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

Abstract

Pre‐eclampsia (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 placenta‐related disorders. In this Review, we summarize the existing knowledge, examining the performance of maternal PlGF, sFlt‐1 and the sFlt‐1/PlGF ratio for screening PE, predicting development of PE in the short term, diagnosing PE, monitoring established PE and predicting other placenta‐related disorders in singleton pregnancy. We also discuss the performance of PlGF and the sFlt‐1/PlGF ratio for predicting PE in twin pregnancy. For first‐trimester screening in singleton pregnancy, a more accurate way of identifying high‐risk women than current practice is to combine maternal PlGF levels with clinical risk factors and ultrasound markers. 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. It has clinical value because it can rule out the development of PE in the 1–4‐week period after the test. Once a diagnosis of PE is established, repeat measurement of sFlt‐1 and PlGF can help monitor progression of the condition and may inform clinical decision‐making regarding the 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 is unclear. The sFlt‐1/PlGF ratio can be used to predict PE in twin pregnancy, although different sFlt‐1/PlGF ratio cut‐offs from those for singleton pregnancy 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 placenta‐related disorders in singleton and twin pregnancy. We propose that tests for these angiogenic factors are integrated more fully into clinical practice.© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Circulating biomarkers associated with placental dysfunction and their utility for predicting fetal growth restriction

“…However, there are several circulating biomarkers that are clearly associated with adverse outcomes, none have yet, either alone or in combination, been shown to be sufficiently reliable to be used in clinical practice [ 147 ]. Some, such as PlGF [ 148 ] and sFlt-1 [ 149 ] show the most promise but require further validation to determine their screening performance. More importantly, however, it is important to determine if a policy of screening for disorders related to placental dysfunction results in improvements in clinical outcomes.…”

Identification of miRNAs Involved in Foetal Growth Restriction Due to Maternal Smoking during Pregnancy

“…A decrease in PLGF is related to the risk of suffering pre-eclampsia, the pathophysiology of which is closely related to that of IUGR. Indeed, PLGF is currently used clinically for the early diagnosis of pre-eclampsia and IUGR [ 26 , 27 , 28 ].…”

Literature Review: The sFlt1/PlGF Ratio and Pregestational Maternal Comorbidities: New Risk Factors to Predict Pre-Eclampsia

“…Using the sFlt1/PlGF ratio may help to make short-term predictions about the development of the disease pathology and also serves as a reason for immediate hospitalization ( Figure 2 ) [ 37 , 38 ].…”