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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]

Background: Women with chronic hypertension are at increased risk for adverse maternal and perinatal outcomes. Maternal serum angiogenic markers, such as soluble fms-like tyrosine kinase 1 and placental growth factor, can be used to triage women with suspected preeclampsia. However, data about these markers in pregnant women with chronic hypertension are scarce.Objective: We aimed to evaluate the predictive accuracy of maternal serum levels of soluble fms-like tyrosine kinase 1, placental growth factor, and their ratio for predicting adverse maternal and perinatal outcomes in women with chronic hypertension.Study Design: This was a retrospective analysis of prospectively collected data from January 2013 to October 2019 at the University of Vienna Hospital, Vienna, Austria. The inclusion criteria were pregnant women with chronic hypertension and suspected preeclampsia. The primary outcome of this study was the prognostic performance of angiogenic markers for the prediction of adverse maternal and perinatal outcomes in pregnant women with chronic hypertension. The accuracy of angiogenic markers for predicting adverse composite outcomes was assessed with a binomial logistic regression. The accuracy of each marker was assessed using receiver operating characteristics curves and area under the curve values. Area under the curve values were compared using De Long's test.Results: Of the 145 included women with chronic hypertension and suspected superimposed preeclampsia, 26 (17.9%) women developed complications (ie, composite adverse maternal or fetal outcomes) within 1 week of assessment (average gestational age at assessment, 29.9 weeks) and 35 (24.1%) developed complications at any time (average gestational age at assessment, 30.1 weeks). In women who developed complications at any time, the median maternal serum soluble fms-like tyrosine kinase-1 to placental growth factor ratio was 149.4 (interquartile range, 64.6-457.4) compared with 8.0 (interquartile range, 3.37-41.2) for women who did not develop complications (P<.001). The area under the curve values for the maternal serum soluble fms-like tyrosine kinase-1 to placental growth factor ratio Z-score (0.95; 95% confidence interval, 0.90-0.99) and placental growth factor level Z-score (0.94; 95% confidence interval, 0.88-0.99) for predicting complications within 1 week of assessment were very high. The area under the curve values for new-onset edema (0.61; 95% confidence interval, 0.52-0.70), proteinuria (0.62; 95% confidence interval, 0.52-0.71), high mean arterial pressure (0.52; 95% confidence interval, 0.50-0.54), and other symptoms of preeclampsia (0.57; 95% confidence interval, 0.49-0.65) were all significantly lower than for the angiogenic markers (P<.001 for all). Women who had an angiogenic imbalance and/or proteinuria had the highest rate of complications (28/57, 49.1%). The rate of complications in women with an angiogenic imbalance and/or proteinuria was significantly higher than in women with either proteinuria, other symptoms, or intrauterine growth restriction in the absence of an angiogenic imbalance (49.1% vs 16.7%; P=.039). The highest positive and negative predictive values for predicting adverse outcomes were demonstrated by an angiogenic imbalance and/or proteinuria criteria with a positive predictive value of 49.1% (95% confidence interval, 50.4%-57.9%) and a negative predictive value of 92% (95% confidence interval, 85.5%-95.8%). Longitudinal changes in measurements of the gestational age-corrected ratio of soluble fms-like tyrosine kinase-1 to placental growth factor up to the last measurement had a significantly higher area under the curve value than the last measurement alone (area under the curve, 0.95; 95% confidence interval, 0.92-0.99 vs 0.87; 95% confidence interval, 0.79-0.95; P=.024) CONCLUSION: Maternal serum angiogenic markers are superior to clinical assessment in predicting adverse maternal and perinatal outcomes in pregnant women with chronic hypertension. Repeated measurements of the ratio of soluble fms-like tyrosine kinase-1 to placental growth factor seems beneficial given the better predictive accuracy compared with a single measurement alone. The use of angiogenic makers should be implemented in clinical management guidelines for pregnant women with chronic hypertension. [ABSTRACT FROM AUTHOR]