University of Oulu

Keikkala, E., Forstén, J., Ritvos, O., Stenman, U.-H., Kajantie, E., Hämäläinen, E., Räikkönen, K., Villa, P. M., & Laivuori, H. (2021). Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women. Pregnancy Hypertension, 25, 116–122.

Serum inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women

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Author: Keikkala, Elina1,2; Forstén, Janina3; Ritvos, Olli4;
Organizations: 1Oulu University Hospital and University of Oulu, Medical Research Center Oulu, PEDEGO Research Unit, Oulu, Finland
2Finnish Institute for Health and Welfare, Population Health Unit, Helsinki and Oulu, Finland
3University of Helsinki and Helsinki University Hospital, Childreńs Hospital, Child Psychiatry, Helsinki, Finland
4Bacteriology and Immunology and Physiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
5Departments of Clinical Chemistry, University of Helsinki, Helsinki and University of Eastern Finland, Kuopio, Finland
6Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
7Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
8Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland
9Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
10Department of Obstetrics and Gynecology, Hyvinkää Hospital, Hyvinkää, Finland
11Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
12Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
13Department of Obstetrics and Gynecology, Tampere University Hospital and Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.5 MB)
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Language: English
Published: Elsevier, 2021
Publish Date: 2021-08-20


Objectives: Maternal serum inhibin-A, pregnancy associated plasma protein-A (PAPP-A) and PAPP-A2 together with placental growth factor (PlGF), maternal risk factors and uterine artery pulsatility index (UtA PI) were analysed to study their ability to predict pre-eclampsia (PE).

Study design: Serial serum samples for the nested case-control study were collected prospectively at 12–14, 18–20 and 26–28 weeks of gestation from 11 women who later developed early-onset PE (EO PE, diagnosis < 34 + 0 weeks of gestation), 34 women who developed late-onset PE (LO PE, diagnosis ≥ 34 + 0 weeks) and 89 controls.

Main outcome measures: Gestational age -adjusted multiples of the median (MoM) values were calculated for biomarker concentrations. Multivariate regression analyses were performed to combine first trimester biomarkers, previously reported results on PlGF, maternal risk factors and UtA PI. Area under curve (AUC) values and 95% confidence intervals (CIs) for the prediction of PE and its subtypes were calculated.

Results: A high first trimester inhibin-A predicted PE (AUC 0.618, 95%CI, 0.513–0.724), whereas PAPP-A and PlGF predicted only EO PE (0.701, 0.562–0.840 and 0.798, 0.686–0.909, respectively). At 26–28 weeks PAPP-A2 and inhibin-A predicted all PE subtypes. In the multivariate setting inhibin-A combined with maternal pre-pregnancy body mass index, prior PE and mean UtA PI predicted PE (0.811,0.726–0.896) and LO PE (0.824, 0.733–0.914).

Conclusions: At first trimester inhibin-A show potential ability to predict not only EO PE but also LO PE whereas PlGF and PAPP-A predict only EO PE. At late second trimester inhibin-A and PAPP-A2 might be useful for short-term prediction of PE.

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Series: Pregnancy hypertension
ISSN: 2210-7789
ISSN-E: 2210-7797
ISSN-L: 2210-7789
Volume: 25
Pages: 116 - 122
DOI: 10.1016/j.preghy.2021.05.024
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Funding: The PREDO project has been supported by EVO research funding (A special Finnish state subsidy for health science research), Academy of Finland, Signe and Ane Gyllenberg Foundation, Sigrid Juselius Foundation, University of Helsinki Research Funds, Research Funds of Oulu University Hospital, Finnish Medical Foundation, Juho Vainio Foundation, Novo Nordisk, Foundation, Jane and Aatos Erkko Foundation, and Päivikki and Sakari Sohlberg Foundation.
Copyright information: © 2021 The Author(s). Published by Elsevier B.V. on behalf of International Society for the Study of Hypertension in Pregnancy. This is an open access article under the CC BY license (