Prognostic value of angiogenic markers in pregnancy with fetal growth restriction.

Objective: Pregnancies with fetal growth restriction (FGR) are at increased risk for pre‐eclampsia. Angiogenic markers including soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) are altered in pregnancies complicated by FGR, but their utility for predicting pre‐eclampsia in growth‐restricted pregnancies is uncertain. This study aimed to evaluate the prognostic value of angiogenic markers for predicting the development of pre‐eclampsia in pregnancies with FGR and suspected pre‐eclampsia. Methods: This was a retrospective study of singleton pregnancies with FGR, defined according to Delphi consensus criteria, which underwent sampling of sFlt‐1 and PlGF for suspicion of pre‐eclampsia at the Medical University of Vienna, Vienna, Austria, between 2013 and 2020. Women with an established diagnosis of pre‐eclampsia at sampling were excluded. Cox regression analysis and logistic regression analysis were performed to evaluate the association of angiogenic markers with the development of pre‐eclampsia at various timepoints. Results: In this cohort of 93 women, pre‐eclampsia was diagnosed in 14 (15.1%) women within 1 week after sampling, 21 (22.6%) within 2 weeks after sampling and 38 (40.9%) at any time after assessment. The sFlt‐1/PlGF ratio consistently showed a stronger association with the development of pre‐eclampsia compared to sFlt‐1 or PlGF alone (pre‐eclampsia within 1 week: area under the receiver‐operating‐characteristics curve, 0.87 vs 0.82 vs 0.72). Models including the sFlt‐1/PlGF ratio were associated more strongly with pre‐eclampsia hazard compared to models including sFlt‐1 or PlGF alone (concordance index, 0.790 vs 0.759 vs 0.755). The risk classification capability of the sFlt‐1/PlGF ratio decreased after the 2‐week timepoint. The established cut‐off value for the sFlt‐1/PlGF ratio of < 38 was effective for ruling out pre‐eclampsia within 2 weeks, with a negative predictive value of 0.933 and sensitivity of 0.952. Conclusions: Use of the sFlt‐1/PlGF ratio is preferrable to the use of PlGF alone for the prediction of pre‐eclampsia in pregnancies with FGR. Established cut‐offs for ruling out the development of pre‐eclampsia in the short term seem to be effective in these patients. © 2023 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]