OBJECTIVE: The soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is mostly elevated some time before and at the clinical onset of preeclampsia. The PROGNOSIS study validated a ratio cut-off of ≤ 38 to rule out onset of preeclampsia for 1 week in women with suspected disease. This analysis assessed the mid-term predictive value of the sFlt-1/PlGF ratio and the effect of repeat measurement vs a single test. METHODS: An exploratory post-hoc analysis of data from PROGNOSIS was performed in pregnant women (≥ 18 years, gestational weeks 24 + 0 to 36 + 6 days at Visit 1) with suspected preeclampsia. Serum samples were collected at first clinic visit and weekly thereafter; sFlt-1 and PlGF levels were measured using Elecsys® sFlt-1 and PlGF immunoassays. We examined whether the 1-week rule-out value of ≤ 38 sFlt-1/PlGF ratio could predict the absence of preeclampsia 2, 3, and 4 weeks post-baseline. We also assessed the value of repeat sFlt-1/PlGF testing by examining the difference in sFlt-1/PlGF ratio 2 and 3 weeks after the first sample in women with/without preeclampsia/adverse fetal outcome. RESULTS: In an analysis of 550 women, preeclampsia was ruled out 2 and 3 weeks post-baseline with high negative predictive value (NPV; 97.9% and 95.7%, respectively). Within 4 weeks, preeclampsia was ruled out with high NPV (94.3%) and high sensitivity and specificity (66.2% and 83.1%, respectively). Women who developed preeclampsia had significantly larger median increases in sFlt-1/PlGF ratio 2 and 3 weeks post-initial visit, vs those who did not (2 weeks: Δ 31.22 vs Δ 1.45, P < 0.001; 3 weeks: Δ 48.97 vs Δ 2.39, P < 0.001). Women who developed preeclampsia and/or a fetal adverse outcome had a significantly greater median increase in sFLt-1/PlGF ratio over the same period (2 weeks: Δ 21.22 vs Δ 1.40, P < 0.001; 3 weeks: Δ 34.95 vs Δ 2.30, P < 0.001). CONCLUSION: The Elecsys® sFlt-1/PlGF immunoassay ratio can help to rule out preeclampsia for 4 weeks in women with suspected preeclampsia. This article is protected by copyright. All rights reserved.
Ultrasound Obstet Gynecol
Angiogenic factors, PROGNOSIS, PlGF, preeclampsia, retesting, rule out, sFlt-1, sFlt-1/PlGF