Angiogenic markers and their longitudinal change for predicting adverse outcomes in pregnant women with chronic hypertension.

ABSTRACT Background Women with chronic hypertension are at increased risk of adverse maternal and perinatal outcomes. Maternal serum angiogenic markers, such as soluble fms like tyrosine kinase-1 (sFlt-1) and placental like growth factor (PlGF), can be used to triage women with suspected preeclampsia. However data on these markers in pregnant women with chronic hypertension are scarce. Objective We aimed to evaluate the predictive accuracy of maternal serum sFlt-1, PlGF 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 University of Vienna Hospital. The inclusion criteria were pregnant women with chronic hypertension and suspected preeclampsia. The primary outcome of the 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 binominal logistic regression. The accuracy of each marker was assessed using receiver operating characteristics curves and area under the curve (AUC) values. AUC 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 (i.e. composite adverse maternal or fetal outcome) within one week of assessment (gestational age at assessment: 29.9 weeks) and 35 (24.1%) developed complications at any time (gestational age at assessment: 30.1 weeks). In women who developed complications at any time the median maternal serum sFlt-1/PlGF ratio was 149.4 (IQR 64.6 – 457.4), compared to 8.0 (IQR 3.37 – 41.2) in women who did not develop complications (P The AUC values of maternal serum sFlt-1/PlGF ratio Z-score (0.95, 95% CI: 0.90–0.99) and PlGF level Z-score (0.94, 95% CI: 0.88–0.99) for predicting complications within one week of assessment were very high. The AUC values of new onset edema (0.61, 95% CI: 0.52–0.70), proteinuria (0.62, 95% CI: 0.52–0.71), high mean arterial pressure (0.52, 95% CI: 0.50–0.54) and other symptoms of preeclampsia (0.57, 95% CI: 0.49–0.65) were all significantly lower compared to angiogenic markers (P Women, who had angiogenic imbalance and/or proteinuria had the highest rate of complications (28/57, 49.1%). The rate of complications in women with angiogenic imbalance and/or proteinuria was significantly higher compared to women with, either proteinuria, other symptoms or fetal growth restriction in the absence of angiogenic imbalance (49.1% vs 16.7%, P=0.039). The highest positive and negative predictive values for predicting adverse outcomes were demonstrated by angiogenic imbalance and/or proteinuria criteria with a positive predictive value of 49.1% (95% CI: 50.4–57.9%) and negative predictive value of 92% (95% CI: 85.5–95.8%). Longitudinal changes in measurements of the gestational age corrected sFlt-1/PlGF ratio up to the last one had a significantly higher AUC value compared to the last measurement alone (AUC: 0.95, 95% CI: 0.92-0.99 vs. 0.87, 95% CI: 0.79–0.95, P=0.024) Conclusions Maternal serum angiogenic markers are superior to clinical assessment in predicting adverse maternal and perinatal outcomes in pregnant women with chronic hypertension. Repeat measurements of the sFlt-1/PlGF ratio seems beneficial, given the better predictive accuracy compared to single measurement alone. The use of angiogenic makers should be implemented in clinical management guidelines of pregnant women with chronic hypertension.