Angiogenic factors and prediction of adverse pregnancy outcomes in suspected preeclampsia: the PROGNOSIS study

Dysregulated angiogenic factors in the maternal circulation, including high soluble fms-like tyrosine kinase-1 (sFlt-1) and low placental growth factor (PlGF), as well as their ratio (sFlt1/PlGF), have been investigated as a diagnostic and prediction marker of preeclampsia. These circulating markers may represent markers for syncytiotrohoblast stress and placentally associated pregnancy complications, which represent major threats to maternal and offspring health globally. The talk will present recently published results from the PROGNOSIS [1,2] study as well as discuss future potential clinical and research implications of the study findings. PROGNOSIS was a prospective, multicenter, observational study in pregnancy where preeclampsia was suspected (gestational weeks 24 to 36+6days). Maternal serum sFlt-1 and PlGF were measured after delivery (the results were unknown for clinicians) using Elecsys® sFlt-1 and PlGF assays (cobas e electrochemiluminescence immunoassay platform). The results from the development and validation cohorts ( n =500 and 550 pregnancies) identified an sFlt-1/PlGF ratio cut-off of 38 to optimally predict preeclampsia and that a ratio of ⩽38 is useful for predicting short-term absence of preeclampsia in women in whom the syndrome is suspected clinically [1]. In our second PROGNOSIS published paper [2], we found that pregnancies with an sFlt-1/PlGF ratio >38 had three-times greater likelihood of preterm delivery and a substantially shorter remaining time to delivery than women with an sFlt-1/PlGF ratio of 38 or lower, whether or not they developed preeclampsia. Women who had iatrogenic preterm delivery (without preeclampsia) had higher median sFlt-1/PlGF ratios at the first study visit versus women with spontaneous preterm or at-term delivery. Clinical implications include the need for testing whether the use of the sFlt1/PlGF ratio to guide clinical decisions, as compared with usual care, will improve clinical outcome for mother and offspring. If cost-efficient, the use of circulating biomarkers can revolutionize the obstetric surveillance in countries that can offer such follow-up.