Prognostic value of angiogenic markers in pregnancy with fetal growth restriction

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.

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.

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.

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.