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 language | English |
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Pages (from-to) | 466-473 |
Number of pages | 8 |
Journal | Ultrasound in Obstetrics and Gynecology |
Volume | 61 |
Issue number | 4 |
Early online date | 3 Oct 2022 |
DOIs | |
Publication status | Published - 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.