sFlt-1/PlGF ratio for prediction of preeclampsia in clinical routine: A pragmatic real-world analysis of healthcare resource utilisation

Abstract

Background We investigated the impact of the soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio to predict short-term risk of preeclampsia on clinical utility and healthcare resource utilisation using real-world data (RWD), and compared findings with health economic modelling from previous studies. Methods and findings This retrospective analysis compared data from the German population of a multicentre clinical study (PROGNOSIS, n = 203; sFlt-1/PlGF ratio blinded and unavailable for decision-making) with RWD from University Hospital Leipzig, Germany (n = 281; sFlt-1/PlGF ratio used to guide clinical decision-making). A subgroup of the RWD cohort with the same inclusion criteria as the PROGNOSIS trial (RWD prediction only, n = 99) was also included. sFlt-1/PlGF ratio was measured using fully automated Elecsys® sFlt-1 and PlGF immunoassays (cobas e analyser; Roche Diagnostics). A similar proportion of women in the RWD and PROGNOSIS cohorts experienced preeclampsia (14.95% vs. 13.79%; p = 0.7938); a smaller proportion of women in the RWD prediction only cohort experienced preeclampsia versus PROGNOSIS (6.06%; p = 0.0526). In women with preeclampsia, median gestational age at delivery (weeks) was comparable in the RWD and PROGNOSIS cohorts (34.0 vs. 34.3, p = 0.5895), but significantly reduced in the RWD prediction only cohort versus PROGNOSIS (27.1, p = 0.0038). sFlt-1/PlGF ratio at baseline visit was not statistically significantly different for the RWD and PROGNOSIS cohorts, irrespective of preeclampsia outcome. Hospitalisations for confirmed preeclampsia were significantly shorter in the RWD cohort versus PROGNOSIS (median 1 vs. 4 days, p = 0.0093); there was no significant difference between RWD prediction only and PROGNOSIS (3 days, p = 0.9638). All-cause hospitalisations were significantly shorter in the RWD (median 1 day; p<0.0001) and RWD prediction only (1 day; p<0.0001) cohorts versus PROGNOSIS (3 days). Conclusions This study supports the findings of previous studies, showing that routine clinical use of the sFlt-1/PlGF ratio may result in shorter duration of hospitalisations, with potential economic benefits.

Literature Review: The sFlt1/PlGF Ratio and Pregestational Maternal Comorbidities: New Risk Factors to Predict Pre-Eclampsia

“…The first data confirming the hypotheses about the imbalance of angiogenic and antiangiogenic proteins in pre-eclampsia patients were collected when Levine et al (2004) found that, in pre-eclampsia, the levels of sFlt-1 increased while those of PlGF decreased [ 14 ]. In the following few years, these data have been repeatedly confirmed [ 7 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”

The endocannabinoidome in human placenta: Possible contribution to the pathogenesis of preeclampsia

“…The most widely used clinical predictor of the development of PE in current clinical practice is the sFLT1/PlGF ratio of above 38 52 . However, depending on the demographic profile tested, even though the predictive value for the development of PE in the following week is very good (99.3%), this value drops significantly for the prediction in the next 4 weeks (36.7% with 66.2% sensitivity and 83.1% specificity) 53 .…”

New immune horizons in therapeutics and diagnostic approaches to Preeclampsia

“…The sFlt-1 to PlGF ratio is increased in pregnant women before the onset of PE with an elevated ratio suggestive of PE, whereas the diagnosis of PE can be ruled out within 1 week for low ratios. [218][219][220][221][222] The search for potential biomarkers for PE yielded no definite markers to predict the disease's onset. Close real-time monitoring of maternal and fetal status and vital parameters is the key before labor onset.…”

“…There are not too many confirmatory, reliable screening or diagnostic tests for PE that could conclusively diagnose this condition with certainty. The sFlt‐1 to PlGF ratio is increased in pregnant women before the onset of PE with an elevated ratio suggestive of PE, whereas the diagnosis of PE can be ruled out within 1 week for low ratios 218–222 . The search for potential biomarkers for PE yielded no definite markers to predict the disease's onset.…”