Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia

Harald Zeisler, Elisa Llurba, Frédéric Chantraine, Manu Vatish, Anne Cathrine Staff, Maria Sennström, Matts Olovsson, Shaun P. Brennecke, Holger Stepan, Deirdre Allegranza,

New England Journal of Medicine · 2016 · 1.7K citations · 31 references

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TL;DR

The sFlt‑1:PlGF ratio rises before clinical preeclampsia, but its predictive value in suspected cases is unclear. The study aimed to determine whether a low ratio predicts absence of preeclampsia within one week and a high ratio predicts presence within four weeks. A prospective, multicenter, observational design derived a cutoff of 38 from 500 women and validated it in 550 additional participants. In validation, a ratio ≤38 had a 99.3 % negative predictive value for one‑week absence (80 % sensitivity, 78 % specificity), while a ratio >38 had a 36.7 % positive predictive value for four‑week diagnosis (66 % sensitivity, 83 % specificity). Funded by Roche Diagnostics.

Abstract

The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is elevated in pregnant women before the clinical onset of preeclampsia, but its predictive value in women with suspected preeclampsia is unclear.We performed a prospective, multicenter, observational study to derive and validate a ratio of serum sFlt-1 to PlGF that would be predictive of the absence or presence of preeclampsia in the short term in women with singleton pregnancies in whom preeclampsia was suspected (24 weeks 0 days to 36 weeks 6 days of gestation). Primary objectives were to assess whether low sFlt-1:PlGF ratios (at or below a derived cutoff) predict the absence of preeclampsia within 1 week after the first visit and whether high ratios (above the cutoff) predict the presence of preeclampsia within 4 weeks.In the development cohort (500 women), we identified an sFlt-1:PlGF ratio cutoff of 38 as having important predictive value. In a subsequent validation study among an additional 550 women, an sFlt-1:PlGF ratio of 38 or lower had a negative predictive value (i.e., no preeclampsia in the subsequent week) of 99.3% (95% confidence interval [CI], 97.9 to 99.9), with 80.0% sensitivity (95% CI, 51.9 to 95.7) and 78.3% specificity (95% CI, 74.6 to 81.7). The positive predictive value of an sFlt-1:PlGF ratio above 38 for a diagnosis of preeclampsia within 4 weeks was 36.7% (95% CI, 28.4 to 45.7), with 66.2% sensitivity (95% CI, 54.0 to 77.0) and 83.1% specificity (95% CI, 79.4 to 86.3).An sFlt-1:PlGF ratio of 38 or lower can be used to predict the short-term absence of preeclampsia in women in whom the syndrome is suspected clinically. (Funded by Roche Diagnostics.).

References

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