Soluble fms-like tyrosine kinase-1 and placental growth factor kinetics during and after pregnancy in women with suspected or confirmed pre-eclampsia

Objectives: To assess the evolution of the soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio in women with suspected or confirmed pre-eclampsia (PE), and to investigate the changes in sFlt-1 and PlGF levels in pre-eclamptic women after delivery. Methods: This was an exploratory study in which secondary analysis was performed on a prospective cohort study that enrolled women with a singleton pregnancy and suspected or confirmed PE from 18 weeks' gestation, carried out between December 2013 and April 2016 at the Department of Obstetrics of the Erasmus Medical Center in Rotterdam. sFlt-1 and PlGF were determined using Roche Diagnostics Elecsys assays in two groups of patients. In the first group, patients with suspected or confirmed PE had sFlt-1 and PlGF levels measured at least twice during their pregnancy. Changes in these biomarkers over the course of pregnancy were compared for patients in this group with a baseline sFlt-1/PlGF ratio of ≤38 and for those with a ratio >38. In the second group, sFlt-1 and PlGF levels of women with PE or HELLP syndrome were measured before and after delivery. For this group, pre- and postpartum sFlt-1 and PlGF levels were compared and half-lives were calculated. Results: Women with suspected or confirmed PE for whom sFlt-1 and PlGF levels were measured at least twice during pregnancy (n=46) had a median gestational age at inclusion of 26 weeks (range, 18-40 weeks). In 27 of the 30 patients with sFlt-1/PlGF ratio ≤38 at baseline, thereby ruling out PE, the sFlt-1/PlGF ratio remained stable for up to 100 days. In the remaining three patients with a ratio ≤38 and in most of the 16 patients with a ratio >38, the ratio increased further. For women diagnosed with PE or HELLP syndrome for whom sFlt-1 and PlGF levels were measured before and after delivery (n=26), median gestational age at inclusion was 29 weeks (range, 16-37 weeks) and median time between antepartum measurement and delivery was 2 days (range, 1-17 days). In this group, after delivery, sFlt-1 dropped to <1% of its pre-delivery value, with a half-life of 1.4±0.3 days, while PlGF dropped to ∼30% of its pre-delivery value, with a half-life of 3.7±4.3 days. Conclusions: Based on this small cohort, up to 10% of pregnant women admitted with suspected or confirmed PE presenting with a sFlt-1/PlGF ratio of ≤38 display a rise in sFlt-1/PlGF ratio in subsequent weeks, implying that repeat determination of the sFlt-1/PlGF ratio is required to exclude definitively a diagnosis of PE. Furthermore, the rapid and pronounced decline in sFlt-1 levels after delivery in patients with PE/HELLP syndrome suggests that sFlt-1, in contrast to PlGF, is almost entirely derived from the placenta.