8 The sFlt-1/PLGF ratio can rule out preeclampsia for up to four weeks in women with suspected preeclampsia: Risk factors, prediction of preeclampsia

Introduction Clinical signs and symptoms of preeclampsia are known to be poorly predictive of who will develop the condition, prompting the investigation of angiogenic biomarkers as potential diagnostic and predictive aids. The Elecsys® immunoassay soluble fms-like tyrosine kinase (sFlt-1)/placental growth factor (PlGF) ratio is Conformite Europeenne-In Vitro Diagnostics approved as a diagnostic aid for preeclampsia, and as an aid in the short-term prediction of preeclampsia (rule out and rule in) in pregnant women with suspected preeclampsia in conjunction with other diagnostic and clinical information. In the Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study (PROGNOSIS), a cut-off value of 38 was derived and validated to rule out preeclampsia and HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome within one week (Zeisler et al. N Engl J Med 2016;374:13–22). However, the ability of the sFlt-1/PlGF ratio to rule out preeclampsia up to four weeks in women with suspected disease has not been determined. Objectives We aimed to establish the negative predictive values (NPVs) applying the Elecsys® immunoassay sFlt-1/PlGF ratio cut-off value of 38 to rule out preeclampsia within two to four weeks after testing in women with suspected preeclampsia. Methods PROGNOSIS was a prospective, observational, multicenter study, which validated the sFlt-1/PlGF ratio cut-off value of 38 to reliably rule out preeclampsia within one week in women who had clinical signs and symptoms of the syndrome (gestational age 24w+0d–36w+6d). We performed a post-hoc analysis of the data from the validation cohort of 550 participants to determine the NPV of this ratio cut-off value to rule out preeclampsia within two, three and four weeks after testing. Results A total of 550 participants from the PROGNOSIS validation cohort were included in this analysis (median age 31years; median pre-pregnancy body mass index 26.2kg/m 2 ; median systolic blood pressure 128.0mmHg; median gestation week 31w+3d; 79 (14%) were current smokers; 418 (76%) were white/Caucasian). Of these, 98 (18%) developed preeclampsia/HELLP syndrome at some point during their pregnancy: 15 (3%) within one week; 41 (7%) within two weeks; 60 (11%) within three weeks; and 71 (13%) within four weeks. The NPV to rule out preeclampsia in women with sFlt-1/PlGF values of 38 and below within two, three and four weeks of testing was 97.9% (95% confidence interval [CI]: 96.0–99.0), 95.7% (95% CI: 93.3–97.5), and 94.3% (95% CI: 91.7–96.3), respectively (Table). Conclusions This post-hoc analysis of PROGNOSIS shows that sFlt-1/PlGF ratios of 38 and below could rule out preeclampsia for up to four weeks after testing with high NPV in women with suspicion of the syndrome.