Should angiogenic markers be included in diagnostic criteria of superimposed pre-eclampsia in women with chronic hypertension?

Binder, J.
Kalafat, Erkan
Palmrich, P.
Pateisky, P.
Khalil, A.
Objective Although the most recent guidance from the International Society for the Study of Hypertension in Pregnancy (ISSHP) has highlighted the role of angiogenic marker assessment in the diagnosis of pre-eclampsia (PE) in women with chronic hypertension, the ISSHP has withheld recommending its implementation due to the limited available evidence in this group of women. Therefore, we aimed to investigate the value of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) assessment in women with chronic hypertension and suspected superimposed PE. Methods This was a retrospective analysis of prospectively collected data recorded in an electronic database between January 2013 and October 2019. Women with chronic hypertension and singleton pregnancy who had suspected superimposed PE were included. Superimposed PE was suspected in women presenting with worsening hypertension, epigastric pain, new-onset edema, dyspnea or neurological symptoms. The exclusion criteria were delivery within 1 week after assessment for reasons other than PE, chronic kidney disease, history of cardiac disease, fetal aneuploidy, genetic syndrome or major structural anomaly and missing pregnancy outcome. Maternal serum angiogenic markers (sFlt-1, PlGF and sFlt-1/PlGF ratio) were measured. The primary outcome was the utility of angiogenic markers in the prediction of superimposed PE. Predictive accuracy was assessed for superimposed PE diagnosed at different timepoints, including within 1 week after assessment and any time before birth. The secondary outcome was comparison of adverse maternal and perinatal outcomes between women with superimposed PE diagnosed according to the traditional ISSHP criteria and those diagnosed according to extended criteria including angiogenic markers. The predictive accuracy of each angiogenic marker was assessed using receiver-operating-characteristics-curve analysis. Area under the curve (AUC) values were compared using De Long's test. A sensitivity analysis was planned for gestational age at assessment. The association of various variables with composite adverse maternal and perinatal outcomes was assessed using binomial regression. Results The study included 142 pregnant women with chronic hypertension and suspected superimposed PE, of whom 25 (17.6%) developed PE within 1 week after assessment, 52 (36.6%) developed PE at any timepoint before birth and 90 (63.4%) delivered without PE. Maternal serum angiogenic imbalance was associated significantly with superimposed PE diagnosed according to the ISSHP criteria within 1 week or at any time after assessment (P 99.9%, 95.6% and > 99.9%, respectively), without a meaningful decrease in specificity. The addition of angiogenic imbalance improved the detection rate for composite adverse perinatal outcome (20.6% increase; 95% CrI, 0.0-42.


Angiogenic markers and their longitudinal change for predicting adverse outcomes in pregnant women with chronic hypertension
Binder, Julia; Kalafat, Erkan; Palmrich, Pilar; Pateisky, Petra; Khalil, Asma (2021-09-01)
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, an...
Prognostic value of angiogenic markers in pregnant women with chronic hypertension
Binder, Julia; Palmrich, Pilar; Kalafat, Erkan; Pateisky, Petra; Oeztuerk, Ebru; Mittelberger, Johanna; Khalil, Asma (2021-09-07)
Women with chronic hypertension face a 5-to 6-fold increased risk of developing preeclampsia compared with normotensive women. Angiogenic markers, especially soluble fms-like kinase 1 (sFlt-1) and placental growth factor (PlGF), were identified as clinically useful markers predicting the development of preeclampsia, but data on the prediction of superimposed preeclampsia are scarce. Therefore, we aimed to evaluate the predictive value of the sFlt-1/PlGF ratio for delivery because of superimposed preeclampsi...
Performance of Antenatal Diagnostic Criteria of Twin-Anemia-Polycythemia Sequence
Liu, Becky; Kalafat, Erkan; Bhide, Amar; Thilaganathan, Basky; Khalil, Asma (2020-09-01)
This study aims to elicit the validation performance of different diagnostic criteria and to evaluate the disease course and perinatal outcomes of pregnancies complicated by twin anemia polycythemia sequence (TAPS). Monochorionic diamniotic (MCDA) twin pregnancies who received serial middle cerebral artery (MCA) peak systolic velocity (PSV) measurements without non-TAPS-related demise or major anomalies were included. Course of disease, antenatal intervention, additional ultrasound features, and perinatal o...
Is umbilicocerebral ratio better than cerebroplacental ratio for predicting adverse pregnancy and neonatal outcomes?
Kalafat, Erkan; Kalaylioglu, Zeynep; Thilaganathan, Basky; Khalil, Asma (Elsevier BV, 2020-09-01)
Objective A secondary analysis of the trial of randomized umbilical and fetal flow in Europe suggested that the umbilicocerebral ratio (UCR) provides better differentiation of neurodevelopmental outcome in the abnormal range compared with that of the cerebroplacental ratio (CPR).1 However, the reported superiority of UCR is controversial.2 This study aimed to compare the CPR and the UCR for predicting operative delivery for presumed fetal compromise and prolonged neonatal unit (NNU) admission in term fetus...
Prognostic Value of Maternal Cardiovascular Hemodynamics in Women With Gestational Hypertension and Chronic Hypertension in Pregnancy
Kalafat, Erkan; Perry, Helen; Bowe, Sophie; Thilaganathan, Basky; Khalil, Asma (Ovid Technologies (Wolters Kluwer Health), 2020-08-01)
This study aimed to assess the prognostic value of cardiovascular assessment in women with gestational hypertension or chronic hypertension for the risk of preeclampsia and need for closer antenatal surveillance. This was a prospective study of pregnancies complicated by gestational hypertension or chronic hypertension presenting to St George's Hospital, between January 2015 and May 2018. A noninvasive ultrasonic cardiac output monitor was used to obtain cardiovascular variables of cardiac output (CO) and s...
Citation Formats
J. Binder, E. Kalafat, P. Palmrich, P. Pateisky, and A. Khalil, “Should angiogenic markers be included in diagnostic criteria of superimposed pre-eclampsia in women with chronic hypertension?,” ULTRASOUND IN OBSTETRICS & GYNECOLOGY, vol. 59, no. 2, pp. 192–201, 2022, Accessed: 00, 2022. [Online]. Available: