Angiogenic imbalance in pre-eclampsia and fetal growth restriction: enhanced soluble Fms-like tyrosine kinase-1 binding or diminished production of placental growth factor?

A. C.M. Kluivers*, A. Biesbroek, W. Visser, L. Saleh, H. Russcher, J. A.H. Danser, R. I. Neuman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

Objectives: To assess levels of total placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and free PlGF in women with pre-eclampsia (PE) with or without a small-for-gestational-age (SGA) neonate in order to establish whether low free PlGF levels associated with PE and SGA are due to enhanced sFlt-1 binding or decreased PlGF production. Methods: This was a secondary analysis of a prospective multicenter cohort study involving 407 pregnancies with suspected or confirmed PE, in which total PlGF levels were calculated from measured sFlt-1 and free PlGF levels. The control group included women who were suspected to have PE at a certain point in pregnancy but did not develop PE. The analysis was stratified according to whether PE was early- or late-onset (gestational age < 34 weeks vs ≥ 34 weeks) and according to the presence of SGA at birth, which was used as a proxy of fetal growth restriction in the absence of Doppler ultrasound and biometric data. Results: In early-onset PE, both women with and those without SGA had lower free (19 and 45 pg/mL) and total (44 and 100 pg/mL) PlGF levels compared with women without PE (free and total PlGF, 300 and 381 pg/mL, respectively). SGA alone did not affect free and total PlGF in this condition (free and total PlGF, 264 and 352 pg/mL, respectively). Observations in women with late-onset PE were similar, although the changes were more modest. Both SGA (gestational age < 34 weeks) and PE were individually associated with increased sFlt-1 and, in women with both PE and SGA, the upregulation of sFlt-1 occurred in a synergistic manner, thus resulting in the highest sFlt-1/free PlGF ratio in this group. This occurred in both early- and late-onset PE. Conclusions: Particularly in pregnancies with early-onset PE and SGA, diminished PlGF production is an important cause of low free PlGF levels. Under such conditions, sFlt-1 lowering is unlikely to restore the angiogenic balance.

Original languageEnglish
Pages (from-to)466-473
Number of pages8
JournalUltrasound in Obstetrics and Gynecology
Volume61
Issue number4
Early online date3 Oct 2022
DOIs
Publication statusPublished - Apr 2023

Bibliographical note

Funding Information:
Roche Diagnostics provided the kits for the soluble fms-like tyrosine kinase-1 and placental growth factor measurements. R.I. Neuman is supported by the Dutch Foundation Lijf en Leven.

Publisher Copyright:
© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fingerprint

Dive into the research topics of 'Angiogenic imbalance in pre-eclampsia and fetal growth restriction: enhanced soluble Fms-like tyrosine kinase-1 binding or diminished production of placental growth factor?'. Together they form a unique fingerprint.

Cite this