) maternal serum from 120 PE pregnancies and 267 control pregnancies and was correlated with clinical parameters. The population screening performance of PP13 in combination with the PE markers pregnancy associated plasma protein A (PAPPA) and free leptin index (fLI) was assessed by Monte Carlo simulation.


In severe PE (including HELLP) cases (n=26) the median PP13 concentration was 35.8 pg/mL (range: 17.8–85.5 pg/mL) and in PE pregnancies (n=10) with birth prior to week 34, the median PP13 concentration was 30.6 pg/mL (13.1–50.1 pg/mL), compared to controls with a median of 54.8 pg/mL (range: 15.4–142.6 pg/mL) (p<0.04). The population screening detection rate (DR) for a false-positive rate of 10% for severe PE and HELLP was 26% for PP13, 28% for PP13+PAPP-A, 33% for PP13+fLI, and 40% for PP13+PAPP-A+fLI.


PP13 is a marker of severe PE and HELLP syndrome. The screening performance of PP13 can be markedly improved by combining it with fLI and PAPP-A.

Keywords: biomarkers; preeclampsia; pregnancy complications; pregnancy outcome; prenatal diagnosis


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About the article

Corresponding author: Michael Christiansen, FRCPath, MD, Professor, Chief Physician, Department for Congenital Disorders, Statens Serum Institut, 5 Artillerivej, 2300S Copenhagen, Denmark, Phone: +4532683657

Received: 2017-04-25

Accepted: 2017-05-23

Published Online: 2017-07-12

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 65–74, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0356.

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