Meta-Analysis and Systematic Review to Assess the Role of Soluble FMS-Like Tyrosine Kinase-1 and Placenta Growth Factor Ratio in Prediction of Preeclampsia

Abstract

Preeclampsia is a major cause of morbidity and mortality worldwide. Numerous candidate biomarkers have been proposed for diagnosis and prediction of preeclampsia. Measurement of maternal circulating angiogenesis biomarker as the ratio of sFlt-1 (soluble FMS-like tyrosine kinase-1; an antiangiogenic factor)/PlGF (placental growth factor; an angiogenic factor) reflects the antiangiogenic balance that characterizes incipient or overt preeclampsia. The ratio increases before the onset of the disease and thus may help in predicting preeclampsia. We conducted a meta-analysis to explore the predictive accuracy of sFlt-1/PlGF ratio in preeclampsia. We included 15 studies with 534 cases with preeclampsia and 19 587 controls. The ratio has a pooled sensitivity of 80% (95% confidence interval, 0.68-0.88), specificity of 92% (95% confidence interval, 0.87-0.96), positive likelihood ratio of 10.5 (95% confidence interval, 6.2-18.0), and a negative likelihood ratio of 0.22 (95% confidence interval, 0.13-0.35) in predicting preeclampsia in both high- and low-risk patients. Most of the studies have not made a distinction between early- and late-onset disease, and therefore, the analysis for it could not be done. It can prove to be a valuable screening tool for preeclampsia and may also help in decision-making, treatment stratification, and better resource allocation.

How to identify pregnant women at risk of pre-eclampsia? — a review of the current literature

“…The pooled sensitivity of sFlt-1:PlGF ratio in predicting PE was 0.80 (95% CI 0.68-0.88) and the pooled specificity was 0.92 (95% CI 0.87-0.96). The positive LR was 10.5 (6.2-18) and negative LR 0.22 (0.13-0.35), which are very similar to the expected performance of a useful prediction test for PE [3]. Therefore, if the test is positive, the probability of having PE increases to 78%, while if the test is negative, it decreases to 7%.…”

“…It included maternal factors, UTPI, MAP, PlGF and serum soluble fms-like tyrosine kinase-1 (sFlt-1) [2]. sFlt-1, also known as soluble vascular endothelial growth factor (VEGF) receptor 1 binds both circulating VEGF and PlGF, thus decreasing their concentration in uteroplacental and maternal circulation [3]. In PE, circulating maternal serum levels of sFlt-1 are increased, and PlGF levels are decreased [13,14].…”

“…In Poland the estimated number of women suffering from hypertension during pregnancy is around 30,000 per year. Although pre-eclampsia (PE) affects 2-3 % of patients, it carries a great risk of maternal and perinatal mortality and morbidity [1][2][3]. According to the World Health Report of 2005, 12% of all maternal deaths were related to eclampsia worldwide [4].…”

Management of hypertension in pregnancy — prevention, diagnosis, treatment and long-term prognosis. A position statement of the Polish Society of Hypertension, Polish Cardiac Society and Polish Society of Gynaecologists and Obstetricians

“…In a normal pregnancy, PLGF and sFlt-1 are the prerequisites necessary for normal placental development. It has also been shown that in women with PE, the sFlt-1 level starts increasing from the second trimester, whereas the PLGF level starts decreasing at the end of the first trimester [113]. Importantly, this decrease in placental growth factor (PLGF) level and the increase in sFlt-1 level precede the onset of PE by even 5 weeks.…”

P‐Glycoprotein (P‐gp)/ABCB1 plays a functional role in extravillous trophoblast (EVT) invasion and is decreased in the pre‐eclamptic placenta

“…Low-dose aspirin has been shown to have a protective effect, 5 and blood tests to identify patients at high risk through elevated soluble FMS-like tyrosine kinase-1:placental growth factor ratios are now being used in certain populations with some success. 6 With regard to IUGR, genetic factors have begun to be compiled. 7 While little is known about PE and IUGR aetiology, placental pathology is known to be involved and may play a central role.…”