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

Elina Keikkala, Janina Forstén, Olli Ritvos, Ulf Håkan Stenman, Eero Kajantie, Esa Hämäläinen, Katri Räikkönen, Pia M. Villa, Hannele Laivuori

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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.

Original languageEnglish
Pages (from-to)116-122
Number of pages7
JournalPregnancy Hypertension
Publication statusPublished - 2021
Publication typeA1 Journal article-refereed


  • inhibin-A
  • Placental growth factor
  • Pre-eclampsia
  • Prediction
  • Pregnancy
  • pregnancy associated plasma protein-A2

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Internal Medicine
  • Obstetrics and Gynaecology


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