Clinical Utility of sFlt-1 and PlGF in Screening, Prediction, Diagnosis and Monitoring of Pre-eclampsia and Fetal Growth Restriction

ABSTRACT Preeclampsia is a serious hypertensive disorder of pregnancy that can deteriorate into eclampsia or HELLP syndrome and ultimately result in severe maternal morbidity or mortality. In addition to possible complications for the mother, preeclampsia and its additional complications can lead to adverse outcomes for infants, both before and after birth. Because of the serious consequences associated with preeclampsia, current practice guidelines recommend the screening of all pregnant patients for risk of preeclampsia in the first trimester and consistent monitoring for the development of preeclampsia later in pregnancy. Recommendations also include that women who are diagnosed with preeclampsia are closely monitored to prevent further complications such as preterm birth, as well as monitoring for fetal growth restriction (FGR). There are serum markers that are known to be related to preeclampsia, such as proangiogenic placental growth factor (PlGF) and antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1). This article is a review aiming to summarize current knowledge about PlGF and sFlt-1, their performance, and potential alteration in diagnosis and monitoring of preeclampsia. Factors such as these have trends that occur in normal pregnancy and different trends that tend to occur in a pregnancy that is abnormal. In a healthy pregnancy, sFlt-1 increases in the third trimester, but in patients who later develop preeclampsia or FGR, it tends to increase sooner. Recent studies have shown that the interaction between sFlt-1 and PlGF reduces the amount of PlGF in circulating in the blood, causing a cascade of other effects. In addition, a decrease in PlGF is known to be associated with the development of preeclampsia. Because of this interaction, the ratio of sFlt-1 to PlGF can be used as a diagnostic tool; an increasing ratio can indicate development of preeclampsia. In addition to predicting preeclampsia, sFlt-1 and PlGF have been shown to be helpful in managing preeclampsia that has already been diagnosed. Monitoring the ratio of sFlt-1 to PlGF has shown a correlation between a higher ratio and imminent preterm delivery due to preeclampsia. It has also proven to be a predictor of other adverse outcomes such as preterm delivery and FGR, as well as stillbirth and complications of multiple pregnancies. Recent data show robust enough associations between sFlt-1 and PlGF that it can reasonably be used for predicting short-term development of preeclampsia, monitoring preeclampsia that has been previously diagnosed and predicting other disorders of the placenta. These factors can be particularly useful in guiding treatment of those whose symptoms are not a clear enough indicator on their own for preeclampsia, but who may be in danger of complications if left untreated. In particular, the most impactful clinical outcome comes when both sFlt-1 and PlGF levels are monitored, as the interaction between the 2 gives the most relevant information, whereas one or the other alone has not been shown to have practical value. Understanding the clinical utility of these levels indicates that there could be many benefits to integrating testing of the sFlt-1/PlGF ratio into preeclampsia screening and testing regimens; it could help clarify the need for treatment and predict the development of complications, which in turn could help clinicians prevent or treat complications for better outcomes for both mother and child.