sFLT1, PlGF, the sFLT1/PlGF Ratio and Their Association with Pre-Eclampsia in Twin Pregnancies—A Review of the Literature

Abstract

Twin pregnancies demonstrate a 2–3-fold higher chance of developing PE compared to singletons, and recent evidence has demonstrated that the sFLT1/PIGF ratio is strongly associated with PE, adverse pregnancy outcomes, as well as imminent deliveries due to PE complications. The primary objective of this systematic review was to summarise the available data on the levels of sFLT1, PlGF and their ratios in twin pregnancies and to investigate their association with the development of PE, adverse pregnancy outcomes and the timing of the delivery. A systematic search of Ovid Embase, Web of Science, Science Direct, PubMed, Ovid Medline, Google Scholar and CINAHL was carried out. sFLT1 levels and the sFLT1/PIGF ratio appeared higher in twins compared to singleton pregnancies, especially in the third trimester, while PlGF levels appeared higher up until the third trimester, with their values showing no difference or being even lower than in singletons thereafter. The sFLT1/PIGF ratio has been reported to be an independent marker of adverse outcomes related to pre-eclampsia and is associated with the mean time until delivery in an inverse manner. Further research is required in order to establish the optimal sFLT1/PIGF cut-off values and to stratify the risk of adverse outcomes in twin pregnancies.

sFlt-1 Levels as a Predicting Tool in Placental Dysfunction Complications in Multiple Pregnancies

“…Angiogenic markers are increasingly becoming part of our clinical practice for the screening, diagnosis, and monitoring of placental dysfunction disorders, especially preE and FGR. However, many questions remain about which markers to dose, the cutoffs to use, and their role in specific obstetric conditions, including their application in the case of multiple pregnancies [28,31].…”

“…In singleton pregnancies, a sFlt-1/PlGF ratio of 38 or less can be used to exclude a diagnosis of preE in women in whom the syndrome is clinically suspected [26], while gestational age-specific sFlt-1/PlGF ratio cut-offs of >85 (20 + 0 to 33 + 6 weeks) and >110 (34 + 0 weeks to delivery) have been shown to be highly suggestive of preE [27]. In multiple pregnancies, there is no clarity on which cut-offs to use [28]. Furthermore, the available data in the literature are still focused exclusively on the sFlt-1/PIGF ratio.…”