Clinical utility of sFlt-1 and PlGF in screening, prediction, diagnosis and monitoring of pre-eclampsia and fetal growth restriction.

Preeclampsia (PE) is characterized by placental and maternal endothelial dysfunction, and associated with fetal growth restriction (FGR), placental abruption, preterm delivery and stillbirth. The angiogenic factors soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) are altered in pregnancies complicated by placental-related disorders. In this review, we summarize existing literature examining the performance of maternal PlGF, sFlt-1 and sFlt-1/PlGF ratio for a) screening and diagnosing PE, b) predicting PE development in the short term, c) monitoring established PE and d) predicting other placental-related disorders. We also discuss the performance of PlGF and the sFlt-1/PlGF ratio for predicting PE in twin pregnancies. For first trimester screening, a more accurate way of identifying high-risk women than current practices is to combine PlGF levels with clinical risk factors and ultrasound markers. To support diagnosis of PE later in pregnancy, the sFlt-1/PlGF ratio has advantages over PlGF because it has a higher pooled sensitivity and specificity for diagnosing and monitoring PE. The sFlt-1/PlGF ratio has clinical value because it can rule out the development of PE in the subsequent 1-4 weeks after the test. Once diagnosis of PE is established, repeated measurement of sFlt-1 and PlGF can help monitor progression of the condition and may inform clinical decision-making around optimal time for delivery. The sFlt-1/PlGF ratio is useful for predicting FGR and preterm delivery, but the association between stillbirth and the angiogenic factors remains unclear. The sFlt-1/PlGF ratio can also be used to predict PE in twin pregnancies, although different sFlt-1/PlGF ratio cut-offs to those of singleton pregnancies should be applied for optimal performance. In summary, PlGF, sFlt-1 and the sFlt-1/PlGF ratio are useful for screening, diagnosing, predicting, and monitoring placental-related disorders in singleton and twin pregnancies; we propose further integration of these angiogenic factor tests in clinical practice. This article is protected by copyright. All rights reserved.