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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. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: To assess the evolution of the soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to placental growth factor (PlGF) ratio in women with suspected or confirmed pre‐eclampsia (PE), and to investigate the changes in sFlt‐1 and PlGF levels in pre‐eclamptic women after delivery. Methods: This was an exploratory study in which secondary analysis was performed on a prospective cohort study that enrolled women with a singleton pregnancy and suspected or confirmed PE from 18 weeks' gestation, carried out between December 2013 and April 2016 at the Department of Obstetrics of the Erasmus Medical Center in Rotterdam. sFlt‐1 and PlGF were determined using Roche Diagnostics Elecsys assays in two groups of patients. In the first group, patients with suspected or confirmed PE had sFlt‐1 and PlGF levels measured at least twice during their pregnancy. Changes in these biomarkers over the course of pregnancy were compared for patients in this group with a baseline sFlt‐1/PlGF ratio of ≤ 38 and for those with a ratio > 38. In the second group, sFlt‐1 and PlGF levels of women with PE or HELLP syndrome were measured before and after delivery. For this group, pre‐ and postpartum sFlt‐1 and PlGF levels were compared and half‐lives were calculated. Results: Women with suspected or confirmed PE for whom sFlt‐1 and PlGF levels were measured at least twice during pregnancy (n = 46) had a median gestational age at inclusion of 26 weeks (range, 18–40 weeks). In 27 of the 30 patients with sFlt‐1/PlGF ratio ≤ 38 at baseline, thereby ruling out PE, the sFlt‐1/PlGF ratio remained stable for up to 100 days. In the remaining three patients with a ratio ≤ 38 and in most of the 16 patients with a ratio > 38, the ratio increased further. For women diagnosed with PE or HELLP syndrome for whom sFlt‐1 and PlGF levels were measured before and after delivery (n = 26), median gestational age at inclusion was 29 weeks (range, 16–37 weeks) and median time between antepartum measurement and delivery was 2 days (range, 1–17 days). In this group, after delivery, sFlt‐1 dropped to < 1% of its pre‐delivery value, with a half‐life of 1.4 ± 0.3 days, while PlGF dropped to ∼30% of its pre‐delivery value, with a half‐life of 3.7 ± 4.3 days. Conclusions: Based on this small cohort, up to 10% of pregnant women admitted with suspected or confirmed PE presenting with a sFlt‐1/PlGF ratio of ≤ 38 display a rise in sFlt‐1/PlGF ratio in subsequent weeks, implying that repeat determination of the sFlt‐1/PlGF ratio is required to exclude definitively a diagnosis of PE. Furthermore, the rapid and pronounced decline in sFlt‐1 levels after delivery in patients with PE/HELLP syndrome suggests that sFlt‐1, in contrast to PlGF, is almost entirely derived from the placenta. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]