The prognostic utility of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PIGF) biomarkers for predicting preeclampsia: a secondary analysis of data from the INSPIRE trial

Objective To compare the prognostic performance of biomarkers soluble fms-like tyrosine kinase-1 (sFlt-1), Placental Growth Factor (PIGF), and sFlt-1/PIGF ratio as continuous values or as a binary cut-off of 38 for predicting preeclampsia (PE) within 7 days. Design Secondary analysis of a randomised clinical trial. Setting Oxford University Hospitals, Oxford, United Kingdom (UK). Population Pregnant women between 24(+0) to 37(+0) weeks of gestation with a clinical suspicion of preeclampsia. Main outcome Onset of preeclampsia within 7 days of the initial biomarker test. Methods Logistic regression model for onset of preeclampsia using: (i) sFlt-1 (ii) PIGF, (iii) sFlt-1/PIGF ratio (continuous), and (iv) sFlt-1/PIGF ratio as a cut-off above or below 38. Results Of the total 370 women, 42 (11.3%) developed PE within 7 days of screening. Models with sFlt-1 and sFlt-1/PIGF ratio (continuous) had greater overall performance than models with PIGF or with sFlt-1/PIGF ratio as a cut-off at 38 (R-2: sFlt-1 = 55%, PIGF = 38%, sFlt-1/PIGF ratio = 57%, sFlt-1/PIGF ratio as cut-off at 38 model = 46%). The discrimination performance was the highest in sFlt-1 and sFlt-1/PIGF ratio (continuous) (c-statistic, sFlt-1 = 0.94, sFlt-1/PIGF ratio (continuous) = 0.94) models compared to PIGF or sFlt-1/PIGF cut-off models (c-statistic, PIGF = 0.87, sFlt-1/PIGF cut-off = 0.89). Conclusion Models using continuous values of sFlt-1 only or sFlt-1/PIGF ratio had better predictive performance compared to a PIGF only or the model with sFlt-1/PIGF ratio as a cut-off at 38. Further studies based on a larger sample size are warranted to substantiate this finding.

Automated summary

This study compared the predictive performance of different biomarkers for the onset of preeclampsia. The results showed that models using continuous values of sFlt-1 and sFlt-1/PIGF ratio had better performance. Further research with a larger sample size is needed to confirm these findings.